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Sample records for hiv-related clinical endpoints

  1. Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials

    DEFF Research Database (Denmark)

    Lifson, A; Rhame, F; Bellosa, W

    2006-01-01

    adjudication between reviewers before diagnostic certainty was assigned. CONCLUSION: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation......PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression...... and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure...

  2. Planning and analyzing clinical trials with composite endpoints

    CERN Document Server

    Rauch, Geraldine; Kieser, Meinhard

    2017-01-01

    This book addresses the most important aspects of how to plan and evaluate clinical trials with a composite primary endpoint to guarantee a clinically meaningful and valid interpretation of the results. Composite endpoints are often used as primary efficacy variables for clinical trials, particularly in the fields of oncology and cardiology. These endpoints combine several variables of interest within a single composite measure, and as a result, all variables that are of major clinical relevance can be considered in the primary analysis without the need to adjust for multiplicity. Moreover, composite endpoints are intended to increase the size of the expected effects thus making clinical trials more powerful. The book offers practical advice for statisticians and medical experts involved in the planning and analysis of clinical trials. For readers who are mainly interested in the application of the methods, all the approaches are illustrated with real-world clinical trial examples, and the software codes requ...

  3. The impact of endpoint measures in rheumatoid arthritis clinical trials

    NARCIS (Netherlands)

    van der Heide, A.; Jacobs, J. W.; Dinant, H. J.; Bijlsma, J. W.

    1992-01-01

    In clinical trials on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), it is common to apply a large number of endpoint measures. This practice has several disadvantages. To determine which endpoint measures are most valuable, reports of

  4. Sample size determination in clinical trials with multiple endpoints

    CERN Document Server

    Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2015-01-01

    This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...

  5. The Asthma Control Questionnaire as a clinical trial endpoint

    DEFF Research Database (Denmark)

    Barnes, P J; Casale, T B; Dahl, Ronald

    2014-01-01

    these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly...

  6. Modeling hard clinical end-point data in economic analyses.

    Science.gov (United States)

    Kansal, Anuraag R; Zheng, Ying; Palencia, Roberto; Ruffolo, Antonio; Hass, Bastian; Sorensen, Sonja V

    2013-11-01

    The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (Models of infrequent events or with numerous health states generally preferred constant event rates. The detailed modeling information and terminology varied, sometimes requiring interpretation. Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are

  7. Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

    Science.gov (United States)

    Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

    2018-06-01

    Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

  8. Is Doubling of Serum Creatinine a Valid Clinical 'Hard' Endpoint in Clinical Nephrology Trials?

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; Perkovic, V.; de Zeeuw, D.

    2011-01-01

    The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large

  9. Using a clinic based creativity initiative to reduce HIV related stigma ...

    African Journals Online (AJOL)

    Methods: This was a repeated cross-sectional survey (October-November 2005 and March-April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) ... Conclusions: The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ...

  10. Clinical features and management of non-HIV related lipodystrophy in children: A systematic review

    Science.gov (United States)

    Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, Scopus and Non-Indexe...

  11. Patients’ preferences for selection of endpoints in cardiovascular clinical trials

    Directory of Open Access Journals (Sweden)

    Robert D. Chow

    2014-02-01

    Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but

  12. 76 FR 51993 - Draft Guidance for Industry on Standards for Clinical Trial Imaging Endpoints; Availability

    Science.gov (United States)

    2011-08-19

    ... clinical trials of therapeutic drugs and biological products. The draft guidance describes standards... important imaging endpoint is used in a clinical trial of a therapeutic drug or biological product... Services to the Chairman of [[Page 51994

  13. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    Science.gov (United States)

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  14. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

    Science.gov (United States)

    Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

    2014-01-01

    To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies

  15. A web-based endpoint adjudication system for interim analyses in clinical trials.

    Science.gov (United States)

    Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis

    2009-02-01

    A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However

  16. Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

    Science.gov (United States)

    Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

    2015-06-25

    Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

  17. Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

    Science.gov (United States)

    Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

    2013-01-01

    Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Using a clinic based creativity initiative to reduce HIV related stigma at the Infectious Diseases Institute, Mulago National Referral Hospital, Uganda.

    Science.gov (United States)

    Neema, S; Atuyambe, L M; Otolok-Tanga, E; Twijukye, C; Kambugu, A; Thayer, L; McAdam, K

    2012-06-01

    Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a major impact on public health interventions. The initiative was to provide activities in the clinic while patients waited to be seen by healthcare professionals. It was envisaged this would contribute to reduction of clinic based stigma felt by clients. This was a repeated cross-sectional survey (October-November 2005 and March-April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) at Mulago, the national referral hospital in Uganda. We utilized quantitative (survey) and qualitative (key informants, focus group discussions) methods to collect the data. Data were collected on stigma before the creativity initiative intervention was implemented, and a second phase survey was conducted to assess effectiveness of the interventions. Clients who attended the IDC before the creativity intervention were about twice as likely to fear catching an infection as those who came after the intervention. The proportion that had fears to be seen by a friend or relative at the clinic decreased. Thus during the implementation of the Creativity intervention, HIV related stigma was reduced in this clinic setting. The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ambiance at the clinic and clients became empowered, with creative, communication and networking skills. Improved knowledge and communication are key in addressing self stigma among HIV positive individuals.

  19. A conscious mouse model of gastric ileus using clinically relevant endpoints

    Directory of Open Access Journals (Sweden)

    Shao Yuanlin

    2005-06-01

    Full Text Available Abstract Background Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. Methods Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. Results Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. Conclusion Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of

  20. Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

    Science.gov (United States)

    Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

    2015-02-10

    Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients.

    Science.gov (United States)

    Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi

    2013-01-01

    Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

  2. Traditional and new composite endpoints in heart failure clinical trials : facilitating comprehensive efficacy assessments and improving trial efficiency

    NARCIS (Netherlands)

    Anker, Stefan D. t; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J.; Ceconi, Claudio; Cowie, Martin R.; AdamCrisp,; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A.; Holcomb, Richard; Honarpour, Narimon; Jukema, J. Wouter; Kim, Albert M.; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A.; McMurray, John J.; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M. C.; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A.; Ruschitzka, Frank

    Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and

  3. The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research.

    Science.gov (United States)

    Roy, Neeta S; Wei, Yi; Kuklinski, Eric; Asbell, Penny A

    2017-05-01

    medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.

  4. Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical trials with ultrasound endpoints.

    Science.gov (United States)

    Allen, John C; Thumboo, Julian; Lye, Weng Kit; Conaghan, Philip G; Chew, Li-Ching; Tan, York Kiat

    2018-03-01

    To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H 0 : ES = 0 versus alternative hypotheses H 1 : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  5. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Hoskin, Peter [Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Mitera, Gunita; Zeng Liang [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Lutz, Stephen [Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, OH (United States); Roos, Daniel [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Linden, Yvette van der [Radiotherapeutic Institute Friesland, Leeuwarden (Netherlands); Hartsell, William [Department of Radiation Oncology, Advocate Good Samaritan Cancer Center, Downers Grove, IL (United States); Kumar, Eshwar [Department of Oncology, Atlantic Health Sciences Cancer Centre, Saint John Regional Hospital, Saint John, NB (Canada)

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  6. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials

    DEFF Research Database (Denmark)

    Bottomley, Andrew; Pe, Madeline; Sloan, Jeff

    2016-01-01

    Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are anal......Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures...... are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient......-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes...

  7. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    International Nuclear Information System (INIS)

    Chow, Edward; Hoskin, Peter; Mitera, Gunita; Zeng Liang; Lutz, Stephen; Roos, Daniel; Hahn, Carol; Linden, Yvette van der; Hartsell, William; Kumar, Eshwar

    2012-01-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  8. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  9. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Science.gov (United States)

    2010-04-01

    ... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... well-controlled. The applicant shall carry out any such studies with due diligence. ...

  10. Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

    Science.gov (United States)

    Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

    2013-03-01

    In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

    Science.gov (United States)

    Zhou, Heng; Lee, J Jack; Yuan, Ying

    2017-09-20

    We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment

    NARCIS (Netherlands)

    de Glas, N. A.; Hamaker, M. E.; Kiderlen, M.; de Craen, A. J. M.; Mooijaart, S. P.; van de Velde, C. J. H.; van Munster, B. C.; Portielje, J. E. A.; Liefers, G. J.; Bastiaannet, E.

    2014-01-01

    With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of

  13. Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

    Science.gov (United States)

    Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

    2018-06-01

    Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

  14. Nonadherence is Associated with Lack of HIV-Related Knowledge

    DEFF Research Database (Denmark)

    Dyrehave, Charlotte; Rasmussen, Dlama Nggida; Hønge, Bo Langhoff

    2016-01-01

    -sectional study included 494 HIV-infected individuals from the Bissau HIV Cohort in Guinea-Bissau. They completed a questionnaire designed for assessment of adherence and HIV-related knowledge. RESULTS: A majority were female, 41% were illiterate, 25% did not take the medicine during the last 4 days, and 23......BACKGROUND: Poor treatment adherence is a main barrier for effective antiretroviral therapy (ART) globally. HIV-related knowledge may affect understanding and utilization of HIV medical information, hence limited health literacy is a known barrier to treatment adherence. DESIGN AND METHODS: A cross......% skipped their medicine during weekends. The most frequent reasons for not taking medicine were simply forgetting, side effects, lack of food, and being too ill to attend the clinic. Nonadherent patients had a lower level of HIV-related knowledge. CONCLUSION: Main barriers for nonadherence were side...

  15. How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

    Directory of Open Access Journals (Sweden)

    Carolin Vegvari

    Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

  16. HIV related renal disease in Africans | Elangovan | IMTU Medical ...

    African Journals Online (AJOL)

    Renal disease is becoming an increasingly prevalent entity in human immunodefi ciency virus (HIV)–infected patients, first diagnosed in AIDS patients in 1984. The HIV-related renal disease represents a spectrum of clinical and histological conditions presenting as acute renal failure, chronic renal failure, glomerulopathies, ...

  17. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2017-10-01

    US Food and Drug Administration Perspective.” Both manuscripts have been attached to annual report submitted to Department of Defenses in November...follow-up, conduct weekly telephone meetings with site data managers , and conduct monthly telephone meetings with site PIs (Months 23-75) Completed...Measurement in Cancer Clinical Trials: The US Food and Drug Administration Perspective. Cancer, 2014 Mar 1;120(5):761-7. doi: 10.1002/cncr.28470

  18. TBI Endpoints Development

    Science.gov (United States)

    2015-10-01

    therapy , and early mild physical activity, which result in fewer symptoms, lower mean severity of symptoms, less social disability, and fewer days off work...developing more precise TBI diagnostic tools, clinical endpoints, and effective therapies . We designed and executed an interactive program that combined...surgery, neuropsychology, neuroradiology, psychiatry, neurology, sports medicine, pediatrics, geriatrics , health economics, biostatistics, and informatics

  19. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    Science.gov (United States)

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  20. Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

    Science.gov (United States)

    Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

    2017-10-01

    Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

  1. Existentially informed HIV-related psychotherapy.

    Science.gov (United States)

    Farber, Eugene W

    2009-09-01

    This article describes an existentially informed approach to conducting psychotherapy with individuals living with the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). Uses of existential concepts to guide a holistic conceptualization of the individual and illuminate core existential concerns and dilemmas in confronting HIV-related challenges are delineated. Applications of existential ideas regarding psychotherapy process and technique in HIV-related psychotherapy also are illustrated. It is concluded that existential psychotherapy offers a conceptual framework that is especially well suited to the work of psychotherapy with individuals living with HIV disease, although the approach has received only limited attention in the HIV-related psychotherapy literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  2. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Laura K Erdman

    Full Text Available Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.We studied children with WHO-defined clinical pneumonia (n = 155 within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30, other infiltrates (n = 31, or normal chest x-ray (n = 94. Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8, 80.8% specificity (72.6-87.1, positive likelihood ratio 4.9 (3.4-7.1, negative likelihood ratio 0

  3. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

    Science.gov (United States)

    Erdman, Laura K.; D’Acremont, Valérie; Hayford, Kyla; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Alamo, Leonor; Streiner, David L.; Genton, Blaise; Kain, Kevin C.

    2015-01-01

    Background Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. Methods We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. Results Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7

  4. Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review.

    Science.gov (United States)

    Bartoszko, Justyna; Vorobeichik, Leon; Jayarajah, Mohandas; Karkouti, Keyvan; Klein, Andrew A; Lamy, Andre; Mazer, C David; Murphy, Mike; Richards, Toby; Englesakis, Marina; Myles, Paul S; Wijeysundera, Duminda N

    2017-06-30

    'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. This scoping review of the previously published literature does not require research ethics approval. The results will be used

  5. Splenic irradiation in HIV-related thrombocytopenia

    International Nuclear Information System (INIS)

    Leung, J.T.; Kuan, R.

    1996-01-01

    Splenic irradiation has been used in patients with HIV-related thrombocytopenia. This retrospective review deals with four patients treated with low dose splenic irradiation. All patients had an increase in platelet count and tolerated the treatment without side effects. However, the treatment response lasted for several months only. 9 refs., 1 tab

  6. A Review of Clinical Trial Endpoints of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension and How They Relate to Patient Outcomes in the United States.

    Science.gov (United States)

    Divers, Christine; Platt, David; Wang, Edward; Lin, Jay; Lingohr-Smith, Melissa; Mathai, Stephen C

    2017-01-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subgroups of pulmonary hypertension and are considered rare diseases. Understanding how endpoints of clinical trials (and patient registry studies) of patients with PAH and CTEPH are associated with patient outcomes is important in order to address the concerns of patients, health care providers, decision makers, and payers. The purpose of this review was to examine how endpoints used in clinical trials and patient registry studies are associated with outcomes of patients with PAH and CTEPH. A PubMed literature search was conducted to retrieve published studies, including randomized phase III clinical trials and observational studies, from years 2000 to May 2015 that evaluated the associations between change in 6-minute walking distance (6MWD), 6MWD thresholds, change in World Health Organization functional class (WHO-FC), and time to clinical worsening with outcomes of patients with PAH and CTEPH. Based on this review of published literature, a reduction in 6MWD as a criterion for PAH worsening, a deterioration in WHO-FC, and delay in the time to clinical worsening are clinically meaningful trial endpoints and are associated with outcomes of patients with PAH and CTEPH. Utilization and standardization of these endpoints will be useful for comparing interventions of clinical trials and therapies. Hospitalizations are frequent among patients with PAH and CTEPH, and total health care costs are high. From a U.S. payer perspective, clinical worsening is an important composite endpoint in that it includes hospitalization, which can be transformed into a preventative cost value associated with efficacious treatment of patients with PAH and CTEPH. In view of the greater number of medications available to treat PAH, the introduction of the first approved therapy to treat CTEPH, and the increasing use of combination pharmacotherapy, reliable prognostic markers of treatment

  7. Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition

    DEFF Research Database (Denmark)

    Zannad, F.; Stough, W.G.; Pitt, B.

    2008-01-01

    Specific criteria have been established to define the occurrence of myocardial infarction (MI) and stroke in cardiovascular clinical trials, but there is not a consistent definition for heart failure. Heart failure events appear to occur at a rate that is similar to stroke and MI in trials...... of hypertension, hyperlipidaemia, diabetes, and coronary heart disease, yet a consistent approach to defining heart failure events has not yet been realized. The wide range of definitions used in clinical trials makes it difficult to interpret new data in the context of existing literature. This inconsistency has...... led to challenges in determining the incidence of heart failure in cardiovascular studies and the effects of interventions on these endpoints. This paper examines issues related to defining heart failure events in cardiovascular clinical trials and presents a definition to formally address this issue...

  8. Angiographic core laboratory reproducibility analyses: implications for planning clinical trials using coronary angiography and left ventriculography end-points.

    Science.gov (United States)

    Steigen, Terje K; Claudio, Cheryl; Abbott, David; Schulzer, Michael; Burton, Jeff; Tymchak, Wayne; Buller, Christopher E; John Mancini, G B

    2008-06-01

    To assess reproducibility of core laboratory performance and impact on sample size calculations. Little information exists about overall reproducibility of core laboratories in contradistinction to performance of individual technicians. Also, qualitative parameters are being adjudicated increasingly as either primary or secondary end-points. The comparative impact of using diverse indexes on sample sizes has not been previously reported. We compared initial and repeat assessments of five quantitative parameters [e.g., minimum lumen diameter (MLD), ejection fraction (EF), etc.] and six qualitative parameters [e.g., TIMI myocardial perfusion grade (TMPG) or thrombus grade (TTG), etc.], as performed by differing technicians and separated by a year or more. Sample sizes were calculated from these results. TMPG and TTG were also adjudicated by a second core laboratory. MLD and EF were the most reproducible, yielding the smallest sample size calculations, whereas percent diameter stenosis and centerline wall motion require substantially larger trials. Of the qualitative parameters, all except TIMI flow grade gave reproducibility characteristics yielding sample sizes of many 100's of patients. Reproducibility of TMPG and TTG was only moderately good both within and between core laboratories, underscoring an intrinsic difficulty in assessing these. Core laboratories can be shown to provide reproducibility performance that is comparable to performance commonly ascribed to individual technicians. The differences in reproducibility yield huge differences in sample size when comparing quantitative and qualitative parameters. TMPG and TTG are intrinsically difficult to assess and conclusions based on these parameters should arise only from very large trials.

  9. Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

    Science.gov (United States)

    Shi, Haolun; Yin, Guosheng

    2018-02-21

    Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications. © 2018, The International Biometric Society.

  10. HIV-Related Stigma, Social Support, and Psychological Distress Among Individuals Initiating ART in Ethiopia.

    Science.gov (United States)

    Parcesepe, Angela; Tymejczyk, Olga; Remien, Robert; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Melaku, Zenebe; Elul, Batya; Nash, Denis

    2018-02-16

    Recent World Health Organization HIV treatment guideline expansion may facilitate timely antiretroviral therapy (ART) initiation. However, large-scale success of universal treatment strategies requires a more comprehensive understanding of known barriers to early ART initiation. This work aims to advance a more comprehensive understanding of interrelationships among three known barriers to ART initiation: psychological distress, HIV-related stigma, and low social support. We analyzed cross-sectional interview data on 1175 adults initiating ART at six HIV treatment clinics in Ethiopia. Experience of each form of HIV-related stigma assessed (e.g., anticipatory, internalized, and enacted) was associated with increased odds of psychological distress. However, among those who reported enacted HIV-related stigma, there was no significant association between social support and psychological distress. Interventions to improve mental health among people living with HIV should consider incorporating components to address stigma, focusing on strategies to prevent or reduce the internalization of stigma, given the magnitude of the relationship between high internalized stigma and psychological distress. Interventions to increase social support may be insufficient to improve the mental health of people living with HIV who experienced enacted HIV-related stigma. Future research should examine alternative strategies to manage the mental health consequences of enacted HIV-related stigma, including coping skills training.

  11. The feasibility of clinical endpoint trials in HIV infection in the highly active antiretroviral treatment (HAART) era

    DEFF Research Database (Denmark)

    Mocroft, A; Neaton, J; Bebchuk, J

    2006-01-01

    the assumptions used in designing ESPRIT, a large randomized clinical trial assessing the clinical benefit of interleukin-2 treatment in patients with HIV infection, to use EuroSIDA to mimic the inclusion criterion of ESPRIT in order to compare the observed event rate in ESPRIT with the projected rate in EuroSIDA......, and to project the required length of ESPRIT. METHODS: Patients in EuroSIDA who satisfied the ESPRIT recruitment criteria were selected. Patients were followed from baseline to new AIDS or death. RESULTS: The incidence of clinical progression in the selected EuroSIDA patients (N = 4482) was 1.5 per 100 PYFU (95...... follow-up required to complete ESPRIT and accrue the 320 events required by protocol would be seven years, 10 months using the projected rates from the EuroSIDA study, and seven years, 11 months if the observed event rate in ESPRIT continued unchanged. LIMITATIONS: Differences between patients recruited...

  12. Stimulating high impact HIV-related cardiovascular research: recommendations from a multidisciplinary NHLBI Working Group on HIV-related heart, lung, and blood disease.

    Science.gov (United States)

    Shah, Monica R; Cook, Nakela; Wong, Renee; Hsue, Priscilla; Ridker, Paul; Currier, Judith; Shurin, Susan

    2015-02-24

    The clinical challenges confronting patients with human immunodeficiency virus (HIV) have shifted from acquired immunodeficiency syndrome (AIDS)-related illnesses to chronic diseases, such as coronary artery disease, chronic lung disease, and chronic anemia. With the growing burden of HIV-related heart, lung, and blood (HLB) disease, the National Heart, Lung, and Blood Institute (NHLBI) recognizes it must stimulate and support HIV-related HLB research. Because HIV offers a natural, accelerated model of common pathological processes, such as inflammation, HIV-related HLB research may yield important breakthroughs for all patients with HLB disease. This paper summarizes the cardiovascular recommendations of an NHLBI Working Group, Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases, charged with identifying scientific priorities in HIV-related HLB disease and developing recommendations to promote multidisciplinary collaboration among HIV and HLB investigators. The working group included multidisciplinary sessions, as well as HLB breakout sessions for discussion of disease-specific issues, with common themes about scientific priorities and strategies to stimulate HLB research emerging in all 3 groups. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. An investigation of clinical studies suggests those with multiple objectives should have at least 90% power for each endpoint.

    NARCIS (Netherlands)

    Borm, G.F.; Houben, R.; Welsing, P.M.J.; Zielhuis, G.A.

    2006-01-01

    BACKGROUND AND OBJECTIVES: Many clinical studies have more than one objective, either formally or informally, but this is not usually taken into account in the determination of the sample size. We investigated the overall power of a study, that is, the probability that all the objectives will be

  14. Design and endpoints of clinical and translational trials in advanced colorectal cancer. a proposal from GROUP Español Multidisciplinar en Cancer Digestivo (GEMCAD).

    Science.gov (United States)

    Carrera, Gemma; Garcia-Albeniz, Xabier; Ayuso, Juan Ramón; Aparicio, Jorge; Castells, Antoni; Codony-Servat, Jordi; Feliu, Jaime; Fuster, David; Gallego, Rosa; Pagés, Mario; Torres, Ferran; Maurel, Joan

    2011-05-01

    Meta-analytic reviews of Randomized Clinical Trials (RCT) have reached contradictory conclusions regarding the benefit of medical interventions in Advanced Colorectal Cancer (ACRC). Surrogate markers of survival benefit, such as response rate (RR) and progression free-survival (PFS) often show contradictory and highly variable correlations. These contradictions can be due to differences in 1) the studies analysed (sources), 2) the quality of clinical trials (intrinsic bias in the design, biased data analysis, heterogeneous PFS definitions) and 3) the second-line strategies between arms. PFS is a more vulnerable target than overall survival (OS), but the latter can also be affected by different biases and additional medical interventions such as secondary resection of metastases or second-line therapies. Therefore the correlation between PFS and survival must be clearly stated if PFS is to be considered as a primary endpoint. Of the differences between studies, only the quality of clinical trials can be improved by a deeper knowledge of both the area of study (i.e. colorectal cancer) and the methodology needed (i.e., clinical and translational trials). The aim of this manuscript is to offer the basic resources to develop experimental trials in ACRC. To this end, techniques for diagnosis and for response assessment are discussed, prognostic factors and treatment standards are critically exposed, and notes about how to design useful translational studies are provided.

  15. Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

    Science.gov (United States)

    Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

    2017-06-01

    Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Understanding HIV-related posttraumatic stress disorder in South ...

    African Journals Online (AJOL)

    A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic review of the literature identified eight relevant studies that put current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%. Even the ...

  17. Avoidance of androgen deprivation therapy in radiorecurrent prostate cancer as a clinically meaningful endpoint for salvage cryoablation.

    Science.gov (United States)

    Ginsburg, Kevin B; Elshafei, Ahmed; Yu, Changhong; Jones, J Stephen; Cher, Michael L

    2017-10-01

    To investigate the ability of salvage cryoablation of the prostate (SCAP) to delay the need for androgen deprivation therapy (ADT) in local recurrence after radiation therapy to the prostate using the Cryo-On-Line Database (COLD) registry. The COLD registry is comprised of a combination of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after radiation therapy were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. We identified 898 patients that have undergone SCAP in the COLD registry. Overall, the calculated 5-year ADT-free survival probability was 0.713. When stratified by D'Amico risk group, 264 high-risk patients (71.9%), 234 intermediate-risk (86.7%),and 228 low-risk (87.7%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 60.7, 73.9, and 82.4%, respectively. Patients with post-SCAP PSA nadir of <0.2 ng/mL had a 5 year ADT-free survival of 87.1% compared to 48.7% with a PSA nadir ≥0.2 ng/mL. Pre-operative ADT use or full versus partial gland SCAP did not have an effect on ADT use post-operatively. In 118 (55.4%) of patients with post-operative biochemical recurrence, ADT was not used. For patients with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding or delaying ADT. The potential to delay ADT and its associated side effects should be a part of counseling sessions with the patient when discussing treatment options for locally recurrent prostate cancer after radiation. Avoidance of ADT is more clinically relevant than PSA elevation. © 2017 Wiley Periodicals, Inc.

  18. EBV AND HIV-RELATED LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Michele Bibas

    2009-12-01

    Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

  19. Cavitary pulmonary tuberculosis HIV-related

    International Nuclear Information System (INIS)

    Busi Rizzi, Elisa; Schinina, Vincenzo; Palmieri, Fabrizio; Girardi, Enrico; Bibbolino, Corrado

    2004-01-01

    Introduction: It was usually assumed that pulmonary tuberculosis (TB) in HIV-seropositive patients represents reactivation TB, despite the radiographic appearance frequently consistent rather with a recent disease. Hence, these radiographic features were considered 'atypical'. We have hypothesised that the so called 'atypical' radiographic features could be due to a greater proportion of primary TB among these patients, representing the typical appearance of primary radiological pattern. Material and methods: We reviewed chest imaging of 219 HIV+ patients with microbiological proven pulmonary tuberculosis, who were assessed for the presence, number, distribution of cavitations and for associated pulmonary parenchymal abnormalities, adenopathies and pleural effusion, and were classified as a primary or post-primary pattern. Results: The patients with post-primary pattern were 50%, and the rate of cavitation was 63%, not wandering off the general population. Cavities still occurred with similar proportion in groups with CD4 200 cells/mm 3 . Conclusion: We suggest that HIV-related pulmonary tuberculosis is typical in its radiological appearances, consistent with those of the general population, and this could be confirmed by the most recent molecular epidemiological techniques that allow to definitely classify the tuberculosis episodes as either primary or post-primary disease

  20. The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

    Science.gov (United States)

    Shiboski, C H; Patton, L L; Webster-Cyriaque, J Y; Greenspan, D; Traboulsi, R S; Ghannoum, M; Jurevic, R; Phelan, J A; Reznik, D; Greenspan, J S

    2009-07-01

    The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

  1. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Science.gov (United States)

    Ricotti, Valeria; Evans, Matthew R B; Sinclair, Christopher D J; Butler, Jordan W; Ridout, Deborah A; Hogrel, Jean-Yves; Emira, Ahmed; Morrow, Jasper M; Reilly, Mary M; Hanna, Michael G; Janiczek, Robert L; Matthews, Paul M; Yousry, Tarek A; Muntoni, Francesco; Thornton, John S

    2016-01-01

    A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (pmuscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  2. HIV-Related Stigma, Shame, and Avoidant Coping: Risk Factors for Internalizing Symptoms Among Youth Living with HIV?

    Science.gov (United States)

    Bennett, David S; Hersh, Jill; Herres, Joanna; Foster, Jill

    2016-08-01

    Youth living with HIV (YLH) are at elevated risk of internalizing symptoms, although there is substantial individual variability in adjustment. We examined perceived HIV-related stigma, shame-proneness, and avoidant coping as risk factors of internalizing symptoms among YLH. Participants (N = 88; ages 12-24) completed self-report measures of these potential risk factors and three domains of internalizing symptoms (depressive, anxiety, and PTSD) during a regularly scheduled HIV clinic visit. Hierarchical regressions were conducted for each internalizing symptoms domain, examining the effects of age, gender, and maternal education (step 1), HIV-related stigma (step 2), shame- and guilt-proneness (step 3), and avoidant coping (step 4). HIV-related stigma, shame-proneness, and avoidant coping were each correlated with greater depressive, anxiety, and PTSD symptoms. Specificity was observed in that shame-proneness, but not guilt-proneness, was associated with greater internalizing symptoms. In multivariable analyses, HIV-related stigma and shame-proneness were each related to greater depressive and PTSD symptoms. Controlling for the effects of HIV-related stigma and shame-proneness, avoidant coping was associated with PTSD symptoms. The current findings highlight the potential importance of HIV-related stigma, shame, and avoidant coping on the adjustment of YLH, as interventions addressing these risk factors could lead to decreased internalizing symptoms among YLH.

  3. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

    Science.gov (United States)

    Bottomley, Andrew; Pe, Madeline; Sloan, Jeff; Basch, Ethan; Bonnetain, Franck; Calvert, Melanie; Campbell, Alicyn; Cleeland, Charles; Cocks, Kim; Collette, Laurence; Dueck, Amylou C; Devlin, Nancy; Flechtner, Hans-Henning; Gotay, Carolyn; Greimel, Eva; Griebsch, Ingolf; Groenvold, Mogens; Hamel, Jean-Francois; King, Madeleine; Kluetz, Paul G; Koller, Michael; Malone, Daniel C; Martinelli, Francesca; Mitchell, Sandra A; Moinpour, Carol M; Musoro, Jammbe; O'Connor, Daniel; Oliver, Kathy; Piault-Louis, Elisabeth; Piccart, Martine; Pimentel, Francisco L; Quinten, Chantal; Reijneveld, Jaap C; Schürmann, Christoph; Smith, Ashley Wilder; Soltys, Katherine M; Taphoorn, Martin J B; Velikova, Galina; Coens, Corneel

    2016-11-01

    Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    NARCIS (Netherlands)

    Keeling, Stephanie O.; Landewe, Robert; van der Heijde, Desiree; Bathon, Joan; Boers, Maarten; Garnero, Patrick; Geusens, Piet; El-Gabalawy, Hani; Inman, Robert D.; Kraus, Virginia B.; Kvien, Tore K.; Mease, Philip J.; Ostergaard, Mikkel; Ritchlin, Chris; Syversen, Silje W.; Maksymowych, Walter P.

    2007-01-01

    A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively

  5. Qualitative exploration of manifestations of HIV-related stigma in ...

    African Journals Online (AJOL)

    Qualitative exploration of manifestations of HIV-related stigma in Kano State, Nigeria. ... Methods: The study was descriptive and cross-sectional, that used qualitative ... Follow-up quantitative and intervention studies are recommended.

  6. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Valeria Ricotti

    Full Text Available A number of promising experimental therapies for Duchenne muscular dystrophy (DMD are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function.15 non-ambulant DMD boys (mean age 13.3 y and 10 age-gender matched healthy controls (mean age 14.6 y were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.. Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation.Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001. A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7, accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9 and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8.These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  7. HIV-related symptoms and patient clusters among Chileans living with HIV.

    Science.gov (United States)

    Araya, A X; Norr, K F; Pérez, C M; Levy, J A; Park, C G; Kim, M J

    2013-01-01

    Identifying both Human immunodeficiency virus (HIV)-related and co-morbid symptoms experienced by people living with HIV (PLWH) who are receiving antiretroviral therapy (ART) treatment is a major challenge for healthcare providers globally. Yet, little research to date has examined the symptoms of illness experienced by PLWH including patients living in Central and South American. To address this gap, this study was designed to identify symptoms of HIV by socio-demographic and/or clinical characteristics among Chilean patients living with the virus. A convenience sample of 209 Chilean PLWH was recruited from an outpatient clinic in Santiago, Chile. A structured interview was used to elicit socio-demographic information and HIV symptoms status. Additional clinical information was obtained through a review of the participants' medical records. Results show that patients' most commonly reported HIV-related symptoms were fear/worries (66%), anxiety (52%), gas/bloating (50%), and thirst (50%). Multivariate analysis revealed a positive association between the number of reported HIV-related symptoms and number of years living with HIV. Having completed college was negatively associated with number of symptoms. Latent class analysis indicated that PLWH in the sample who had completed college were two times more likely to experience a mild intensity of HIV-related symptoms than their lesser educated counterparts. Similarly, logistic regression revealed that college-educated PLWH were twice as likely to be classified in the subgroup reporting mild intensity of symptoms than those who lacked a college degree. Overall, the study's results reveal that many Chilean PLWH, even those with high CD4 counts and low or undetectable viral loads, are not symptom free. The findings point to the need for clinicians to tailor a plan of care for individuals living with HIV that is based on their symptomatology.

  8. New MR imaging observation in HIV-related cognitive impairment (AIDS dementia complex)

    International Nuclear Information System (INIS)

    Ketonen, L.; Kieburtz, K.D.; Zetteimaier, A.; Simon, J.H.; Kido, D.K.

    1989-01-01

    MR findings have been reported on the acquired immunodeficiency syndrome (AIDS) demential complex, but the findings are late relative to clinical signs. This paper reports on a new MR finding observed in patients with human immunodeficiency virus (HIV)-related cognitive impairment studied early in the disease process. Fifty-two patients had a total of 86 MR images. Al images were obtained with a 1.5-T system (protondensity, spin-echo, TR/TE = 2,000/30 [repetition time/echo time, msec]). High-signal lesions were seen in the region of the splenium of the corpus callosum and in the crura of the fornices. The lesions demonstrated no contrast enhancement with Gd-DTPA. Pathologic examination was performed in four patients. The fornix-subcallosal abnormality may have relevance to the memory dysfunction in patients with HIV-related cognitive impairment

  9. Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles: A Consensus Document From the Mitral Valve Academic Research Consortium.

    Science.gov (United States)

    Stone, Gregg W; Vahanian, Alec S; Adams, David H; Abraham, William T; Borer, Jeffrey S; Bax, Jeroen J; Schofer, Joachim; Cutlip, Donald E; Krucoff, Mitchell W; Blackstone, Eugene H; Généreux, Philippe; Mack, Michael J; Siegel, Robert J; Grayburn, Paul A; Enriquez-Sarano, Maurice; Lancellotti, Patrizio; Filippatos, Gerasimos; Kappetein, Arie Pieter

    2015-07-21

    Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Cardiac neuronal imaging with 123I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    International Nuclear Information System (INIS)

    Petretta, Mario; Pellegrino, Teresa; Cuocolo, Alberto

    2014-01-01

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with 123 I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of 123 I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present the results

  11. Cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    Energy Technology Data Exchange (ETDEWEB)

    Petretta, Mario [University Federico II, Department of Translational Medicine, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy)

    2014-09-15

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with {sup 123}I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of {sup 123}I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present

  12. Analysis of cause-specific failure endpoints using simple proportions: an example from a randomized controlled clinical trial in early breast cancer

    International Nuclear Information System (INIS)

    Panzarella, Tony; Meakin, J. William

    1998-01-01

    Purpose: To describe a statistically valid method for analyzing cause-specific failure data based on simple proportions, that is easy to understand and apply, and outline under what conditions its implementation is well-suited. Methods and Materials: In the comparison of treatment groups, time to first failure (in any site) was analyzed first, followed by an analysis of the pattern of first failure, preferably at the latest complete follow-up time common to each group. Results: A retrospective analysis of time to contralateral breast cancer in 777 early breast cancer patients was undertaken. Patients previously treated by mastectomy plus radiation therapy to the chest wall and regional nodal areas were randomized to receive further radiation and prednisone (R+P), radiation alone (R), or no further treatment (NT). Those randomized to R+P had a statistically significantly delayed time to first failure compared to the group randomized to NT (p = 0.0008). Patients randomized to R also experienced a delayed time to first failure compared to NT, but the difference was not statistically significant (p 0.14). At 14 years from the date of surgery (the latest common complete follow-up time) the distribution of first failures was statistically significantly different between R+P and NT (p = 0.005), but not between R and NT (p = 0.09). The contralateral breast cancer first failure rate at 14 years from surgery was 7.2% for NT, 4.6% for R, and 3.7% for R+P. The corresponding Kaplan-Meier estimates were 13.2%, 8.2%, and 5.4%, respectively. Conclusion: Analyzing cause-specific failure data using methods developed for survival endpoints is problematic. We encourage the use of the two-step analysis strategy described when, as in the example presented, competing causes of failure are not likely to be statistically independent, and when a treatment comparison at a single time-point is clinically relevant and feasible; that is, all patients have complete follow-up to this point

  13. HIV-related neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Schütz SG

    2013-09-01

    Full Text Available Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP related to human immunodeficiency virus (HIV is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pain

  14. Raising awareness of HIV-related stigma and its associated ...

    African Journals Online (AJOL)

    HIV Aids will remain a problem for a long time. Many people with HIV/AIDS still live in fear of discovery because of the prevalent stigma and its associated prejudice and discrimination. This article examines how HIV-related stigma and its associated prejudice and discrimination can be addressed in a classroom ± in the field ...

  15. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    Karl Peltzer

    2014-01-03

    Jan 3, 2014 ... To cite this article: Karl Peltzer (2013) HIV-related symptoms and management in HIV and antiretroviral therapy patients ...... Fear/worry. 14.2. 22. 2.5. 20 ..... Internalized Stigma, Discrimination, and Depression among Men and.

  16. Primary endpoint results of the OMEGA Study: One-year clinical outcomes after implantation of a novel platinum chromium bare metal stent

    Energy Technology Data Exchange (ETDEWEB)

    Wang, John C., E-mail: john.wang@medstar.net [MedStar Union Memorial Hospital, Baltimore MD (United States); Carrié, Didier, E-mail: carrie.didier@chu-toulouse.fr [Centre Hôpital Universitaire Rangueil, Toulouse (France); Masotti, Monica, E-mail: MASOTTI@clinic.ub.es [Hospital Clinic, University of Barcelona (Spain); Erglis, Andrejs, E-mail: a.a.erglis@stradini.lv [Pauls Stradins Clinical University Hospital, University of Latvia, Riga (Latvia); Mego, David, E-mail: David.Mego@arheart.com [Arkansas Heart Hospital, Little Rock, AR (United States); Watkins, Matthew W., E-mail: Matthew.Watkins@vtmednet.org [University of Vermont Medical Center, Burlington VT (United States); Underwood, Paul, E-mail: Paul.underwood@bsci.com [Boston Scientific, Marlborough MA USA (United States); Allocco, Dominic J., E-mail: Dominic.allocco@bsci.com [Boston Scientific, Marlborough MA USA (United States); Hamm, Christian W., E-mail: C.Hamm@kerckhoff-klinik.de [Kerckhoff Heart and Thoraxcenter, Bad Nauheim (Germany)

    2015-03-15

    Background/purpose: Bare metal stents (BMS) have similar rates of death and myocardial infarction (MI) compared to drug-eluting stents (DES). DES lower repeat revascularization rates compared to BMS, but may have higher rates of late stent thrombosis (ST) potentially due to impaired endothelialization requiring longer dual anti-platelet therapy (DAPT). OMEGA evaluated a novel BMS designed to have improved deliverability and radiopacity, in comparison to currently available platforms. Methods/materials: OMEGA was a prospective, multicenter, single-arm study enrolling 328 patients at 37 sites (US and Europe). Patients received the OMEGA stent (bare platinum chromium element stent) for the treatment of de novo native coronary artery lesions (≤ 28 mm long; diameter ≥ 2.25 mm to ≤ 4.50 mm). The primary endpoint was 9-month target lesion failure (TLF: cardiac death, target vessel-related MI, target lesion revascularization [TLR]) compared to a prespecified performance goal (PG) based on prior generation BMS. All major cardiac events were independently adjudicated. DAPT was required for a minimum of 1 month post procedure. Results: In the OMEGA study, the mean age was 65; 17% had diabetes mellitus. The primary endpoint was met; 9 month TLF rate was 11.5%, and the upper 1-sided 95% confidence bound of 14.79% was less than the prespecified PG of 21.2% (p < 0.0001). One-year event rates were low including a TLF rate of 12.8% and an ST rate of 0.6% at 12 months. Conclusions: One-year outcomes of OMEGA show low rates of TLF, revascularization and ST. This supports safety and efficacy of the OMEGA BMS for the treatment of coronary artery disease. - Highlights: • The OMEGA study evaluated a novel platinum chromium bare metal stent. • OMEGA enrolled 328 patients at 37 sites (US and Europe). • The primary endpoint of 9 month target lesion failure was 11.5%. • One-year event rates were low including an ST rate of 0.6% at 12 months.

  17. Primary endpoint results of the OMEGA Study: One-year clinical outcomes after implantation of a novel platinum chromium bare metal stent

    International Nuclear Information System (INIS)

    Wang, John C.; Carrié, Didier; Masotti, Monica; Erglis, Andrejs; Mego, David; Watkins, Matthew W.; Underwood, Paul; Allocco, Dominic J.; Hamm, Christian W.

    2015-01-01

    Background/purpose: Bare metal stents (BMS) have similar rates of death and myocardial infarction (MI) compared to drug-eluting stents (DES). DES lower repeat revascularization rates compared to BMS, but may have higher rates of late stent thrombosis (ST) potentially due to impaired endothelialization requiring longer dual anti-platelet therapy (DAPT). OMEGA evaluated a novel BMS designed to have improved deliverability and radiopacity, in comparison to currently available platforms. Methods/materials: OMEGA was a prospective, multicenter, single-arm study enrolling 328 patients at 37 sites (US and Europe). Patients received the OMEGA stent (bare platinum chromium element stent) for the treatment of de novo native coronary artery lesions (≤ 28 mm long; diameter ≥ 2.25 mm to ≤ 4.50 mm). The primary endpoint was 9-month target lesion failure (TLF: cardiac death, target vessel-related MI, target lesion revascularization [TLR]) compared to a prespecified performance goal (PG) based on prior generation BMS. All major cardiac events were independently adjudicated. DAPT was required for a minimum of 1 month post procedure. Results: In the OMEGA study, the mean age was 65; 17% had diabetes mellitus. The primary endpoint was met; 9 month TLF rate was 11.5%, and the upper 1-sided 95% confidence bound of 14.79% was less than the prespecified PG of 21.2% (p < 0.0001). One-year event rates were low including a TLF rate of 12.8% and an ST rate of 0.6% at 12 months. Conclusions: One-year outcomes of OMEGA show low rates of TLF, revascularization and ST. This supports safety and efficacy of the OMEGA BMS for the treatment of coronary artery disease. - Highlights: • The OMEGA study evaluated a novel platinum chromium bare metal stent. • OMEGA enrolled 328 patients at 37 sites (US and Europe). • The primary endpoint of 9 month target lesion failure was 11.5%. • One-year event rates were low including an ST rate of 0.6% at 12 months

  18. Research gaps in neonatal HIV-related care

    Directory of Open Access Journals (Sweden)

    Mary-Ann Davies

    2015-05-01

    Full Text Available The South African prevention of mother to child transmission programme has made excellentprogress in reducing vertical HIV transmission, and paediatric antiretroviral therapyprogrammes have demonstrated good outcomes with increasing treatment initiation inyounger children and infants. However, both in South Africa and across sub-Saharan African,lack of boosted peri-partum prophylaxis for high-risk vertical transmission, loss to followup,and failure to initiate HIV-infected infants on antiretroviral therapy (ART before diseaseprogression are key remaining gaps in neonatal HIV-related care. In this issue of the Southern African Journal of HIV Medicine, experts provide valuable recommendations for addressingthese gaps. The present article highlights a number of areas where evidence is lacking toinform guidelines and programme development for optimal neonatal HIV-related care.

  19. The intermediate endpoint effect in logistic and probit regression

    Science.gov (United States)

    MacKinnon, DP; Lockwood, CM; Brown, CH; Wang, W; Hoffman, JM

    2010-01-01

    Background An intermediate endpoint is hypothesized to be in the middle of the causal sequence relating an independent variable to a dependent variable. The intermediate variable is also called a surrogate or mediating variable and the corresponding effect is called the mediated, surrogate endpoint, or intermediate endpoint effect. Clinical studies are often designed to change an intermediate or surrogate endpoint and through this intermediate change influence the ultimate endpoint. In many intermediate endpoint clinical studies the dependent variable is binary, and logistic or probit regression is used. Purpose The purpose of this study is to describe a limitation of a widely used approach to assessing intermediate endpoint effects and to propose an alternative method, based on products of coefficients, that yields more accurate results. Methods The intermediate endpoint model for a binary outcome is described for a true binary outcome and for a dichotomization of a latent continuous outcome. Plots of true values and a simulation study are used to evaluate the different methods. Results Distorted estimates of the intermediate endpoint effect and incorrect conclusions can result from the application of widely used methods to assess the intermediate endpoint effect. The same problem occurs for the proportion of an effect explained by an intermediate endpoint, which has been suggested as a useful measure for identifying intermediate endpoints. A solution to this problem is given based on the relationship between latent variable modeling and logistic or probit regression. Limitations More complicated intermediate variable models are not addressed in the study, although the methods described in the article can be extended to these more complicated models. Conclusions Researchers are encouraged to use an intermediate endpoint method based on the product of regression coefficients. A common method based on difference in coefficient methods can lead to distorted

  20. PALLIATIVE TREATMENT FOR HIV-RELATED KAPOSrS SARCOMA

    African Journals Online (AJOL)

    HIV AND CANCER. P Ilarnardt, ME CkE, Dip On

      HIV-RELATED. KAPOSrS SARCOMA. NOVEMBER ~003. METHODS. Our study included 54 males and 46 females with HIV ...

  1. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  2. HIV-Related discrimination in European health care settings.

    Science.gov (United States)

    Nöstlinger, Christiana; Rojas Castro, Daniela; Platteau, Tom; Dias, Sonia; Le Gall, Jean

    2014-03-01

    This cross-sectional European study assessed self-reported HIV-related discrimination and its associated factors in health care settings. Socio-demographics, health status, support needs relating to sexual and reproductive health (SRH), and self-reported HIV-related discrimination were measured using an anonymous survey in a sample of 1549 people living with HIV from 14 countries. Thirty-two per cent of the participants had experienced HIV-related discrimination during the previous 3 years; almost half of them felt discriminated against by health care providers. For this type of discrimination, logistic regression analysis revealed significant associations with not being a migrant (OR: 2.0; IC 1.0-3.7; psex practices (OR: 1.8; IC 1.0-3.2; pgender had a protective effect (OR: 0.2; IC 0.0-0.9; pdiscrimination. Improving health care providers' communication skills, and fostering openness about SRH topics in HIV care could contribute to destigmatization of PLHIV.

  3. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    DEFF Research Database (Denmark)

    Keeling, Stephanie O; Landewe, Robert; van der Heijde, Desiree

    2007-01-01

    OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker...... of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants...

  4. Shared Contract-Obedient Endpoints

    Directory of Open Access Journals (Sweden)

    Étienne Lozes

    2012-12-01

    Full Text Available Most of the existing verification techniques for message-passing programs suppose either that channel endpoints are used in a linear fashion, where at most one thread may send or receive from an endpoint at any given time, or that endpoints may be used arbitrarily by any number of threads. The former approach usually forbids the sharing of channels while the latter limits what is provable about programs. In this paper we propose a midpoint between these techniques by extending a proof system based on separation logic to allow sharing of endpoints. We identify two independent mechanisms for supporting sharing: an extension of fractional shares to endpoints, and a new technique based on what we call reflexive ownership transfer. We demonstrate on a number of examples that a linear treatment of sharing is possible.

  5. Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

    Science.gov (United States)

    Dutton, P; Love, S B; Billingham, L; Hassan, A B

    2018-05-01

    Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

  6. Anticoagulation Endpoints with Clinical Implementation of Warfarin Pharmacogenetic Dosing in a Real-World Setting – A Proposal for a New Pharmacogenetic Dosing Approach

    Science.gov (United States)

    Arwood, Meghan J.; Deng, Jiexin; Drozda, Katarzyna; Pugach, Oksana; Nutescu, Edith A.; Schmidt, Stephan; Duarte, Julio D.; Cavallari, Larisa H.

    2016-01-01

    Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8±5.8, 7.2±4.7, and 5.4±4.6 days, P=0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P=0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic-derived dosing nomogram optimized for a heterogeneous patient population. PMID:28032893

  7. Improved Endpoints for Cancer Immunotherapy Trials

    Science.gov (United States)

    Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

    2010-01-01

    Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

  8. Calorimetry end-point predictions

    International Nuclear Information System (INIS)

    Fox, M.A.

    1981-01-01

    This paper describes a portion of the work presently in progress at Rocky Flats in the field of calorimetry. In particular, calorimetry end-point predictions are outlined. The problems associated with end-point predictions and the progress made in overcoming these obstacles are discussed. The two major problems, noise and an accurate description of the heat function, are dealt with to obtain the most accurate results. Data are taken from an actual calorimeter and are processed by means of three different noise reduction techniques. The processed data are then utilized by one to four algorithms, depending on the accuracy desired to determined the end-point

  9. Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

    Directory of Open Access Journals (Sweden)

    Donald Bruce

    2009-03-01

    Full Text Available Two experiments were conducted to determine: 1 whether the adult male transgenic sickle cell mouse (Tg58 × Tg98; TSCM, exhibits the patterns of reproductive endpoints (hypogonadism characteristic of men with sickle cell disease (SCD and 2 whether hydroxyurea (HU exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM (N = 10/group for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ± 0.004g that was further decreased on day 56 (0.06 ± 0.003g; treatment x time interaction compared with controls (day 28, 0.15 ± 0.01g; day 56, 2, 0.16 ± 0.01g. Concomitant with a 52% shrinkage (P<0.001 in area of testes in 56 days of HU treatment, testes from HU-treated TSCM exhibited significant atrophic

  10. Biomarkers and correlative endpoints for immunotherapy trials.

    Science.gov (United States)

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

  11. HIV-related politics in long-term perspective.

    Science.gov (United States)

    Friedman, S R

    1998-06-01

    Some long-term, large-scale socio-economic changes may affect the politics of HIV and other emerging viruses such as hepatitis C. It is useful to ask why the potential peace dividend of the early 1990s failed to provide adequate resources for HIV-related social and medical service delivery in developed or developing nations. This failure can be understood by looking at long-term global economic trends and the pressures they put on governments and corporations. They have produced a period in which fundamental issues of political and economic structure are at stake and, often, the response is a divide-and-rule politics to promote stability. National politics differ in terms of the extent to which such a 'politics of scapegoating' is institutionalized and in terms of which groups are scapegoated. Groups such as drug injectors, gay and bisexual men and sex traders are particularly likely to be targeted both by the scapegoaters and by HIV. Given this framework, how should public health professionals and activists engaged in HIV-related issues respond? Under what circumstances should we orient efforts upwards towards corporate, political or bureaucratic leaders? Under what circumstances, and how, should we orient towards popular forces? Relatedly, we need to consider an issue we often ignore: What do we have to offer potential allies? That is, in terms of their goals, philosophies and needs, why should they ally with us?

  12. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

    Science.gov (United States)

    Kalra, Lalit; Irshad, Saddif; Hodsoll, John; Simpson, Matthew; Gulliford, Martin; Smithard, David; Patel, Anita; Rebollo-Mesa, Irene

    2015-11-07

    Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52

  13. Associations between health literacy, HIV-related knowledge, and information behavior among persons living with HIV in the Dominican Republic.

    Science.gov (United States)

    Stonbraker, Samantha; Smaldone, Arlene; Luft, Heidi; Cushman, Linda F; Lerebours Nadal, Leonel; Halpern, Mina; Larson, Elaine

    2018-05-01

    To determine the health literacy levels of persons living with human immunodeficiency virus (HIV) (PLWH) at a health clinic in the Dominican Republic (DR) and assess associations between health literacy, HIV-related knowledge, and health information behavior (how patients need, seek, receive, and use information). Cross-sectional, descriptive. Participants were 107 PLWH attending the Clinic. A theoretically based, 64-item survey assessing information behavior and HIV-related knowledge was administered in Spanish through individual interviews. Health literacy was assessed using the Short Assessment of Health Literacy-Spanish and English. On average, participants were 40.8 years old and had lived with HIV for 7.7 years. The majority (69.2%) had low health literacy. HIV-related knowledge and information behavior varied by health literacy level and uncertainty regarding a main indicator of disease progression, viral load, was demonstrated regardless of health literacy level. Participants with low health literacy were less likely to answer questions or answer questions correctly and many participants (39.2%) indicated viral transmission can occur through supernatural means. Findings demonstrate unmet information need and that information received may not always be understood. Methods to improve health education are needed to ensure patients receive health information in an understandable way. © 2017 Wiley Periodicals, Inc.

  14. Understanding HIV-related stigma among Indonesian nurses.

    Science.gov (United States)

    Waluyo, Agung; Culbert, Gabriel J; Levy, Judith; Norr, Kathleen F

    2015-01-01

    Evidence indicates widespread stigmatization of persons living with HIV (PLWH) in Indonesia. Such attitudes among health care workers could impede the country's policies for effective diagnosis and medical treatment of PLWH. Nonetheless, research to guide interventions to reduce stigma in health care settings is lacking. Also, the contributions of workplace, religion, and HIV knowledge to nurses' HIV-related stigma are poorly understood. Our cross-sectional study aimed to describe factors associated with nurses' stigmatizing attitudes toward PLWH. Four hundred nurses recruited from four hospitals in Jakarta, Indonesia, were surveyed using the Nurse AIDS Attitude Scale to measure stigma. Stigmatizing attitudes were significantly predicted by education, HIV training, perceived workplace stigma, religiosity, Islamic religious identification, and affiliation with the Islamic hospital. HIV knowledge was not a significant predictor of stigmatizing attitudes. Organization changes fostering workplace diversity are likely to substantially reduce stigmatizing attitudes in nurses. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  15. Presidential Elections and HIV-Related National Policies and Programs.

    Science.gov (United States)

    Holtgrave, David R; Bonacci, Robert A; Valdiserri, Ronald O

    2017-03-01

    The November 2016 general election and subsequent voting of the Electoral College resulted in the selection of Donald Trump as President of the United States. The incoming Administration ran a campaign that indicated a desire for substantial change in health policy, including the repeal of the Affordable Care Act (ACA). President Trump has said very little directly about HIV programs and policies, but some campaign positions (such as the repeal of the ACA) would clearly and substantially impact the lives of persons living with HIV. In this editorial, we highlight important HIV-related goals to which we must recommit ourselves, and we underscore several key points about evidence-based advocacy that are important to revisit at any time (but most especially when there is a change in Administration).

  16. Situating experiences of HIV-related stigma in Swaziland.

    Science.gov (United States)

    Root, R

    2010-01-01

    With the world's highest antenatal HIV prevalence rate (39.2%), Swaziland has also been described as among the most stigmatising. Yet, only recently was an anti-HIV stigma and discrimination (S&D) platform included in the government's National Multisectoral HIV and AIDS Policy. This study draws on a medical anthropological project in rural Swaziland to examine experiences of stigma among people living with HIV/AIDS (PLWH). Qualitative methods included a semi-structured questionnaire and interviews (n=40) to identify patterns of stigma across three domains: verbal, physical and social. Key informant interviews (n=5) were conducted with health personnel and support group leaders. Descriptive statistics were situated within a thematic analysis of open-ended content. Among the findings, participants reported extensive HIV-related rumouring (36.4%) and pejorative name-calling (37.5%). Nearly one in five (18.2%) could no longer partake of family meals. Homesteads, which are an organising principle of Swazi life, were often markedly stigmatising environments. In contrast to documented discrimination in health care settings, the health centre emerged as a space where PLWH could share information and support. Given the UNAIDS call for national partners to 'know your epidemic' by tracking the prevalence of HIV-related S&D, results from this study suggested that unless 'knowing your epidemic' includes the lived experiences of HIV stigma that blister into discernible patterns, effectiveness of national initiatives is likely to be limited. Multidisciplinary and locale-specific studies are especially well suited in examining the cultural dynamics of HIV stigma and in providing grounded data that deepen the impact of comprehensive HIV/AIDS policies and programming.

  17. Endpoints in pediatric pain studies

    NARCIS (Netherlands)

    M. van Dijk (Monique); I. Ceelie (Ilse); D. Tibboel (Dick)

    2011-01-01

    textabstractAssessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the

  18. Factors Associated with Pregnant Women’s Anticipations and Experiences of HIV-related Stigma in Rural Kenya

    Science.gov (United States)

    Cuca, Yvette P.; Onono, Maricianah; Bukusi, Elizabeth; Turan, Janet M.

    2012-01-01

    Pregnant women who fear or experience HIV-related stigma may not get care for their own health or medications to reduce perinatal transmission of HIV. This study examined factors associated with anticipating and experiencing HIV-related stigma among 1,777 pregnant women attending antenatal care clinics in rural Kenya. Women were interviewed at baseline, offered HIV testing and care, and a sub-set was re-interviewed at 4–8 weeks postpartum. Women who were older, had less education, whose husbands had other wives, and who perceived community discrimination against people with HIV had significantly greater adjusted odds of anticipating HIV stigma. Over half of the HIV-positive women interviewed postpartum reported having experienced stigma, much of which was self-stigma. Women experiencing minor depression, and those whose family knew of their HIV status had significantly greater adjusted odds of experiencing stigma. Lack of women’s empowerment, as well as depression, may be important risk factors for HIV-related stigma and discrimination. PMID:22799618

  19. HIV-related sexual risk behavior among African American adolescent girls.

    Science.gov (United States)

    Danielson, Carla Kmett; Walsh, Kate; McCauley, Jenna; Ruggiero, Kenneth J; Brown, Jennifer L; Sales, Jessica M; Rose, Eve; Wingood, Gina M; Diclemente, Ralph J

    2014-05-01

    Latent class analysis (LCA) is a useful statistical tool that can be used to enhance understanding of how various patterns of combined sexual behavior risk factors may confer differential levels of HIV infection risk and to identify subtypes among African American adolescent girls. Data for this analysis is derived from baseline assessments completed prior to randomization in an HIV prevention trial. Participants were African American girls (n=701) aged 14-20 years presenting to sexual health clinics. Girls completed an audio computer-assisted self-interview, which assessed a range of variables regarding sexual history and current and past sexual behavior. Two latent classes were identified with the probability statistics for the two groups in this model being 0.89 and 0.88, respectively. In the final multivariate model, class 1 (the "higher risk" group; n=331) was distinguished by a higher likelihood of >5 lifetime sexual partners, having sex while high on alcohol/drugs, less frequent condom use, and history of sexually transmitted diseases (STDs), when compared with class 2 (the "lower risk" group; n=370). The derived model correctly classified 85.3% of participants into the two groups and accounted for 71% of the variance in the latent HIV-related sexual behavior risk variable. The higher risk class also had worse scores on all hypothesized correlates (e.g., self-esteem, history of sexual assault or physical abuse) relative to the lower risk class. Sexual health clinics represent a unique point of access for HIV-related sexual risk behavior intervention delivery by capitalizing on contact with adolescent girls when they present for services. Four empirically supported risk factors differentiated higher versus lower HIV risk. Replication of these findings is warranted and may offer an empirical basis for parsimonious screening recommendations for girls presenting for sexual healthcare services.

  20. Bayesian model selection techniques as decision support for shaping a statistical analysis plan of a clinical trial: An example from a vertigo phase III study with longitudinal count data as primary endpoint

    Directory of Open Access Journals (Sweden)

    Adrion Christine

    2012-09-01

    Full Text Available Abstract Background A statistical analysis plan (SAP is a critical link between how a clinical trial is conducted and the clinical study report. To secure objective study results, regulatory bodies expect that the SAP will meet requirements in pre-specifying inferential analyses and other important statistical techniques. To write a good SAP for model-based sensitivity and ancillary analyses involves non-trivial decisions on and justification of many aspects of the chosen setting. In particular, trials with longitudinal count data as primary endpoints pose challenges for model choice and model validation. In the random effects setting, frequentist strategies for model assessment and model diagnosis are complex and not easily implemented and have several limitations. Therefore, it is of interest to explore Bayesian alternatives which provide the needed decision support to finalize a SAP. Methods We focus on generalized linear mixed models (GLMMs for the analysis of longitudinal count data. A series of distributions with over- and under-dispersion is considered. Additionally, the structure of the variance components is modified. We perform a simulation study to investigate the discriminatory power of Bayesian tools for model criticism in different scenarios derived from the model setting. We apply the findings to the data from an open clinical trial on vertigo attacks. These data are seen as pilot data for an ongoing phase III trial. To fit GLMMs we use a novel Bayesian computational approach based on integrated nested Laplace approximations (INLAs. The INLA methodology enables the direct computation of leave-one-out predictive distributions. These distributions are crucial for Bayesian model assessment. We evaluate competing GLMMs for longitudinal count data according to the deviance information criterion (DIC or probability integral transform (PIT, and by using proper scoring rules (e.g. the logarithmic score. Results The instruments under study

  1. Bayesian model selection techniques as decision support for shaping a statistical analysis plan of a clinical trial: an example from a vertigo phase III study with longitudinal count data as primary endpoint.

    Science.gov (United States)

    Adrion, Christine; Mansmann, Ulrich

    2012-09-10

    A statistical analysis plan (SAP) is a critical link between how a clinical trial is conducted and the clinical study report. To secure objective study results, regulatory bodies expect that the SAP will meet requirements in pre-specifying inferential analyses and other important statistical techniques. To write a good SAP for model-based sensitivity and ancillary analyses involves non-trivial decisions on and justification of many aspects of the chosen setting. In particular, trials with longitudinal count data as primary endpoints pose challenges for model choice and model validation. In the random effects setting, frequentist strategies for model assessment and model diagnosis are complex and not easily implemented and have several limitations. Therefore, it is of interest to explore Bayesian alternatives which provide the needed decision support to finalize a SAP. We focus on generalized linear mixed models (GLMMs) for the analysis of longitudinal count data. A series of distributions with over- and under-dispersion is considered. Additionally, the structure of the variance components is modified. We perform a simulation study to investigate the discriminatory power of Bayesian tools for model criticism in different scenarios derived from the model setting. We apply the findings to the data from an open clinical trial on vertigo attacks. These data are seen as pilot data for an ongoing phase III trial. To fit GLMMs we use a novel Bayesian computational approach based on integrated nested Laplace approximations (INLAs). The INLA methodology enables the direct computation of leave-one-out predictive distributions. These distributions are crucial for Bayesian model assessment. We evaluate competing GLMMs for longitudinal count data according to the deviance information criterion (DIC) or probability integral transform (PIT), and by using proper scoring rules (e.g. the logarithmic score). The instruments under study provide excellent tools for preparing decisions

  2. An analysis of clinical and treatment related prognostic factors on outcome using biochemical control as an end-point in patients with prostate cancer treated with external beam irradiation

    International Nuclear Information System (INIS)

    Horwitz, Eric M.; Vicini, Frank A.; Ziaja, Ellen L.; Dmuchowski, Carl F.; Stromberg, Jannifer S.; Gustafson, Gary S.; Martinez, Alvaro A.

    1997-01-01

    Purpose: We reviewed our institution's experience in treating patients with clinically localized prostate cancer with external beam irradiation (RT) to determine if previously analyzed clinical and treatment related prognostic factors affected outcome when biochemical control was used as an end-point to evaluate results. Materials and methods: Between 1 January 1987 and 31 December 1991, 470 patients with clinically localized prostate cancer were treated with external beam RT using localized prostate fields at William Beaumont Hospital. Biochemical control was defined as PSA nadir ≤1.5 ng/ml within 1 year of treatment. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase. Prognostic factors, including the total number of days in treatment, the method of diagnosis, a history of any pretreatment transurethral resection of the prostate (TURP) and the type of boost were analyzed. Results: Median follow-up was 48 months. No statistically significant difference in rates of biochemical control were noted for treatment time, overall time (date of biopsy to completion of RT), history of any pretreatment TURP, history of diagnosis by TURP, or boost techniques. Patients diagnosed by TURP had a significant improvement in the overall rate of biochemical control (P < 0.03) compared to transrectal/transperineal biopsy. The 5-year actuarial rates were 58 versus 39%, respectively. This improvement was not evident when pretreatment PSA, T stage, or Gleason score were controlled for. On multivariate analysis, no variable was associated with outcome. When analysis was limited to a more favorable group of patients (T1/T2 tumors, pretreatment PSA ≤20 ng/ml and Gleason score <7), none of these variables were significantly predictive of biochemical control when controlling for pretreatment PSA, T stage and Gleason score. Conclusions: No significant effect of treatment time, overall time, pretreatment

  3. Re-analysis of clinical and treatment related prognostic factors on outcome using biochemical control as an end-point in patients with prostate cancer treated with external beam irradiation

    International Nuclear Information System (INIS)

    Ziaja, Ellen L.; Horwitz, Eric M.; Vicini, Frank A.; Dmuchowski, Carl F.; Brabbins, Donald S.; Gustafson, Gary S.; Hollander, Jay; Matter, Richard C.; Stromberg, Jannifer S.; Martinez, Alvaro A.

    1996-01-01

    Purpose: Prostate specific antigen (PSA) has been established as the most important prognostic factor for prostate cancer. We reviewed our experience treating patients with clinically localized prostate cancer with external beam irradiation (RT) to evaluate if previously defined clinical and treatment related prognostic factors remain valid when biochemical control was used as an end-point to evaluate results. Methods and Materials: Between 1/87 and 12/91, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58 - 70.4 Gy) using a 4 field or arc technique. Pre- and post-treatment serum PSA levels were recorded. Biochemical control was defined as PSA nadir ≤ 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if 2 consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase. Patients (pts) were divided into 3 groups according to total number of days on treatment: ≤ 49 days (≤ 7 weeks)- 21 pts; 50-63 days (8-9 weeks)- 429 pts; and ≥ 64 days (≥ 9 weeks)- 15 pts. Patients were also divided into groups with respect to the method of diagnosis: TURP (81 pts), or other means (399 pts). Patients were further divided into 2 groups: 1) if they had ever had a pre-treatment TURP (170 pts) or 2) if they had not (310 pts). Patients were divided into 2 groups according to boost technique: bilateral arcs (459 pts) or 4 field box (21 pts). Patients were also divided into groups according to total RT dose: ≤ 70 Gy (421 pts) or > 70 Gy (59 pts). Patients were further subdivided into 3 dose groups: 70 Gy (59 pts). Results: Median follow-up is 48 months (range 3 - 112 months). No statistically significant difference in rates of biochemical control were noted for treatment time, overall time (date of biopsy to completion of RT), or treatment time divided into

  4. HIV-related travel restrictions: trends and country characteristics.

    Science.gov (United States)

    Chang, Felicia; Prytherch, Helen; Nesbitt, Robin C; Wilder-Smith, Annelies

    2013-06-03

    Increasingly, HIV-seropositive individuals cross international borders. HIV-related restrictions on entry, stay, and residence imposed by countries have important consequences for this mobile population. Our aim was to describe the geographical distribution of countries with travel restrictions and to examine the trends and characteristics of countries with such restrictions. In 2011, data presented to UNAIDS were used to establish a list of countries with and without HIV restrictions on entry, stay, and residence and to describe their geographical distribution. The following indicators were investigated to describe the country characteristics: population at mid-year, international migrants as a percentage of the population, Human Development Index, estimated HIV prevalence (age: 15-49), presence of a policy prohibiting HIV screening for general employment purposes, government and civil society responses to having non-discrimination laws/regulations which specify migrants/mobile populations, government and civil society responses to having laws/regulations/policies that present obstacles to effective HIV prevention, treatment, care, and support for migrants/mobile populations, Corruption Perception Index, and gross national income per capita. HIV-related restrictions exist in 45 out of 193 WHO countries (23%) in all regions of the world. We found that the Eastern Mediterranean and Western Pacific Regions have the highest proportions of countries with these restrictions. Our analyses showed that countries that have opted for restrictions have the following characteristics: smaller populations, higher proportions of migrants in the population, lower HIV prevalence rates, and lack of legislation protecting people living with HIV from screening for employment purposes, compared with countries without restrictions. Countries with a high proportion of international migrants tend to have travel restrictions - a finding that is relevant to migrant populations and travel

  5. HIV-related ocular microangiopathic syndrome and color contrast sensitivity.

    Science.gov (United States)

    Geier, S A; Hammel, G; Bogner, J R; Kronawitter, U; Berninger, T; Goebel, F D

    1994-06-01

    Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton-wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CCS deficits in patients with HIV disease are primarily associated with the number of cotton

  6. Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy.

    Science.gov (United States)

    Lodwick, Rebecca K; Nakagawa, Fumiyo; van Sighem, Ard; Sabin, Caroline A; Phillips, Andrew N

    2015-01-01

    It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29-100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.

  7. Establishing a group of endpoints to support collective operations without specifying unique identifiers for any endpoints

    Science.gov (United States)

    Archer, Charles J.; Blocksom, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanghon

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  8. An Intersectional Perspective on Access to HIV-Related Healthcare for Transgender Women

    Science.gov (United States)

    Lacombe-Duncan, Ashley

    2016-01-01

    Abstract Transgender women experience decreased access to HIV-related healthcare relative to cisgender people, in part due to pervasive transphobia in healthcare. This perspective describes intersectionality as a salient theoretical approach to understanding this disparity, moving beyond transphobia to explore how intersecting systems of oppression, including cisnormativity, sexism/transmisogyny, classism, racism, and HIV-related, gender nonconformity, substance use, and sex work stigma influence HIV-related healthcare access for transgender women living with HIV. This perspective concludes with a discussion of how intersectionality-informed studies can be enhanced through studying underexplored intersections and bringing attention to women's resiliency and empowerment. PMID:29159304

  9. HIV-related chronic lung disease in adolescents: are we prepared for the future?

    Science.gov (United States)

    Goussard, Pierre; Gie, Robert P

    2017-12-01

    Chronic lung diseases (CLD) are the most chronic disease occurring in adolescents living with human immunodeficiency virus (ALHIV). In ALHIV who received antiretroviral therapy (ART) late in childhood, bronchiectasis, bronchiolitis obliterans and interstitial pneumonitis are common. In adolescents who received ART early in life the spectrum of CLD has changed with asthma and chronic obstructive pulmonary disease being common. Areas covered: The aim of this paper was to review CLD in ALHIV. We conducted a literature review of electronic databases focusing on CLD that were common prior to the introduction of ART (1996-2004), the present situation where ART is widely available (2005 to 2016), and articles which aided us speculating on the impact of HIV-related CLD in adolescents transitioning to adult HIV-clinics. Amongst the approximately 2.1 million adolescents living with HIV, CLD commonly occurs. Awareness of the CLD amongst ALHIV needs to be raised to ensure that disease appropriate treatment is available to these vulnerable adolescents. Expert commentary: As adolescents' transition from pediatric HIV-clinics to adult HIV-clinics the evidence shows that adolescents might not receive optimal care if adult pulmonologists are not aware of the CLD that commonly occur in ALHIV.

  10. The people living with HIV stigma survey UK 2015: HIV-related sexual rejection and other experiences of stigma and discrimination among gay and heterosexual men.

    Science.gov (United States)

    Hibbert, M; Crenna-Jennings, W; Kirwan, P; Benton, L; Lut, I; Okala, S; Asboe, D; Jeffries, J; Kunda, C; Mbewe, R; Morris, S; Morton, J; Nelson, M; Thorley, L; Paterson, H; Ross, M; Reeves, I; Sharp, L; Sseruma, W; Valiotis, G; Wolton, A; Jamal, Z; Hudson, A; Delpech, V

    2018-05-27

    We aim to understand the difference in stigma and discrimination, in particular sexual rejection, experienced between gay and heterosexual men living with HIV in the UK. The People Living with HIV StigmaSurvey UK 2015 recruited a convenience sample of persons with HIV through over 120 cross sector community organisations and 46 HIV clinics to complete an online survey. 1162 men completed the survey, 969 (83%) gay men and 193 (17%) heterosexual men, 92% were on antiretroviral therapy. Compared to heterosexual men, gay men were significantly more likely to report worrying about workplace treatment in relation to their HIV (21% vs. 11%), worrying about HIV-related sexual rejection (42% vs 21%), avoiding sex because of their HIV status (37% vs. 23%), and experiencing HIV-related sexual rejection (27% vs. 9%) in the past 12 months. In a multivariate logistic regression controlling for other sociodemographic factors, being gay was a predictor of reporting HIV-related sexual rejection in the past 12 months (aOR 2.17, CI 1.16, 4.02). Both gay and heterosexual men living with HIV experienced stigma and discrimination in the past 12 months, and this was higher for gay men in terms of HIV-related sexual rejection. Due to the high proportion of men reporting sexual rejection, greater awareness and education of the low risk of transmission of HIV among people on effective treatment is needed to reduce stigma and sexual prejudice towards people living with HIV.

  11. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    Science.gov (United States)

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  12. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

    Science.gov (United States)

    Gilbert, Peter B.; Gabriel, Erin E.; Huang, Ying; Chan, Ivan S.F.

    2015-01-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of

  13. Framing Mechanisms Linking HIV-Related Stigma, Adherence to Treatment, and Health Outcomes

    Science.gov (United States)

    Hatcher, Abigail M.; Weiser, Sheri D.; Johnson, Mallory O.; Rice, Whitney S.; Turan, Janet M.

    2017-01-01

    We present a conceptual framework that highlights how unique dimensions of individual-level HIV-related stigma (perceived community stigma, experienced stigma, internalized stigma, and anticipated stigma) might differently affect the health of those living with HIV. HIV-related stigma is recognized as a barrier to both HIV prevention and engagement in HIV care, but little is known about the mechanisms through which stigma leads to worse health behaviors or outcomes. Our conceptual framework posits that, in the context of intersectional and structural stigmas, individual-level dimensions of HIV-related stigma operate through interpersonal factors, mental health, psychological resources, and biological stress pathways. A conceptual framework that encompasses recent advances in stigma science can inform future research and interventions aiming to address stigma as a driver of HIV-related health. PMID:28426316

  14. HIV-Related Stigma Among Spanish-speaking Latinos in an Emerging Immigrant Receiving City.

    Science.gov (United States)

    Dolwick Grieb, Suzanne M; Shah, Harita; Flores-Miller, Alejandra; Zelaya, Carla; Page, Kathleen R

    2017-08-01

    HIV-related stigma has been associated with a reluctance to test for HIV among Latinos. This study assessed community HIV-related stigma within an emerging Latino immigrant receiving city. We conducted a brief survey among a convenience sample of 312 Spanish-speaking Latinos in Baltimore, Maryland. HIV-related stigma was assessed through six items. Associations between stigma items, socio-demographic characteristics, and HIV testing history were considered. Gender, education, and religiosity were significantly associated with stigmatizing HIV-related beliefs. For example, men were 3.4 times more likely to hold more than three stigmatizing beliefs than women, and were also twice as likely as women to report feeling hesitant to test for HIV for fear of people's reaction if the test is positive. These findings can help inform future stigma interventions in this community. In particular, we were able to distinguish between drivers of stigma such as fear and moralistic attitudes, highlighting specific actionable items.

  15. Screening for HIV-related PTSD: sensitivity and specificity of the 17-item Posttraumatic Stress Diagnostic Scale (PDS) in identifying HIV-related PTSD among a South African sample.

    Science.gov (United States)

    Martin, L; Fincham, D; Kagee, A

    2009-11-01

    The identification of HIV-positive patients who exhibit criteria for Posttraumatic Stress Disorder (PTSD) and related trauma symptomatology is of clinical importance in the maintenance of their overall wellbeing. This study assessed the sensitivity and specificity of the 17-item Posttraumatic Stress Diagnostic Scale (PDS), a self-report instrument, in the detection of HIV-related PTSD. An adapted version of the PTSD module of the Composite International Diagnostic Interview (CIDI) served as the gold standard. 85 HIV-positive patients diagnosed with HIV within the year preceding data collection were recruited by means of convenience sampling from three HIV clinics within primary health care facilities in the Boland region of South Africa. A significant association was found between the 17-item PDS and the adapted PTSD module of the CIDI. A ROC curve analysis indicated that the 17-item PDS correctly discriminated between PTSD caseness and non-caseness 74.9% of the time. Moreover, a PDS cut-off point of > or = 15 yielded adequate sensitivity (68%) and 1-specificity (65%). The 17-item PDS demonstrated a PPV of 76.0% and a NPV of 56.7%. The 17-item PDS can be used as a brief screening measure for the detection of HIV-related PTSD among HIV-positive patients in South Africa.

  16. A Structural Equation Model of HIV-related Symptoms, Depressive Symptoms, and Medication Adherence

    OpenAIRE

    Yoo-Jeong, Moka; Waldrop-Valverde, Drenna; McCoy, Katryna; Ownby, Raymond L

    2016-01-01

    Adherence to combined antiretroviral therapy (cART) remains critical in management of HIV infection. This study evaluated depression as a potential mechanism by which HIV-related symptoms affect medication adherence and explored if particular clusters of HIV symptoms are susceptible to this mechanism. Baseline data from a multi-visit intervention study were analyzed among 124 persons living with HIV (PLWH). A bifactor model showed two clusters of HIV-related symptom distress: general HIV-rela...

  17. Modeling Structural, Dyadic, and Individual Factors: The Inclusion and Exclusion Model of HIV Related Behavior

    OpenAIRE

    Albarracin, Dolores; Tannenbaum, Melanie B.; Glasman, Laura R.; Rothman, Alexander J.

    2010-01-01

    Changing HIV-related behaviors requires addressing the individual, dyadic, and structural influences that shape them. This supplement of AIDS & Behavior presents frameworks that integrate these three influences on behavior. Concepts from these frameworks were selected to model the processes by which structural factors affect individual HIV-related behavior. In the Inclusion/Exclusion Model, material and symbolic inclusions and exclusions (sharing versus denying resources) regulate individuals...

  18. Effect of education of primary health care workers on HIV-related oral lesions in Nairobi East district

    Directory of Open Access Journals (Sweden)

    Lucina N. Koyio

    2012-04-01

    Full Text Available Background. An estimated 90% of HIV-infected people are likely to develop oral lesions in the course of HIV infection. Oro-pharyngeal candidiasis (OPC, an early marker for HIV-infection, can be diagnosed during an oral examination (OE. Primary healthcare (PHC providers in Kenya are neither trained nor sufficiently equipped to perform this simple, cheap and non-invasive examination. The PHC system in Kenya offers an opportunity to integrate early recognition and management of oral lesions into general health care. This study aims to estimate the effect of a multifaceted intervention for PHC providers in training them to perform an OE. Specifically, our primary objective is to establish whether the intervention is effective in increasing: i the frequency of early detection of HIV-related oral lesions; and ii referral rates for HIV-testing. Design and methods. The study has been designed in two parts: a retrospective clinical data record study and a prospective cohort study with pre-post control group design, carried out in 2 administrative divisions in Nairobi East district. The intervention group will receive one day of training on recognition of HIV-related oral lesions and other common oral conditions. Reminder sessions will be held at individual health facilities. Routine tally sheets will be used to record all patients with HIV-related oral lesions, dental caries and periodontal disease. A convenience sample of all the PHC in a division will be used. It will not be possible to blind investigators or assessors. Expected impact of the study for Public Health. Early recognition and treatment of HIV infection influences long-term survival rates and will reduce healthcare expenditure.

  19. Perspectives of HIV-related stigma in a community in Vietnam: a qualitative study.

    Science.gov (United States)

    Gaudine, Alice; Gien, Lan; Thuan, Tran T; Dung, Do V

    2010-01-01

    While HIV/AIDS is increasing in Vietnam, very few published studies focus on HIV-related stigma in Vietnam. This study reports on findings from a community development project to reduce HIV-related stigma within one community in Vietnam. The purpose of this qualitative study is to describe HIV-related stigma from the perspective of three groups within one community in Vietnam: people living with HIV, their family members, and community members and leaders, including health care professionals. SETTING, PARTICIPANTS AND METHODS: Fifty-eight individuals from a poor, industrial district on the outskirts of a large city participated in the study and were asked to describe HIV-related stigma. Interviews were conducted with 10 people living with HIV, 10 family members of a person living with HIV, and 10 community members and 5 community leaders including health care professionals. We also conducted three focus groups, one with people living with HIV (n=8), one with family members of people living with HIV (n=8), and one with community leaders including health care professionals (n=7). Stigma across the three groups is characterized by four dimensions of HIV-related stigma: feeling shamed and scorned, behaving differently, stigma due to association, and fear of transmission. The manifestation of these dimensions differs for each group. Four themes of HIV-related stigma as described by people living with HIV are: being avoided, experiencing anger and rejection, being viewed as a social ill, and hiding the illness. Seven themes of HIV-related stigma as described by family members are: shunned by neighbors, viewed as poor parents, discriminated by health professionals, overhearing discussions about people with HIV, maintaining the secret, financial hardship for family, and fear of contracting HIV. Four themes of HIV-related stigma as described by community members and leaders including health professionals are: stigma as a fair reward, avoidance and shunning by neighbors

  20. A Grounded Theory Study of HIV-Related Stigma in U.S.-Based Health Care Settings.

    Science.gov (United States)

    Davtyan, Mariam; Olshansky, Ellen F; Brown, Brandon; Lakon, Cynthia

    Despite progress made in the treatment and care of people living with HIV (PLWH), HIV-related stigma has remained persistent. Health care settings and workers have been identified as important sources of stigma. Studies have addressed the construct of stigma in U.S. health care settings, but mainly from the perspectives of PLWH. We used Grounded Theory to understand how health care workers conceptualized HIV-related stigma and to develop a model to project a purposive view of stigma in health care settings. Our model indicates that stigma may be rooted in historically derogatory representations of HIV and intensified by power inequalities. Stigma may be triggered by fear, inadequate clinical education and training, unintentional behaviors, and limited contact with PLWH. Study participants perceived stigma as injurious to patient and provider health outcomes. Additional research on provider perceptions of stigma and programs that encourage empowerment, communication, and training may be necessary for stigma reduction. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  1. Trial endpoints for drug approval in oncology: Chemoprevention.

    Science.gov (United States)

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  2. Knowledge of HIV-related disabilities and challenges in accessing care: Qualitative research from Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Lena Morgon Banks

    Full Text Available While the rapid expansion in antiretroviral therapy access in low and middle income countries has resulted in dramatic declines in mortality rates, many people living with HIV face new or worsening experiences of disability. As nearly 1 in 20 adults are living with HIV in sub-Saharan Africa-many of whom are likely to develop disabling sequelae from long-term infection, co-morbidities and side effects of their treatment-understanding the availability and accessibility of services to address HIV-related disabilities is of vital importance. The aim of this study thus is to explore knowledge of HIV-related disabilities amongst stakeholders working in the fields of HIV and disability and factors impacting uptake and provision of interventions for preventing, treating or managing HIV-related disabilities.In-depth, semi-structured interviews were conducted with ten stakeholders based in Harare, Zimbabwe, who were working in the fields of either disability or HIV. Stakeholders were identified through a priori stakeholder analysis. Thematic Analysis, complemented by constant comparison as described in Grounded Theory, was used to analyse findings.All key informants reported some level of knowledge of HIV-related disability, mostly from observations made in their line of work. However, they reported no interventions or policies were in place specifically to address HIV-related disability. While referrals between HIV and rehabilitation providers were not uncommon, no formal mechanisms had been established for collaborating on prevention, identification and management. Additional barriers to accessing and providing services to address HIV-related disabilities included: the availability of resources, including trained professionals, supplies and equipment in both the HIV and rehabilitation sectors; lack of disability-inclusive adaptations, particularly in HIV services; heavy centralization of available services in urban areas, without accessible, affordable

  3. Understanding HIV-related posttraumatic stress disorder in South Africa: a review and conceptual framework.

    Science.gov (United States)

    Young, Charles

    2011-06-01

    A number of epidemiological studies have attempted to measure the prevalence of HIV-related posttraumatic stress disorder (PTSD) in sub-Saharan Africa. A systematic review of the literature identified eight relevant studies that put current estimates of the prevalence of HIV-related PTSD between 4.2% and 40%. Even the lower estimates suggest that PTSD in response to the trauma of being diagnosed and living with HIV is a significant mental health burden. However, a conceptual framework to advance our understanding of the prevalence and phenomenology of HIV-related PTSD is lacking. This article argues that the Ehlers & Clark (2000) cognitive model of PTSD provides a useful conceptual framework for understanding HIV-related PTSD in South Africa. The model emphasises the role of trauma appraisals in the development and maintenance of PTSD, which can also be usefully applied to some of the other psychological disorders associated with HIV infection. The model appears to fit some of the important research findings, and it offers insights into the relationships between HIV-related PTSD and other psychological disorders, HIV stigma, the high prevalence of non-HIV traumatic events, occasional problems with the delivery of antiretroviral drugs in the South African public health service, the unpredictable course of HIV illness, and the quality of HIV testing and counselling. Implications for individual treatment strategies and broader public health interventions are briefly discussed.

  4. A Structural Equation Model of HIV-related Symptoms, Depressive Symptoms, and Medication Adherence.

    Science.gov (United States)

    Yoo-Jeong, Moka; Waldrop-Valverde, Drenna; McCoy, Katryna; Ownby, Raymond L

    2016-05-01

    Adherence to combined antiretroviral therapy (cART) remains critical in management of HIV infection. This study evaluated depression as a potential mechanism by which HIV-related symptoms affect medication adherence and explored if particular clusters of HIV symptoms are susceptible to this mechanism. Baseline data from a multi-visit intervention study were analyzed among 124 persons living with HIV (PLWH). A bifactor model showed two clusters of HIV-related symptom distress: general HIV-related symptoms and gastrointestinal (GI) symptoms. Structural equation modeling showed that both general HIV-related symptoms and GI symptoms were related to higher levels of depressive symptoms, and higher levels of depressive symptoms were related to lower levels of medication adherence. Although general HIV-related symptoms and GI symptoms were not directly related to adherence, they were indirectly associated with adherence via depression. The findings highlight the importance of early recognition and evaluation of symptoms of depression, as well as the underlying physical symptoms that might cause depression, to improve medication adherence.

  5. HIV-Related Stigma and Discriminatory Attitudes among a Semi-Urban Population.

    Science.gov (United States)

    Lugova, Halyna; Mon, Aye Aye; Daher, Aqil Mohammad; Suleiman, Adlina

    2015-09-01

    Stigma and discriminatory attitudes (SDAs) have a negative impact on human immunodeficiency virus (HIV) prevention, testing, and treatment as well as on family and social networks. There is a lack of understanding about HIV-related SDAs among people living outside large cities. This study is aimed to determine the level of HIV-related SDAs among a semi-urban population in Malaysia and to compare the SDA results among people with different sociodemographic characteristics. A sample of 106 respondents was generated by convenience sampling during the screening campaign in Alor Gajah, Malaysia. Data collection was carried out based on a pre-tested questionnaire via face-to-face interviews. More than half of the respondents (62.3%) thought that an HIV-positive teacher should not be allowed to continue teaching at school; 81.1% were unsure or were unwilling to care for their family member with AIDS at home; 81.2% thought children with HIV/AIDS should not continue to be raised in families; and 77.3% thought they would not reveal if a family member had HIV/AIDS. Priority should be given to evidence-based interventions to reduce HIV-related SDAs. This study did not reveal any significant relationship between sociodemographic profiles and HIV-related SDAs. Therefore, further research with a larger sample size is needed to investigate the underlying causes of HIV-related SDAs.

  6. Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

    Science.gov (United States)

    Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

    2017-08-15

    Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

  7. Five criteria for using a surrogate endpoint to predict treatment effect based on data from multiple previous trials.

    Science.gov (United States)

    Baker, Stuart G

    2018-02-20

    A surrogate endpoint in a randomized clinical trial is an endpoint that occurs after randomization and before the true, clinically meaningful, endpoint that yields conclusions about the effect of treatment on true endpoint. A surrogate endpoint can accelerate the evaluation of new treatments but at the risk of misleading conclusions. Therefore, criteria are needed for deciding whether to use a surrogate endpoint in a new trial. For the meta-analytic setting of multiple previous trials, each with the same pair of surrogate and true endpoints, this article formulates 5 criteria for using a surrogate endpoint in a new trial to predict the effect of treatment on the true endpoint in the new trial. The first 2 criteria, which are easily computed from a zero-intercept linear random effects model, involve statistical considerations: an acceptable sample size multiplier and an acceptable prediction separation score. The remaining 3 criteria involve clinical and biological considerations: similarity of biological mechanisms of treatments between the new trial and previous trials, similarity of secondary treatments following the surrogate endpoint between the new trial and previous trials, and a negligible risk of harmful side effects arising after the observation of the surrogate endpoint in the new trial. These 5 criteria constitute an appropriately high bar for using a surrogate endpoint to make a definitive treatment recommendation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  8. Proximate Context of HIV-Related Stigma and Women's Use of Skilled Childbirth Services in Uganda.

    Science.gov (United States)

    Ng, Courtney K; Tsai, Alexander C

    2017-01-01

    HIV-related stigma compromises both HIV prevention and treatment and has recently been described as a barrier to utilization of skilled childbirth services in sub-Saharan Africa. This study uses the 2011 Uganda Demographic Health Survey to estimate the associations between HIV-related stigma, measured both at the individual and community level, and use of facility delivery among women. Consistent with theoretical predictions, higher levels of stigma are associated with reduced likelihood of facility delivery. The negative relationship between stigma and facility delivery is especially pronounced when stigma is measured at the community level, highlighting the importance of understanding the proximate context of HIV-related stigma and its potential effects on behavior. Reducing the stigma of HIV will be critical to achieving the twin goals of reducing overall maternal mortality and preventing mother-to-child HIV transmission.

  9. Modeling structural, dyadic, and individual factors: the inclusion and exclusion model of HIV related behavior.

    Science.gov (United States)

    Albarracin, Dolores; Tannenbaum, Melanie B; Glasman, Laura R; Rothman, Alexander J

    2010-12-01

    Changing HIV-related behaviors requires addressing the individual, dyadic, and structural influences that shape them. This supplement of AIDS & Behavior presents frameworks that integrate these three influences on behavior. Concepts from these frameworks were selected to model the processes by which structural factors affect individual HIV-related behavior. In the Inclusion/Exclusion Model, material and symbolic inclusions and exclusions (sharing versus denying resources) regulate individuals' ability and motivation to detect, prevent, and treat HIV. Structural interventions create inclusions that increase one's ability or motivation to perform these behaviors or exclusions that hinder one's ability or motivation to execute counterproductive behaviors. The need to expand research regarding multilevel influences on HIV-related behavior is also discussed, particularly concerning further understanding of sustained behavior change and effective dissemination of evidence-based intervention strategies.

  10. Endpoints and cutpoints in head and neck oncology trials: methodical background, challenges, current practice and perspectives.

    Science.gov (United States)

    Hezel, Marcus; von Usslar, Kathrin; Kurzweg, Thiemo; Lörincz, Balazs B; Knecht, Rainald

    2016-04-01

    This article reviews the methodical and statistical basics of designing a trial, with a special focus on the process of defining and choosing endpoints and cutpoints as the foundations of clinical research, and ultimately that of evidence-based medicine. There has been a significant progress in the treatment of head and neck cancer in the past few decades. Currently available treatment options can have a variety of different goals, depending e.g. on tumor stage, among other factors. The outcome of a specific treatment in clinical trials is measured using endpoints. Besides classical endpoints, such as overall survival or organ preservation, other endpoints like quality of life are becoming increasingly important in designing and conducting a trial. The present work is based on electronic research and focuses on the solid methodical and statistical basics of a clinical trial, on the structure of study designs and on the presentation of various endpoints.

  11. HIV-related stigma in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

    Science.gov (United States)

    Ion, Allyson; Wagner, Anne C; Greene, Saara; Loutfy, Mona R

    2017-02-01

    HIV-related stigma is associated with many psychological challenges; however, minimal research has explored how perceived HIV-related stigma intersects with psychosocial issues that mothers living with HIV may experience including depression, perceived stress and social isolation. The present study aims to describe the correlates and predictors of HIV-related stigma in a cohort of women living with HIV (WLWH) from across Ontario, Canada during pregnancy and early postpartum. From March 2011 to December 2012, WLWH ≥ 18 years (n = 77) completed a study instrument measuring independent variables including sociodemographic characteristics, perceived stress, depression symptoms, social isolation, social support and perceived racism in the third trimester and 3, 6 and 12 months postpartum. Multivariable linear regression was employed to explore the relationship between HIV-related stigma and multiple independent variables. HIV-related stigma generally increased from pregnancy to postpartum; however, there were no significant differences in HIV-related stigma across all study time points. In multivariable regression, depression symptoms and perceived racism were significant predictors of overall HIV-related stigma from pregnancy to postpartum. The present analysis contributes to our understanding of HIV-related stigma throughout the pregnancy-motherhood trajectory for WLWH including the interactional relationship between HIV-related stigma and other psychosocial variables, most notably, depression and racism.

  12. Barriers to men who have sex with men attending HIV related health ...

    African Journals Online (AJOL)

    2014-04-22

    Apr 22, 2014 ... The objectives of the study were to: (i) determine how stigma and discrimination affect MSM attendance to HIV related health services; .... Data analysis .... go to private hospitals where they will pay and get proper services ..... Commission, Zanzibar AIDS Commission, National Bureau of Statistics, Office of ...

  13. HIV-related restrictions on entry, residence and stay in the WHO European Region: a survey

    DEFF Research Database (Denmark)

    Lazarus, Jeff; Curth, Nadja; Weait, Matthew

    2010-01-01

    Back in 1987, the World Health Organization (WHO) concluded that the screening of international travellers was an ineffective way to prevent the spread of HIV. However, some countries still restrict the entrance and/or residency of foreigners with an HIV infection. HIV-related travel restrictions...

  14. HIV-related disabilities: an extra burden to HIV and AIDS healthcare ...

    African Journals Online (AJOL)

    Background: Healthcare workers have been at the forefront of dealing with the impact of HIV and AIDS at all stages of the pandemic. This brings new challenges to include disability into HIV care. However, the implications for healthcare workers in an already fragile health system along with HIV-related disabilities in ...

  15. HIV-related stigma and NGO-isation in India: a historico-empirical analysis.

    Science.gov (United States)

    Nambiar, Devaki

    2012-06-01

    In response to World Bank critiques in 2007, the Indian Ministry of Health and Family Welfare declared that human immunodeficiency virus (HIV)-related stigma was a barrier to the participation of non-governmental organisations (NGOs) in the implementation of HIV prevention targeted interventions. Taking a deeper view of HIV-related stigma as a historically inflected process of devaluation, this article details the history and transformation of NGO involvement in the HIV epidemic from 1986 through economic liberalisation in the 1990s up to the Second National AIDS Control Programme (NACP II 1999-2006). It additionally examines findings from interviews and participant observation of NGO workers (N = 24) from four targeted intervention NGOs in Delhi funded under NACP II. Analysis reveals that a second wave of HIV-related NGO involvement has mushroomed in the past two decades, affording NGO workers multiple pathways to credibility in the Indian response to the epidemic. Contradictions embedded in the overlap of these pathways produce stigma, reflecting 'adverse incorporation' of the NGO workers. Drawing upon noteworthy exceptions to this trend from the first wave of Indian HIV-related NGOs, the article calls for NGO participation as an explicitly political project of addressing the social inequalities that shape stigma as well as vulnerability to illness writ large. © 2011 The Author. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  16. HIV prevention intervention to reduce HIV-related stigma: evidence from China.

    Science.gov (United States)

    Li, Li; Liang, Li-Jung; Lin, Chunqing; Wu, Zunyou; Rotheram-Borus, Mary Jane

    2010-01-02

    The National Institute of Mental Health Collaborative HIV/Sexually Transmitted Disease Prevention Trial provided a unique opportunity to test whether, with the community-based diffusion of HIV/sexually transmitted disease prevention information and an elevated understanding of HIV, the level of stigmatizing attitudes toward people living with HIV/AIDS in the community would be reduced. A total of 4510 market workers in Fuzhou, China, participated in the study, and longitudinal analyses included study samples of 3785 participants in the 12-month follow-up and 3716 participants in the 24-month follow-up. We graphically examined the change in HIV-related stigma indicators over time between control and intervention groups using boxplot and kernel density estimation. A logistic regression analysis with proportional odds model was further used to examine the intervention effect on HIV-related stigmatizing attitudes. Compared with no change over time for the control group, the intervention successfully reduced the level of HIV-related stigmatizing attitudes among the target population at the 12-month follow-up, and the effect increased by two-fold (with respect to odds ratios) at the 24-month follow-up. The intervention demonstrated positive attitude changes associated with HIV-related stigma. Our results show the importance of social norms, rather than simply individual behaviors, in developing and implementing stigma reduction campaigns.

  17. Radiation therapy in the treatment of HIV-related Kaposi's sarcoma.

    Science.gov (United States)

    Donato, Vittorio; Guarnaccia, Roberta; Dognini, Jessica; de Pascalis, Giovanni; Caruso, Cristina; Bellagamba, Rita; Morrone, Aldo

    2013-05-01

    Kaposi's sarcoma (KS) is the most frequent neoplasm occurring in patients with HIV-related AIDS and very often exhibits multifocal distribution so that a systemic approach is needed. KS is considered a radiosensitive tumor and (RT) has always played an important role in the therapeutic strategy of its various forms. RT is a valuable means of pain relief, bleeding control and edema palliation, but it is also an effective treatment modality for local control of skin and mucosal lesions in KS. The purpose of the present article is to report the results obtained by the Radiotherapy Unit of S. Camillo-Forlanini Hospital in Rome in the management of 38 AIDS-associated KS lesions and to assess the efficacy of RT in the treatment and local control of KS. Eighteen patients histologically-diagnosed with HIV-related KS underwent RT in the period between January 2002 and January 2012 at the Radiotherapy Unit of S. Camillo-Forlanini Hospital in Rome. In all cases, the lesions caused pain or discomfort and a thorough careful clinical evaluation had indicated a radiation treatment. A total of 38 lesions were treated with radiotherapy. Fifteen patients received systemic chemotherapy. Eight patients with multiple cutaneous lesions on their legs and arms were treated with a radiation schedule prescribing extended cutaneous irradiation using 6-18 MeV electron beam energy, 200 cGy per fraction and a total dose between 24-30 Gy, according to the depth of lesions. One of these patients had also a cutaneous lesion on an eyelid that was treated with a radiation schedule using 6 MeV electron beam energy and bolus of 1 cm, 200 cGy per fraction and a total dose of 30 Gy. Seven patients with single cutaneous lesions on the legs and arms were treated using a photon regimen of 6 Mv energy, 200 cGy per fraction and a total dose between 20 and 36 Gy. Two patients had oral mucosa lesions and they were treated with a radiation schedule prescribing irradiation using 6 Mev photon regimen and personal

  18. Couple interdependence impacts HIV-related health behaviours among pregnant couples in southwestern Kenya: a qualitative analysis.

    Science.gov (United States)

    Rogers, Anna Joy; Achiro, Lillian; Bukusi, Elizabeth A; Hatcher, Abigail M; Kwena, Zachary; Musoke, Pamela L; Turan, Janet M; Weke, Elly; Darbes, Lynae A

    2016-01-01

    mention experiencing violence or relationship dissolution, or having difficulty coping with HIV-related stigma. We found that interdependence theory may provide key insights into health-related attitudes and behaviours adopted by pregnant couples. Interventions that invest in strengthening relationships, such as couple counselling during pregnancy, may improve adoption of beneficial HIV-related health behaviours. Future research should explore adaptation of existing evidence-based couple counselling interventions to local contexts, in order to address modifiable relationship characteristics that can increase interdependence and improve HIV-related health outcomes.

  19. Effect of Education of Primary Health Care Workers on HIV-related Oral Lesions in Nairobi East District.

    Science.gov (United States)

    Koyio, Lucina N; van der Sanden, Wil J M; van der Ven, Andre; Creugers, Nico; Merkx, Matthias A W; Frencken, Jo E

    2012-06-15

    An estimated 90% of HIV-infected people are likely to develop oral lesions in the course of HIV infection. Oro-pharyngeal candidiasis (OPC), an early marker for HIV-infection, can be diagnosed during an oral examination (OE). Primary healthcare (PHC) providers in Kenya are neither trained nor sufficiently equipped to perform this simple, cheap and non-invasive examination. The PHC system in Kenya offers an opportunity to integrate early recognition and management of oral lesions into general health care. This study aims to estimate the effect of a multifaceted intervention for PHC providers in training them to perform an OE. Specifically, our primary objective is to establish whether the intervention is effective in increasing: i) the frequency of early detection of HIV-related oral lesions; and ii) referral rates for HIV-testing. THE STUDY HAS BEEN DESIGNED IN TWO PARTS: a retrospective clinical data record study and a prospective cohort study with pre-post control group design, carried out in 2 administrative divisions in Nairobi East district. The intervention group will receive one day of training on recognition of HIV-related oral lesions and other common oral conditions. Reminder sessions will be held at individual health facilities. Routine tally sheets will be used to record all patients with HIV-related oral lesions, dental caries and periodontal disease. A convenience sample of all the PHC in a division will be used. It will not be possible to blind investigators or assessors. Expected impact of the study for Public Health. Early recognition and treatment of HIV infection influences long-term survival rates and will reduce healthcare expenditure. The project is funded by the Netherlands organisation for international cooperation in higher education (NUFFIC). We would like to thank all participating health facilities and health care workers for their willingness to take part in this study. LNK also thanks the Kenya Ministry of Public Health and Sanitation

  20. Voluntary counseling and testing (VCT) for changing HIV-related risk behavior in developing countries.

    Science.gov (United States)

    Fonner, Virginia A; Denison, Julie; Kennedy, Caitlin E; O'Reilly, Kevin; Sweat, Michael

    2012-09-12

    Voluntary counseling and testing (VCT) continues to play a critical role in HIV prevention, care and treatment. In recent years, different modalities of VCT have been implemented, including clinic-, mobile- and home-based testing and counseling. This review assesses the effects of all VCT types on HIV-related risk behaviors in low- and middle-income countries. The primary objective of this review is to systematically review the literature examining the efficacy of VCT in changing HIV-related risk behaviors in developing countries across various populations. Five electronic databases - PubMed, Excerpta Medica Database (EMBASE), PsycINFO, Sociological Abstracts, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) - were searched using predetermined key words and phrases. Hand-searching was conducted in four key journals including AIDS, AIDS and Behavior, AIDS Education and Prevention, and AIDS Care; the tables of contents of these four journals during the included time period were individually screened for relevant articles. The reference lists of all articles included in the review were screened to identify any additional studies; this process was iterated until no additional articles were found. To be included in the review, eligible studies had to meet the following inclusion criteria: 1) Take place in a low- or middle-income country as defined by the World Bank, 2) Published in a peer-reviewed journal between January 1, 1990 and July 6, 2010, 3) Involve client-initiated VCT, including pre-test counseling, HIV-testing, and post-test counseling, and 4) Use a pre/post or multi-arm design that compares individuals before and after receiving VCT or individuals who received VCT to those who did not, and 5) Report results pertaining to behavioral, psychological, biological, or social HIV-related outcomes. All citations were initially screened and all relevant citations were independently screened by two reviewers to assess eligibility. For all

  1. Adoption of HIV-related services among urban US hospitals: 1988 and 1991.

    Science.gov (United States)

    LeBlanc, A J; Hurley, R E

    1995-09-01

    Recent reports document that US hospitals vary considerably, notably by ownership, in the number of acquired immunodeficiency syndrome (AIDS) patients they treat. Still, little is known about other types of hospital response to human immunodeficiency virus (HIV) and AIDS and the relative strength of ownership as a determining factor. With annual survey data from the American Hospital Association the authors examine the formal adoption of HIV-related services among urban US hospitals at the turn of the decade. Descriptive analyses of 2 years of data (1988 and 1991) are presented. A multivariate logistic regression analysis, conducted on the 1991 data, tests for unique ownership effects on the likelihood that hospitals are heavy investors in HIV-related care. Patterns of service adoption for 1991 strongly resemble those for 1988. Nearly three fourths of urban US hospitals offer general inpatient AIDS care, and over half provide HIV testing. Few urban hospitals offer outpatient services; even fewer operate AIDS units. A substantial minority report no formal adoption of HIV-related services. For-profit hospitals stand out as least likely to formally adopt these HIV-related services. Those adopting a comprehensive set of HIV-related services typically are public or secular, not-for-profit in ownership, large, affiliated with a medical school, and high volume users of Medicaid funding. The logistic regression analysis suggests that public ownership is a key determinant of greater service investment, even after controlling for other explanatory factors. This study appears to mirror a familiar pattern of hospital response to undercompensated care in the United States.

  2. HIV-related sexual risk behaviors among male-to-female transgender people in Nepal.

    Science.gov (United States)

    Bhatta, Dharma Nand

    2014-05-01

    Transgender women are a vulnerable and key risk group for HIV, and most research has shown an increased frequency of HIV infection among this minority population. This study examined the prevalence of HIV-related sexual risk behaviors and the socio-demographic correlates with HIV-related sexual risk behaviors among male-to-female (MtF) transgender persons. Data were collected from a sample of 232 individuals through venue-based and snowball sampling and face-to-face interviews. The HIV-related sexual risk behaviors among the MtF transgender persons were: sex without using a condom (48.3%; 95% confidence interval (CI) 41.8-54.8), unprotected anal sex (68.1%; 95% CI 62.0-74.2), and unprotected sex with multiple partners (88.4%; 95% CI 84.3-92.5). Statistically significant differences were found for age, income, education, alcohol habit, and sex with more than two partners per day for these three different HIV-related sexual risk behaviors. MtF transgender persons with a secondary or higher level of education were three times (OR 2.93) more likely to have unprotected sex with multiple partners compared to those with a primary level or no education. Age, education, income, frequency of daily sexual contact, and an alcohol habit remain significant with regard to HIV-related sexual risk behavior. There is an urgent need for programs and interventions to reduce risky sexual behaviors in this minority population. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  3. HIV-related stigma in African and Afro-Caribbean communities in the Netherlands: Manifestations, consequences and coping

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Shiripinda, I.; Bruin, de M.; Pryor, J.B.; Schaalma, H.P.

    2012-01-01

    HIV-related stigma in African and Afro-Caribbean diaspora communities in the Netherlands was investigated. Interviews with HIV-positive and HIV-negative community members demonstrated that HIV-related stigma manifests as social distance, physical distance, words and silence. The psychological

  4. HIV-related stigma in African and Afro-Caribbean communities in the Netherlands: manifestations, consequences and coping

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Shiripinda, I.; de Bruin, M.; Pryor, J.B.; Schaalma, H.P.

    2012-01-01

    HIV-related stigma in African and Afro-Caribbean diaspora communities in the Netherlands was investigated. Interviews with HIV-positive and HIV-negative community members demonstrated that HIV-related stigma manifests as social distance, physical distance, words and silence. The psychological

  5. Is Socio-Economic Status a Determinant of HIV-Related Stigma Attitudes in Zimbabwe? Findings from Project Accept.

    Science.gov (United States)

    Mateveke, Kudzanai; Singh, Basant; Chingono, Alfred; Sibanda, E; Machingura, Ian

    2016-08-17

    HIV related stigma and discrimination is a known barrier for HIV prevention and care. We aimed to assess the relationship between socio-economic status (SES) and HIV related stigma in Zimbabwe. This paper uses data from Project Accept , which examined the impact of community-based voluntary counseling and testing intervention on HIV incidence and stigma. Total of 2522 eligible participants responded to a psychometric assessment tool, which assessed HIV related stigma and discrimination attitudes on 4 point Likert scale. The tool measured three components of HIV-related stigma: shame, blame and social isolation, perceived discrimination, and equity. Participants' ownership of basic assets was used to assess the socio-economic status. Shame, blame and social isolation component of HIV related stigma was found to be significantly associated with medium [odds ratio (OR)=1.73, Pstigma and discrimination programs to be effective, they should take into account the socio-economic context of target population.

  6. Establishing a group of endpoints in a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  7. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  8. A summation free β+-endpoint spectrometer

    International Nuclear Information System (INIS)

    Keller, H.; Kirchner, R.; Klepper, O.; Roeckl, E.; Schardt, D.; Simon, R.S.; Kleinheinz, P.; Liang, C.F.; Paris, P.

    1990-08-01

    A β + -endpoint spectrometer is described, where positrons are observed in an 11-mm thick silicon detector in coincidence with subsequent γ-rays meausred in a germanium detector, and where the summing of the positron energy with the annihilation radiation is prevented by detecting both 511-keV quanta in opposite segments of a BGO ring surrounding the silicon detector. The procedure of measuring and analyzing the data is outlined for the decay of the 11/2 - -isomer of 149 Tb; its endpoint energy is determined to be 1853(10) keV, in agreement with the literature. The accuracy and reliability of β + -endpoint measurements is discussed in comparison to the EC/β + -ratio method. (orig.)

  9. End-point sharpness in thermometric titrimetry.

    Science.gov (United States)

    Tyrrell, H J

    1967-07-01

    It is shown that the sharpness of an end-point in a thermometric titration where the simple reaction A + B right harpoon over left harpoon AB takes place, depends on Kc(A') where K is the equilibrium constant for the reaction, and c(A') is the total concentration of the titrand (A) in the reaction mixture. The end-point is sharp if, (i) the enthalpy change in the reaction is not negligible, and (ii) Kc(A') > 10(3). This shows that it should, for example, be possible to titrate 0.1 M acid, pK(A) = 10, using a thennometric end-point. Some aspects of thermometric titrimetry when Kc(A') < 10(3) are also considered.

  10. Forecasting interest rates with shifting endpoints

    DEFF Research Database (Denmark)

    Van Dijk, Dick; Koopman, Siem Jan; Wel, Michel van der

    2014-01-01

    We consider forecasting the term structure of interest rates with the assumption that factors driving the yield curve are stationary around a slowly time-varying mean or ‘shifting endpoint’. The shifting endpoints are captured using either (i) time series methods (exponential smoothing) or (ii......) long-range survey forecasts of either interest rates or inflation and output growth, or (iii) exponentially smoothed realizations of these macro variables. Allowing for shifting endpoints in yield curve factors provides substantial and significant gains in out-of-sample predictive accuracy, relative...... to stationary and random walk benchmarks. Forecast improvements are largest for long-maturity interest rates and for long-horizon forecasts....

  11. Considerations in choosing a primary endpoint that measures durability of virological suppression in an antiretroviral trial.

    Science.gov (United States)

    Gilbert, P B; Ribaudo, H J; Greenberg, L; Yu, G; Bosch, R J; Tierney, C; Kuritzkes, D R

    2000-09-08

    At present, many clinical trials of anti-HIV-1 therapies compare treatments by a primary endpoint that measures the durability of suppression of HIV-1 replication. Several durability endpoints are compared. Endpoints are compared by their implicit assumptions regarding surrogacy for clinical outcomes, sample size requirements, and accommodations for inter-patient differences in baseline plasma HIV-1-RNA levels and in initial treatment response. Virological failure is defined by the non-suppression of virus levels at a prespecified follow-up time T(early virological failure), or by relapse. A binary virological failure endpoint is compared with three time-to-virological failure endpoints: time from (i) randomization that assigns early failures a failure time of T weeks; (ii) randomization that extends the early failure time T for slowly responding subjects; and (iii) virological response that assigns non-responders a failure time of 0 weeks. Endpoint differences are illustrated with Agouron's trial 511. In comparing high with low-dose nelfinavir (NFV) regimens in Agouron 511, the difference in Kaplan-Meier estimates of the proportion not failing by 24 weeks is 16.7% (P = 0.048), 6.5% (P = 0.29) and 22.9% (P = 0.0030) for endpoints (i), (ii) and (iii), respectively. The results differ because NFV suppresses virus more quickly at the higher dose, and the endpoints weigh this treatment difference differently. This illustrates that careful consideration needs to be given to choosing a primary endpoint that will detect treatment differences of interest. A time from randomization endpoint is usually recommended because of its advantages in flexibility and sample size, especially at interim analyses, and for its interpretation for patient management.

  12. Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications.

    Science.gov (United States)

    Liberti, Lawrence; Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M; Leufkens, Hubert

    2015-06-01

    Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in

  13. Masculinity and HIV: Dimensions of Masculine Norms that Contribute to Men's HIV-Related Sexual Behaviors.

    Science.gov (United States)

    Fleming, Paul J; DiClemente, Ralph J; Barrington, Clare

    2016-04-01

    Numerous studies have documented a relationship between masculine norms and men's HIV-related sexual behaviors, but intervening upon this relationship requires a nuanced understanding of the specific aspects of masculine norms that shape men's sexual behaviors. We integrate theories on masculinities with empirical HIV research to identify specific dimensions of masculine norms that influence men's HIV-related sexual behaviors. We identify three major dimensions of masculine norms that shape men's sexual behavior: (1) uncontrollable male sex drive, (2) capacity to perform sexually, and (3) power over others. While the existing literature does help explain the relationship between masculine norms and men's sexual behaviors several gaps remain including: a recognition of context-specific masculinities, an interrogation of the positive influences of masculinity, adoption of an intersectional approach, assessment of changes in norms and behaviors over time, and rigorous evaluations of gender-transformative approaches. Addressing these gaps in future research may optimize prevention efforts.

  14. Social cohesion, social participation, and HIV related risk among female sex workers in Swaziland.

    Directory of Open Access Journals (Sweden)

    Virginia A Fonner

    Full Text Available Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social cohesion among sex workers and social participation of sex workers in the larger community, and HIV-related risk in Swaziland using respondent-driven sampling. Relationships between social cohesion, social participation, and HIV-related risk factors were assessed using logistic regression. HIV prevalence among the sample was 70.4% (223/317. Social cohesion was associated with consistent condom use in the past week (adjusted odds ratio [AOR] = 2.25, 95% confidence interval [CI]: 1.30-3.90 and was associated with fewer reports of social discrimination, including denial of police protection. Social participation was associated with HIV testing (AOR = 2.39, 95% CI: 1.36-4.03 and using condoms with non-paying partners (AOR = 1.99, 95% CI: 1.13-3.51, and was inversely associated with reported verbal or physical harassment as a result of selling sex (AOR = 0.55, 95% CI: 0.33-0.91. Both social capital constructs were significantly associated with collective action, which involved participating in meetings to promote sex worker rights or attending HIV-related meetings/ talks with other sex workers. Social- and structural-level interventions focused on building social cohesion and social participation among sex workers could provide significant protection from HIV infection for female sex workers in Swaziland.

  15. Social Cohesion, Social Participation, and HIV Related Risk among Female Sex Workers in Swaziland

    OpenAIRE

    Fonner, Virginia A.; Kerrigan, Deanna; Mnisi, Zandile; Ketende, Sosthenes; Kennedy, Caitlin E.; Baral, Stefan

    2014-01-01

    Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social ...

  16. Social Cohesion, Social Participation, and HIV Related Risk among Female Sex Workers in Swaziland

    Science.gov (United States)

    Fonner, Virginia A.; Kerrigan, Deanna; Mnisi, Zandile; Ketende, Sosthenes; Kennedy, Caitlin E.; Baral, Stefan

    2014-01-01

    Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social cohesion among sex workers and social participation of sex workers in the larger community, and HIV-related risk in Swaziland using respondent-driven sampling. Relationships between social cohesion, social participation, and HIV-related risk factors were assessed using logistic regression. HIV prevalence among the sample was 70.4% (223/317). Social cohesion was associated with consistent condom use in the past week (adjusted odds ratio [AOR]  = 2.25, 95% confidence interval [CI]: 1.30–3.90) and was associated with fewer reports of social discrimination, including denial of police protection. Social participation was associated with HIV testing (AOR = 2.39, 95% CI: 1.36–4.03) and using condoms with non-paying partners (AOR = 1.99, 95% CI: 1.13–3.51), and was inversely associated with reported verbal or physical harassment as a result of selling sex (AOR = 0.55, 95% CI: 0.33–0.91). Both social capital constructs were significantly associated with collective action, which involved participating in meetings to promote sex worker rights or attending HIV-related meetings/ talks with other sex workers. Social- and structural-level interventions focused on building social cohesion and social participation among sex workers could provide significant protection from HIV infection for female sex workers in Swaziland. PMID:24498125

  17. Workplace and HIV-related sexual behaviours and perceptions among female migrant workers

    OpenAIRE

    YANG, H.; LI, X.; STANTON, B.; FANG, X.; LIN, D.; MAO, R.; LIU, H.; CHEN, X.; SEVERSON, R.

    2005-01-01

    Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment esta...

  18. Social cohesion, social participation, and HIV related risk among female sex workers in Swaziland.

    Science.gov (United States)

    Fonner, Virginia A; Kerrigan, Deanna; Mnisi, Zandile; Ketende, Sosthenes; Kennedy, Caitlin E; Baral, Stefan

    2014-01-01

    Social capital is important to disadvantaged groups, such as sex workers, as a means of facilitating internal group-related mutual aid and support as well as access to broader social and material resources. Studies among sex workers have linked higher social capital with protective HIV-related behaviors; however, few studies have examined social capital among sex workers in sub-Saharan Africa. This cross-sectional study examined relationships between two key social capital constructs, social cohesion among sex workers and social participation of sex workers in the larger community, and HIV-related risk in Swaziland using respondent-driven sampling. Relationships between social cohesion, social participation, and HIV-related risk factors were assessed using logistic regression. HIV prevalence among the sample was 70.4% (223/317). Social cohesion was associated with consistent condom use in the past week (adjusted odds ratio [AOR] = 2.25, 95% confidence interval [CI]: 1.30-3.90) and was associated with fewer reports of social discrimination, including denial of police protection. Social participation was associated with HIV testing (AOR = 2.39, 95% CI: 1.36-4.03) and using condoms with non-paying partners (AOR = 1.99, 95% CI: 1.13-3.51), and was inversely associated with reported verbal or physical harassment as a result of selling sex (AOR = 0.55, 95% CI: 0.33-0.91). Both social capital constructs were significantly associated with collective action, which involved participating in meetings to promote sex worker rights or attending HIV-related meetings/ talks with other sex workers. Social- and structural-level interventions focused on building social cohesion and social participation among sex workers could provide significant protection from HIV infection for female sex workers in Swaziland.

  19. Exposing the cancer genome atlas as a SPARQL endpoint

    Science.gov (United States)

    Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

    2011-01-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

  20. Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

    Directory of Open Access Journals (Sweden)

    Sandberg DavidE

    2010-08-01

    Full Text Available Psychological outcomes in persons with congenital adrenal hyperplasia (CAH have received substantial attention. The objectives of this paper were to (1 catalog psychological endpoints assessed in CAH outcome studies and (2 classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68% investigated endpoints related to psychosexual differentiation. The preponderance of studies (76% examined a direct relationship (i.e., inferring causality between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

  1. Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis

    Science.gov (United States)

    Katz, Ingrid T; Ryu, Annemarie E; Onuegbu, Afiachukwu G; Psaros, Christina; Weiser, Sheri D; Bangsberg, David R; Tsai, Alexander C

    2013-01-01

    Introduction Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical

  2. Sperm count as a surrogate endpoint for male fertility control.

    Science.gov (United States)

    Benda, Norbert; Gerlinger, Christoph

    2007-11-30

    When assessing the effectiveness of a hormonal method of fertility control in men, the classical approach used for the assessment of hormonal contraceptives in women, by estimating the pregnancy rate or using a life-table analysis for the time to pregnancy, is difficult to apply in a clinical development program. The main reasons are the dissociation of the treated unit, i.e. the man, and the observed unit, i.e. his female partner, the high variability in the frequency of male intercourse, the logistical cost and ethical concerns related to the monitoring of the trial. A reasonable surrogate endpoint of the definite endpoint time to pregnancy is sperm count. In addition to the avoidance of the mentioned problems, trials that compare different treatments are possible with reasonable sample sizes, and study duration can be shorter. However, current products do not suppress sperm production to 100 per cent in all men and the sperm count is only observed with measurement error. Complete azoospermia might not be necessary in order to achieve an acceptable failure rate compared with other forms of male fertility control. Therefore, the use of sperm count as a surrogate endpoint must rely on the results of a previous trial in which both the definitive- and surrogate-endpoint results were assessed. The paper discusses different estimation functions of the mean pregnancy rate (corresponding to the cumulative hazard) that are based on the results of sperm count trial and a previous trial in which both sperm count and time to pregnancy were assessed, as well as the underlying assumptions. Sample size estimations are given for pregnancy rate estimation with a given precision.

  3. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  4. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    OpenAIRE

    Bonnetain Franck; Bedenne Laurent; Methy Nicolas

    2010-01-01

    Abstract Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opin...

  5. Refining Current Scientific Priorities and Identifying New Scientific Gaps in HIV-Related Heart, Lung, Blood, and Sleep Research.

    Science.gov (United States)

    Twigg, Homer L; Crystal, Ronald; Currier, Judith; Ridker, Paul; Berliner, Nancy; Kiem, Hans-Peter; Rutherford, George; Zou, Shimian; Glynn, Simone; Wong, Renee; Peprah, Emmanuel; Engelgau, Michael; Creazzo, Tony; Colombini-Hatch, Sandra; Caler, Elisabet

    2017-09-01

    The National Heart, Lung, and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood, and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14-15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: (1) HIV-related HLBS comorbidities in the antiretroviral era; (2) HIV cure; (3) HIV prevention; and (4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV. The 2015 Working Group represented an opportunity for the NHLBI to obtain expert advice on HIV/AIDS scientific priorities and approaches over the next decade.

  6. Gender and ethnicity differences in HIV-related stigma experienced by people living with HIV in Ontario, Canada.

    Science.gov (United States)

    Loutfy, Mona R; Logie, Carmen H; Zhang, Yimeng; Blitz, Sandra L; Margolese, Shari L; Tharao, Wangari E; Rourke, Sean B; Rueda, Sergio; Raboud, Janet M

    2012-01-01

    This study aimed to understand gender and ethnicity differences in HIV-related stigma experienced by 1026 HIV-positive individuals living in Ontario, Canada that were enrolled in the OHTN Cohort Study. Total and subscale HIV-related stigma scores were measured using the revised HIV-related Stigma Scale. Correlates of total stigma scores were assessed in univariate and multivariate linear regression. Women had significantly higher total and subscale stigma scores than men (total, median = 56.0 vs. 48.0, pwomen, Black individuals had the highest, Aboriginal and Asian/Latin-American/Unspecified people intermediate, and White individuals the lowest total stigma scores. The gender-ethnicity interaction term was significant in multivariate analysis: Black women and Asian/Latin-American/Unspecified men reported the highest HIV-related stigma scores. Gender and ethnicity differences in HIV-related stigma were identified in our cohort. Findings suggest differing approaches may be required to address HIV-related stigma based on gender and ethnicity; and such strategies should challenge racist and sexist stereotypes.

  7. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  8. Evaluation of early efficacy endpoints for proof-of-concept trials.

    Science.gov (United States)

    Chen, Cong; Sun, Linda; Li, Chih-Lin

    2013-03-11

    A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

  9. Sexual experience and HIV-related knowledge among Belgian university students: a questionnaire study.

    Science.gov (United States)

    Degroote, Sophie; Vogelaers, Dirk; Liefhooghe, Griet; Vermeir, Peter; Vandijck, Dominique M

    2014-05-15

    Adolescents are a risk group for acquiring sexually transmitted diseases, including HIV. Correct knowledge about transmission mechanisms is a prerequisite to taking appropriate precautions to avoid infection. This study aimed at assessing the level of HIV-related knowledge among university students as a first step in developing targeted interventions. We used a self-developed HIV knowledge questionnaire, supplemented with socio-demographic and sexual behaviour questions. The questionnaire was composed of 59 items from different existing questionnaires. It included general statements and statements about prevention, transmission and treatment of HIV. There were 357 (79.7%) female and 93 (20.3%) male participants and their median age was 20 (IQR 19-21). On average 42/59 (71.2%) questions were answered correctly, 5/59 (8.5%) were answered incorrectly and 12/59 (20.3%) were unknown . The best and worse scores were seen on the prevention questions and the treatment questions, respectively. HIV-related knowledge is higher in older students and in students with a health-related education. Students with sexual experience, with five or more partners and students who have been tested on STDs have a higher HIV-related knowledge. Knowledge on prevention and transmission of HIV is fairly good among university students and knowledge is higher among students with more sexual experience. They still have some misconceptions (e.g. HIV is spread by mosquitoes) and they are ignorant of a substantial number of statements (e.g. risk for infection through oral sex).

  10. A Smartphone App to Screen for HIV-Related Neurocognitive Impairment.

    Science.gov (United States)

    Robbins, Reuben N; Brown, Henry; Ehlers, Andries; Joska, John A; Thomas, Kevin G F; Burgess, Rhonda; Byrd, Desiree; Morgello, Susan

    2014-02-01

    Neurocognitive Impairment (NCI) is one of the most common complications of HIV-infection, and has serious medical and functional consequences. However, screening for it is not routine and NCI often goes undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as limited screening tests, the need for specialized equipment and apparatuses, and highly trained personnel to administer, score and interpret screening tests. To address these challenges, we developed a novel smartphone-based screening tool, NeuroScreen , to detect HIV-related NCI that includes an easy-to-use graphical user interface with ten highly automated neuropsychological tests. To examine NeuroScreen's : 1) acceptability among patients and different potential users; 2) test construct and criterion validity; and 3) sensitivity and specificity to detect NCI. Fifty HIV+ individuals were administered a gold-standard neuropsychological test battery, designed to detect HIV-related NCI, and NeuroScreen . HIV+ test participants and eight potential provider-users of NeuroScreen were asked about its acceptability. There was a high level of acceptability of NeuroScreen by patients and potential provider-users. Moderate to high correlations between individual NeuroScreen tests and paper-and-pencil tests assessing the same cognitive domains were observed. NeuroScreen also demonstrated high sensitivity to detect NCI. NeuroScreen, a highly automated, easy-to-use smartphone-based screening test to detect NCI among HIV patients and usable by a range of healthcare personnel could help make routine screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust psychometric properties and acceptability, further testing with larger and less neurocognitively impaired samples is warranted.

  11. Social Determinants of HIV-Related Stigma in Faith-Based Organizations.

    Science.gov (United States)

    Coleman, Jason D; Tate, Allan D; Gaddist, Bambi; White, Jacob

    2016-03-01

    To examine the association between social factors in faith-based settings (including religiosity and proximity to people living with HIV/AIDS) and HIV stigma. A total of 1747 congregants from primarily African American faith-based organizations of Project FAITH (Fostering AIDS Initiatives That Heal), a South Carolina statewide initiative to address HIV-related stigma, completed a survey. Female gender (P = .001), higher education (P stigma and with lower odds of stigmatizing attitudes (P stigma in African American communities.

  12. Spatial clustering of all-cause and HIV-related mortality in a rural South African population (2000-2006.

    Directory of Open Access Journals (Sweden)

    Elias Namosha

    Full Text Available Sub-Saharan Africa bears a disproportionate burden of HIV infection. Knowledge of the spatial distribution of HIV outcomes is vital so that appropriate public health interventions can be directed at locations most in need. In this regard, spatial clustering analysis of HIV-related mortality events has not been performed in a rural sub-Saharan African setting.Kulldorff's spatial scan statistic was used to identify HIV-related and all-cause mortality clusters (p<0.05 in a population-based demographic surveillance survey in rural KwaZulu Natal, South Africa (2000-2006. The analysis was split pre (2000-2003 and post (2004-2006 rollout of antiretroviral therapy, respectively. Between 2000-2006 a total of 86,175 resident individuals ≥15 years of age were under surveillance and 5,875 deaths were recorded (of which 2,938 were HIV-related over 343,060 person-years of observation (crude all-cause mortality rate 17.1/1000. During both time periods a cluster of high HIV-related (RR = 1.46/1.51, p = 0.001 and high all-cause mortality (RR = 1.35/1.38, p = 0.001 was identified in peri-urban communities near the National Road. A consistent low-risk cluster was detected in the urban township in both time periods (RR = 0.60/0.39, p = 0.003/0.005 and in the first time period (2000-2003 a large cluster of low HIV-related and all-cause mortality in a remote rural area was identified.HIV-related and all-cause mortality exhibit strong spatial clustering tendencies in this population. Highest HIV-related mortality and all-cause mortality occurred in the peri-urban communities along the National Road and was lowest in the urban township and remote rural communities. The geography of HIV-related mortality corresponded closely to the geography of HIV prevalence, with the notable exception of the urban township where high HIV-related mortality would have been expected on the basis of the high HIV prevalence. Our results suggest that HIV treatment

  13. HIV-Related Self-Stigma and Health-Related Quality of Life of People Living With HIV in Finland.

    Science.gov (United States)

    Nobre, Nuno; Pereira, Marco; Roine, Risto P; Sutinen, Jussi; Sintonen, Harri

    We examined how HIV-related self-stigma was associated with different domains of quality of life (QoL), as measured by the World Health Organization Quality of Life in HIV-infected persons instrument (WHOQOL-HIV-Bref), and health-related quality of life (HRQoL) as measured by the generic 15D (15-dimensional measure of HRQoL), to identify the factors associated with self-stigma of people living with HIV (PLWH). The study sample included 440 patients living with HIV followed at the Infectious Disease Clinic of Helsinki University Hospital. Participants with more severe self-stigma reported significantly lower QoL and HRQoL. Male gender, cohabiting with a partner, and disclosure of HIV status were associated with less self-stigma; high education level and financial difficulties were associated with greater self-stigma. Having lived longer with HIV, being unemployed, and living alone were also predictors of self-stigma via financial difficulties. The findings suggest that self-stigma is a complex and multidimensional phenomenon that impacts the HRQoL of PLWH. Psychosocial interventions to enhance the well-being of PLWH are increasingly needed. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  14. Depressive Symptoms Mediate the Effect of HIV-Related Stigmatization on Medication Adherence Among HIV-Infected Men Who Have Sex with Men.

    Science.gov (United States)

    Mitzel, Luke D; Vanable, Peter A; Brown, Jennifer L; Bostwick, Rebecca A; Sweeney, Shannon M; Carey, Michael P

    2015-08-01

    This study tested the hypothesis that depressive symptoms would mediate the association of HIV-related stigma to medication adherence. We recruited HIV-infected men who have sex with men (MSM; N = 66; 66 % White, 23 % African-American) from an outpatient infectious disease clinic, and asked them to complete self-report measures. Mediational analyses showed that depressive symptoms fully mediated the association between HIV-related stigma and adherence. That is, stigma-related experiences were positively associated with depressive symptoms and negatively associated with adherence, and, in the final model, depressive symptoms remained a significant correlate of adherence while stigma did not. A test of the indirect effect of stigma on adherence through depressive symptoms was also significant (unstandardized b = -0.19; bootstrap 95 % CI -0.45 to -0.01). These results highlight the importance of treating depressive symptoms in interventions aiming to improve medication adherence among HIV-infected MSM.

  15. Measuring HIV-related stigma among healthcare providers: a systematic review.

    Science.gov (United States)

    Alexandra Marshall, S; Brewington, Krista M; Kathryn Allison, M; Haynes, Tiffany F; Zaller, Nickolas D

    2017-11-01

    In the United States, HIV-related stigma in the healthcare setting is known to affect the utilization of prevention and treatment services. Multiple HIV/AIDS stigma scales have been developed to assess the attitudes and behaviors of the general population in the U.S. towards people living with HIV/AIDS, but fewer scales have been developed to assess HIV-related stigma among healthcare providers. This systematic review aimed to identify and evaluate the measurement tools used to assess HIV stigma among healthcare providers in the U.S. The five studies selected quantitatively assessed the perceived HIV stigma among healthcare providers from the patient or provider perspective, included HIV stigma as a primary outcome, and were conducted in the U.S. These five studies used adapted forms of four HIV stigma scales. No standardized measure was identified. Assessment of HIV stigma among providers is valuable to better understand how this phenomenon may impact health outcomes and to inform interventions aiming to improve healthcare delivery and utilization.

  16. Social Networking Technology Use and Engagement in HIV Related Risk and Protective Behaviors among Homeless Youth

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-01-01

    Preliminary studies with homeless youth find surprisingly pervasive social media use and suggest youths’ online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical first step in intervention development is gaining greater understanding of how homeless youth use social media especially as it relates to whom they connect to and around what topics. Given the salience of Social Networking Sites in the lives of these otherwise difficult to reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N=1046) were recruited through three drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether or not they engage in risk or protective behaviors. Implications for interventions and further research are discussed. PMID:27337044

  17. Endpoint singularities in unintegrated parton distributions

    CERN Document Server

    Hautmann, F

    2007-01-01

    We examine the singular behavior from the endpoint region x -> 1 in parton distributions unintegrated in both longitudinal and transverse momenta. We identify and regularize the singularities by using the subtraction method, and compare this with the cut-off regularization method. The counterterms for the distributions with subtractive regularization are given in coordinate space by compact all-order expressions in terms of eikonal-line operators. We carry out an explicit calculation at one loop for the unintegrated quark distribution. We discuss the relation of the unintegrated parton distributions in subtractive regularization with the ordinary parton distributions.

  18. Exposing the cancer genome atlas as a SPARQL endpoint.

    Science.gov (United States)

    Deus, Helena F; Veiga, Diogo F; Freire, Pablo R; Weinstein, John N; Mills, Gordon B; Almeida, Jonas S

    2010-12-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Is socio-economic status a determinant of HIV-related stigma attitudes in Zimbabwe? Findings from Project Accept

    Directory of Open Access Journals (Sweden)

    Kudzanai Mateveke

    2016-08-01

    Full Text Available HIV related stigma and discrimination is a known barrier for HIV prevention and care. We aimed to assess the relationship between socio-economic status (SES and HIV related stigma in Zimbabwe. This paper uses data from Project Accept, which examined the impact of community-based voluntary counseling and testing intervention on HIV incidence and stigma. Total of 2522 eligible participants responded to a psychometric assessment tool, which assessed HIV related stigma and discrimination attitudes on 4 point Likert scale. The tool measured three components of HIVrelated stigma: shame, blame and social isolation, perceived discrimination, and equity. Participants’ ownership of basic assets was used to assess the socio-economic status. Shame, blame and social isolation component of HIV related stigma was found to be significantly associated with medium [odds ratio (OR=1.73, P<0.01] and low SES (OR=1.97, P<0.01, indicating more stigmatizing attitudes by participants belonging to medium and low SES in comparison to high SES. For HIV related stigma and discrimination programs to be effective, they should take into account the socio-economic context of target population.

  20. Helicopter EMS: Research Endpoints and Potential Benefits

    Directory of Open Access Journals (Sweden)

    Stephen H. Thomas

    2012-01-01

    Full Text Available Patients, EMS systems, and healthcare regions benefit from Helicopter EMS (HEMS utilization. This article discusses these benefits in terms of specific endpoints utilized in research projects. The endpoint of interest, be it primary, secondary, or surrogate, is important to understand in the deployment of HEMS resources or in planning further HEMS outcomes research. The most important outcomes are those which show potential benefits to the patients, such as functional survival, pain relief, and earlier ALS care. Case reports are also important “outcomes” publications. The benefits of HEMS in the rural setting is the ability to provide timely access to Level I or Level II trauma centers and in nontrauma, interfacility transport of cardiac, stroke, and even sepsis patients. Many HEMS crews have pharmacologic and procedural capabilities that bring a different level of care to a trauma scene or small referring hospital, especially in the rural setting. Regional healthcare and EMS system's benefit from HEMS by their capability to extend the advanced level of care throughout a region, provide a “backup” for areas with limited ALS coverage, minimize transport times, make available direct transport to specialized centers, and offer flexibility of transport in overloaded hospital systems.

  1. The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

    Science.gov (United States)

    Krischer, Jeffrey P

    2013-09-01

    This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

  2. To be or not to be sick and tired: Managing the visibility of HIV and HIV-related fatigue.

    Science.gov (United States)

    Schuft, Laura; Duval, Estelle; Thomas, Julie; Ferez, Sylvain

    2017-01-01

    This article takes a new direction in exploring HIV-related fatigue by adopting a qualitative interactionist approach. We analyse the social meanings attributed to fatigue among people living with HIV in France, the social gains and losses of its visibility and the social frames that condition its discursive and physical expression. The two-part methodology combines grounded theory analysis of 50 transcribed unstructured interviews conducted across France and participant observations within four HIV-related associations. Results reveal that the visibility of fatigue is in part dependent on the visibility of this stigmatized illness. The expression of fatigue is therefore closely linked with disclosure and concerns about HIV stigma. The degree to which HIV and HIV-related fatigue are rendered (in)visible also depends on structural factors including gender prescriptions, as well as context effects such as the type of social or 'care' relations involved in the social frame of interaction.

  3. Online resources for persons recently diagnosed with HIV/AIDS: an analysis of HIV-related webpages.

    Science.gov (United States)

    Horvath, Keith J; Harwood, Eileen M; Courtenay-Quirk, Cari; McFarlane, Mary; Fisher, Holly; Dickenson, Tina; Kachur, Rachel; Rosser, B R Simon; O'Leary, Ann

    2010-07-01

    The Internet is a major source of HIV-related information and resources for persons recently diagnosed with HIV/AIDS (PRDHA). This study examined the types of HIV-related websites that appear as a result of HIV-related keyword searches and the extent to which website information targets PRDHA. The first page of HIV-related webpages from 18 keyword searches was coded. Among 137 webpages meeting inclusion criteria, 63% represented HIV-informational websites, 31% targeted HIV-positive individuals, and over half contained or provided access to HIV prevention, treatment, and transmission information. Thirty-three percent of webpages contained or provided access to PRDHA-targeted information, with a greater percentage of those webpages having mobile, non-English, and "Ask the Expert" features compared with non-PRDHA targeted webpages. Implications for PRDHA include the following: (1) they should explore HIV-related websites to gain insight into the credibility of the information contained on those sites; (2) PRDHA must be aware that HIV-related websites have the potential to elicit dated, emotionally distressing, or irrelevant information; and (3) to obtain information that relates to their demographic and situational profile, they may wish to use specific key terms (e.g., "HIV women") rather than attempting to navigate webpages that arise from general search terms (e.g., "HIV"). Recommendations for future development of online resources for PRDHA include providing HIV-relevant information in a stepwise fashion, providing demographically targeted HIV information, and greater utilization of mobile technology.

  4. Extracting gluino endpoints with event topology patterns

    Energy Technology Data Exchange (ETDEWEB)

    Pietsch, N. [Hamburg Univ. (Germany). Inst. fuer Experimentalphysik; Reuter, J.; Sakurai, K.; Wiesler, D. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2012-06-15

    In this paper we study the gluino dijet mass edge measurement at the LHC in a realistic situation including both SUSY and combinatorical backgrounds together with effects of initial and final state radiation as well as a finite detector resolution. Three benchmark scenarios are examined in which the dominant SUSY production process and also the decay modes are different. Several new kinematical variables are proposed to minimize the impact of SUSY and combinatorial backgrounds in the measurement. By selecting events with a particular number of jets and leptons, we attempt to measure two distinct gluino dijet mass edges originating from wino g {yields} jjW and bino g {yields}jjB decay modes, separately. We determine the endpoints of distributions of proposed and existing variables and show that those two edges can be disentangled and measured within good accuracy, irrespective of the presence of ISR, FSR, and detector effects.

  5. HIV Co-receptor usage in HIV-related non-hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Reid Erin

    2012-03-01

    Full Text Available Abstract In this study 15 banked samples of HIV-related Non-Hodgkin's Lymphoma (NHL cases were tested for HIV co-receptor usage and SDF1 3'A polymorphism. Reportable tropism from 9 plasma samples had 1 (11.1% HIV case with CXCR4 and 8 (88.9% with CCR5 usage, even though most of the cases occurred at a late stage of HIV (2/3 had CD4 counts below 200, where expected CXCR4 usage would be 60%. Based on the expected proportion of less than 50% CCR5 in chronically infected individuals, this would suggest that in NHL may be associated with CCR5 usage (P = 0.04.

  6. Understanding HIV-Related Stigma Among Women in the Southern United States: A Literature Review.

    Science.gov (United States)

    Darlington, Caroline K; Hutson, Sadie P

    2017-01-01

    Societal stigmatization of HIV/AIDS due to assumptions about transmission and associated behaviors plays a substantial role in the psychosocial well-being of people living with this chronic illness, particularly for women in traditionally conservative geographic regions. Known for social conservatism, the Southern United States (US) holds the highest incidence rate of HIV infection in the US. A systematic search of four databases was used to identify 27 relevant scientific articles pertaining to HIV-related stigma among women living with HIV/AIDS in the Southern US. These studies revealed a rudimentary understanding of stigma sources, effects, and stigma-reduction interventions in this population. Due to the cultural specificity of stigma, further differentiation of stigma in discrete sectors of the South as well as a dialogue about the moral implications of stigma is necessary to lay the groundwork for patient-centered interventions to mitigate the destructive effects of stigma experienced by women in this region.

  7. Radiological endpoints relevant to ecological risk assessment

    International Nuclear Information System (INIS)

    Harrison, F.

    1997-01-01

    Because of the potential risk from radiation due to the releases of radionuclides from anthropogenic activities, considerable research was performed to determine for humans the levels of dose received, their responses to the doses and mechanisms of action of radioactivity on living matter. More recently, there is an increased interest in the effects of radioactivity on non-human species. There are differences in approach between risk assessment for humans and ecosystems. For protection of humans, the focus is the individual and the endpoint of primary concern is cancer induction. For protection of ecosystems, the focus is on population stability and the endpoint of concern is reproductive success for organisms important ecologically and economically. For these organisms, information is needed on their responses to irradiation and the potential impact of the doses absorbed on their reproductive success. Considerable information is available on the effects of radiation on organisms from different phyla and types of ecosystems. Databases useful for assessing risk from exposures of populations to radioactivity are the effects of irradiation on mortality, fertility and sterility, the latter two of which are important components of reproductive success. Data on radiation effects on mortality are available both from acute and chronic irradiation. In relation to radiation effects, reproductive success for a given population is related to a number of characteristics of the species, including inherent radiosensitivity of reproductive tissues and early life stages, processes occurring during gametogenesis, reproductive strategy and exposure history. The available data on acute and chronic radiation doses is reviewed for invertebrates, fishes and mammals. The information reviewed indicates that wide ranges in responses with species can be expected. Parameters that most likely contribute to inherent radiosensitivity are discussed. (author)

  8. Low dose radiation in the treatment of HIV related benign lymphoepithelial lesions of the parotid gland

    International Nuclear Information System (INIS)

    Tchelebi, Anca E.; Ming Teng; Moscatello, Augustine; Moorthy, Chitti R.; Kaufmann, Thomas; Ahmed, Tauseef

    1996-01-01

    Purpose/Objective: To determine the effectiveness of Radiation Therapy (RT) in the treatment of human immunodeficiency virus (HIV) related benign lymphoepithelial (BLL) of the parotid gland. Materials and Methods: The records of 16 patients treated between 1991 to 1995 with BLL were retrospectively reviewed. Three patients had bilateral disease, thus 19 parotid glands were radiated. Only (2(16)) had AIDS. Virtually all patients were on antiretroviral therapy. There were 11 males and 5 females. The median age was 38 years (range 31 to 58 years). The median duration of parotid enlargement was 1.5 years (range 1 month to 6 years). All patients had biopsy prior to treatment. Histopathology revealed two patterns: solid or cystic. Patient were treated using electron beam RT. The beam energy was determined by computed transaxial tomography. The median dose delivered was 1000 cGy in 5 fractions over 5 days (range 600 cGy to 2160 cGy in daily fractions ranging from 180 cGy to 200 cGy). Results: Six parotid glands achieved a complete response (CR), 5 a partial response (PR), while 8 were non-responders (NR). Our overall response rate was therefore 58% Of the NR's, 3 patients were re-treated. Two achieved a PR, one was an NR. Toxicity was minimal and limited to mild xerostomia. Conclusion: RT in patients with HIV related BLL is well tolerated. Our preliminary results show that while this modality of treatment has marked activity in the solid pattern. Higher doses may be required for large lesions or cystic in nature

  9. Persisting stigma reduces the utilisation of HIV-related care and support services in Viet Nam

    Directory of Open Access Journals (Sweden)

    Thanh Duong Cong

    2012-11-01

    Full Text Available Abstract Background Seeking and utilisation of HIV prevention, treatment, care, and support services for people living with HIV is often hampered by HIV-related stigma. The study aimed to explore the perceptions and experiences regarding treatment, care, and support amongst people living with HIV in Viet Nam, where the HIV epidemic is concentrated among injecting drug users, sex workers, and men who have sex with men. Methods In-depth interviews and focus group discussions were conducted during September 2007 in 6 districts in Hai Phong with a very high HIV prevalence among injecting drug users. The information obtained was analysed and merged within topic areas. Illustrative quotes were selected. Results Stigma and discrimination against people living with HIV in the community and healthcare settings was commonly reported, and substantially hampered the seeking and the utilisation of HIV-related services. The informants related the high level of stigma to the way the national HIV preventive campaigns played on fear, by employing a “scare tactic” mainly focusing on drug users and sex workers, who were defined as “social evils” in the anti-drug and anti-prostitution policy. There was a strong exclusion effect caused by the stigma, with serious implications, such as loss of job opportunities and isolation. The support and care provided by family members was experienced as vital for the spirit and hope for the future among people living with HIV. Conclusions A comprehensive care and support programme is needed. The very high levels of stigma experienced seem largely to have been created by an HIV preventive scare tactic closely linked to the “social evil“ approach in the national policy on drug and prostitution. In order to reduce the stigma and create more effective interventions, this tactic will have to be replaced with approaches that create better legal and policy environments for drug users and sex workers.

  10. Effects of a performance and quality improvement intervention on the work environment in HIV-related care: a quasi-experimental evaluation in Zambia.

    Science.gov (United States)

    Bazant, Eva; Sarkar, Supriya; Banda, Joseph; Kanjipite, Webby; Reinhardt, Stephanie; Shasulwe, Hildah; Mulilo, Joyce Monica Chongo; Kim, Young Mi

    2014-12-20

    Human resource shortages and reforms in HIV-related care make it challenging for frontline health care providers in southern Africa to deliver high-quality services. At health facilities of the Zambian Defence Forces, a performance and quality improvement approach was implemented to improve HIV-related care and was evaluated in 2010/2011. Changes in providers' work environment and perceived quality of HIV-related care were assessed to complement data of provider performance. The intervention involved on-site training, supportive supervision, and action planning focusing on detailed service delivery standards. The quasi-experimental evaluation collected pre- and post-intervention data from eight intervention and comparison facilities matched on defence force branch and baseline client volume. Overall, 101 providers responded to a 24-item questionnaire on the work environment, covering topics of drugs, supplies, and equipment; training, feedback, and supervision; compensation; staffing; safety; fulfilment; and HIV services quality. In bivariate analysis and multivariate analyses, we assessed changes within each study group and between the two groups. In the bivariate analysis, the intervention group providers reported improvements in the work environment on adequacy of equipment, feeling safe from harm, confidence in clinical skills, and reduced isolation, while the comparison group reported worsening of the work environment on supplies, training, safety, and departmental morale.In the multivariate analysis, the intervention group's improvement and the comparison group's decline were significant on perceived adequacy of drugs, supplies, and equipment; constructive feedback received from supervisor and co-workers; and feeling safe from physical harm (all P equipment). Further, the item "provider lacks confidence in some clinical skills" declined in the intervention group but increased in the comparison group (P = -0.005). In multivariate analysis, changes in perceived

  11. Communicating in complex situations: a normative approach to HIV-related talk among parents who are HIV+.

    Science.gov (United States)

    Edwards, Laura L; Donovan-Kicken, Erin; Reis, Janet S

    2014-01-01

    Parents with HIV/AIDS are confronted with unique challenges when discussing HIV-related information with their children. Strategies for navigating these challenges effectively have not been systematically examined. In this study, we conducted in-depth interviews with 76 parents with HIV/AIDS who had children ages 10-18 years. Guided by O'Keefe and Delia's definition of a complex communication situation and Goldsmith's normative approach to interpersonal communication, we examined parents' goals for discussing HIV-related information, factors that made conversations challenging, and instances where these conversational purposes conflicted with one another. Our data reveal the following parent-adolescent communication predicaments: relaying safety information about HIV while minimizing child anxiety, modeling open family communication without damaging one's parental identity, and balancing parent-child relational needs amid living with an unpredictable health condition. Parents also described a variety of strategies for mitigating challenges when discussing HIV-related topics. Strategies parents perceived as effective included reframing HIV as a chronic, manageable illness; keeping talk educational; and embedding HIV-related topics within more general conversations. The theoretical and practical applications of these findings are discussed with regard to their relevance to health communication scholars and HIV care professionals.

  12. Adapting the Information-Motivation-Behavioral Skills Model: Predicting HIV-Related Sexual Risk among Sexual Minority Youth

    Science.gov (United States)

    Fisher, Colleen M.

    2012-01-01

    Young sexual minority males are among those at highest risk for HIV infection, yet we know relatively little about the impact of sexual identity development on HIV risk. This study used cross-sectional data to investigate factors associated with HIV-related sexual risk among a sample of sexual minority males (n = 156), ages 14 to 21 years, using…

  13. Beliefs Contributing to HIV-related Stigma in African and Afro-Caribbean Communities in the Netherlands

    NARCIS (Netherlands)

    Stutterheim, S.E.; Bos, A.E.R.; Kesteren, van N.M.C.; Shiripinda, I.; Pryor, J.B.; Bruin, de M.; Schaalma, H.P.

    2012-01-01

    Thirty years after the first diagnosis, people living with HIV (PLWH) around the world continue to report stigmatizing experiences. In this study, beliefs contributing to HIV-related stigma in African and Afro-Caribbean diaspora communities and their cultural context were explored through

  14. Serum urate as surrogate endpoint for flares in people with gout

    DEFF Research Database (Denmark)

    Stamp, Lisa K; Birger Morillon, Melanie; Taylor, William J

    2018-01-01

    Objectives The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical tr...

  15. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative

    DEFF Research Database (Denmark)

    Myles, P S; Boney, O; Botti, M

    2018-01-01

    Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus...

  16. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  18. Sample size determination for equivalence assessment with multiple endpoints.

    Science.gov (United States)

    Sun, Anna; Dong, Xiaoyu; Tsong, Yi

    2014-01-01

    Equivalence assessment between a reference and test treatment is often conducted by two one-sided tests (TOST). The corresponding power function and sample size determination can be derived from a joint distribution of the sample mean and sample variance. When an equivalence trial is designed with multiple endpoints, it often involves several sets of two one-sided tests. A naive approach for sample size determination in this case would select the largest sample size required for each endpoint. However, such a method ignores the correlation among endpoints. With the objective to reject all endpoints and when the endpoints are uncorrelated, the power function is the production of all power functions for individual endpoints. With correlated endpoints, the sample size and power should be adjusted for such a correlation. In this article, we propose the exact power function for the equivalence test with multiple endpoints adjusted for correlation under both crossover and parallel designs. We further discuss the differences in sample size for the naive method without and with correlation adjusted methods and illustrate with an in vivo bioequivalence crossover study with area under the curve (AUC) and maximum concentration (Cmax) as the two endpoints.

  19. Ordered kinematic endpoints for 5-body cascade decays

    Energy Technology Data Exchange (ETDEWEB)

    Klimek, Matthew D. [Theory Group, Department of Physics and Texas Cosmology Center,University of Texas at Austin, 2515 Speedway, Stop C1608, Austin, TX, 78712 (United States)

    2016-12-23

    We present expressions for the kinematic endpoints of 5-body cascade decay chains proceeding through all possible combinations of 2-body and 3-body decays, with one stable invisible particle in the final decay stage. When an invariant mass can be formed in multiple ways by choosing different final state particles from a common vertex, we introduce techniques for finding the sub-leading endpoints for all indistinguishable versions of the invariant mass. In contrast to short decay chains, where sub-leading endpoints are linearly related to the leading endpoints, we find that in 5-body decays, they provide additional independent constraints on the mass spectrum.

  20. Perceived Neighborhood Quality and HIV-related Stigma among African Diasporic Youth; Results from the African, Caribbean, and Black Youth (ACBY) Study.

    Science.gov (United States)

    Kerr, Jelani; Northington, Toya; Sockdjou, Tamara; Maticka-Tyndale, Eleanor

    2018-01-01

    Socio-environmental factors such as neighborhood quality are increasingly recognized drivers of HIV disparities. Additionally, HIV- related stigma heightens HIV vulnerability among youth in the African Diaspora. However, little research examines the intersection of neighborhood quality and HIV- related stigma. This study uses survey data (N=495) from African, Caribbean, and Black youth in a midsized city in Ontario, Canada to address this research deficit. Analysis of variance and multivariate ordinary least squares regressions were conducted to determine differences in HIV- related stigma by neighborhood quality, experiences of discrimination, HIV- knowledge, and demographic factors. Residents in more socially disordered neighborhoods (p<.05), males (p<.0001), African- Muslim youth (p<.01), and individuals with lower HIV- knowledge (p<.0001) endorsed stigmatizing beliefs more often. Addressing neighborhood disadvantage may have implications for HIV- related stigma. More research should be conducted to understand the impact of socio- environmental disadvantage and HIV- related stigma.

  1. A systematic comparison of recurrent event models for application to composite endpoints.

    Science.gov (United States)

    Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

    2018-01-04

    Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

  2. Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study.

    Science.gov (United States)

    Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

    2014-12-03

    While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effects of antiretroviral therapy. We examined associations between linkage to HIV care, postpartum depression, and internalized stigma in a population with a high risk of depression: newly diagnosed HIV-positive pregnant women. In this prospective observational study, data were obtained from 135 HIV-positive women from eight antenatal clinics in the rural Nyanza Province of Kenya at their first antenatal visit (prior to testing HIV-positive for the first time) and subsequently at 6 weeks after giving birth. At 6 weeks postpartum, women who had not linked to HIV care after testing positive at their first antenatal visit had higher levels of depression and internalized stigma, compared to women who had linked to care. Internalized stigma mediated the effect of linkage to care on depression. Furthermore, participants who had both linked to HIV care and initiated antiretroviral therapy reported the lowest levels of depressive symptoms. These results provide further support for current efforts to ensure that women who are newly diagnosed with HIV during pregnancy become linked to HIV care as early as possible, with important benefits for both physical and mental health.

  3. Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

    NARCIS (Netherlands)

    Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J.; Belani, Chandra P.; Shepherd, Frances A.; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T.; Dahlberg, Suzanne E.; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E.; Parmar, Mahesh; Tierney, Jayne F.; Le Pechoux, Cécile; Michiels, Stefan; Burdett, S.; Fisher, D.; Le Péchoux, C.; Mauguen, A.; Michiels, S.; Pignon, J. P.; Tierney, J. F.; Belani, C. P.; Collette, L.; Dahlberg, S.; Eisen, T.; Mandrekar, S.; O'Brien, M.; Parmar, M.; Pang, H.; Paulus, R.; Crawford, J.; Sause, W.; Schild, S. E.; Shepherd, F.; Arriagada, R.; Atagi, S.; Auperin, A.; Ball, D.; Baumann, M.; Behrendt, K.; Belderbos, J.; Koning, C. C. E.; Uitterhoeve, A.

    2013-01-01

    The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We

  4. Workplace and HIV-related sexual behaviours and perceptions among female migrant workers

    Science.gov (United States)

    YANG, H.; LI, X.; STANTON, B.; FANG, X.; LIN, D.; MAO, R.; LIU, H.; CHEN, X.; SEVERSON, R.

    2007-01-01

    Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment establishments (e.g. restaurants, stalls, domestic service, factories, etc.). About 10% of women in the entertainment establishments reported having sold sex, 30% having multiple sexual partners and 40% having sex with men with multiple sexual partners. The rate of consistent condom use was less than 15%. They also tended to have a higher level of perceptions of both peer risk involvement and positive expectancy of risk behaviours, and lower perceptions of severity of STDs and HIV. For women who were not sexually experienced, those working in ‘stalls’ or ‘domestic service’ tended to perceive higher peer risk involvement, less severity of HIV infection, and less effectiveness of protective behaviour. The occupational pattern of sexual risk behaviours and perceptions observed in the current study indicates employment conditions are associated with HIV risk. Intervention strategies should be tailored to address occupational-related factors. PMID:16120499

  5. Toward Automating HIV Identification: Machine Learning for Rapid Identification of HIV-Related Social Media Data.

    Science.gov (United States)

    Young, Sean D; Yu, Wenchao; Wang, Wei

    2017-02-01

    "Social big data" from technologies such as social media, wearable devices, and online searches continue to grow and can be used as tools for HIV research. Although researchers can uncover patterns and insights associated with HIV trends and transmission, the review process is time consuming and resource intensive. Machine learning methods derived from computer science might be used to assist HIV domain experts by learning how to rapidly and accurately identify patterns associated with HIV from a large set of social data. Using an existing social media data set that was associated with HIV and coded by an HIV domain expert, we tested whether 4 commonly used machine learning methods could learn the patterns associated with HIV risk behavior. We used the 10-fold cross-validation method to examine the speed and accuracy of these models in applying that knowledge to detect HIV content in social media data. Logistic regression and random forest resulted in the highest accuracy in detecting HIV-related social data (85.3%), whereas the Ridge Regression Classifier resulted in the lowest accuracy. Logistic regression yielded the fastest processing time (16.98 seconds). Machine learning can enable social big data to become a new and important tool in HIV research, helping to create a new field of "digital HIV epidemiology." If a domain expert can identify patterns in social data associated with HIV risk or HIV transmission, machine learning models could quickly and accurately learn those associations and identify potential HIV patterns in large social data sets.

  6. HIV-related knowledge and perceptions by academic major: Implications for university interventions

    Directory of Open Access Journals (Sweden)

    Matthew Lee Smith

    2014-03-01

    Full Text Available Most universities offer human sexuality courses, although they are not required for graduation. While students in health-related majors may receive sexuality education in formal settings, majority of college students never receive formal sexual health or HIV/AIDS-related education, which may lead to elevated engagement in high-risk sexual behaviors. This study examines perceived knowledge about HIV/AIDS, perceived risk, and perceived consequences among college students by two distinct classifications of academic majors. Data were collected from 510 college students. Binary and multinomial logistic regressions were performed to compare HIV-related covariates by academic major category. Limited differences were observed by Science, Technology, Engineering, and Mathematics (STEM categorization. Relative to health and kinesiology (HK majors, those who self-reported being completely knowledgeable about HIV were less likely to be physical sciences, math, engineering, business (PMEB [OR=0.41, P=0.047] or education, humanities, and social sciences (EHS majors [OR=0.25, P=0.004]. PMEB majors were less likely to report behavioral factors as a risk for contracting HIV [OR=0.86, P=0.004] and perceived acquiring HIV would be more detrimental to their quality of life [OR=2.14, P=0.012], but less detrimental to their mental wellbeing [OR=0.58, P=0.042]. Findings can inform college-wide campaigns and interventions to raise HIV/AIDS awareness and improve college health.

  7. Understanding and mitigating HIV-related resource-based stigma in the era of antiretroviral therapy.

    Science.gov (United States)

    Holmes, Kathleen; Winskell, Kate

    2013-01-01

    The perception in low-resource settings that investment of resources in people living with HIV (PLHIV) is wasted because AIDS is both an incurable and deadly disease is known as resource-based stigma. In this paper, we draw on in-depth interviews (IDI), focus group discussions (FGD), and key informant interviews (KII) with 77 HIV-positive microfinance participants and nongovernmental organization leaders to examine resource-based stigma in the context of increased access to antiretroviral therapy (ART) at an individual, household, and community level in Côte d'Ivoire. The purpose of this exploratory paper is to examine: (1) resource-based stigmatization in the era of ART and (2) the relationship among microfinance, a poverty-reduction intervention, and HIV stigmatization. The frequency with which resource-based stigma was discussed by respondents suggests that it is an important component of HIV-related stigma in this setting. It affected PLHIV's access to material as well as social resources, leading to economic discrimination and social devaluation. Participation in village savings and loans groups, however, mitigated resource-based HIV stigma, suggesting that in the era of increased access to antiretroviral therapy, economic programs should be considered as one possible HIV stigma-reduction intervention.

  8. Workplace and HIV-related sexual behaviours and perceptions among female migrant workers.

    Science.gov (United States)

    Yang, H; Li, X; Stanton, B; Fang, X; Lin, D; Mao, R; Liu, H; Chen, X; Severson, R

    2005-10-01

    Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment establishments (e.g. restaurants, stalls, domestic service, factories, etc.). About 10% of women in the entertainment establishments reported having sold sex, 30% having multiple sexual partners and 40% having sex with men with multiple sexual partners. The rate of consistent condom use was less than 15%. They also tended to have a higher level of perceptions of both peer risk involvement and positive expectancy of risk behaviours, and lower perceptions of severity of STDs and HIV. For women who were not sexually experienced, those working in 'stalls' or 'domestic service' tended to perceive higher peer risk involvement, less severity of HIV infection, and less effectiveness of protective behaviour. The occupational pattern of sexual risk behaviours and perceptions observed in the current study indicates employment conditions are associated with HIV risk. Intervention strategies should be tailored to address occupational-related factors.

  9. Female sex workers' empowerment strategies amid HIV-related socioeconomic vulnerabilities in Cameroon.

    Science.gov (United States)

    Cange, Charles W; LeBreton, Matthew; Saylors, Karen; Billong, Serge; Tamoufe, Ubald; Fokam, Pamella; Baral, Stefan

    2017-10-01

    Research has consistently demonstrated that female sex workers use a variety of empowerment strategies to protect one another and their families. This study examines the strategies Cameroonian sex workers employ to do so. In-depth interviews and focus-group discussions were conducted with 100 sex workers. Coded texts were analysed for recurring themes. Sex workers reported being concerned with physical violence and sexual assault and demands from authorities for bribes to avoid fines and/or imprisonment. Women described strategies such as 'looking out for' each other when faced with security threats. Many reported staying in sex work to provide for their children through education and other circumstances to allow them to lead a better life. Sex worker mothers reported not using condoms when clients offered higher pay, or with intimate partners, even when they understood the risk of HIV transmission to themselves. Concern for their children's quality of life took precedence over HIV-related risks, even when sex workers were the children's primary carers. A sex worker empowerment programme with a focus on family-oriented services could offer an effective and novel approach to increasing coverage of HIV prevention, treatment and care in Cameroon.

  10. Qualitative study of HIV related stigma and discrimination: What women say in Iran.

    Science.gov (United States)

    Oskouie, Fatemeh; Kashefi, Farzaneh; Rafii, Forough; Gouya, Mohammad Mehdi

    2017-07-01

    HIV-related stigma is a major social problem of people living with HIV. Stigma against these people, especially women, interferes with the prevention, diagnosis and treatment of HIV. This study examined the experiences of HIV infected women who were stigmatized, as well as the strategies used to tackle the issue. Twenty-five women living with HIV were examined using in-depth, semi-structured interviews. The data obtained was analyzed using content analysis method in MAXQDA10. The finding of this study was classified into four themes: fear, shame, rejection by family or friends and feelings of frustration. The participant strategies adopted to the perceived stigma and discrimination included isolation, nondisclosure, and loss of follow-up. HIV in women has different social interposition. It is necessary to intervene, so as to alleviate the effect of stigma on HIV infected women, in order that they gain the ability to accomplish wellness, increase life span and improve quality of life. Nurses, midwives and other professionals need to be involved to ensure public policy in providing supportive environments, and decrease stigma.

  11. Global Reduction in HIV-related Maternal Mortality: ART as a Key Strategy

    Directory of Open Access Journals (Sweden)

    Hamisu M. Salihu, MD, PhD

    2015-12-01

    Full Text Available Dr. Holtz and colleagues present a synthesis of evidence from published studies over the previous decade on the collective impact of HIV-targeted interventions on maternal mortality. Amongst an assortment of interventions [that include antiretroviral therapy (ART, micronutrients (multivitamins, vitamin A and selenium, and antibiotics], only ART reduced maternal mortality among HIV-infected pregnant and post-partum mothers. These findings have fundamental and global strategic implications. They are also timely since they provide the evidence that ART reduces HIV-related maternal mortality, and by further enhancing access to ART in HIV-challenged and poor regions of the world, significant improvement in maternal morbidity and mortality indices could be attained. The paper bears good tidings and sound scientific proof that the financial investment made globally by government and non-governmental organizations and agencies to reduce the global burden of HIV/AIDS primarily by making ART more accessible to regions of the world most affected by the epidemic is beginning to show beneficial effects not only in terms of numerical reductions in the rates of new cases of HIV/AIDS among women, but also in maternal mortality levels.

  12. Hippeastrum hybridum anthocyanins as indicators of endpoint in acid

    African Journals Online (AJOL)

    Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong.

  13. Hippeastrum hybridum anthocyanins as indicators of endpoint in ...

    African Journals Online (AJOL)

    Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong ...

  14. Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

    Science.gov (United States)

    Angel, Juana; Steele, A Duncan; Franco, Manuel A

    2014-01-01

    Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

  15. HIV Among Indigenous peoples: A Review of the Literature on HIV-Related Behaviour Since the Beginning of the Epidemic.

    Science.gov (United States)

    Negin, Joel; Aspin, Clive; Gadsden, Thomas; Reading, Charlotte

    2015-09-01

    From the early days of the HIV epidemic, Indigenous peoples were identified as a population group that experiences social and economic determinants-including colonialism and racism-that increase exposure to HIV. There are now substantial disparities in HIV rates between Indigenous and non-Indigenous peoples in some countries. We conducted a comprehensive literature review to assess the evidence on HIV-related behaviors and determinants in four countries-Australia, Canada, New Zealand and the United States-in which Indigenous peoples share important features of colonization and marginalization. We identified 107 articles over more than 20 years. The review highlights the determinants of HIV-related behaviors including domestic violence, stigma and discrimination, and injecting drug use. Many of the factors associated with HIV risk also contribute to mistrust of health services, which in turn contributes to poor HIV and health outcomes among Indigenous peoples.

  16. Sex inequalities in HIV-related practices in the Brazilian population aged 15 to 64 years old, 2008

    Directory of Open Access Journals (Sweden)

    Ana Roberta Pati Pascom

    2011-01-01

    Full Text Available The objective of this study is to analyze gender differences in HIV-related practices in the Brazilian population. A national survey was carried out in 2008 with a sample size of 8,000 individuals aged 15-64 years old. The sampling was stratified by macro geographical region and urban/rural areas. Logistic regression models were used to investigate the main predictors of consistent condom use. The results showed that women have less sexy, start sexual life later than men, have fewer casual sexual partners, but use condom less frequently than men. On the other hand, the coverage of HIV testing is significantly greater among women. Significant differences by gender were seen in all HIV-related risky practices. The greater vulnerability was always associated with women, with exception of HIV testing. The low proportion of condom use in infidelity situations was a problem for box sexes and deserves special consideration when developing prevention strategies.

  17. Access and management of HIV-related diseases in resource-constrained settings: a workshop report.

    Science.gov (United States)

    Dimba, Eao; Yengopal, V; Joshua, E; Thavarajah, R; Balasundaram, S

    2016-04-01

    With advancement of medical interventions, the lifespan of people living with HIV has increased globally. However, low- and middle-income countries (LMICs) which bear the greatest burden of the HIV pandemic face a constant challenge in addressing the treatment needs of immune-suppressed patients. An analysis of the current management protocols and access to medication in resource-poor settings was conducted at this workshop, with emphasis on the situation in resource-poor settings. The participants developed a consensus document based on the need to respond to the constantly changing HIV pandemic. Provision of oral health care must be guided by interconnecting principles based on population based strategies that address upstream determinants of health. Basic oral health coverage in developing countries can only be realized with a strong foundation at the primary health level. Early diagnosis of HIV-related comorbidities including the adverse effects of ARVs is essential for the improvement of treatment outcomes. Standardization of oral health care delivery mechanisms will facilitate evaluation at national and regional levels. Oral health care workers have a moral obligation to participate in sustained campaigns to reduce the social stigma associated with HIV/AIDS in their work places at every stage of the referral chain. Future research also needs to realign itself towards prevention using the common risk factor approach, which has a broader impact on non-communicable diseases, which are increasingly affecting patients with HIV/AIDS as their life expectancies increase. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. HIV-related high-risk behaviors among Chinese migrant construction laborers in Nantong, Jiangsu.

    Directory of Open Access Journals (Sweden)

    Xun Zhuang

    Full Text Available HIV transmission in rural areas of China is being fueled in part by migrant workers who acquire HIV outside of their hometowns. Recent surveillance statistics indicate that HIV prevalence among returning migrants has increased significantly.We conducted a community-based cross-sectional study to assess HIV-related knowledge, attitudes and behaviors among migrant returnees in Nantong, Jiangsu Province, one of the largest exporters of migrant laborers.A total of 1625 subjects were enrolled with a response rate of 89%. All participants were male and of the majority Han ethnicity. The mean age was 39.0 years (SD = 6.7; range: 18 to 63, and most had a stable partner (N = 1533, 94.3%. Most correctly identified the major modes of HIV transmission (68.9%-82.0%, but fewer were able to identify ways that HIV cannot be transmitted. Nearly one-third of participants held positive attitudes toward having multiple sex partners, and nearly half believed that sex work should be legalized. Multiple logistic regression analysis indicated that risky sexual behavior (defined as sex with a casual or commercial sex partner was associated with no stable partner; working abroad; correct condom use; age <22 at first sex; higher coital frequency; and having a positive attitude towards multiple sex partners.We found high levels of reported sex with a casual or commercial sex partner and low levels of consistent condom use. HIV prevention interventions among migrant workers need to focus on younger migrants, migrants without stable partners, and migrants who travel abroad for work.

  19. Prevalence of Internalized HIV-Related Stigma Among HIV-Infected Adults in Care, United States, 2011-2013.

    Science.gov (United States)

    Baugher, Amy R; Beer, Linda; Fagan, Jennifer L; Mattson, Christine L; Freedman, Mark; Skarbinski, Jacek; Shouse, R Luke

    2017-09-01

    HIV-infected U.S. adults have reported internalized HIV-related stigma; however, the national prevalence of stigma is unknown. We sought to determine HIV-related stigma prevalence among adults in care, describe which socio-demographic groups bear the greatest stigma burden, and assess the association between stigma and sustained HIV viral suppression. The Medical Monitoring Project measures characteristics of U.S. HIV-infected adults receiving care using a national probability sample. We used weighted data collected from June 2011 to May 2014 and assessed self-reported internalized stigma based on agreement with six statements. Overall, 79.1% endorsed ≥1 HIV-related stigma statements (n = 13,841). The average stigma score was 2.4 (out of a possible high score of six). White males had the lowest stigma scores while Hispanic/Latina females and transgender persons who were multiracial or other race had the highest. Although stigma was associated with viral suppression, it was no longer associated after adjusting for age. Stigma was common among HIV-infected adults in care. Results suggest individual and community stigma interventions may be needed, particularly among those who are Stigma was not independently associated with viral suppression; however, this sample was limited to adults in care. Examining HIV-infected persons not in care may elucidate stigma's association with viral suppression.

  20. "Why are you pregnant? What were you thinking?": How women navigate experiences of HIV-related stigma in medical settings during pregnancy and birth.

    Science.gov (United States)

    Greene, Saara; Ion, Allyson; Kwaramba, Gladys; Smith, Stephanie; Loutfy, Mona R

    2016-01-01

    Having children is a growing reality for women living with HIV in Canada. It is imperative to understand and respond to women's unique experiences and psychosocial challenges during pregnancy and as mothers including HIV-related stigma. This qualitative study used a narrative methodological approach to understand women's experiences of HIV-related stigma as they navigate health services in pregnancy (n = 66) and early postpartum (n = 64). Narratives of women living with HIV expose the spaces where stigmatizing practices emerge as women seek perinatal care and support, as well as highlight the relationship between HIV-related stigma and disclosure, and the impact this has on women's pregnancy and birthing experiences.

  1. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization...

  2. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

  3. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

    Science.gov (United States)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G; Ostergaard, Mikkel; Maksymowych, Walter P; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

    2007-03-01

    There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

  4. Ecosystem services as assessment endpoints for ecological risk assessment.

    Science.gov (United States)

    Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G

    2016-07-01

    Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag

  5. Social-cultural factors of HIV-related stigma among the Chinese general population in Hong Kong.

    Science.gov (United States)

    Yeo, Tien Ee Dominic; Chu, Tsz Hang

    2017-10-01

    HIV-related stigma in the wider community compounds the suffering of people living with HIV (PLWH) and hampers effective HIV prevention and care. This study examines the level of public stigma toward PLWH in Hong Kong and associated social-cultural factors. A telephone survey was conducted in June-July 2016 with 1080 Chinese adults aged 18-94 randomly selected from the general population. The results indicate substantial degree of public stigma toward PLWH. Overall, 58.1% of the participants endorsed at least one statement indicating negative social judgment of PLWH. Over 40% attributed HIV infections to irresponsible behaviors and nearly 30% perceived most PLWH as promiscuous. About 20% considered HIV to be a punishment for bad behavior and believed that PLWH should feel ashamed of themselves. These statistics indicate that HIV-related stigma among the general Hong Kong population had no noticeable reduction in a decade but is lower than that among rural and urban populations in China. Our findings suggest that the lower stigma in Hong Kong may be linked to higher education levels rather than Hongkongers' more Westernized outlook. The results of a multiple regression analysis showed that education level (β = -.19), homophobia (β = .30), and conformity to norms (β = .14) were independent predictors of HIV-related stigma but not age, income, or cultural orientations. By differentiating between associated social-cultural factors, this study provides a more nuanced understanding of the layered nature of HIV-related stigma: not broadly grounded in religion or Chinese culture but stemming from more specific social-cultural beliefs - perceptions of norm violation and negative attitudes toward homosexuality, which were not mutually exclusive. These findings have implications for HIV-related stigma reduction by providing evidence for the importance of addressing homophobia. Existing HIV publicity activities should be re-examined for inadvertent contribution

  6. Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus document

    NARCIS (Netherlands)

    A.P. Kappetein (Arie Pieter); S.J. Head (Stuart); P. Généreux (Philippe); N. Piazza (Nicolo); N.M. van Mieghem (Nicolas); E.H. Blackstone (Eugene); T.G. Brott (Thomas); D.J. Cohen (David J.); D.E. Cutlip (Donald); G.A. van Es (Gerrit Anne); R.T. Hahn (Rebecca); A.J. Kirtane (Ajay); M. Krucoff (Mitchell); S. Kodali (Susheel); M.J. Mack (Michael); R. Mehran (Roxana); J. Rodés-Cabau (Josep); P. Vranckx (Pascal); J.G. Webb (John); S.W. Windecker (Stephan); P.W.J.C. Serruys (Patrick); M.B. Leon (Martin)

    2012-01-01

    textabstractObjectives: The aim of the current Valvular Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)- clinical endpoints to make them more suitable to the present and future needs of clinical trials.

  7. Endpoint behavior of high-energy scattering cross sections

    International Nuclear Information System (INIS)

    Chay, Junegone; Kim, Chul

    2010-01-01

    In high-energy processes near the endpoint, there emerge new contributions associated with spectator interactions. Away from the endpoint region, these new contributions are suppressed compared to the leading contribution, but the leading contribution becomes suppressed as we approach the endpoint and the new contributions become comparable. We present how the new contributions scale as we reach the endpoint and show that they are comparable to the suppressed leading contributions in deep inelastic scattering by employing a power-counting analysis. The hadronic tensor in deep inelastic scattering is shown to factorize including the spectator interactions, and it can be expressed in terms of the light cone distribution amplitudes of initial hadrons. We also consider the contribution of the spectator contributions in Drell-Yan processes. Here the spectator interactions are suppressed compared to double parton annihilation according to the power counting.

  8. Understanding HIV-related stigma in older age in rural Malawi.

    Science.gov (United States)

    Freeman, Emily

    2016-09-01

    The combination of HIV- and age-related stigma exacerbates prevalence of HIV infection and late diagnosis and initiation of anti-retroviral therapy among older populations (Moore, 2012; Richards et al. 2013). Interventions to address these stigmas must be grounded in understanding of situated systems of beliefs about illness and older age. This study analyses constructions of HIV and older age that underpinned the stigmatisation of older adults with HIV in rural Balaka, Malawi. It draws on data from a series of in-depth interviews (N = 135) with adults aged 50-∼90 (N = 43) in 2008-2010. Around 40% (n = 18) of the sample had HIV. Dominant understandings of HIV in Balaka pertained to the sexual transmission of the virus and poor prognosis of those infected. They intersected with understandings of ageing. Narratives about older age and HIV in older age both centred on the importance of having bodily, moral and social power to perform broadly-defined "work". Those who could not work were physically and socially excluded from the social world. This status, labelled as "child-like", was feared by all participants. In participants' narratives, growing old involves a gradual decline in the power required to produce one's membership of the social world through work. HIV infection in old age is understood to accelerate this decline. Understandings of the sexual transmission of HIV, in older age, imply the absence of moral power and in turn, loss of social power. The prognosis of those with HIV, in older age, reflects and causes amplified loss of bodily power. In generating dependency, this loss of bodily power infantilises older care recipients and jeopardises their family's survival, resulting in further loss of social power. This age-and HIV-related loss of power to produce social membership through work is the discrediting attribute at the heart of the stigmatisation of older people with HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study

    OpenAIRE

    Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

    2014-01-01

    Background While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effect...

  10. HIV-Related Stigma and HIV Prevention Uptake Among Young Men Who Have Sex with Men and Transgender Women in Thailand.

    Science.gov (United States)

    Logie, Carmen H; Newman, Peter A; Weaver, James; Roungkraphon, Surachet; Tepjan, Suchon

    2016-02-01

    HIV-related stigma is a pervasive structural driver of HIV. With an HIV epidemic among young men who have sex with men (MSM) and transgender women (TG) in Thailand characterized as explosive, we conducted a cross-sectional survey among MSM and TG aged 18-30 years. From April-August 2013, participants recruited using venue-based sampling from gay entertainment sites and community-based organizations completed a tablet-assisted survey interview in Thai language. We conducted multiple logistic regression to assess correlations between HIV-related stigma (felt-normative, vicarious domains) and socio-demographic variables, HIV vulnerabilities (gay entertainment employment, sex work, forced sex history), and HIV prevention uptake (condom use, HIV testing, rectal microbicide acceptability). Among participants (n = 408), 54% identified as gay, 25% transgender, and 21% heterosexual. Two-thirds (65.7%) were employed at gay entertainment venues, 67.0% had more than three male partners (past month), 55.6% had been paid for sex, and 4.5% were HIV-positive. One-fifth (21.3%) reported forced sex. Most participants reported experiencing felt-normative and vicarious HIV-related stigma. Adjusting for socio-demographics, participants with higher total HIV-related stigma scores had significantly lower odds of HIV testing and rectal microbicide acceptability, and higher odds of having experienced forced sex. Both vicarious and felt-normative dimensions of HIV-related stigma were inversely associated with HIV testing and rectal microbicide acceptability. Our findings suggest that HIV-related stigma harms the health of HIV-negative MSM and TG at high risk for HIV infection. HIV-related interventions and research among young MSM and TG in Thailand should address multiple dimensions of HIV-related stigma as a correlate of risk and a barrier to accessing prevention.

  11. HIV-related stigma and symptoms of post-traumatic stress disorder and depression in HIV-infected individuals: does social support play a mediating or moderating role?

    Science.gov (United States)

    Breet, Elsie; Kagee, Ashraf; Seedat, Soraya

    2014-01-01

    HIV stigma plays a major role in the etiology of psychological distress among persons living with HIV, but may be ameliorated by social support. This cross-sectional study examined whether social support mediates or moderates the relationship between HIV stigma and psychological symptoms. We recruited a convenience sample of 210 individuals living with HIV in three peri-urban communities in the Western Cape, South Africa. People living with HIV and AIDS (PLWHA) completed self-report questionnaires that assessed HIV-related stigma, social support, post-traumatic stress disorder (PTSD) and depression. Product-term regression analyses showed that social support played a mediating role in the relationship between HIV-related stigma and symptoms of PTSD (not depression). Social support did not, however, moderate the relationship between HIV-related stigma and PTSD or depression. The results indicate that perceived HIV-related stigma may decrease PLWHA's perceived level of social support, which in turn may increase PTSD symptoms. Moreover, these findings suggest that despite the protective role of social support, there are other factors that affect the relationship between HIV-related stigma and mental health that hinder the buffering role of social support in this relationship. These findings may have implications for designing and implementing interventions that increase perceived social support and decrease perceived HIV-related stigma, which in turn may decrease symptoms of PTSD among PLWHA.

  12. Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Gori E

    2016-11-01

    -α across the three groups. Regarding plasma lipoproteins, HDL-c levels were reduced in HIV ART-naïve (P=0.002 and ART-receiving (P=0.015 subjects compared to HIV-uninfected subjects. Similarly, TC levels were lower in the HIV-infected than in the HIV-uninfected group regardless of whether the patients were undergoing ART or not (P<0.001. IL-10 levels correlated with TC levels in the HIV-uninfected group but not in the HIV-infected groups. Levels of HDL-c were reduced, while IL-10 plasma concentrations were elevated in HIV-infected individuals. A correlation observed in HIV-uninfected individuals between anti-inflammatory cytokine IL-10 and TC was lost in HIV-infected individuals. Clinical significance of these differences needs to be ascertained with respect to HIV-related CVD risk. Keywords: HIV, inflammation, cytokines, antiretroviral therapy, cardiovascular disease risk

  13. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    Directory of Open Access Journals (Sweden)

    Bonnetain Franck

    2010-06-01

    Full Text Available Abstract Background Overall survival (OS is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL. Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1 to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80 in the first round and 20% (16/80 in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings

  14. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    International Nuclear Information System (INIS)

    Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

    2010-01-01

    Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position N1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than

  15. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists.

    Science.gov (United States)

    Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

    2010-06-10

    Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69

  16. Assessing changes in HIV-related legal and policy environments: Lessons learned from a multi-country evaluation.

    Science.gov (United States)

    Ferguson, Laura; Nicholson, Alexandra; Henry, Ian; Saha, Amitrajit; Sellers, Tilly; Gruskin, Sofia

    2018-01-01

    There is growing recognition in the health community that the legal environment-including laws, policies, and related procedures-impacts vulnerability to HIV and access to HIV-related services both positively and negatively. Assessing changes in the legal environment and how these affect HIV-related outcomes, however, is challenging, and understanding of appropriate methodologies nascent. We conducted an evaluation of a UNDP project designed to strengthen legal environments to support the human rights of key populations, in particular LGBT populations, women and girls, affected by HIV in sub-Saharan Africa. We analyzed data on activities designed to improve legal environments through a systematic document review and 53 qualitative interviews. The project made substantial strides towards legal change in many places, and examples provide broader lessons for work in this area. Two core pillars appear fundamental: a government-led participatory assessment of the legal environment, and building the capacity of those impacted by and engaged in this work. Systematic attention to human rights is vital: it can help open new spaces for dialogue among diverse stakeholders, foster new collaborations, and ensure local ownership, nuanced understanding of the political landscape, attention to marginalized populations, and accountability for (in)action. Entry points for effecting legal change go beyond "HIV laws" to also include other laws, national policies and strategies. Conducting legal environment assessments, multi-stakeholder dialogues, action planning and related activities, alongside capacity building, can contribute to changes in knowledge and attitudes directly relevant to reforming laws that are found to be harmful. Shorter-term goals along the causal pathway to legal change (e.g. changes in policy) can constitute interim markers of success, and recognition of these can maintain momentum. Increasing understanding of progress towards changes in the legal environment

  17. Assessing changes in HIV-related legal and policy environments: Lessons learned from a multi-country evaluation.

    Directory of Open Access Journals (Sweden)

    Laura Ferguson

    Full Text Available There is growing recognition in the health community that the legal environment-including laws, policies, and related procedures-impacts vulnerability to HIV and access to HIV-related services both positively and negatively. Assessing changes in the legal environment and how these affect HIV-related outcomes, however, is challenging, and understanding of appropriate methodologies nascent.We conducted an evaluation of a UNDP project designed to strengthen legal environments to support the human rights of key populations, in particular LGBT populations, women and girls, affected by HIV in sub-Saharan Africa. We analyzed data on activities designed to improve legal environments through a systematic document review and 53 qualitative interviews.The project made substantial strides towards legal change in many places, and examples provide broader lessons for work in this area. Two core pillars appear fundamental: a government-led participatory assessment of the legal environment, and building the capacity of those impacted by and engaged in this work. Systematic attention to human rights is vital: it can help open new spaces for dialogue among diverse stakeholders, foster new collaborations, and ensure local ownership, nuanced understanding of the political landscape, attention to marginalized populations, and accountability for (inaction. Entry points for effecting legal change go beyond "HIV laws" to also include other laws, national policies and strategies.Conducting legal environment assessments, multi-stakeholder dialogues, action planning and related activities, alongside capacity building, can contribute to changes in knowledge and attitudes directly relevant to reforming laws that are found to be harmful. Shorter-term goals along the causal pathway to legal change (e.g. changes in policy can constitute interim markers of success, and recognition of these can maintain momentum. Increasing understanding of progress towards changes in the legal

  18. HIV-related stigma and psychological distress: the harmful effects of specific stigma manifestations in various social settings.

    Science.gov (United States)

    Stutterheim, Sarah E; Pryor, John B; Bos, Arjan E R; Hoogendijk, Robert; Muris, Peter; Schaalma, Herman P

    2009-11-13

    Recent research has shown that experiences of stigmatization have an adverse impact on the psychological well being of people living with HIV/AIDS (PLWHA). Most studies investigating this relationship employ an aggregate measure of stigma. Although this approach provides useful information about the psychological implications of HIV-related stigma in general, it neglects to acknowledge the possibility that some manifestations in specific settings may be psychologically more detrimental than others. The present study examines which specific stigma experiences are most strongly related to psychological distress across a number of social settings. A cross-sectional survey was administered to 667 PLWHA in the Netherlands. We examined participants' experiences of 11 manifestations of HIV-related stigma in six social settings. Linear regression analyses were conducted to determine which setting-specific manifestations best predict psychological distress after controlling for marital status, education and health status. Three manifestations in family settings, namely receiving advice to conceal one's status, being avoided and being treated with exaggerated kindness, and one manifestation in healthcare settings, namely awkward social interaction, best predicted psychological distress in PLWHA. Manifestations of HIV-related stigma vary according to setting. Certain manifestations in specific social settings impact the psychological well being of PLWHA more than others. In this study, certain experiences of stigmatization with PLWHA's families and in healthcare settings were more strongly related to psychological distress than experiences occurring in other social settings. These findings suggest that stigma reduction interventions focusing on these influential settings may benefit the psychological well being of PLWHA.

  19. Differences in HIV-related behaviors at Lugufu refugee camp and surrounding host villages, Tanzania

    Directory of Open Access Journals (Sweden)

    Mbaruku Godfrey

    2008-10-01

    Full Text Available Abstract Background An HIV behavioral surveillance survey was undertaken in November 2005 at Lugufu refugee camp and surrounding host villages, located near western Tanzania's border with the Democratic Republic of Congo (DRC. Methods The sample size was 1,743 persons based on cluster survey methodology. All members of selected households between 15–49 years old were eligible respondents. Questions included HIV-related behaviors, population displacement, mobility, networking and forced sex. Data was analyzed using Stata to measure differences in proportions (chi-square and differences in means (t-test between gender, age groups, and settlement location for variables of interest. Results Study results reflect the complexity of factors that may promote or inhibit HIV transmission in conflict-affected and displaced populations. Within this setting, factors that may increase the risk of HIV infections among refugees compared to the population in surrounding villages include young age of sexual initiation among males (15.9 years vs. 19.8 years, p = .000, high-risk sex partners in the 15–24 year age group (40% vs. 21%, χ2 33.83, p = .000, limited access to income (16% vs. 51% χ2 222.94, p = .000, and the vulnerability of refugee women, especially widowed, divorced and never-married women, to transactional sex (married vs. never married, divorced, widowed: for 15–24 age group, 4% and 18% respectively, χ2 8.07, p = .004; for 25–49 age group, 4% and 23% respectively, χ2 21.46, p = .000. A majority of both refugee and host village respondents who experienced forced sex in the past 12 months identified their partner as perpetrator (64% camp and 87% in villages. Although restrictions on movements in and out of the camp exist, there was regular interaction between communities. Condom use was found to be below 50%, and expanded population networks may also increase opportunities for HIV transmission. Availability of refugee health services may be

  20. HIV-Related Self-Stigma and Health-Related Quality of Life of People Living With HIV in Finland

    OpenAIRE

    Nobre, Nuno; Pereira, Marco; Roine, Risto P.; Sutinen, Jussi; Sintonen, Harri

    2017-01-01

    We examined how HIV-related self-stigma was associated with different domains of quality of life (QoL), as measured by the World Health Organization Quality of Life in HIV-infected persons instrument (WHOQOL-HIV-Bref), and health-related quality of life (HRQoL) as measured by the generic 15D (15-dimensional measure of HRQoL), to identify the factors associated with self-stigma of people living with HIV (PLWH). The study sample included 440 patients living with HIV followed at the Infectious D...

  1. Associations between HIV-related stigma, racial discrimination, gender discrimination, and depression among HIV-positive African, Caribbean, and Black women in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen; James, Llana; Tharao, Wangari; Loutfy, Mona

    2013-02-01

    Abstract African, Caribbean, and Black (ACB) women are greatly overrepresented in new HIV infections in comparison with Canada's general population. Social and structural factors such as HIV-related stigma, gender discrimination, and racial discrimination converge to increase vulnerability to HIV infection among ACB women by reducing access to HIV prevention services. Stigma and discrimination also present barriers to treatment, care, and support and may contribute to mental health problems. We administered a cross-sectional survey to HIV-positive ACB women (n=173) across Ontario in order to examine the relationships between HIV-related stigma, gender discrimination, racial discrimination, and depression. One-third of participants reported moderate/severe depression scores using the Beck Depression Inventory Fast-Screen guidelines. Hierarchical block regression, moderation, and mediation analyses were conducted to measure associations between independent (HIV-related stigma, gender discrimination, racial discrimination), moderator/mediator (social support, resilient coping), and dependent (depression) variables. Findings included: (1) HIV-related stigma was associated with increased depression; (2) resilient coping was associated with reduced depression but did not moderate the influence of HIV-related stigma on depression; and (3) the effects of HIV-related stigma on depression were partially mediated through resilient coping. HIV-related stigma, gender discrimination, and racial discrimination were significantly correlated with one another and with depression, highlighting the salience of examining multiple intersecting forms of stigma. Generalizability of findings may be limited due to nonrandom sampling. Findings emphasize the importance of multi-component interventions, including building resilient coping skills, mental health promotion and assessment, and stigma reduction programs.

  2. Acculturation and HIV-related sexual behaviours among international migrants: a systematic review and meta-analysis.

    Science.gov (United States)

    Du, Hongfei; Li, Xiaoming

    2015-01-01

    This review examines the global literature regarding the relationship between acculturation and HIV-related sexual behaviours among international migrants. Seventy-nine articles published in English-language journals prior to July 2012 met the criteria for inclusion. We conducted a systematic review and subset meta-analysis of correlations between acculturation and five types of sexual behaviours including condom use, multiple partnerships, early sexual initiation, sexually transmitted diseases (STDs) and other unsafe sexual practices. Immigrants high in mainstream acculturation were more likely to have multiple partnerships, early sexual initiation, STDs and unsafe sex (rs ranged from 0.10 to 0.16), but acculturation was not associated with condom use (r = 0.02). Gender moderated the relationships between acculturation and multiple partnerships, STDs and unsafe sex. The relationship between acculturation and unsafe sex also varied across ethnicity. These findings suggest that acculturation may serve as a risk factor towards immigrants' HIV-related sexual health. We offered a theoretical framework and suggested applying cross-cultural and longitudinal designs in future research on acculturation and health behaviours.

  3. Acculturation and HIV-related sexual behaviors among international migrants: A systematic review and meta-analysis

    Science.gov (United States)

    Li, Xiaoming

    2014-01-01

    This review examines the global literature regarding the relationship between acculturation and HIV-related sexual behaviors among international migrants. Seventy-nine articles published in English-language journals prior to July 2012 met the criteria for inclusion. We conducted a systematic review and subset meta-analysis of correlations between acculturation and five types of sexual behaviors including condom use, multiple partnerships, early sexual initiation, sexually transmitted diseases (STDs), and other unsafe sexual practices. Immigrants high in mainstream acculturation were more likely to have multiple partnerships, early sexual initiation, STDs, and unsafe sex (rs ranged from .10 to .16), but acculturation was not associated with condom use (r = .02). Gender moderated the relationships between acculturation and multiple partnerships, STDs, and unsafe sex. The relationship between acculturation and unsafe sex also varied across ethnicity. These findings suggest that acculturation may serve as a risk factor towards immigrants’ HIV-related sexual health. We offered a theoretical framework and suggested applying cross-cultural and longitudinal designs in future research on acculturation and health behaviors. PMID:25793493

  4. Social Networking Technology Use and Engagement in HIV-Related Risk and Protective Behaviors Among Homeless Youth.

    Science.gov (United States)

    Barman-Adhikari, Anamika; Rice, Eric; Bender, Kimberly; Lengnick-Hall, Rebecca; Yoshioka-Maxwell, Amanda; Rhoades, Harmony

    2016-07-01

    Preliminary studies with homeless youth have found surprisingly pervasive social media use and suggest that youth's online interactions may be associated with their HIV-related risk and protective behaviors. As homeless youth are transient and difficult to engage in place-based services, social media may represent a novel venue for intervention. A critical 1st step in intervention development is gaining greater understanding of how homeless youth use social media, especially as it relates to who they connect to and around what topics. Given the salience of social networking sites in the lives of these otherwise difficult-to-reach adolescents, and their potential to disseminate prevention interventions, this study assessed associations between online social networking technology use and HIV risk behaviors among homeless youth in Los Angeles, California. Homeless youth ages 13 through 24 (N = 1,046) were recruited through 3 drop-in centers and surveyed about their social media use and self-reported HIV-related risk behaviors. Results suggest that social media use is widely prevalent among this population, and the content of these online interactions is associated with whether youth engage in risk or protective behaviors. Implications for interventions and further research are discussed.

  5. Masculinity and HIV: Dimensions of masculine norms that contribute to men’s HIV-related sexual behaviors

    Science.gov (United States)

    Fleming, Paul J.; DiClemente, Ralph J.; Barrington, Clare

    2016-01-01

    Numerous studies have documented a relationship between masculine norms and men’s HIV-related sexual behaviors, but intervening upon this relationship requires a nuanced understanding of the specific aspects of masculine norms that shape men’s sexual behaviors. We integrate theories on masculinities with empirical HIV research to identify specific dimensions of masculine norms that influence men’s HIV-related sexual behaviors. We identify three major dimensions of masculine norms that shape men’s sexual behavior: 1) uncontrollable male sex drive, 2) capacity to perform sexually, and 3) power over others. While the existing literature does help explain the relationship between masculine norms and men’s sexual behaviors several gaps remain including: a recognition of context-specific masculinities, an interrogation of the positive influences of masculinity, adoption of an intersectional approach, assessment of changes in norms and behaviors over time, and rigorous evaluations of gender-transformative approaches. Addressing these gaps in future research may optimize prevention efforts. PMID:26696261

  6. Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests

    International Nuclear Information System (INIS)

    Arts, Gertie H.P.; Belgers, J. Dick M.; Hoekzema, Conny H.; Thissen, Jac T.N.M.

    2008-01-01

    The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth. - A range of endpoints is more representative of macrophyte fitness than biomass and growth only

  7. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    NARCIS (Netherlands)

    Lassere, Marissa N.; Johnson, Kent R.; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G.; Ostergaard, Mikkel; Maksymowych, Walter P.; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O.; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

    2007-01-01

    OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to

  8. Sexual abuse during childhood and adolescence as predictors of HIV-related sexual risk during adulthood among female sexual partners of injection drug users.

    Science.gov (United States)

    Klein, H; Chao, B S

    1995-03-01

    This study explores the relationship of sexual abuse during childhood and adolescence with HIV-related sexual risk behaviors during adulthood among female sexual partners of injection drug users. It analyzed data that was gathered between 1990 and 1993, which included a sample of 2794 women from the US, Mexico, and Puerto Rico. 6 HIV-related sexual risk behaviors that occurred during the month prior to interview were examined; namely, number of sexual partners, number of drug-injecting sexual partners, number of sexual intercourse while high on alcohol and/or other drugs, number of times trading sex for drugs and/or money, proportion of all sexual acts involving protection, and overall HIV-related sexual risk. The results showed that more than one-third of the women (36.3%) experienced some form of sexual abuse during childhood, whereas 34.4% reported that they had been abused sexually during adolescence; 1 in 5 women (18.4%) stated being abused during both periods. The results further indicate that there is a strong link between sexual abuse victimization early in life and involvement later in life in HIV-related sexual risk behaviors. It was found out that certain forms of sexual abuse, such as forced exposure and touching of one's sexual parts were more strongly related than other forms of sexual abuse to subsequent involvement in HIV-related sexual behaviors.

  9. Examining anxiety sensitivity as an explanatory construct underlying HIV-related stigma: Relations to anxious arousal, social anxiety, and HIV symptoms among persons living with HIV.

    Science.gov (United States)

    Brandt, Charles P; Paulus, Daniel J; Jardin, Charles; Heggeness, Luke; Lemaire, Chad; Zvolensky, Michael J

    2017-05-01

    Persons living with HIV (PLHIV) are a health disparity subgroup of the overall population for mental and physical health problems. HIV-related stigma has been shown to increase anxiety symptoms and HIV symptoms among PLHIV. However, little is known about factors that may impact the relations between HIV-related stigma and anxiety symptoms and HIV symptoms among PLHIV. To address this gap in the literature, the current study examined anxiety sensitivity (i.e., the extent to which individuals believe anxiety and anxiety-related sensations) in the relation between HIV-related stigma, social anxiety, anxious arousal, and HIV symptoms among a sample of 87 PLHIV (60.9% cis gender male, 52.9% Black, non-Hispanic). Results indicated that anxiety sensitivity mediated the relations between HIV-related stigma and the dependent variables, with effect sizes indicating moderate to large effects of anxiety sensitivity on these relations. Findings suggest that anxiety sensitivity be a mechanistic factor in the relations between HIV-related stigma and social anxiety, anxious arousal, and HIV symptoms, and therefore, be important element in efforts to reduce mental/physical health disparity among this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  11. Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium.

    Science.gov (United States)

    Seltzer, Jonathan H; Heise, Ted; Carson, Peter; Canos, Daniel; Hiatt, Jo Carol; Vranckx, Pascal; Christen, Thomas; Cutlip, Donald E

    2017-08-01

    This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence. Copyright © 2017. Published by Elsevier Inc.

  12. Biomechanical constraints on the feedforward regulation of endpoint stiffness.

    Science.gov (United States)

    Hu, Xiao; Murray, Wendy M; Perreault, Eric J

    2012-10-01

    Although many daily tasks tend to destabilize arm posture, it is still possible to have stable interactions with the environment by regulating the multijoint mechanics of the arm in a task-appropriate manner. For postural tasks, this regulation involves the appropriate control of endpoint stiffness, which represents the stiffness of the arm at the hand. Although experimental studies have been used to evaluate endpoint stiffness control, including the orientation of maximal stiffness, the underlying neural strategies remain unknown. Specifically, the relative importance of feedforward and feedback mechanisms has yet to be determined due to the difficulty separately identifying the contributions of these mechanisms in human experiments. This study used a previously validated three-dimensional musculoskeletal model of the arm to quantify the degree to which the orientation of maximal endpoint stiffness could be changed using only steady-state muscle activations, used to represent feedforward motor commands. Our hypothesis was that the feedforward control of endpoint stiffness orientation would be significantly constrained by the biomechanical properties of the musculoskeletal system. Our results supported this hypothesis, demonstrating substantial biomechanical constraints on the ability to regulate endpoint stiffness throughout the workspace. The ability to regulate stiffness orientation was further constrained by additional task requirements, such as the need to support the arm against gravity or exert forces on the environment. Together, these results bound the degree to which slowly varying feedforward motor commands can be used to regulate the orientation of maximum arm stiffness and provide a context for better understanding conditions in which feedback control may be needed.

  13. First report of HIV-related oral manifestations in Mali | Tamí-Maury ...

    African Journals Online (AJOL)

    OM prevalence during the first month of HIV care was 31.4%, being oral candidiasis the commonest lesion. 73.2% and 82.5% of the patients with OM had CD4 count < 200 cells/mm3 and were classified as WHO clinical stage III or IV. WHO clinical stage III and VI patients had 5.4-fold increased odds of having any OM (both ...

  14. HIV-related knowledge, attitudes and risk perception amongst nurses, doctors and other healthcare workers in rural India.

    Science.gov (United States)

    Kermode, Michelle; Holmes, Wendy; Langkham, Biangtung; Thomas, Mathew Santhosh; Gifford, Sandy

    2005-09-01

    People with HIV in India frequently encounter discrimination while seeking and receiving healthcare services. The knowledge and attitudes of healthcare workers (HCWs) influences the willingness and ability of people with HIV to access care, and the quality of the care they receive. Previous studies of HIV-related knowledge and attitudes amongst Indian HCWs have been conducted primarily in large urban hospitals. The objective of this study was to asses HIV-related knowledge, attitudes and risk perception among a group of rural north Indian HCWs, and to identify predictors of willingness to provide care for patients with HIV infection. A cross-sectional survey of 266 HCWs (78% female) from seven rural north Indian health settings was undertaken in late 2002. A self-administered written questionnaire was made available in English and Hindi, and the response rate was 87 per cent. Information was gathered regarding demographic details (age, sex, duration of employment, job category); HIV-related knowledge and attitudes; risk perception; and previous experience caring for HIV-positive patients. Logistic regression modelling was undertaken to identify factors associated with willingness to care for patients with HIV. The HCWs in this study generally had a positive attitude to caring for people with HIV. However, this was tempered by substantial concerns about providing care, and the risk of occupational infection with HIV was perceived by most HCWs to be high. After controlling for confounding, HCWs willingness to provide care for patients with HIV was strongly associated with having previously cared for patients with HIV (P = 0.001). Knowledge of HIV transmission and perception of risk were not associated with willingness to provide care. The findings of this study showed a general willingness of HCWs to provide care for patients with HIV, tempered by concerns regarding provision of such care. Strategies to address HCWs concerns are likely to ameliorate the

  15. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

    Science.gov (United States)

    Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-01-01

    Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to

  16. A Structural Equation Model of HIV-Related Stigma, Racial Discrimination, Housing Insecurity and Wellbeing among African and Caribbean Black Women Living with HIV in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Carmen H Logie

    Full Text Available African and Caribbean Black women in Canada have new HIV infection rates 7 times higher than their white counterparts. This overrepresentation is situated in structural contexts of inequities that result in social, economic and health disparities among African and Caribbean Black populations. Economic insecurity is a distal driver of HIV vulnerability, reducing access to HIV testing, prevention and care. Less is known about how economic insecurity indicators, such as housing security, continue to influence the lives of women living with HIV following HIV-positive diagnoses. The aim of this study was to test a conceptual model of the pathways linking HIV-related stigma, racial discrimination, housing insecurity, and wellbeing (depression, social support, self-rated health. We implemented a cross-sectional survey with African and Caribbean Black women living with HIV in 5 Ontario cities, and included 157 participants with complete data in the analyses. We conducted structural equation modeling using maximum likelihood estimation to evaluate the hypothesized conceptual model. One-fifth (22.5%; n = 39 of participants reported housing insecurity. As hypothesized, racial discrimination had significant direct effects on: HIV-related stigma, depression and social support, and an indirect effect on self-rated health via HIV-related stigma. HIV-related stigma and housing insecurity had direct effects on depression and social support, and HIV-related stigma had a direct effect on self-rated health. The model fit the data well: χ2 (45, n = 154 = 54.28, p = 0.387; CFI = 0.997; TLI = 0.996; RMSEA = 0.016. Findings highlight the need to address housing insecurity and intersecting forms of stigma and discrimination among African and Caribbean Black women living with HIV. Understanding the complex relationships between housing insecurity, HIV-related stigma, racial discrimination, and wellbeing can inform multi-level interventions to reduce stigma and enhance

  17. Can a short film impact HIV-related risk and stigma perceptions? Results from an experiment in Abuja, Nigeria.

    Science.gov (United States)

    Lapinski, Maria Knight; Nwulu, Paul

    2008-09-01

    HIV/AIDS-related stigma is believed to result in negative social consequences for people with the disease and to be a deterrent to HIV serostatus testing. The ability of communicators to change people's stigma perceptions and subsequently impact decisions to test, however, is not well understood. Based on the entertainment-education approach, this article presents the results of a field experiment conducted in Abuja, Nigeria, testing a mediated intervention designed to reduce HIV-related stigma and risk perceptions. The results indicate that the intervention was effective relative to a control in impacting perceptions of the severity of HIV and some stigma-related attitudes, particularly for male participants; and that for this sample, risk and stigma perceptions significantly impact intentions to test for HIV. It also showed that severity perceptions mediated the relationship between viewing the film and testing intent.

  18. Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

    Science.gov (United States)

    Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

    2008-10-01

    Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

  19. Examining relationships of intimate partner violence and food insecurity with HIV-related risk factors among young pregnant Liberian women.

    Science.gov (United States)

    Willie, Tiara C; Kershaw, Trace S; Callands, Tamora A

    2018-04-22

    Gender inequities place women at an increased risk for HIV acquisition, and this association may particularly disenfranchize young pregnant women. Intimate partner violence (IPV) and food insecurity may contribute to gender differences in power, thereby influencing HIV disparities between women and men. Factors influencing gender disparities in HIV are unique and country-specific within sub-Saharan Africa, yet these factors are understudied among women in Liberia. This paper sought to examine the unique contributions and intersections of intimate partner violence (IPV) and food insecurity with HIV-related risk factors among young pregnant women in Liberia. Between March 2016 and August 2016, cross-sectional data collected from 195 women aged 18-30, residing in Monrovia, Liberia who were receiving prenatal services were used to examine the independent and interaction effects of IPV and food insecurity on HIV-related risk factors (i.e., sexual partner concurrency, economically-motivated relationships). IPV (31.3%) and food insecurity (47.7%) were prevalent. Young women who experience IPV are more likely to report food insecurity (p insecurity were more likely to start a new relationship for economic support (ps insecurity were more likely to report engaging in transactional sex (ps insecurity (ps > 0.05). IPV and food insecurity each uniquely heighten young Liberian women's vulnerability to HIV. Intervention and policy efforts are need to promote and empower women's sexual health through integrated sexual and reproductive health services, and reduce IPV and food insecurity among pregnant Liberian women.

  20. Health Care Use and HIV-Related Behaviors of Black and Latina Transgender Women in 3 US Metropolitan Areas: Results From the Transgender HIV Behavioral Survey.

    Science.gov (United States)

    Denson, Damian J; Padgett, Paige M; Pitts, Nicole; Paz-Bailey, Gabriela; Bingham, Trista; Carlos, Juli-Ann; McCann, Pamela; Prachand, Nikhil; Risser, Jan; Finlayson, Teresa

    2017-07-01

    HIV prevalence estimates among transgender women in the United States are high, particularly among racial/ethnic minorities. Despite increased HIV risk and evidence of racial disparities in HIV prevalence among transgender women, few data are available to inform HIV prevention efforts. A transgender HIV-related behavioral survey conducted in 2009 in 3 US metropolitan areas (Chicago, Houston, and Los Angeles County), used respondent-driven sampling to recruit 227 black (n = 139) and Latina (n = 88) transgender women. We present descriptive statistics on sociodemographic, health care, and HIV-risk behaviors. Of 227 transgender women enrolled, most were economically and socially disadvantaged: 73% had an annual income of less than $15,000; 62% lacked health insurance; 61% were unemployed; and 46% reported being homeless in the past 12 months. Most (80%) had visited a health care provider and over half (58%) had tested for HIV in the past 12 months. Twenty-nine percent of those who reported having an HIV test in the past 24 months self-reported being HIV positive. Most of the sample reported hormone use (67%) in the past 12 months and most hormone use was under clinical supervision (70%). Forty-nine percent reported condomless anal sex in the past 12 months and 16% reported ever injecting drugs. These findings reveal the socioeconomic challenges and behavioral risks often associated with high HIV risk reported by black and Latina transgender women. Despite low health insurance coverage, the results suggest opportunities to engage transgender women in HIV prevention and care given their high reported frequency of accessing health care providers.

  1. 'What do I know? Should I participate?' Considerations on participation in HIV related research among HIV infected adults in Bangalore, South India.

    Science.gov (United States)

    Rodrigues, Rashmi J; Antony, Jimmy; Krishnamurthy, Shubha; Shet, Anita; De Costa, Ayesha

    2013-01-01

    India has the highest number of HIV infected persons in the world after South Africa. Much HIV related behavioral, clinical and laboratory based research is ongoing in India. Yet little is known on Indian HIV patients' knowledge of research, their processes of decision making and motives for participation. We aimed to explore these areas among HIV infected individuals to understand their reasons for participating in research. This is a cross sectional survey among 173 HIV infected adults at a tertiary level hospital in Bangalore, India, done between October 2010 and January 2011. A pre-tested questionnaire was administered to the participants by trained research assistants to assess their knowledge regarding research, willingness to participate, decision making and determinants of participation. Participants were presented with five hypothetical HIV research studies. Each study had a different level of intervention and time commitment. Of respondents, 103(60%), said that research meant 'to discover something new' and 138(80%) were willing to participate in research. A third of the respondents were unaware of their right to refuse participation. Willingness to participate in research varied with level of intervention. It was the lowest for the hypothetical study involving sensitive questions followed by the hypothetical drug trial; and was the highest for the hypothetical cross sectional questionnaire based study (pWomen were less likely to make autonomous decisions for participation in interventional studies. Despite a majority willing to participate, over a third of respondents did not have any knowledge of research or the voluntary nature of participation. This has ethical implications. Researchers need to focus on enabling potential research participants understand the concepts of research, promote autonomous decisions, especially by women and restrict therapeutic misconception.

  2. 'What do I know? Should I participate?' Considerations on participation in HIV related research among HIV infected adults in Bangalore, South India.

    Directory of Open Access Journals (Sweden)

    Rashmi J Rodrigues

    Full Text Available BACKGROUND: India has the highest number of HIV infected persons in the world after South Africa. Much HIV related behavioral, clinical and laboratory based research is ongoing in India. Yet little is known on Indian HIV patients' knowledge of research, their processes of decision making and motives for participation. We aimed to explore these areas among HIV infected individuals to understand their reasons for participating in research. METHODOLOGY/PRINCIPAL FINDINGS: This is a cross sectional survey among 173 HIV infected adults at a tertiary level hospital in Bangalore, India, done between October 2010 and January 2011. A pre-tested questionnaire was administered to the participants by trained research assistants to assess their knowledge regarding research, willingness to participate, decision making and determinants of participation. Participants were presented with five hypothetical HIV research studies. Each study had a different level of intervention and time commitment. Of respondents, 103(60%, said that research meant 'to discover something new' and 138(80% were willing to participate in research. A third of the respondents were unaware of their right to refuse participation. Willingness to participate in research varied with level of intervention. It was the lowest for the hypothetical study involving sensitive questions followed by the hypothetical drug trial; and was the highest for the hypothetical cross sectional questionnaire based study (p<0.0015. Individual health benefits and altruism were the primary motives for participation in research and indicate the presence of therapeutic misconception. Women were less likely to make autonomous decisions for participation in interventional studies. CONCLUSIONS/SIGNIFICANCE: Despite a majority willing to participate, over a third of respondents did not have any knowledge of research or the voluntary nature of participation. This has ethical implications. Researchers need to focus on

  3. Choice of futility boundaries for group sequential designs with two endpoints

    Directory of Open Access Journals (Sweden)

    Svenja Schüler

    2017-08-01

    Full Text Available Abstract Background In clinical trials, the opportunity for an early stop during an interim analysis (either for efficacy or for futility may relevantly save time and financial resources. This is especially important, if the planning assumptions required for power calculation are based on a low level of evidence. For example, when including two primary endpoints in the confirmatory analysis, the power of the trial depends on the effects of both endpoints and on their correlation. Assessing the feasibility of such a trial is therefore difficult, as the number of parameter assumptions to be correctly specified is large. For this reason, so-called ‘group sequential designs’ are of particular importance in this setting. Whereas the choice of adequate boundaries to stop a trial early for efficacy has been broadly discussed in the literature, the choice of optimal futility boundaries has not been investigated so far, although this may have serious consequences with respect to performance characteristics. Methods In this work, we propose a general method to construct ‘optimal’ futility boundaries according to predefined criteria. Further, we present three different group sequential designs for two endpoints applying these futility boundaries. Our methods are illustrated by a real clinical trial example and by Monte-Carlo simulations. Results By construction, the provided method of choosing futility boundaries maximizes the probability to correctly stop in case of small or opposite effects while limiting the power loss and the probability of stopping the study ‘wrongly’. Our results clearly demonstrate the benefit of using such ‘optimal’ futility boundaries, especially compared to futility boundaries commonly applied in practice. Conclusions As the properties of futility boundaries are often not considered in practice and unfavorably chosen futility boundaries may imply bad properties of the study design, we recommend assessing the

  4. Social networks and social support among ball-attending African American men who have sex with men and transgender women are associated with HIV-related outcomes.

    Science.gov (United States)

    Arnold, Emily A; Sterrett-Hong, Emma; Jonas, Adam; Pollack, Lance M

    2018-02-01

    The House Ball Community (HBC) is an understudied network of African American men who have sex with men and transgender women, who join family-like houses that compete in elaborate balls in cities across the United States. From 2011 to 2012, we surveyed 274 recent attendees of balls in the San Francisco Bay Area, focusing on social networks, social support, and HIV-related behaviours. Participants with a high percentage of alters who were supportive of HIV testing were significantly more likely to have tested in the past six months (p = .02), and less likely to have engaged in unprotected anal intercourse (UAI) in the past three months (p = .003). Multivariate regression analyses of social network characteristics, and social support, revealed that testing in the past six months was significantly associated with social support for safer sex, instrumental social support, and age. Similarly, UAI in the past three months was significantly associated with social support for safer sex, homophily based on sexual identity and HIV status. HIV-related social support provided through the HBC networks was correlated with recent HIV testing and reduced UAI. Approaches utilising networks within alternative kinship systems, may increase HIV-related social support and improve HIV-related outcomes.

  5. Knowledge Distribution and Power Relations in HIV-Related Education and Prevention for Gay Men: An Application of Bernstein to Australian Community-Based Pedagogical Devices

    Science.gov (United States)

    McInnes, David; Murphy, Dean

    2011-01-01

    This paper seeks to make a theoretical and analytic intervention into the field of HIV-related education and prevention by applying the pedagogy framework of Basil Bernstein to a series of pedagogical devices developed and used in community-based programmes targeting gay men in Australia. The paper begins by outlining why it is such an…

  6. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the

  7. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; de Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; de Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.; Gras, A. Luuk; van Wout, Angelique B.; Arnedo-Valero, Mireia; Sierra, Mariana de Paz; Rodriguez, Ana Torrecilla; Garcia, Juan Gonzalez; Arribas, Jose R.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Francioli, P.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Prins, Yerly S. J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Boer, K.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Vrouenraets, S. M. E.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Pronk, M. J. H.; Bravenboer, B.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; van der Feltz, M.; Nouwen, J. L.; Gelinck, L. B. S.; Verbon, A.; Rijnders, B. J. A.; van de Ven-de Ruiter, E. D.; Slobbe, L.; Haag, Den; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; van den Broek, P. J.; van Dissel, J. T.; Arend, S. M.; van Nieuwkoop, C.; de Boer, M. J. G.; Jolink, H.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; van Houte, D. P. F.; Polée, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; Juttmann, J. R.; van Kasteren, M. E. E.; Brouwer, A. E.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Stek, C. J.; Hoepelman, I. M.; Mudrikova, T.; Schneider, M. M. E.; Jaspers, C. A. J. J.; Ellerbroek, P. M.; Peters, E. J. G.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; van der Hilst, J. C. H.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; Margolick, Joseph B.; Plankey, Michael; Crain, Barbara; Dobs, Adrian; Farzadegan, Homayoon; Gallant, Joel; Johnson-Hill, Lisette; Sacktor, Ned; Selnes, Ola; Shepard, James; Thio, Chloe; Phair, John P.; Wolinsky, Steven M.; Badri, Sheila; Conover, Craig; O'Gorman, Maurice; Ostrow, David; Palella, Frank; Ragin, Ann; Detels, Roger; Martínez-Maza, Otoniel; Aronow, Aaron; Bolan, Robert; Breen, Elizabeth; Butch, Anthony; Fahey, John; Jamieson, Beth; Miller, Eric N.; Oishi, John; Vinters, Harry; Visscher, Barbara R.; Wiley, Dorothy; Witt, Mallory; Yang, Otto; Young, Stephen; Zhang, Zuo Feng; Rinaldo, Charles R.; Becker, James T.; Cranston, Ross D.; Martinson, Jeremy J.; Mellors, John W.; Silvestre, Anthony J.; Stall, Ronald D.; Muñoz, Alvaro; Abraham, Alison; Althoff, Keri; Cox, Christopher; D'Souza, Gypsyamber; Gange, Stephen J.; Golub, Elizabeth; Schollenberger, Janet; Seaberg, Eric C.; Su, Sol; Huebner, Robin E.; Dominguez, Geraldina; Moroni, M.; Angarano, G.; Antinori, A.; Carosi, G.; Cauda, R.; Monforte, A. d'Arminio; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Sagnelli, E.; Viale, P. L.; Von Schlosser, F.; d'Arminio Monforte, A.; Ammassari, A.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; de Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; Fanti, I.; Formenti, T.; Galli, Laura; Lorenzini, Patrizia; Montroni, M.; Giacometti, A.; Costantini, A.; Riva, A.; Tirelli, U.; Martellotta, F.; Ladisa, N.; Lazzari, G.; Verucchi, G.; Castelli, F.; Scalzini, A.; Minardi, C.; Bertelli, D.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Carnevale, G.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Leoncini, F.; Mazzotta, F.; Pozzi, M.; Cassola, G.; Viscoli, G.; Viscoli, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, P.; Rizzardini, G.; Ridolfo, A. L.; Foschi, A.; Salpietro, S.; Galli, A.; Bigoloni, A.; Spagnuolo, V.; Merli, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Bisio, L.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; de Marco, M.; Ferrari, C.; Borghi, R.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Narciso, P.; Tozzi, V.; Vullo, V.; d'Avino, A.; Zaccarelli, M.; Gallo, L.; Acinapura, R.; Capozzi, M.; Libertone, R.; Trotta, M. P.; Tebano, G.; Cattelan, A. M.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Raise, N. N.; Ebo, F.; Pellizzer, G.; Manfrin, V.; Law, M.; Petoumenos, K.; McManus, H.; Wright, S.; Bendall, C.; Moore, R.; Edwards, S.

    2013-01-01

    Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV

  8. Sensation Seeking and Risk-Taking Propensity as Mediators in the Relationship between Childhood Abuse and HIV-Related Risk Behavior

    Science.gov (United States)

    Bornovalova, Marina A.; Gwadz, Marya A.; Kahler, Christopher; Aklin, W. M.; Lejuez, C. W.

    2008-01-01

    Objectives: Although a wealth of literature suggests that childhood physical, emotional, and sexual abuse are related to later-life HIV-related risk behaviors, few studies have explored disinhibition (e.g., impulsivity, risk-taking propensity, and sensation-seeking) as a risk factor in this relationship. Method: This cross-sectional study examined…

  9. The development and psychometric analysis of the Chinese HIV-Related Fatigue Scale.

    Science.gov (United States)

    Li, Su-Yin; Wu, Hua-Shan; Barroso, Julie

    2016-04-01

    To develop a Chinese version of the human immunodeficiency virus-related Fatigue Scale and examine its reliability and validity. Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus-positive people has not yet been developed for use in Chinese-speaking countries. A methodologic study involving instrument development and psychometric evaluation was used. The human immunodeficiency virus-related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus-positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's α for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test-retest reliability. The correlation between the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus-related Fatigue Scale scores of human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. The internal consistency and test-retest reliability of the Chinese version of the human immunodeficiency virus-related Fatigue Scale were 0·97 and 0·686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus-related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus-related Fatigue Scale could be used to effectively

  10. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive

    Science.gov (United States)

    Nixon, Stephanie A; Cameron, Cathy; Hanass-Hancock, Jill; Simwaba, Phillimon; Solomon, Patricia E; Bond, Virginia A; Menon, Anitha; Richardson, Emma; Stevens, Marianne; Zack, Elisse

    2014-01-01

    Introduction Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs), there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. Methods This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Results Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1) disability-related discrimination heightened when seeking HIV services, (2) communication barriers and related concerns with confidentiality, and (3) movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants’ profound concerns about poverty and unmet basic needs. Discussion This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Conclusions Despite the growing body of literature on increased

  11. Perceptions of HIV-related health services in Zambia for people with disabilities who are HIV-positive.

    Science.gov (United States)

    Nixon, Stephanie A; Cameron, Cathy; Hanass-Hancock, Jill; Simwaba, Phillimon; Solomon, Patricia E; Bond, Virginia A; Menon, Anitha; Richardson, Emma; Stevens, Marianne; Zack, Elisse

    2014-01-01

    Despite the emerging body of literature on increased vulnerability to HIV among people with disabilities (PWDs), there is a dearth of evidence related to experiences of PWDs who have become HIV-positive. This priority was identified by a disability advocacy organization in Lusaka, Zambia, where the prevalence of HIV and of disability is each approximately 15%. The purpose of this study was to explore perceptions and experiences of HIV-related health services for PWDs who are also living with HIV in Lusaka, Zambia. This qualitative, interpretive study involved in-depth, semi-structured, one-on-one interviews with two groups of participants in Lusaka, Zambia: 21 PWDs who had become HIV-positive, and 11 people working in HIV and/or disability. PWDs had physical, hearing, visual and/or intellectual impairments. Interviews were conducted in English, Nyanja, Bemba or Zambian sign language. Descriptive and thematic analyses were conducted by a multidisciplinary, international research team. Participants described their experiences with HIV-related health services in terms of the challenges they faced. In particular, they encountered three main challenges while seeking care and treatment: (1) disability-related discrimination heightened when seeking HIV services, (2) communication barriers and related concerns with confidentiality, and (3) movement and mobility challenges related to seeking care and collecting antiretroviral therapy. These experiences were further shaped by participants' profound concerns about poverty and unmet basic needs. This study demonstrates how PWDs who are HIV-positive have the same HIV care, treatment and support needs as able-bodied counterparts, but face avoidable barriers to care. Many challenges mirror concerns identified with HIV prevention, suggesting that efforts to promote inclusion and reduce stigma could have widespread benefits. Despite the growing body of literature on increased risk of exposure to HIV among HIV-negative PWDs, this is

  12. Two-temperature LATE-PCR endpoint genotyping

    Directory of Open Access Journals (Sweden)

    Reis Arthur H

    2006-12-01

    Full Text Available Abstract Background In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. Results Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of

  13. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  14. Is automated kinetic measurement superior to end-point for advanced oxidation protein product?

    Science.gov (United States)

    Oguz, Osman; Inal, Berrin Bercik; Emre, Turker; Ozcan, Oguzhan; Altunoglu, Esma; Oguz, Gokce; Topkaya, Cigdem; Guvenen, Guvenc

    2014-01-01

    Advanced oxidation protein product (AOPP) was first described as an oxidative protein marker in chronic uremic patients and measured with a semi-automatic end-point method. Subsequently, the kinetic method was introduced for AOPP assay. We aimed to compare these two methods by adapting them to a chemistry analyzer and to investigate the correlation between AOPP and fibrinogen, the key molecule responsible for human plasma AOPP reactivity, microalbumin, and HbA1c in patients with type II diabetes mellitus (DM II). The effects of EDTA and citrate-anticogulated tubes on these two methods were incorporated into the study. This study included 93 DM II patients (36 women, 57 men) with HbA1c levels > or = 7%, who were admitted to the diabetes and nephrology clinics. The samples were collected in EDTA and in citrate-anticoagulated tubes. Both methods were adapted to a chemistry analyzer and the samples were studied in parallel. In both types of samples, we found a moderate correlation between the kinetic and the endpoint methods (r = 0.611 for citrate-anticoagulated, r = 0.636 for EDTA-anticoagulated, p = 0.0001 for both). We found a moderate correlation between fibrinogen-AOPP and microalbumin-AOPP levels only in the kinetic method (r = 0.644 and 0.520 for citrate-anticoagulated; r = 0.581 and 0.490 for EDTA-anticoagulated, p = 0.0001). We conclude that adaptation of the end-point method to automation is more difficult and it has higher between-run CV% while application of the kinetic method is easier and it may be used in oxidative stress studies.

  15. Increasing HIV-related knowledge, communication, and testing intentions among Latinos: Protege tu Familia: Hazte la Prueba.

    Science.gov (United States)

    Rios-Ellis, Britt; Espinoza, Lilia; Bird, Mara; Garcia, Melawhy; D'Anna, Laura Hoyt; Bellamy, Laura; Scolari, Rosana

    2010-08-01

    Latinos are less likely to be aware of their HIV seropositivity than African Americans and Whites. 'Protege tu Familia: Hazte la Prueba' is a culturally and linguistically-sensitive HIV/AIDS prevention and testing program targeting Latino families. Using community-based participatory research techniques, Spanish-speaking bicultural community health workers helped develop and then used an educational flip chart and materials to conduct outreach and HIV prevention education in diverse settings. The intervention was created to increase HIV/AIDS-related knowledge, to improve communication regarding sexual risk, and to augment intentions to use condoms and test for HIV. A secondary purpose was to decrease HIV-related stigma by improving knowledge about transmission and reducing homophobia. Participants demonstrated significant increases in HIV knowledge, intention to practice safer sex and communicate sexual risk to partner(s), and intention to test for HIV. Improvements were also found in self-reported comfort levels when interacting with and caring for the HIV positive, thus decreasing HIV/AIDS-related stigma.

  16. Change in HIV-related stigma in South Africa between 2004 and 2016: a cross-sectional community study.

    Science.gov (United States)

    J Visser, Maretha

    2018-06-01

    A critical component of an AIDS-free generation is to reduce HIV-related stigma. Previous research predicted that stigma would decline over time with increased contact with PLWH, understanding of the disease and availability of treatment. The aim of the research was to explore change in stigma over a 12-year period, by comparing data collected from two large cross-sectional samples from South African communities in 2004 (before the roll-out of antiretroviral treatment (ART)) and in 2016. Students recruited respondents according to criteria related to age, gender, race and area of living. A survey assessing moral judgement and interpersonal distance was used to assess personal and perceived community stigma. Responses to ten identical items used in the 2004 and 2016 data collection were compared. Personal stigma attached to HIV decreased significantly over time, except in respect of having close contact with PLWH, such as dating and befriending. Perceived community stigma remained high in all subgroups. It is argued that perceived community stigma contributes to high levels of internalised stigma among PLWH. Interventions should focus on helping PLWH to cope with perceived stigma and strategies to address stereotyping, which contributes to perceived community stigma.

  17. Blocking the benefit of group-based HIV-prevention efforts during adolescence: the problem of HIV-related stigma.

    Science.gov (United States)

    Barker, David H; Swenson, Rebecca R; Brown, Larry K; Stanton, Bonita F; Vanable, Peter A; Carey, Michael P; Valois, Robert F; Diclemente, Ralph J; Salazar, Laura F; Romer, Daniel

    2012-04-01

    HIV-related stigma has been shown to impede HIV-antibody testing and safer sexual practices in adults. Less is known about its effects on prevention programs among at-risk youth. This study examined the longitudinal relationships between HIV-stigma and HIV-knowledge following completion of a validated group-based intervention. Data were provided by 1,654 African-American adolescents who participated in a large multi-city prevention trial (Project iMPACCS). Participants were randomly assigned to an empirically-validated skill-based intervention or a general health promotion control group. Both stigma and knowledge were assessed at baseline and post-intervention. Results suggested that adolescents participating in the intervention showed improvements in knowledge and decreases in stigma when compared to controls. Improvements in stigma appeared to be partly driven by improvements in knowledge. Higher baseline stigma was shown to reduce gains in knowledge in both the treatment and control groups. Results suggest that HIV-stigma can interfere with how youth identify with and internalize messages from group-based prevention trials.

  18. The impact of HIV-related stigma on older and younger adults living with HIV disease: does age matter?

    Science.gov (United States)

    Emlet, Charles A; Brennan, David J; Brennenstuhl, Sarah; Rueda, Sergio; Hart, Trevor A; Rourke, Sean B

    2015-01-01

    The purpose of this study was to examine the independent influence of age on levels of HIV-related stigma experienced by adults living with HIV/AIDS. To accomplish this, cross-sectional data from the Ontario HIV Treatment Network Cohort Study were used to determine whether older age is associated with overall stigma among HIV-positive adults living in Ontario, Canada (n = 960). The relationship was also tested for enacted, anticipated, and internalized stigma. Covariates included sociodemographic (e.g., gender, sexual orientation, race) and psychosocial variables (e.g., depression). Modifying effects of covariates were also investigated. Those 55 and older have significantly lower overall and internalized stigma than adults under age 40, even when accounting for gender, sexual orientation, income, time since diagnosis, depression, maladaptive coping, and social support. Age does not predict enacted or Anticipated Stigma when accounting for the demographic and psychosocial variables. A significant interaction between depression and age suggests that stigma declines with age among those who are depressed but increases to age 50 and then decreases in older age groups among those who are not depressed. Age matters when it comes to understanding stigma among adults living with HIV/AIDS; however, the relationship between age and stigma is complex, varying according to stigma type and depression level.

  19. Verification of models for ballistic movement time and endpoint variability.

    Science.gov (United States)

    Lin, Ray F; Drury, Colin G

    2013-01-01

    A hand control movement is composed of several ballistic movements. The time required in performing a ballistic movement and its endpoint variability are two important properties in developing movement models. The purpose of this study was to test potential models for predicting these two properties. Twelve participants conducted ballistic movements of specific amplitudes using a drawing tablet. The measured data of movement time and endpoint variability were then used to verify the models. This study was successful with Hoffmann and Gan's movement time model (Hoffmann, 1981; Gan and Hoffmann 1988) predicting more than 90.7% data variance for 84 individual measurements. A new theoretically developed ballistic movement variability model, proved to be better than Howarth, Beggs, and Bowden's (1971) model, predicting on average 84.8% of stopping-variable error and 88.3% of aiming-variable errors. These two validated models will help build solid theoretical movement models and evaluate input devices. This article provides better models for predicting end accuracy and movement time of ballistic movements that are desirable in rapid aiming tasks, such as keying in numbers on a smart phone. The models allow better design of aiming tasks, for example button sizes on mobile phones for different user populations.

  20. Cortical plasticity as a new endpoint measurement for chronic pain

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2011-07-01

    Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

  1. A yeast screening system for simultaneously monitoring multiple genetic endpoints

    International Nuclear Information System (INIS)

    Dixon, M.L.; Mortimer, R.K.

    1986-01-01

    Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

  2. Parametric Study of Beta-Endpoint Energy in Direct Energy Converters

    Science.gov (United States)

    2007-01-01

    value to the endpoint energy of nickel-63 ( Ni63 ), whose endpoint energy is 66 keV. Only an approximation is sought. Nickel-63 is an easily...is known to vary from Sr90’s spectrum, where instead of peaking at approximately one third of the endpoint energy, the peak of Ni63 ’s output spectrum

  3. How "humane" is your endpoint? Refining the science-driven approach for termination of animal studies of chronic infection.

    OpenAIRE

    Nuno H Franco; Margarida Correia-Neves; I Anna S Olsson

    2012-01-01

    Public concern on issues such as animal welfare or the scientific validity and clinical value of animal research is growing, resulting in increasing regulatory demands for animal research. Abiding to the most stringent animal welfare standards, while having scientific objectives as the main priority, is often challenging. To do so, endpoints of studies involving severe, progressive diseases need to be established considering how early in the disease process the scientific objectives can be ac...

  4. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

    Science.gov (United States)

    Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-07-13

    To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living

  5. Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy

    International Nuclear Information System (INIS)

    Song, Ting; Zhou, Linghong; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Jiang, Steve B; Gu, Xuejun

    2015-01-01

    In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient’s unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient’s geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control. (paper)

  6. 'Triply cursed': racism, homophobia and HIV-related stigma are barriers to regular HIV testing, treatment adherence and disclosure among young Black gay men.

    Science.gov (United States)

    Arnold, Emily A; Rebchook, Gregory M; Kegeles, Susan M

    2014-06-01

    In the USA, young Black gay men are disproportionately impacted upon by HIV. In this qualitative study consisting of in-depth interviews with 31 young Black gay men and nine service providers, where we used thematic analysis to guide our interpretations, we found that HIV-related stigma and homophobia, within the larger societal context of racism, were related to sexual risk behaviour, reluctance to obtain HIV testing or care, lower adherence to treatment medication, and non-disclosure of a positive HIV status to sexual partners. Participants experienced homophobia and HIV-related stigma from churches and families within the Black community and from friends within the Black gay community, which otherwise provide support in the face of racism. Vulnerability to HIV was related to strategies that young Black gay men enacted to avoid being stigmatised or as a way of coping with alienation and rejection.

  7. “Triply cursed”: Racism, homophobia, and HIV-related stigma are barriers to regular HIV testing, treatment adherence, and disclosure among young Black gay men

    Science.gov (United States)

    Arnold, Emily A.; Rebchook, Gregory M.; Kegeles, Susan M.

    2014-01-01

    In the USA, young Black gay men are disproportionately impacted by HIV. In this qualitative study consisting of in-depth interviews with 31 young Black gay men and 9 service providers, where we used thematic analysis to guide our interpretations, we found that HIV-related stigma and homophobia, within the larger societal context of racism, were related to sexual risk behaviour, reluctance to obtain HIV testing or care, lower adherence to treatment medication, and disclosure of a positive HIV status to sexual partners. Participants experienced homophobia and HIV-related stigma from churches and families within the Black community, and from friends within the Black gay community, that otherwise provide support in the face of racism. Vulnerability to HIV was related to strategies that young Black gay men enacted to avoid being stigmatised or as a way of coping with their alienation and rejection. PMID:24784224

  8. Low dose response analysis through a cytogenetic end-point

    International Nuclear Information System (INIS)

    Bojtor, I.; Koeteles, G.J.

    1998-01-01

    The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

  9. Hausdorff dimension of exponential parameter rays and their endpoints

    International Nuclear Information System (INIS)

    Bailesteanu, Mihai; Balan, Horia Vlad; Schleicher, Dierk

    2008-01-01

    We investigate the set I of parameters κ for which the singular value of z map e z + κ converges to ∞. The set I consists of uncountably many parameter rays, plus landing points of some of these rays (Förster et al 2008 Proc Am. Math. Soc. 136 at press (Preprint math.DS/0311427)). We show that the parameter rays have Hausdorff dimension 1, which implies (Qiu 1994 Acta Math. Sin. (N.S.) 10 362–8) that the ray endpoints in I alone have dimension 2. Analogous results were known for dynamical planes of exponential maps (Karpińska 1999 C. R. Acad. Sci. Paris Sér. I: Math. 328 1039–44; Schleicher and Zimmer 2003 J. Lond. Math. Soc. 67 380–400); our result shows that this also holds in parameter space

  10. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  11. Cryptosporidium and other intestinal parasitic infections among HIV patients in southern Ethiopia: significance of improved HIV-related care.

    Science.gov (United States)

    Shimelis, Techalew; Tassachew, Yayehyirad; Lambiyo, Tariku

    2016-05-10

    Intestinal parasitic infections are known to cause gastroenteritis, leading to higher morbidity and mortality, particularly in people living with HIV/AIDS. This study aimed to determine the prevalence of Cryptosporidium and other intestinal parasitic infections among HIV patients receiving care at a hospital in Ethiopia where previous available baseline data helps assess if improved HIV-related care has reduced infection rates. A cross-sectional study was conducted at Hawassa University Hospital in southern Ethiopia from May, 2013 to March, 2014. A consecutive sample of 491 HIV- infected patients with diarrhea or a CD4 T cell count intestinal parasites. The study was approved by the Institutional Review Board of the College of Medicine and Health Sciences, Hawassa University. Physicians managed participants found to be infected with any pathogenic intestinal parasite. The overall prevalence of intestinal parasitic infections among the study population was 35.8 %. The most prevalent parasites were Cryptosporidium (13.2 %), followed by Entamoeba histolytica/dispar (10.2 %), and Giardia lamblia (7.9 %). The rate of single and multiple infections were 25.5 and 10.3 %, respectively. Patients with a CD4 T cell count intestinal parasitic infection or cryptosporidiosis compared to those with counts ≥ 200 cells/μl, but with some type of diarrhea. The study shows high prevalence of intestinal parasitic infections in the study population. However, the results in the current report are significantly lower compared to previous findings in the same hospital. The observed lower infection rate is encouraging and supports the need to strengthen and sustain the existing intervention measures in order to further reduce intestinal parasitic infections in people living with HIV/AIDS.

  12. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    OpenAIRE

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the ...

  13. Influence of religious affiliation and education on HIV knowledge and HIV-related sexual behaviors among unmarried youth in rural central Mozambique.

    Science.gov (United States)

    Noden, Bruce H; Gomes, Aurelio; Ferreira, Aldina

    2010-10-01

    The interactions between religious affiliation, education, HIV knowledge, and HIV-related sexual behaviors among African church youth are poorly understood. In this socio-demographic study, 522 unmarried youth 12-28 years old in rural central Mozambique were surveyed with a structured questionnaire. Using binary logistic regression analysis, we used religious affiliation and education to measure influence on (1) HIV transmission and prevention knowledge and attitudes and (2) HIV-related sexual behaviors among youth. Religiously affiliated males were more likely than non-religious males to know when a condom should be used, respond correctly to HIV transmission questions and respond with less stigma to HIV-related scenarios. Increased levels of education among males corresponded significantly to increased knowledge of condom usage and HIV prevention strategies and less likelihood to respond with stigma. Only education levels influenced young female responses. Religious affiliation and education had minimal effects on sexual activity, condom usage, and multiple partnerships. African Independent Church/Zionist males were 1.6 times more likely to be sexually inexperienced than non-religious males but were also significantly less likely to use condoms (0.23, p=0.024). Non-religious youth were most likely to have visited sex workers and did not use condoms. These results suggest that religious affiliation, possibly as the result of educational opportunities afforded by religious-affiliated schools, is contributing to increased HIV transmission and prevention knowledge among youth in rural Central Mozambique but not influencing HIV-related sexual behavior. The need exists to strengthen the capacity of religious congregations to teach about HIV/AIDS and target non-religious youth with HIV transmission and prevention information.

  14. HIV-related stigma and self-disclosure: the mediating and moderating role of anticipated discrimination among people living with HIV/AIDS in Akure Nigeria.

    Science.gov (United States)

    Olley, B O; Ogunde, M J; Oso, P O; Ishola, A

    2016-01-01

    Although links between HIV-related stigma and self-disclosure of HIV status among people living with HIV have been well established, it is unclear whether levels of perceived discrimination are differentially associated with self-disclosure. The present study using a multi-factorial survey design investigated the role of stigma and other self-related factors (e.g., anticipated discrimination, self-esteem, HIV-related factors [e.g., drug use combination; knowledge of duration of HIV diagnosis] and socio-demographic factors [e.g., multiple spouse; age, gender, educational level] and psychological distress [depression]) in self-disclosure among People living with HIV/AIDs has been added (PLWHA) on follow-up management in State Specialist Hospital Akure, Nigeria. One hundred and thirty nine HIV/AIDS patients (49 males and 90 females) participated in the study. Mean age and mean time in months since diagnosis were 39.56 ± 10.26 and 37.78 ± 48.34, respectively. Four variables: multiple spouse, anticipated discrimination, HIV-related stigma and self-esteem were related to self-disclosure at (p discrimination mediated the relationship between self-esteem (Sobel test: z = 2.09, Aroian = 2.06, p  .05, self-esteem t (5, 137) = .59, p > .05 and anticipated discrimination were non-significant, suggesting a non-moderation effect of discrimination and disclosure. The results indicate that anticipated discrimination may impact HIV-related stigma to reduce self-disclosure among the PLWHAs in Akure, Nigeria. Interventions should incorporate anticipated discrimination in educational programs of HIV stigma in encouraging self-disclosure among PLWHAs.

  15. Exploring HIV-related stigma among HIV-infected men who have sex with men in Beijing, China: a correlation study.

    Science.gov (United States)

    Li, Zhen; Hsieh, Evelyn; Morano, Jamie P; Sheng, Yu

    2016-11-01

    Human immunodeficiency virus (HIV)-related stigma among HIV-infected men who have sex with men (MSM) has been associated with adverse health outcomes, including poor adherence to antiretroviral therapy and care, and increased participation in behaviors linked to higher rates of HIV transmission. In China, the incidence of HIV is growing more rapidly among MSM than among other subgroups. This study characterizes and quantifies HIV stigma among HIV-infected MSM in Beijing, China, which arguably may be driving this epidemic. A cross-sectional survey study was performed among 266 HIV-positive MSM in Beijing, China, in 2014. The Berger HIV Stigma Scale was used to measure levels of HIV-related stigma. Participants additionally answered questions regarding socio-demographic characteristics and HIV-associated risk factors; previously validated Mandarin-language scales assessed depression, coping style, and social support networks. Multivariable linear regression models were used to identify variables significantly associated with HIV stigma. The mean overall HIV stigma score among the study population was 112.78 ± 18.11 (score range: 40-160). Higher HIV stigma scores were positively associated with depression (β = 7.99, 95% CI:3.69, 12.29, p stigma. The results of this study can inform the development of culturally sensitive interventions to reduce HIV-related stigma among MSM with HIV in China, with the overarching goal of reducing HIV transmission in this vulnerable population.

  16. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    International Nuclear Information System (INIS)

    Andronikou, Savvas; Ackermann, Christelle; Laughton, Barbara; Cotton, Mark; Tomazos, Nicollette; Spottiswoode, Bruce; Mauff, Katya; Pettifor, John M.

    2015-01-01

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  17. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa); Ackermann, Christelle [University of Stellenbosch, Department of Radiology, Stellenbosch (South Africa); Laughton, Barbara; Cotton, Mark [Stellenbosch University and Tygerberg Children' s Hospital, Children' s Infectious Diseases Research Unit, Stellenbosch (South Africa); Tomazos, Nicollette [University of Cape Town, Faculty of Commerce, Department of Management Studies, Cape Town (South Africa); Spottiswoode, Bruce [University of Cape Town, MRC/UCT Medical Imaging Research Unit, Department of Human Biology, Cape Town (South Africa); Mauff, Katya [University of Cape Town, Department of Statistical Sciences, Cape Town (South Africa); Pettifor, John M. [University of the Witwatersrand, MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, Witwatersrand (South Africa)

    2015-07-15

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  18. HIV-related stigma and optimism as predictors of anxiety and depression among HIV-positive men who have sex with men in the United Kingdom and Ireland.

    Science.gov (United States)

    Murphy, Patrick J; Garrido-Hernansaiz, Helena; Mulcahy, Fiona; Hevey, David

    2018-03-01

    This study investigated the associations between forms of HIV-related optimism, HIV-related stigma, and anxiety and depression among HIV-positive men who have sex with men (MSM) in the United Kingdom and Ireland. HIV health optimism (HHO) and HIV transmission optimism (HTO) were hypothesised to be protective factors for anxiety and depression, while the components of HIV-related stigma (enacted stigma, disclosure concerns, concern with public attitudes, and internalised stigma) were hypothesised to be risk factors. Data were collected from 278 HIV-positive MSM using an online questionnaire. The prevalence of psychological distress was high, with close to half (48.9%) of all participants reporting symptoms of anxiety, and more than half (57.9%) reporting symptoms of depression. Multiple linear regressions revealed that both anxiety and depression were positively predicted by internalised stigma and enacted stigma, and negatively predicted by HHO. For both anxiety and depression, internalised stigma was the strongest and most significant predictor. The results highlight the continued psychological burden associated with HIV infection among MSM, even as community support services are being defunded across the United Kingdom and Ireland. The results point to the need for clinicians and policy makers to implement stigma reduction interventions among this population.

  19. Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.

    Science.gov (United States)

    Lambert, Thomas; Nahler, Alexander; Rohla, Miklos; Reiter, Christian; Grund, Michael; Kammler, Jürgen; Blessberger, Hermann; Kypta, Alexander; Kellermair, Jörg; Schwarz, Stefan; Starnawski, Jennifer A; Lichtenauer, Michael; Weiss, Thomas W; Huber, Kurt; Steinwender, Clemens

    2016-10-01

    Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. A comparison of height and weight velocity as a part of the composite endpoint in pediatric HIV.

    Science.gov (United States)

    Benjamin, Daniel K; Miller, Wiliam C; Benjamin, Daniel K; Ryder, Robert W; Weber, David J; Walter, Emmanuel; McKinney, Ross E

    2003-11-07

    HIV adversely affects growth in children. Pediatric AIDS Clinical Trial Group (PACTG) protocols often use weight velocity [changes in weight z-score for age (WAZ)] as a part of the composite endpoint for phase II and III clinical trials. However, WAZ and height velocity (HAZ) have not been critically compared for their utility as part of the composite endpoint. HAZ and WAZ were compared to predict laboratory and clinical progression of HIV in a retrospective cohort study of HIV-infected children with data from PACTG Protocol 300. In both bivariable and multivariable analyses, changes in HAZ were more closely linked to subsequent progression than WAZ. Children with improved HAZ were somewhat less likely to exhibit virological failure [odds ratio (OR), 0.76; 95% confidence interval (CI) 0.51-1.14], than children with improved WAZ (OR, 1.45; 95% CI, 0.99,2.11). Children who had improved HAZ were less likely to exhibit immunological failure (OR, 0.7; 95% CI, 0.49-1.00), than children with improved WAZ (OR, 1.13; 95% CI, 0.82-1.57). Children who had improved HAZ were less likely to have other forms of clinical progression of HIV (OR, 0.55; 95% CI, 0.31-0.99), than children who had improved WAZ (OR, 1.0; 95% CI, 1.58-1.94). Increases in HAZ were associated with reduced risk of subsequent clinical progression and subsequent immune reconstitution and weakly associated with declines in HIV RNA. Changes in WAZ were not associated with laboratory outcomes relevant to pediatric HIV infection. Height velocity should be considered as a component of a composite clinical endpoint in future PACTG trials.

  1. Patient-reported outcomes in insomnia: development of a conceptual framework and endpoint model.

    Science.gov (United States)

    Kleinman, Leah; Buysse, Daniel J; Harding, Gale; Lichstein, Kenneth; Kalsekar, Anupama; Roth, Thomas

    2013-01-01

    This article describes qualitative research conducted with patients with clinical diagnoses of insomnia and focuses on the development of a conceptual framework and endpoint model that identifies a hierarchy and interrelationships of potential outcomes in insomnia research. Focus groups were convened to discuss how patients experience insomnia and to generate items for patient-reported questionnaires on insomnia and associated daytime consequences. Results for the focus group produced two conceptual frameworks: one for sleep and one for daytime impairment. Each conceptual framework consists of hypothesized domains and items in each domain based on patient language taken from the focus group. These item pools may ultimately serve as a basis to develop new questionnaires to assess insomnia.

  2. Prevalence and predictors of HIV-related stigma among institutional- and community-based caregivers of orphans and vulnerable children living in five less-wealthy countries

    Directory of Open Access Journals (Sweden)

    Messer Lynne C

    2010-08-01

    Full Text Available Abstract Background In the face of the HIV/AIDS epidemic that has contributed to the dramatic increase in orphans and abandoned children (OAC worldwide, caregiver attitudes about HIV, and HIV-related stigma, are two attributes that may affect caregiving. Little research has considered the relationship between caregiver attributes and caregiver-reported HIV-related stigma. In light of the paucity of this literature, this paper will describe HIV-related stigma among caregivers of OAC in five less wealthy nations. Methods Baseline data were collected between May 2006 through February 2008. The sample included 1,480 community-based and 192 institution-based caregivers. Characteristics of the community-based and institution-based caregivers are described using means and standard deviations for continuous variables or counts and percentages for categorical variables. We fit logistic regression models, both for the full sample and separately for community-based and institution-based caregivers, to explore predictors of acceptance of HIV. Results Approximately 80% of both community-based and institution-based caregivers were female; and 84% of institution-based caregivers, compared to 66% of community-based caregivers, said that they would be willing to care for a relative with HIV. Similar proportions were reported when caregivers were asked if they were willing to let their child play with an HIV-infected child. In a multivariable model predicting willingness to care for an HIV-infected relative, adjusted for site fixed effects, being an institution-based caregiver was associated with greater willingness (less stigma than community-based caregivers. Decreased willingness was reported by older respondents, while willingness increased with greater formal education. In the adjusted models predicting willingness to allow one's child to play with an HIV-infected child, female gender and older age was associated with less willingness. However, willingness

  3. The role of HIV-related stigma in utilization of skilled childbirth services in rural Kenya: a prospective mixed-methods study.

    Directory of Open Access Journals (Sweden)

    Janet M Turan

    Full Text Available Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.From 2007-2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598; 411 (69% were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48 aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22-0.88.Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of

  4. The role of HIV-related stigma in utilization of skilled childbirth services in rural Kenya: a prospective mixed-methods study.

    Science.gov (United States)

    Turan, Janet M; Hatcher, Abigail H; Medema-Wijnveen, José; Onono, Maricianah; Miller, Suellen; Bukusi, Elizabeth A; Turan, Bulent; Cohen, Craig R

    2012-01-01

    Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services. From 2007-2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22-0.88). Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among

  5. Depressive Symptoms, Disclosure, HIV-Related Stigma, and Coping Following HIV Testing Among Outpatients in Uganda: A Daily Process Analysis.

    Science.gov (United States)

    Kiene, Susan M; Dove, Meredith; Wanyenze, Rhoda K

    2018-05-01

    As efforts to end the HIV epidemic accelerate there is emphasis on reaching those living with undiagnosed HIV infection. Newly diagnosed individuals face a number of psychosocial challenges, yet we know little about depressive symptoms in the weeks immediately following diagnosis and how disclosure, coping, and other factors may affect short and longer-term depressive symptoms. Purposively sampled Ugandan outpatients completed structured interviews immediately prior to testing for HIV, daily for 28 days after receiving their test results, and at 3 and 6 months post-test. The sample included a total of 244 participants: 20 who tested HIV positive at baseline and who provided 342 daily data points, and 224 who tested HIV negative at baseline and who provided 4388 daily data points. We used linear mixed effects modeling to examine changes in depressive symptom scores over the 28 day daily interview period and predictors of depressive symptom scores and changes over time. Results from the mixed modeling revealed that while those diagnosed with HIV showed initially high depressive symptoms following diagnosis, their symptoms decreased significantly and on average fell below the cutoff for possible depression approximately 15 days after diagnosis. Among those who tested HIV-negative, on average their depressive symptoms were below the cutoff for possible depression and did not change over time. Among those diagnosed with HIV, disclosure, especially to a partner, on a particular day was associated with higher depressive symptoms that day. However, those who disclosed to their partner during the 28 days after diagnosis had significantly lower depression scores by the end of the 28 days as well as lower depression scores 3 and 6 months after diagnosis than did those who did not disclose to their partner during the 28 days after diagnosis. Scoring higher on HIV-related stigma on a particular day was associated with higher depressive symptoms that day and engaging

  6. The Use of Female Sex Workers Among Men in Nepal: Prevalence, STIs/HIV-Related Risk Behaviors, and Gender Ideology

    Science.gov (United States)

    Shrestha, Roman; Karki, Pramila; Copenhaver, Michael

    2016-01-01

    Heterosexual sex involving female sex workers (FSWs) is widely documented for its role in facilitating the spread of sexually transmitted infections (STIs)/HIV. Critical to such studies, and increasingly considered essential to HIV prevention efforts, is the gender constructs and power dynamics within relationships. However, little efforts have been made, which focus on male clients of FSWs, particularly on the relationship between gender ideologies and men’s sexual contact with FSWs, within the Nepali context. The present study aims to fill this critical gap by assessing the prevalence of use of FSWs and its association with STIs/HIV-related risk behaviors and gender ideologies among Nepali men. We used data from the nationally representative Nepal Demographic Health Survey (NDHS) 2011. For the purpose of analyses, we included a sample of 4,121 men, aged 15–49 years. During data analyses, we used multivariate logistic regression models, adjusted for the following variables: age, region, residence, religion, educational level, wealth index, employment status, and cigarette smoking status. Of the total sample, approximately 5% reported the use of FSWs in their lifetime. In regression models, men who had sex with FSWs were more likely to report a history of STIs [adjusted odds ratio (aOR): 3.03; 95% confidence interval (CI): 1.69–5.43; P < 0.001], not using condom all the time (aOR: 1.31; 95% CI: 1.05–2.12; P = 0.010), more than one sexual partner (aOR: 3.75; 95% CI: 2.18–5.23; P < 0.001), and have had early sexual debut (aOR: 2.60; 95% CI: 1.85–3.67; P < 0.001). Respondents reporting the endorsement of violence against wives (aOR: 1.65; 95% CI: 1.01–2.84; P = 0.04) and male sexual entitlement (aOR: 1.63; 95% CI: 1.21–2.32; P = 0.001) were significantly more likely to report sexual contact with FSWs. Our findings highlight the need to develop and implement specifically tailored interventions toward male clients of FSWs, with a particular emphasis on

  7. The Use of Female Sex Workers Among Men in Nepal: Prevalence, STIs/HIV-Related Risk Behaviors, and Gender Ideology.

    Science.gov (United States)

    Shrestha, Roman; Karki, Pramila; Copenhaver, Michael

    Heterosexual sex involving female sex workers (FSWs) is widely documented for its role in facilitating the spread of sexually transmitted infections (STIs)/HIV. Critical to such studies, and increasingly considered essential to HIV prevention efforts, is the gender constructs and power dynamics within relationships. However, little efforts have been made, which focus on male clients of FSWs, particularly on the relationship between gender ideologies and men's sexual contact with FSWs, within the Nepali context. The present study aims to fill this critical gap by assessing the prevalence of use of FSWs and its association with STIs/HIV-related risk behaviors and gender ideologies among Nepali men. We used data from the nationally representative Nepal Demographic Health Survey (NDHS) 2011. For the purpose of analyses, we included a sample of 4,121 men, aged 15-49 years. During data analyses, we used multivariate logistic regression models, adjusted for the following variables: age, region, residence, religion, educational level, wealth index, employment status, and cigarette smoking status. Of the total sample, approximately 5% reported the use of FSWs in their lifetime. In regression models, men who had sex with FSWs were more likely to report a history of STIs [adjusted odds ratio (aOR): 3.03; 95% confidence interval (CI): 1.69-5.43; P < 0.001], not using condom all the time (aOR: 1.31; 95% CI: 1.05-2.12; P = 0.010), more than one sexual partner (aOR: 3.75; 95% CI: 2.18-5.23; P < 0.001), and have had early sexual debut (aOR: 2.60; 95% CI: 1.85-3.67; P < 0.001). Respondents reporting the endorsement of violence against wives (aOR: 1.65; 95% CI: 1.01-2.84; P = 0.04) and male sexual entitlement (aOR: 1.63; 95% CI: 1.21-2.32; P = 0.001) were significantly more likely to report sexual contact with FSWs. Our findings highlight the need to develop and implement specifically tailored interventions toward male clients of FSWs, with a particular emphasis on promoting

  8. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    Science.gov (United States)

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

  9. Inconsistent selection and definition of local and regional endpoints in breast cancer research.

    Science.gov (United States)

    Moossdorff, M; van Roozendaal, L M; Schipper, R-J; Strobbe, L J A; Voogd, A C; Tjan-Heijnen, V C G; Smidt, M L

    2014-12-01

    Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  10. Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.

    Science.gov (United States)

    Tapia, Milagritos D; Armah, George; Breiman, Robert F; Dallas, Michael J; Lewis, Kristen D C; Sow, Samba O; Rivers, Stephen B; Levine, Myron M; Laserson, Kayla F; Feikin, Daniel R; Victor, John C; Ciarlet, Max; Neuzil, Kathleen M; Steele, A Duncan

    2012-04-27

    The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Sensitive endpoints in extended one-generation reproductive toxicity study versus two generation?

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    . The protocol includes assessment of novel endpoints of concern and developmental landmarks such as anogenital distance, nipple retention (both sensitive endpoints for anti-androgenic effects in male offspring) and mammary gland development (sensitive endpoint for oestrogen action) and may also include...... during critical period of development in contrast to the parental generation. Retrospective analysis of available two-generation studies, however, indicate that the assessment included in the study of other endpoints in the male offspring such as histopathology of reproductive organs and semen quality...

  12. Exposure to pornographic videos and its effect on HIV-related sexual risk behaviours among male migrant workers in southern India.

    Science.gov (United States)

    Mahapatra, Bidhubhusan; Saggurti, Niranjan

    2014-01-01

    Research on pornography and its association with HIV-related sexual behaviours is limited in India. This study aims to examine the prevalence and correlates of viewing pornographic videos and examine its associations with HIV-related sexual risk behaviours among male migrant workers in India. Data were drawn from a cross-sectional survey conducted in 2007-08 across 21 districts in four states of India. Respondents included 11,219 male migrants aged 18 years or older, who had migrated to at least two places in the past two years for work. Bivariate and multivariate methods were used to examine the association between viewing pornography and HIV-related sexual risk behaviours. Two-fifths (40%) of the migrants had viewed pornographic videos in one month prior to the survey. Migrants aged 25-29 years, literate, unmarried and away from native village for more than five years were more likely to view pornography than their counterparts. Migrants who viewed pornographic videos were more likely to engage in paid (Adjusted odds ratio [AOR]: 4.2, 95% confidence interval [CI]: 3.7-4.8) and unpaid sex (AOR: 4.2, 95% CI: 3.7-4.7), report inconsistent condom use in paid sex (AOR: 2.3, 95% CI: 1.7-3.0) and experience STI-like symptoms (AOR: 1.7, 95% CI: 1.5-1.8) than their counterparts. The findings regarding migrants' exposure to pornography and its linkage with high HIV risk behaviour suggest that the HIV prevention programmes for migrants need to be more innovative to communicate on the negative-effects of viewing pornography. More importantly, programmes need to find alternative ways to engage migrants in infotainment activities during their leisure time in an effort to reduce their exposure to pornographic videos as well as risky sexual behaviours.

  13. Exposure to pornographic videos and its effect on HIV-related sexual risk behaviours among male migrant workers in southern India.

    Directory of Open Access Journals (Sweden)

    Bidhubhusan Mahapatra

    Full Text Available OBJECTIVE: Research on pornography and its association with HIV-related sexual behaviours is limited in India. This study aims to examine the prevalence and correlates of viewing pornographic videos and examine its associations with HIV-related sexual risk behaviours among male migrant workers in India. METHODS: Data were drawn from a cross-sectional survey conducted in 2007-08 across 21 districts in four states of India. Respondents included 11,219 male migrants aged 18 years or older, who had migrated to at least two places in the past two years for work. Bivariate and multivariate methods were used to examine the association between viewing pornography and HIV-related sexual risk behaviours. RESULTS: Two-fifths (40% of the migrants had viewed pornographic videos in one month prior to the survey. Migrants aged 25-29 years, literate, unmarried and away from native village for more than five years were more likely to view pornography than their counterparts. Migrants who viewed pornographic videos were more likely to engage in paid (Adjusted odds ratio [AOR]: 4.2, 95% confidence interval [CI]: 3.7-4.8 and unpaid sex (AOR: 4.2, 95% CI: 3.7-4.7, report inconsistent condom use in paid sex (AOR: 2.3, 95% CI: 1.7-3.0 and experience STI-like symptoms (AOR: 1.7, 95% CI: 1.5-1.8 than their counterparts. CONCLUSIONS: The findings regarding migrants' exposure to pornography and its linkage with high HIV risk behaviour suggest that the HIV prevention programmes for migrants need to be more innovative to communicate on the negative-effects of viewing pornography. More importantly, programmes need to find alternative ways to engage migrants in infotainment activities during their leisure time in an effort to reduce their exposure to pornographic videos as well as risky sexual behaviours.

  14. Will a quadruple multiplexed point-of-care screening strategy for HIV-related co-infections be feasible and impact detection of new co-infections in at-risk populations? Results from cross-sectional studies.

    Science.gov (United States)

    Pai, Nitika Pant; Dhurat, Rachita; Potter, Martin; Behlim, Tarannum; Landry, Geneviève; Vadnais, Caroline; Rodrigues, Camilla; Joseph, Lawrence; Shetty, Anjali

    2014-12-15

    Multiplexed point-of-care (POC) devices can rapidly screen for HIV-related co-infections (eg, hepatitis C (HCV), hepatitis B (HBV), syphilis) in one patient visit, but global evidence for this approach remains limited. This study aimed to evaluate a multiplex POC testing strategy to expedite screening for HIV-related co-infections in at-risk populations. A multiplex strategy was developed with two subsequent versions of an investigational device Miriad. It was evaluated in two non-comparable settings and populations in two countries for feasibility of conduct, detection of new infections, preference and accuracy. Version 1 was evaluated in 375 sexually transmitted disease clinic attendees in Mumbai, India; version 2 was evaluated in 119 injection drug users in Montreal, Canada. Feasibility (completion rate) of the multiplex strategy was high (86.1% Mumbai; 92.4% Montreal). A total of 170 new infections were detected in Mumbai (56 HIV, 75 HBV, 37 syphilis, 2 HCV) versus 2 in Montreal. Preference was 60% in Mumbai and 97% in Montreal. Miriad version 1 specificities were high: HIV 99.7% (98.3% to 100%), HBV 99.3% (97.6% to 99.9%), HCV 99.7% (98.5% to 99.9%), syphilis 85.2% (80.9% to 88.8%); sensitivities were as follows: HIV 100% (94.8% to 100%), HBV 13.3% (6.6% to 23.2%), HCV 50% (1.3% to 98.7%), syphilis 86.1% (70.5% to 95.3%). With version 2, specificities improved: HIV 100% (97.2% to 100%), HBV 100% (97.3% to 100%), HCV 85.3% (73.8% to 93.0%), syphilis 98.1% (93.3% to 99.8%); sensitivities were: HIV 100% (47.3% to 100%), HCV 80.4% (66.1% to 90.6%), syphilis 100% (22.4% to 100%). A quad multiplex POC strategy for HIV and co-infections was feasible to operationalise and preferred by patients in both settings. Many new infections were identified in Mumbai and accuracy improved with version 2 of the assay. Such a strategy will help expedite screening for co-infections, particularly where baseline screening is low. These findings are valuable to practitioners

  15. Right-handed currents at B→ K l+l− kinematic endpoint

    Indian Academy of Sciences (India)

    2017-10-09

    Oct 9, 2017 ... The recent LHCb measured values of these observables are used to conclude an evidence of right-handed currents at the kinematic endpoint of this decay mode. As the conclusion is drawn at the maximum dilepton invariant mass square ( q 2 ) kinematic endpoint, it relies only on heavy quark symmetries ...

  16. Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

  17. Restoration for the future: endpoints, targets, and indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo. Schweitzer

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

  18. OPERA models for predicting physicochemical properties and environmental fate endpoints.

    Science.gov (United States)

    Mansouri, Kamel; Grulke, Chris M; Judson, Richard S; Williams, Antony J

    2018-03-08

    The collection of chemical structure information and associated experimental data for quantitative structure-activity/property relationship (QSAR/QSPR) modeling is facilitated by an increasing number of public databases containing large amounts of useful data. However, the performance of QSAR models highly depends on the quality of the data and modeling methodology used. This study aims to develop robust QSAR/QSPR models for chemical properties of environmental interest that can be used for regulatory purposes. This study primarily uses data from the publicly available PHYSPROP database consisting of a set of 13 common physicochemical and environmental fate properties. These datasets have undergone extensive curation using an automated workflow to select only high-quality data, and the chemical structures were standardized prior to calculation of the molecular descriptors. The modeling procedure was developed based on the five Organization for Economic Cooperation and Development (OECD) principles for QSAR models. A weighted k-nearest neighbor approach was adopted using a minimum number of required descriptors calculated using PaDEL, an open-source software. The genetic algorithms selected only the most pertinent and mechanistically interpretable descriptors (2-15, with an average of 11 descriptors). The sizes of the modeled datasets varied from 150 chemicals for biodegradability half-life to 14,050 chemicals for logP, with an average of 3222 chemicals across all endpoints. The optimal models were built on randomly selected training sets (75%) and validated using fivefold cross-validation (CV) and test sets (25%). The CV Q 2 of the models varied from 0.72 to 0.95, with an average of 0.86 and an R 2 test value from 0.71 to 0.96, with an average of 0.82. Modeling and performance details are described in QSAR model reporting format and were validated by the European Commission's Joint Research Center to be OECD compliant. All models are freely available as an open

  19. Defining the end-point of mastication: A conceptual model.

    Science.gov (United States)

    Gray-Stuart, Eli M; Jones, Jim R; Bronlund, John E

    2017-10-01

    properties define the end-point texture and enduring sensory perception of the food. © 2017 Wiley Periodicals, Inc.

  20. A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guozhu, E-mail: gzhang6@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Roell, Kyle R., E-mail: krroell@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Truong, Lisa, E-mail: lisa.truong@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Reif, David M., E-mail: dmreif@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC (United States)

    2017-01-01

    Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

  1. Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint

    International Nuclear Information System (INIS)

    Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

    2015-01-01

    The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L −1 , which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. - Highlights: • Ecotoxicological effect of exposure to copper was tested on a customized ecosystem. • Equilibrium point of biomasses in the customized ecosystem was used as an endpoint. • Exposure–response relationship in a community level was built on equilibrium point. • A threshold concentration incorporating ecological interactions was derived. - The equilibrium biomass incorporating ecological interactions in a customized ecosystem was used as an endpoint to calculate the threshold concentration at a community level

  2. A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring.

    Science.gov (United States)

    Lewandowski, Robert J; Wang, Dingxin; Gehl, James; Atassi, Bassel; Ryu, Robert K; Sato, Kent; Nemcek, Albert A; Miller, Frank H; Mulcahy, Mary F; Kulik, Laura; Larson, Andrew C; Salem, Riad; Omary, Reed A

    2007-10-01

    Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable liver cancer. This study was conducted to test the hypothesis that angiographic endpoints during TACE are measurable and reproducible by comparing subjective angiographic versus objective magnetic resonance (MR) endpoints of TACE. The study included 12 consecutive patients who presented for TACE for surgically unresectable HCC or progressive hepatic metastases despite chemotherapy. All procedures were performed with a dedicated imaging system. Angiographic series before and after TACE were reviewed independently by three board-certified interventional radiologists. A subjective angiographic chemoembolization endpoint (SACE) classification scheme, modified from an established angiographic grading system in the cardiology literature, was designed to assist in reproducibly classifying angiographic endpoints. Reproducibility in SACE classification level was compared among operators, and MR imaging perfusion reduction was compared with SACE levels for each observer. Twelve patients successfully underwent 15 separate TACE sessions. SACE levels ranged from I through IV. There was moderate agreement in SACE classification (kappa = 0.46 +/- 0.12). There was no correlation between SACE level and MR perfusion reduction (r = 0.16 for one operator and 0.02 for the other two). Angiographic endpoints during TACE vary widely, have moderate reproducibility among operators, and do not correlate with functional MR imaging perfusion endpoints. Future research should aim to determine ideal angiographic and functional MR imaging endpoints for TACE according to outcome measures such as imaging response, pathologic response, and survival.

  3. A Moderated Mediation Model of HIV-Related Stigma, Depression, and Social Support on Health-Related Quality of Life among Incarcerated Malaysian Men with HIV and Opioid Dependence.

    Science.gov (United States)

    Shrestha, Roman; Copenhaver, Michael; Bazazi, Alexander R; Huedo-Medina, Tania B; Krishnan, Archana; Altice, Frederick L

    2017-04-01

    Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support. Incarcerated HIV-infected men with opioid dependence (N = 301) were recruited from the HIV units in Kajang prison in Malaysia. Participants completed surveys assessing demographic characteristics, HIV-related stigma, depression, social support, and HRQoL. Results showed that the effect of HIV-related stigma on HRQoL was mediated via depression (a1:β = 0.1463, p depression was negatively associated with HRQOL (β = -0.0317, p = 0.0133). This indicated that the predicted influence of HIV-related stigma on HRQoL via depression had negative effect on HRQoL for individuals with low social support. The results suggest that social support can buffer the negative impact of depression on HRQoL and highlights the need for future interventions to target these psychosocial factors in order to improve HRQoL among incarcerated PLH.

  4. The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

    Science.gov (United States)

    Lassere, Marissa N

    2008-06-01

    There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

  5. A step towards standardization: A method for end-point titer determination by fluorescence index of an automated microscope. End-point titer determination by fluorescence index.

    Science.gov (United States)

    Carbone, Teresa; Gilio, Michele; Padula, Maria Carmela; Tramontano, Giuseppina; D'Angelo, Salvatore; Pafundi, Vito

    2018-05-01

    Indirect Immunofluorescence (IIF) is widely considered the Gold Standard for Antinuclear Antibody (ANA) screening. However, the high inter-reader variability remains the major disadvantage associated with ANA testing and the main reason for the increasing demand of the computer-aided immunofluorescence microscope. Previous studies proposed the quantification of the fluorescence intensity as an alternative for the classical end-point titer evaluation. However, the different distribution of bright/dark light linked to the nature of the self-antigen and its location in the cells result in different mean fluorescence intensities. The aim of the present study was to correlate Fluorescence Index (F.I.) with end-point titers for each well-defined ANA pattern. Routine serum samples were screened for ANA testing on HEp-2000 cells using Immuno Concepts Image Navigator System, and positive samples were serially diluted to assign the end-point titer. A comparison between F.I. and end-point titers related to 10 different staining patterns was made. According to our analysis, good technical performance of F.I. (97% sensitivity and 94% specificity) was found. A significant correlation between quantitative reading of F.I. and end-point titer groups was observed using Spearman's test and regression analysis. A conversion scale of F.I. in end-point titers for each recognized ANA-pattern was obtained. The Image Navigator offers the opportunity to improve worldwide harmonization of ANA test results. In particular, digital F.I. allows quantifying ANA titers by using just one sample dilution. It could represent a valuable support for the routine laboratory and an effective tool to reduce inter- and intra-laboratory variability. Copyright © 2018. Published by Elsevier B.V.

  6. Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

    Science.gov (United States)

    Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

    2017-10-05

    The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results

  7. Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

    Science.gov (United States)

    Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

  8. The interpolation method based on endpoint coordinate for CT three-dimensional image

    International Nuclear Information System (INIS)

    Suto, Yasuzo; Ueno, Shigeru.

    1997-01-01

    Image interpolation is frequently used to improve slice resolution to reach spatial resolution. Improved quality of reconstructed three-dimensional images can be attained with this technique as a result. Linear interpolation is a well-known and widely used method. The distance-image method, which is a non-linear interpolation technique, is also used to convert CT value images to distance images. This paper describes a newly developed method that makes use of end-point coordinates: CT-value images are initially converted to binary images by thresholding them and then sequences of pixels with 1-value are arranged in vertical or horizontal directions. A sequence of pixels with 1-value is defined as a line segment which has starting and end points. For each pair of adjacent line segments, another line segment was composed by spatial interpolation of the start and end points. Binary slice images are constructed from the composed line segments. Three-dimensional images were reconstructed from clinical X-ray CT images, using three different interpolation methods and their quality and processing speed were evaluated and compared. (author)

  9. High heterogeneity of HIV-related sexual risk among transgender people in Ontario, Canada: a province-wide respondent-driven sampling survey

    Directory of Open Access Journals (Sweden)

    Bauer Greta R

    2012-04-01

    Full Text Available Abstract Background Studies of HIV-related risk in trans (transgender, transsexual, or transitioned people have most often involved urban convenience samples of those on the male-to-female (MTF spectrum. Studies have detected high prevalences of HIV-related risk behaviours, self-reported HIV, and HIV seropositivity. Methods The Trans PULSE Project conducted a multi-mode survey using respondent-driven sampling to recruit 433 trans people in Ontario, Canada. Weighted estimates were calculated for HIV-related risk behaviours, HIV testing and self-reported HIV, including subgroup estimates for gender spectrum and ethno-racial groups. Results Trans people in Ontario report a wide range of sexual behaviours with a full range of partner types. High proportions – 25% of female-to-male (FTM and 51% of MTF individuals – had not had a sex partner within the past year. Of MTFs, 19% had a past-year high-risk sexual experience, versus 7% of FTMs. The largest behavioural contributors to HIV risk were sexual behaviours some may assume trans people do not engage in: unprotected receptive genital sex for FTMs and insertive genital sex for MTFs. Overall, 46% had never been tested for HIV; lifetime testing was highest in Aboriginal trans people and lowest among non-Aboriginal racialized people. Approximately 15% of both FTM and MTF participants had engaged in sex work or exchange sex and about 2% currently work in the sex trade. Self-report of HIV prevalence was 10 times the estimated baseline prevalence for Ontario. However, given wide confidence intervals and the high proportion of trans people who had never been tested for HIV, estimating the actual prevalence was not possible. Conclusions Results suggest potentially higher than baseline levels of HIV; however low testing rates were observed and self-reported prevalences likely underestimate seroprevalence. Explicit inclusion of trans people in epidemiological surveillance statistics would provide much

  10. A brief, standardized tool for measuring HIV-related stigma among health facility staff: results of field testing in China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis.

    Science.gov (United States)

    Nyblade, Laura; Jain, Aparna; Benkirane, Manal; Li, Li; Lohiniva, Anna-Leena; McLean, Roger; Turan, Janet M; Varas-Díaz, Nelson; Cintrón-Bou, Francheska; Guan, Jihui; Kwena, Zachary; Thomas, Wendell

    2013-11-13

    Within healthcare settings, HIV-related stigma is a recognized barrier to access of HIV prevention and treatment services and yet, few efforts have been made to scale-up stigma reduction programs in service delivery. This is in part due to the lack of a brief, simple, standardized tool for measuring stigma among all levels of health facility staff that works across diverse HIV prevalence, language and healthcare settings. In response, an international consortium led by the Health Policy Project, has developed and field tested a stigma measurement tool for use with health facility staff. Experts participated in a content-development workshop to review an item pool of existing measures, identify gaps and prioritize questions. The resulting questionnaire was field tested in six diverse sites (China, Dominica, Egypt, Kenya, Puerto Rico and St. Christopher & Nevis). Respondents included clinical and non-clinical staff. Questionnaires were self- or interviewer-administered. Analysis of item performance across sites examined both psychometric properties and contextual issues. The key outcome of the process was a substantially reduced questionnaire. Eighteen core questions measure three programmatically actionable drivers of stigma within health facilities (worry about HIV transmission, attitudes towards people living with HIV (PLHIV), and health facility environment, including policies), and enacted stigma. The questionnaire also includes one short scale for attitudes towards PLHIV (5-item scale, α=0.78). Stigma-reduction programmes in healthcare facilities are urgently needed to improve the quality of care provided, uphold the human right to healthcare, increase access to health services, and maximize investments in HIV prevention and treatment. This brief, standardized tool will facilitate inclusion of stigma measurement in research studies and in routine facility data collection, allowing for the monitoring of stigma within healthcare facilities and evaluation of

  11. Endpoint behavior of the pion distribution amplitude in QCD sum rules with nonlocal condensates

    International Nuclear Information System (INIS)

    Mikhailov, S. V.; Pimikov, A. V.; Stefanis, N. G.

    2010-01-01

    Starting from the QCD sum rules with nonlocal condensates for the pion distribution amplitude, we derive another sum rule for its derivative and its ''integral derivatives''--defined in this work. We use this new sum rule to analyze the fine details of the pion distribution amplitude in the endpoint region x∼0. The results for endpoint-suppressed and flattop (or flatlike) pion distribution amplitudes are compared with those we obtained with differential sum rules by employing two different models for the distribution of vacuum-quark virtualities. We determine the range of values of the derivatives of the pion distribution amplitude and show that endpoint-suppressed distribution amplitudes lie within this range, while those with endpoint enhancement--flat-type or Chernyak-Zhitnitsky like--yield values outside this range.

  12. 78 FR 49530 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop

    Science.gov (United States)

    2013-08-14

    ...] Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop AGENCY: Food and Drug... for Drug Evaluation and Research, in cosponsorship with the American College of Gastroenterology, the... American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, and the Pediatric IBD...

  13. On weighted hardy inequalities on semiaxis for functions vanishing at the endpoints

    Directory of Open Access Journals (Sweden)

    Stepanov Vladimir

    1997-01-01

    Full Text Available We study the weighted Hardy inequalities on the semiaxis of the form for functions vanishing at the endpoints together with derivatives up to the order . The case is completely characterized.

  14. The effect of adherence to statin therapy on cardiovascular mortality: quantification of unmeasured bias using falsification end-points

    Directory of Open Access Journals (Sweden)

    Maarten J. Bijlsma

    2016-04-01

    Full Text Available Abstract Background To determine the clinical effectiveness of statins on cardiovascular mortality in practice, observational studies are needed. Control for confounding is essential in any observational study. Falsification end-points may be useful to determine if bias is present after adjustment has taken place. Methods We followed starters on statin therapy in the Netherlands aged 46 to 100 years over the period 1996 to 2012, from initiation of statin therapy until cardiovascular mortality or censoring. Within this group (n = 49,688, up to 16 years of follow-up, we estimated the effect of adherence to statin therapy (0 = completely non-adherent, 1 = fully adherent on ischemic heart diseases and cerebrovascular disease (ICD10-codes I20-I25 and I60-I69 as well as respiratory and endocrine disease mortality (ICD10-codes J00-J99 and E00-E90 as falsification end points, controlling for demographic factors, socio-economic factors, birth cohort, adherence to other cardiovascular medications, and diabetes using time-varying Cox regression models. Results Falsification end-points indicated that a simpler model was less biased than a model with more controls. Adherence to statins appeared to be protective against cardiovascular mortality (HR: 0.70, 95 % CI 0.61 to 0.81. Conclusions Falsification end-points helped detect overadjustment bias or bias due to competing risks, and thereby proved to be a useful technique in such a complex setting.

  15. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    OpenAIRE

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas

    2016-01-01

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...

  16. "Inside These Fences Is Our Own Little World": Prison-Based HIV Testing and HIV-Related Stigma Among Incarcerated Men and Women.

    Science.gov (United States)

    Muessig, Kathryn E; Rosen, David L; Farel, Claire E; White, Becky L; Filene, Eliza J; Wohl, David A

    2016-04-01

    Correctional facilities offer opportunities to provide comprehensive HIV services including education, testing, treatment, and coordination of post- release care. However, these services may be undermined by unaddressed HIV stigma. As part of a prison-based HIV testing study, we interviewed 76 incarcerated men and women from the North Carolina State prison system. The sample was 72% men, median age 31.5 years (range: 19 to 60). Thematic analysis revealed high levels of HIV-related fear and stigma, homophobia, incomplete HIV transmission knowledge, beliefs that HIV is highly contagious within prisons ("HIV miasma"), and the View of HIV testing as protective. Interviewees described social distancing behaviors and coping mechanisms they perceived to be protective, including knowing their HIV status and avoiding contact with others and shared objects. Interviewees endorsed universal testing, public HIV status disclosure, and segregation of HIV-positive inmates. Intensified education and counseling efforts are needed to ameliorate entrenched HIV-transmission fears and stigmatizing beliefs.

  17. HIV-Related Stress and Life Chaos Mediate the Association Between Poverty and Medication Adherence Among People Living with HIV/AIDS.

    Science.gov (United States)

    Kalichman, Seth C; Kalichman, Moira O

    2016-12-01

    HIV treatment depends on high-levels of antiretroviral therapy (ART) adherence, which is severely impeded by poverty. Men and women living with HIV infection (N = 92) completed computerized interviews of demographic and health characteristics, poverty markers, stressful life events, and life chaos, as well as unannounced pill counts to determine prospective medication adherence and medical record chart abstractions for HIV viral load. Poverty markers were associated with both stressors and chaos, and the direct effects of all three factors predicted ART non-adherence. The multiple mediation model showed that accounting for stressors and chaos resulted in a non-significant association between poverty markers and ART adherence. The indirect effect of poverty markers on adherence through life chaos was significant, whereas the indirect effect of poverty markers on adherence through stressors was not significant. Factors that render HIV-related stress and create chaos offer intervention targets that are more amenable to change than poverty itself.

  18. The Medical Imaging & Technology Alliance conference on research endpoints appropriate for Medicare coverage of new PET radiopharmaceuticals.

    Science.gov (United States)

    Hillman, Bruce J; Frank, Richard A; Abraham, Brian C

    2013-09-01

    The outcomes of a 2011 Medical Imaging & Technology Alliance (MITA) conference helped shape considerations about what might be the most appropriate pathways for the regulatory and payment considerations of new PET radiopharmaceuticals. As follow-up to that conference, MITA convened a second conference of stakeholders to advise payers on what might be acceptable endpoints for clinical trials to support the coverage of novel PET agents. The conference involved experts on imaging and clinical research, providers of PET services, as well as representatives of interested medical societies, the PET industry, and the regulatory and payer communities. The principal outcome of their deliberations was that it was unrealistic to expect trials of new PET radiopharmaceuticals to directly demonstrate a health benefit. Rather, intermediate outcomes, such as a positive change in patient management, would be more efficient and appropriate.

  19. Development of Cardiovascular and Neurodevelopmental Metrics as Sublethal Endpoints for the Fish Embryo Toxicity Test.

    Science.gov (United States)

    Krzykwa, Julie C; Olivas, Alexis; Jeffries, Marlo K Sellin

    2018-06-19

    The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods, as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet weight, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, eye size and cardiovascular related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological and cardiovascular endpoints measured, length, eye size and pericardial area were found to more responsive than the other endpoints, respectively. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole effluent toxicity testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Sexual Behaviors, Healthcare Interactions, and HIV-Related Perceptions Among Adults Age 60 Years and Older: An Investigation by Race/Ethnicity.

    Science.gov (United States)

    Glaude-Hosch, Jonathan A; Smith, Matthew Lee; Heckman, Timothy G; Miles, Toni P; Olubajo, Babatunde A; Ory, Marcia G

    2015-01-01

    Older adults are remaining sexually active for longer periods of time, underscoring the need to assess sexual activity patterns in this group and identify differences by race/ethnicity, some of which may have implications for the development and implementation of sexual risk reduction interventions. Using data from the 2010 National Social Life, Health, and Aging Project, this study examined responses from 1,429 adults aged 60 years and older. Multinomial logistic regression compared sexual behaviors, health-related indicators, interactions with healthcare professionals, and HIV-related perceptions across participants' race/ethnicity. Approximately 81% of participants self-reported as non-Hispanic white, 10.59% as African American, and 8.05% as Hispanic. On average, participants were 69.9 years of age. In the previous year, 49.3% of participants engaged in sexual intercourse; only 3% used condoms. The majority of participants (83.1%) visited a physician at least twice in the previous year, 30.9% had discussed sex with a physician since turning 50, and 14.2% had been tested for HIV. Relative to non-Hispanic whites, African Americans were more likely to be divorced (OR=3.23, Psexually transmitted infection (STI) diagnoses (OR=1.67, P=0.030); and have paid for sex (OR=2.83, P=0.002). Although African Americans had greater perceived risk for HIV infection (OR=1.66, P=0.046), they were less likely to have discussed sex with a physician since turning 50 (OR=0.45, P=0.009). Contextualized interventions to improve patient-provider communication and proactive screening behaviors in sexually-active and aging African Americans are needed.

  1. A narrative analysis positioning HIV relative to personal (sexual) relationship challenges in an agony aunt column in the Western Cape, South Africa - Aunty Mona's "love advice".

    Science.gov (United States)

    Viljoen, Lario; Thorne, Marguerite; Thomas, Angelique; Bond, Virginia; Hoddinott, Graeme

    2016-01-01

    HIV prevalence and incidence in South Africa remain high, making HIV a part of everyday life. Community narratives on HIV treatment and prevention are important and influence official and unofficial health messaging and community perceptions and understandings of HIV. We explore how contributors and the columnist of an agony aunt column position HIV relative to choices made about love, partnership, and sex over three years. We analysed all columns of an agony aunt series (Antie Mona) published between December 2012 and November 2015. The column is published in a South African, Afrikaans-language newspaper "Son", prioritising sensationalist news items. Trends were identified through narrative analysis. Data were managed in ATLAS.ti and inductive, iterative coding conducted. It was found that letters to the agony aunt rarely refer to HIV directly (less than 7%). Euphemisms such as diseases of the flesh and the great flu were more commonly used instead of HIV or AIDS. Letters addressed HIV in three ways: direct references to experiences living with HIV; direct questions about HIV prevention; and scenarios where HIV could (from a public health perspective) have been the main concern, but everyday issues took precedence. The majority of letters fell into this latter category where the writers focused on the immediate concerns of good sexual relations, problems related to love and romantic relationships, good moral behaviour of others, and issues of oppressive life conditions rather than on HIV directly. The findings illustrate that informal, public contributions to health information, such as agony aunts, are important narratives that inform popular perspectives on HIV and health. A better appreciation of this context would allow health implementers to ensure that these role players receive updated health messaging to avoid the risk of HIV-related stigma where HIV is used as a moral rod to punish perceived moral transgressions.

  2. Dependence of PERT endpoint on endogenous lipase activity.

    Science.gov (United States)

    Gao, Wen-Yi; Mulberg, Andrew E

    2014-11-01

    To clarify and to understand the potential for misinterpretation of change in fecal fat quantitation during pancreatic enzyme replacement therapy (PERT) trials for treatment of exocrine pancreatic insufficiency. Analysis of clinical trials submitted to the U.S. Food and Drug Administration (FDA) for approval of PERT that enrolled 123 cystic fibrosis adult and pediatric patients treated with Creon, Pertzye, Ultresa, and Zenpep. The CFA% defines lipase activity as a percentage of converting substrate of "Total Daily Dietary Fat Intake." PERT trials performed to date have modified the definition to converting the "Shared Daily Fat Intake," generating "Partial CFA" for the exogenous lipase: the higher the activity of coexisting endogenous lipase, the lower the "Partial CFA" of exogenous measured. This review shows that "Partial CFA" is not CFA. Enrollment of patients with low HPLA during treatment may improve the interpretability of "Partial CFA" measured by PERT trials.

  3. Availability of essential drugs for managing HIV-related pain and symptoms within 120 PEPFAR-funded health facilities in East Africa: a cross-sectional survey with onsite verification.

    Science.gov (United States)

    Harding, Richard; Simms, Victoria; Penfold, Suzanne; Downing, Julia; Powell, Richard A; Mwangi-Powell, Faith; Namisango, Eve; Moreland, Scott; Gikaara, Nancy; Atieno, Mackuline; Kataike, Jennifer; Nsubuga, Clare; Munene, Grace; Banga, Geoffrey; Higginson, Irene J

    2014-04-01

    World Health Organization's essential drugs list can control the highly prevalent HIV-related pain and symptoms. Availability of essential medicines directly influences clinicians' ability to effectively manage distressing manifestations of HIV. To determine the availability of pain and symptom controlling drugs in East Africa within President's Emergency Plan for AIDS Relief-funded HIV health care facilities. Directly observed quantitative health facilities' pharmacy stock review. We measured availability, expiration and stock-outs of specified drugs required for routine HIV management, including the World Health Organization pain ladder. A stratified random sample in 120 President's Emergency Plan for AIDS Relief-funded HIV care facilities (referral and district hospitals, health posts/centres and home-based care providers) in Kenya and Uganda. Non-opioid analgesics (73%) and co-trimoxazole (64%) were the most commonly available drugs and morphine (7%) the least. Drug availability was higher in hospitals and lower in health centres, health posts and home-based care facilities. Facilities generally did not use minimum stock levels, and stock-outs were frequently reported. The most common drugs had each been out of stock in the past 6 months in 47% of facilities stocking them. When a minimum stock level was defined, probability of a stock-out in the previous 6 months was 32.6%, compared to 45.5% when there was no defined minimum stock level (χ (2) = 5.07, p = 0.024). The data demonstrate poor essential drug availability, particularly analgesia, limited by facility type. The lack of strong opioids, isoniazid and paediatric formulations is concerning. Inadequate drug availability prevents implementation of simple clinical pain and symptom control protocols, causing unnecessary distress. Research is needed to identify supply chain mechanisms that lead to these problems.

  4. SU-D-204-01: A Methodology Based On Machine Learning and Quantum Clustering to Predict Lung SBRT Dosimetric Endpoints From Patient Specific Anatomic Features

    Energy Technology Data Exchange (ETDEWEB)

    Lafata, K; Ren, L; Wu, Q; Kelsey, C; Hong, J; Cai, J; Yin, F [Duke University Medical Center, Durham, NC (United States)

    2016-06-15

    Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space to identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong

  5. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

    International Nuclear Information System (INIS)

    Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

    2010-01-01

    Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID 50 s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca 2+ deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

  6. Personal contact with HIV-positive persons is associated with reduced HIV-related stigma: cross-sectional analysis of general population surveys from 26 countries in sub-Saharan Africa.

    Science.gov (United States)

    Chan, Brian T; Tsai, Alexander C

    2017-01-11

    HIV-related stigma hampers treatment and prevention efforts worldwide. Effective interventions to counter HIV-related stigma are greatly needed. Although the "contact hypothesis" suggests that personal contact with persons living with HIV (PLHIV) may reduce stigmatizing attitudes in the general population, empirical evidence in support of this hypothesis is lacking. Our aim was to estimate the association between personal contact with PLHIV and HIV-related stigma among the general population of sub-Saharan Africa. Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 26 African countries between 2003 and 2008. We fitted multivariable logistic regression models with country-level fixed effects, specifying social distance as the dependent variable and personal contact with PLHIV as the primary explanatory variable of interest. We analyzed data from 206,717 women and 91,549 men living in 26 sub-Saharan African countries. We estimated a statistically significant negative association between personal contact with PLHIV and desires for social distance (adjusted odds ratio [AOR] = 0.80; p  interventions should be developed and tested to reduce the stigma of HIV.

  7. Predictive validity of endpoints used in electrophysiological modelling of migraine in the trigeminovascular system.

    Science.gov (United States)

    Farkas, Bence; Kardos, Péter; Orosz, Szabolcs; Tarnawa, István; Csekő, Csongor; Lévay, György; Farkas, Sándor; Lendvai, Balázs; Kovács, Péter

    2015-11-02

    The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

    Science.gov (United States)

    Zakour, Sihem Ben; Taleb, Hassen

    2017-09-01

    Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

  9. Bioremediation of hydrocarbon-contaminated soils: are treatability and ecotoxicity endpoints related?

    International Nuclear Information System (INIS)

    Visser, S.

    1999-01-01

    To determine if there is a relationship between biotreatability and ecotoxicity endpoints in a wide range of hydrocarbon-contaminated soils, including medium and heavy crude oil-contaminated flare pit wastes and lubrication oil contaminated soil, research was conducted. Each test material was analyzed for pH, water repellency, electrical conductivity, available N and P, total extractable hydrocarbons, oil and grease, and toxicity to seedling emergence, root elongation in barley, lettuce and canola, earthworm survival and luminescent bacteria (Microtox), prior to, and following three months of bioremediation in the laboratory. By monitoring soil respiration, progress of the bioremediation process and determination of a treatment endpoint were assessed. The time required to attain a treatment endpoint under laboratory conditions can range from 30 days to 100 days depending on the concentration of hydrocarbons and degree of weathering. Most flare pits are biotreatable, averaging a loss of 25-30% of hydrocarbons during bioremediation. Once a treatment endpoint is achieved, residual hydrocarbons contents almost always exceeds Alberta Tier I criteria for mineral oil and grease. As a result of bioremediation treatments, hydrophobicity is often reduced from severe to low. Many flare pit materials are still moderately to extremely toxic after reaching a treatment endpoint. (Abstract only)

  10. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Zhendong Yang

    2015-12-01

    Full Text Available Aflatoxins B1 (AFB1, deoxynivalenol (DON, fumonisin B1 (FB1, T-2 toxin (T-2, and zearalenone (ZEA are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  11. Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint.

    Science.gov (United States)

    Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

    2015-09-01

    The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L(-1), which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Note on simultaneous inferences about non-inferiority and superiority for a primary and a secondary endpoint.

    Science.gov (United States)

    Guilbaud, Olivier

    2011-11-01

    In their review of challenges to multiple testing in clinical trials, Hung and Wang (2010) considered the situation where a treatment is to be compared with an active comparator and the aim is to show non-inferiority and (if possible) superiority with respect to a primary and a secondary endpoint. This note extends their discussion of this particular situation, taking the sequentially rejective procedure they used for illustration as a starting point. Some alternative multiple testing procedures (MTPs) are considered, and corresponding simultaneous confidence regions are discussed that provide additional information "for free". The choice may then be based on the properties of these MTPs and corresponding confidence regions. 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Meeting report: Measuring endocrine-sensitive endpoints within the first years of life

    DEFF Research Database (Denmark)

    Arbuckle, T.E.; Hauser, R.; Swan, S.H.

    2008-01-01

    An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine......-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove...... on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions....

  14. Deep inelastic scattering near the endpoint in soft-collinear effective theory

    International Nuclear Information System (INIS)

    Chay, Junegone; Kim, Chul

    2007-01-01

    We apply the soft-collinear effective theory to deep inelastic scattering near the endpoint region. The forward scattering amplitude and the structure functions are shown to factorize as a convolution of the Wilson coefficients, the jet functions, and the parton distribution functions. The behavior of the parton distribution functions near the endpoint region is considered. It turns out that it evolves with the Altarelli-Parisi kernel even in the endpoint region, and the parton distribution function can be factorized further into a collinear part and the soft Wilson line. The factorized form for the structure functions is obtained by the two-step matching, and the radiative corrections or the evolution for each factorized part can be computed in perturbation theory. We present the radiative corrections of each factorized part to leading order in α s , including the zero-bin subtraction for the collinear part

  15. Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

    DEFF Research Database (Denmark)

    Dellavalle, B; Kirchhoff, J; Maretty, L

    2014-01-01

    SUMMARY Defining appropriate and objective endpoints for animal research can be difficult. Previously we evaluated and implemented a body temperature (BT) of ECM) and were interested in a similar endpoint for a model of severe malarial...... anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...

  16. A systematic review of interventions to reduce HIV-related stigma and discrimination from 2002 to 2013: how far have we come?

    Science.gov (United States)

    Stangl, Anne L; Lloyd, Jennifer K; Brady, Laura M; Holland, Claire E; Baral, Stefan

    2013-11-13

    HIV-related stigma and discrimination continue to hamper efforts to prevent new infections and engage people in HIV treatment, care and support programmes. The identification of effective interventions to reduce stigma and discrimination that can be integrated into national responses is crucial to the success of the global AIDS response. We conducted a systematic review of studies and reports that assessed the effectiveness of interventions to reduce HIV stigma and discrimination between 1 January 2002 and 1 March 2013. Databases searched for peer-reviewed articles included PubMed, Scopus, EBSCO Host -CINAHL Plus, Psycinfo, Ovid, Sociofile and Popline. Reports were obtained from the www.HIVAIDSClearinghouse.eu, USAID Development Experience Clearinghouse, UNESCO HIV and AIDS Education Clearinghouse, Google, WHO and UNAIDS. Ancestry searches for articles included in the systematic review were also conducted. Studies of any design that sought to reduce stigma as a primary or secondary objective and included pre- and post-intervention measures of stigma were included. Of 2368 peer-reviewed articles and reports identified, 48 were included in our review representing 14 different target populations in 28 countries. The majority of interventions utilized two or more strategies to reduce stigma and discrimination, and ten included structural or biomedical components. However, most interventions targeted a single socio-ecological level and a single domain of stigma. Outcome measures lacked uniformity and validity, making both interpretation and comparison of study results difficult. While the majority of studies were effective at reducing the aspects of stigma they measured, none assessed the influence of stigma or discrimination reduction on HIV-related health outcomes. Our review revealed considerable progress in the stigma-reduction field. However, critical challenges and gaps remain which are impeding the identification of effective stigma-reduction strategies that can

  17. A systematic review of interventions to reduce HIV-related stigma and discrimination from 2002 to 2013: how far have we come?

    Science.gov (United States)

    Stangl, Anne L; Lloyd, Jennifer K; Brady, Laura M; Holland, Claire E; Baral, Stefan

    2013-01-01

    Introduction HIV-related stigma and discrimination continue to hamper efforts to prevent new infections and engage people in HIV treatment, care and support programmes. The identification of effective interventions to reduce stigma and discrimination that can be integrated into national responses is crucial to the success of the global AIDS response. Methods We conducted a systematic review of studies and reports that assessed the effectiveness of interventions to reduce HIV stigma and discrimination between 1 January 2002 and 1 March 2013. Databases searched for peer-reviewed articles included PubMed, Scopus, EBSCO Host –CINAHL Plus, Psycinfo, Ovid, Sociofile and Popline. Reports were obtained from the www.HIVAIDSClearinghouse.eu, USAID Development Experience Clearinghouse, UNESCO HIV and AIDS Education Clearinghouse, Google, WHO and UNAIDS. Ancestry searches for articles included in the systematic review were also conducted. Studies of any design that sought to reduce stigma as a primary or secondary objective and included pre- and post-intervention measures of stigma were included. Results Of 2368 peer-reviewed articles and reports identified, 48 were included in our review representing 14 different target populations in 28 countries. The majority of interventions utilized two or more strategies to reduce stigma and discrimination, and ten included structural or biomedical components. However, most interventions targeted a single socio-ecological level and a single domain of stigma. Outcome measures lacked uniformity and validity, making both interpretation and comparison of study results difficult. While the majority of studies were effective at reducing the aspects of stigma they measured, none assessed the influence of stigma or discrimination reduction on HIV-related health outcomes. Conclusions Our review revealed considerable progress in the stigma-reduction field. However, critical challenges and gaps remain which are impeding the identification of

  18. Evidence of increased STI/HIV-related risk behavior among male perpetrators of intimate partner violence in Guatemala: results from a national survey.

    Science.gov (United States)

    Hembling, John; Andrinopoulos, Katherine

    2014-01-01

    Intimate partner violence (IPV) is a significant public health problem with a demonstrated link to increased sexually transmitted infection (STI)/HIV-related risk and vulnerability. While IPV is an important issue in Central America, the link to STI/HIV risk has not been explored in this region. In this study, the relationship between emotional and physical/sexual IPV and the STI/HIV-related risk behaviors of sex worker patronage and infidelity is assessed among male IPV perpetrators using data from a national survey conducted in 2009 in Guatemala (n = 4773 married/partnered men). Bivariate associations between background characteristics and emotional and physical IPV perpetration were explored. Logistic regression models were run to test associations between IPV for each sexual risk behavior. Perpetration of emotional and physical/sexual IPV was more common among married/partnered men who were older than 24, had more education, lived in urban areas, or were in common law versus married unions. Reports of past-year emotional IPV perpetration increased as wealth quintile increased. After adjusting for demographics and other characteristics, physical/sexual IPV perpetration was associated with past-year infidelity (AOR 1.9, 95% CI: 1.1-3.6). Lifetime emotional IPV (AOR 1.4, 95% CI: 1.1-1.7) and physical/sexual IPV 1.6 (95% CI 1.2-2.0) were positively associated with a history of sex worker patronage. Endorsement of traditional gender role norms showed a marginally positive association with past-year infidelity in the adjusted model (AOR 1.3, 95% CI 1.0-1.8). The study findings from Guatemala reinforce the growing evidence globally that male IPV perpetrators are more likely to engage in risky sexual behavior, including sex worker patronage and main partner infidelity. The concurrency of violence and increased STI/HIV risk may compound the health risks for female victims of IPV who also face injury and psychological trauma. Integration of prevention and screening of

  19. A pilot study of cognitive training with and without transcranial direct current stimulation to improve cognition in older persons with HIV-related cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ownby RL

    2016-10-01

    Full Text Available Raymond L Ownby,1 Amarilis Acevedo2 1Department of Psychiatry and Behavioral Medicine, 2College of Psychology, Nova Southeastern University, Fort Lauderdale, FL, USA Background: In spite of treatment advances, HIV infection is associated with cognitive deficits. This is even more important as many persons with HIV infection age and experience age-related cognitive impairments. Both computer-based cognitive training and transcranial direct current stimulation (tDCS have shown promise as interventions to improve cognitive function. In this study, we investigate the acceptability and efficacy of cognitive training with and without tDCS in older persons with HIV. Patients and methods: In this single-blind randomized study, participants were 14 individuals of whom 11 completed study procedures (mean age =51.5 years; nine men and two women with HIV-related mild neurocognitive disorder. Participants completed a battery of neuropsychological and self-report measures and then six 20-minute cognitive training sessions while receiving either active or sham anodal tDCS over the left dorsolateral prefrontal cortex. After training, participants completed the same measures. Success of the blind and participant reactions were assessed during a final interview. Assessments were completed by an assessor blind to treatment assignment. Pre- and post-training changes were evaluated via analysis of covariance yielding estimates of effect size. Results: All participants believed that they had been assigned to active treatment; nine of the 11 believed that the intervention had improved their cognitive functioning. Both participants who felt the intervention was ineffective were assigned to the sham condition. None of the planned tested interactions of time with treatment was significant, but 12 of 13 favored tDCS (P=0.08. All participants indicated that they would participate in similar studies in the future. Conclusion: Results show that both cognitive training via

  20. Reducing sample size by combining superiority and non-inferiority for two primary endpoints in the Social Fitness study.

    Science.gov (United States)

    Donkers, Hanneke; Graff, Maud; Vernooij-Dassen, Myrra; Nijhuis-van der Sanden, Maria; Teerenstra, Steven

    2017-01-01

    In randomized controlled trials, two endpoints may be necessary to capture the multidimensional concept of the intervention and the objectives of the study adequately. We show how to calculate sample size when defining success of a trial by combinations of superiority and/or non-inferiority aims for the endpoints. The randomized controlled trial design of the Social Fitness study uses two primary endpoints, which can be combined into five different scenarios for defining success of the trial. We show how to calculate power and sample size for each scenario and compare these for different settings of power of each endpoint and correlation between them. Compared to a single primary endpoint, using two primary endpoints often gives more power when success is defined as: improvement in one of the two endpoints and no deterioration in the other. This also gives better power than when success is defined as: improvement in one prespecified endpoint and no deterioration in the remaining endpoint. When two primary endpoints are equally important, but a positive effect in both simultaneously is not per se required, the objective of having one superior and the other (at least) non-inferior could make sense and reduce sample size. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Radiometric titration of officinal radiopharmaceuticals using radioactive kryptonates as end-point indicators. I

    International Nuclear Information System (INIS)

    Toelgyessy, J.; Dillinger, P.; Harangozo, M.; Jombik, J.

    1980-01-01

    A method for the determination of salicylic, acetylsalicylic and benzoic acids in officinal pharmaceutical based on radiometric titration with 0.1 mol.l -1 NaOH was developed. The end-point was detected with the aid of radioactive glass kryptonate. After the end-point, the excess titrant attacks the glass surface layers and this results in releasing 85 Kr, and consequently, in decreasing the radioactivity of the kryptonate employed. The radioactive kryptonate used as an indicator was prepared by the bombardment of glass with accelerated 85 Kr ions. The developed method is simple, accurate and correct. (author)

  2. A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

    Science.gov (United States)

    Benacer, Douadi; Zain, Siti Nursheena Mohd; Lewis, John W; Khalid, Mohd Khairul Nizam Mohd; Thong, Kwai Lin

    2017-01-01

    This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains. Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively. The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.1pg/µl of leptospiral DNA and sensitivity of 103 leptospires/ml in both spiked urine and water. Our duplex endpoint PCR assay is suitable for rapid early detection of Leptospira with high sensitivity and specificity.

  3. Comparison of methods for accurate end-point detection of potentiometric titrations

    International Nuclear Information System (INIS)

    Villela, R L A; Borges, P P; Vyskočil, L

    2015-01-01

    Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper

  4. Comparison of methods for accurate end-point detection of potentiometric titrations

    Science.gov (United States)

    Villela, R. L. A.; Borges, P. P.; Vyskočil, L.

    2015-01-01

    Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper.

  5. Verifying Elimination Programs with a Special Emphasis on Cysticercosis Endpoints and Postelimination Surveillance

    Directory of Open Access Journals (Sweden)

    Sukwan Handali

    2012-01-01

    Full Text Available Methods are needed for determining program endpoints or postprogram surveillance for any elimination program. Cysticercosis has the necessary effective strategies and diagnostic tools for establishing an elimination program; however, tools to verify program endpoints have not been determined. Using a statistical approach, the present study proposed that taeniasis and porcine cysticercosis antibody assays could be used to determine with a high statistical confidence whether an area is free of disease. Confidence would be improved by using secondary tests such as the taeniasis coproantigen assay and necropsy of the sentinel pigs.

  6. “Inside These Fences is Our Own Little World”: Prison-Based HIV Testing and HIV-Related Stigma Among Incarcerated Men and Women

    Science.gov (United States)

    Muessig, Kathryn E.; Rosen, David L.; Farel, Claire E.; White, Becky L.; Filene, Eliza J.; Wohl, David A.

    2016-01-01

    Correctional facilities offer opportunities to provide comprehensive HIV services including education, testing, treatment, and coordination of post-release care. However, these services may be undermined by unaddressed HIV stigma. As part of a prison-based HIV testing study, we interviewed 76 incarcerated men and women from the North Carolina State prison system. The sample was 72% men, median age 31.5 years (range: 19 to 60). Thematic analysis revealed high levels of HIV-related fear and stigma, homophobia, incomplete HIV transmission knowledge, beliefs that HIV is highly contagious within prisons (“HIV miasma”), and the view of HIV testing as protective. Interviewees described social distancing behaviors and coping mechanisms they perceived to be protective, including knowing their HIV status and avoiding contact with others and shared objects. Interviewees endorsed universal testing, public HIV status disclosure, and segregation of HIV-positive inmates. Intensified education and counseling efforts are needed to ameliorate entrenched HIV-transmission fears and stigmatizing beliefs. PMID:27459162

  7. Female autonomy as a contributing factor to women's HIV-related knowledge and behaviour in three culturally contrasting States in India.

    Science.gov (United States)

    Bloom, Shelah S; Griffiths, Paula L

    2007-07-01

    Factors contributing to India's vulnerability to the AIDS epidemic include pervasive poverty, low levels of education and high gender stratification. This study uses data collected in the 1998-99 National Family Health Survey-2 (NFHS-2) to investigate the relationship between aspects of women's autonomy and four measures of HIV-related knowledge and behaviour--awareness and knowledge of HIV/AIDS, condom awareness and condom use--in three culturally contrasting states in India: Kerala (n=2884), Karnataka (n=4357) and Uttar Pradesh (n=8981). The NFHS-2 is a nationally representative survey of India, with a sampling scheme that was designed such that each state sample can be generalized back to represent ever-married women aged 15-49 living in the state. Kerala scores highest in the four health outcome measures, followed by Karnataka and then Uttar Pradesh, but condom use is lowest in Karnataka. Kerala also leads in the four dimensions of autonomy examined and in socio-demographic status, followed again by Karnataka and Uttar Pradesh. Despite these observed differences, in all three states, women with greater autonomy as measured by this study were more likely to be knowledgeable about AIDS and condoms and to use condoms, after controlling for socio-demographic factors. These results concur with other studies focusing on women's autonomy and health outcomes around the world, and point to the importance of incorporating a gender-based approach to AIDS prevention programmes in India.

  8. Intervention induced changes on parenting practices, youth self-pride and sexual norms to reduce HIV-related behaviors among rural African American youths.

    Science.gov (United States)

    Murry, Velma McBride; Berkel, Cady; Chen, Yi-Fu; Brody, Gene H; Gibbons, Frederick X; Gerrard, Meg

    2011-09-01

    AIDS is the leading killer of African Americans between the ages of 25 and 44, many of whom became infected when they were teenagers or young adults. The disparity in HIV infection rate among African Americans youth residing in rural Southern regions of the United States suggests that there is an urgent need to identify ways to promote early preventive intervention to reduce HIV-related risk behavior. The Strong African American Families (SAAF) program, a preventive intervention for rural African American parents and their 11-year-olds, was specially designed to deter early sexual onset and the initiation and escalation of alcohol and drug use among rural African American preadolescents. A clustered-randomized prevention trial was conducted, contrasting families who took part in SAAF with control families. The trial, which included 332 families, indicated that intervention-induced changes occurred in intervention-targeted parenting, which in turn facilitated changes in youths' internal protective processes and positive sexual norms. Long-term follow up assessments when youth were 17 years old revealed that intervention-induced changes in parenting practices mediated the effect of intervention-group influences on changes in the onset and escalation of risky sexual behaviors over 65 months through its positive influence on adolescents' self-pride and their sexual norms. The findings underscore the powerful effects of parenting practices among rural African American families that over time serve a protective role in reducing youth's risk behavior, including HIV vulnerable behaviors.

  9. HIV-related stigma, social norms, and HIV testing in Soweto and Vulindlela, South Africa: National Institutes of Mental Health Project Accept (HPTN 043).

    Science.gov (United States)

    Young, Sean D; Hlavka, Zdenek; Modiba, Precious; Gray, Glenda; Van Rooyen, Heidi; Richter, Linda; Szekeres, Greg; Coates, Thomas

    2010-12-15

    HIV testing is necessary to curb the increasing epidemic. However, HIV-related stigma and perceptions of low likelihood of societal HIV testing may reduce testing rates. This study aimed to explore this association in South Africa, where HIV rates are extraordinarily high. Data were taken from the Soweto and Vulindlela, South African sites of Project Accept, a multinational HIV prevention trial. Self-reported HIV testing, stigma, and social norms items were used to study the relationship between HIV testing, stigma, and perceptions about societal testing rates. The stigma items were broken into 3 factors: negative attitudes, negative perceptions about people living with HIV, and perceptions of fair treatment for people living with HIV (equity). Results from a univariate logistic regression suggest that history of HIV testing was associated with decreased negative attitudes about people living with HIV/AIDS, increased perceptions that people living with HIV/AIDS experience discrimination, and increased perceptions that people with HIV should be treated equitably. Results from a multivariate logistic regression confirm these effects and suggest that these differences vary according to sex and age. Compared with people who had never tested for HIV, those who had previously tested were more likely to believe that the majority of people have tested for HIV. Data suggest that interventions designed to increase HIV testing in South Africa should address stigma and perceptions of societal testing.

  10. The relationship between risk networks' patterns of crack cocaine and alcohol consumption and HIV-related sexual behaviors among adult injection drug users: a prospective study.

    Science.gov (United States)

    Latkin, C A; Mandell, W; Vlahov, D

    1996-11-01

    Social context may be an important determinant of drug and alcohol consumption and HIV-related behaviors. To assess the influence of peers on drug users' risk behaviors this study examined the association between individual level and group level behaviors. This analysis reports on the prospective association between baseline self-reported drug and alcohol use of the network members of injection drug users, and self-reported sexual behaviors and alcohol use at 5-month follow-up. Participants were a nontreatment sample of inner-city injection drug users who volunteered for a network-oriented HIV preventive intervention. They were predominantly unemployed, African American males. Of the 71 index participants who completed both the baseline and follow-up interviews, 227 of their drug network members were enrolled in the study. At baseline indexes' sexual risk behaviors were significantly associated with their drug network members' level of crack cocaine use. At follow-up higher levels of alcohol and crack use among drug network members were associated with indexes' reports of multiple sex partners and increased alcohol consumption. Higher levels of crack use among the drug network members were associated with the indexes' reporting casual sex partners at follow-up. These results highlight the importance of studying the role of peer group influence and the social context of risk behaviors.

  11. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ... exposure measures is suitable for documenting BE (e.g., transdermal delivery systems and certain rectal and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1464] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted...

  12. Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

    DEFF Research Database (Denmark)

    Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

    2012-01-01

    Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin...

  13. Can joint sound assess soft and hard endpoints of the Lachman test?: A preliminary study.

    Science.gov (United States)

    Hattori, Koji; Ogawa, Munehiro; Tanaka, Kazunori; Matsuya, Ayako; Uematsu, Kota; Tanaka, Yasuhito

    2016-05-12

    The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

  14. Coulometric Titration of Ethylenediaminetetraacetate (EDTA) with Spectrophotometric Endpoint Detection: An Experiment for the Instrumental Analysis Laboratory

    Science.gov (United States)

    Williams, Kathryn R.; Young, Vaneica Y.; Killian, Benjamin J.

    2011-01-01

    Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

  15. A covariant open bosonic string field theory including the endpoint and middlepoint interaction

    International Nuclear Information System (INIS)

    Liu, B.G.; Northwest Univ., Xian; Chen, Y.X.

    1988-01-01

    Extending the usual endpoint and midpoint interactions, we introduce numerous kinds of interactions, labelled by a parameter λ and obtain a non-commutative and associative string field algebra by adding up all interactions. With this algebra we develop a covariant open bosonic string field theory, which reduces to Witten's open bosonic string field theory under a special string length choice. (orig.)

  16. Using an Ecosystem Approach to complement protection schemes based on organism-level endpoints

    International Nuclear Information System (INIS)

    Bradshaw, Clare; Kapustka, Lawrence; Barnthouse, Lawrence; Brown, Justin; Ciffroy, Philippe; Forbes, Valery; Geras'kin, Stanislav; Kautsky, Ulrik; Bréchignac, François

    2014-01-01

    Radiation protection goals for ecological resources are focussed on ecological structures and functions at population-, community-, and ecosystem-levels. The current approach to radiation safety for non-human biota relies on organism-level endpoints, and as such is not aligned with the stated overarching protection goals of international agencies. Exposure to stressors can trigger non-linear changes in ecosystem structure and function that cannot be predicted from effects on individual organisms. From the ecological sciences, we know that important interactive dynamics related to such emergent properties determine the flows of goods and services in ecological systems that human societies rely upon. A previous Task Group of the IUR (International Union of Radioecology) has presented the rationale for adding an Ecosystem Approach to the suite of tools available to manage radiation safety. In this paper, we summarize the arguments for an Ecosystem Approach and identify next steps and challenges ahead pertaining to developing and implementing a practical Ecosystem Approach to complement organism-level endpoints currently used in radiation safety. - Highlights: • An Ecosystem Approach to radiation safety complements the organism-level approach. • Emergent properties in ecosystems are not captured by organism-level endpoints. • The proposed Ecosystem Approach better aligns with management goals. • Practical guidance with respect to system-level endpoints is needed. • Guidance on computational model selection would benefit an Ecosystem Approach

  17. Impact of confinement housing on study end-points in the calf model of cryptosporidiosis.

    Science.gov (United States)

    Graef, Geneva; Hurst, Natalie J; Kidder, Lance; Sy, Tracy L; Goodman, Laura B; Preston, Whitney D; Arnold, Samuel L M; Zambriski, Jennifer A

    2018-04-01

    Diarrhea is the second leading cause of death in children confinement housing, and Interval Collection (IC), which permits use of box stalls. CFC mimics human challenge model methodology but it is unknown if confinement housing impacts study end-points and if data gathered via this method is suitable for generalization to human populations. Using a modified crossover study design we compared CFC and IC and evaluated the impact of housing on study end-points. At birth, calves were randomly assigned to confinement (n = 14) or box stall housing (n = 9), or were challenged with 5 x 107 C. parvum oocysts, and followed for 10 days. Study end-points included fecal oocyst shedding, severity of diarrhea, degree of dehydration, and plasma cortisol. Calves in confinement had no significant differences in mean log oocysts enumerated per gram of fecal dry matter between CFC and IC samples (P = 0.6), nor were there diurnal variations in oocyst shedding (P = 0.1). Confinement housed calves shed significantly more oocysts (P = 0.05), had higher plasma cortisol (P = 0.001), and required more supportive care (P = 0.0009) than calves in box stalls. Housing method confounds study end-points in the calf model of cryptosporidiosis. Due to increased stress data collected from calves in confinement housing may not accurately estimate the efficacy of chemotherapeutics targeting C. parvum.

  18. Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

    International Nuclear Information System (INIS)

    Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H.

    2013-01-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  19. Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

    International Nuclear Information System (INIS)

    Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope

    2013-01-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  20. Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

    Energy Technology Data Exchange (ETDEWEB)

    Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope [Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States)

    2013-07-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  1. Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H. [Pacific Northwest National Laboratory, Richland, Washington (United States)

    2013-07-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  2. End-point construction and systematic titration error in linear titration curves-complexation reactions

    NARCIS (Netherlands)

    Coenegracht, P.M.J.; Duisenberg, A.J.M.

    The systematic titration error which is introduced by the intersection of tangents to hyperbolic titration curves is discussed. The effects of the apparent (conditional) formation constant, of the concentration of the unknown component and of the ranges used for the end-point construction are

  3. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  4. HIV-related stigma, racial discrimination, and gender discrimination: Pathways to physical and mental health-related quality of life among a national cohort of women living with HIV.

    Science.gov (United States)

    Logie, Carmen H; Wang, Ying; Lacombe-Duncan, Ashley; Wagner, Anne C; Kaida, Angela; Conway, Tracey; Webster, Kath; de Pokomandy, Alexandra; Loutfy, Mona R

    2018-02-01

    Social inequities compromise health-related quality of life (HR-QoL) among women living with HIV (WLWH). Little is known about health impacts of intersecting stigma based on HIV status, race and gender among WLWH or potential mechanisms to promote HR-QoL. We tested pathways from multiple types of stigma (HIV-related, racial, gender) to physical and mental HR-QoL utilizing baseline survey data from a national cohort of WLWH in Canada (2013-2015). Structural equation modeling was conducted using maximum likelihood estimation methods to test the direct effects of HIV-related stigma, racial discrimination, and gender discrimination on HR-QoL and indirect effects via social support and economic insecurity, adjusting for socio-demographic factors. Among 1425 WLWH (median age: 43years [IQR=35-50]), HIV-related stigma and gender discrimination had significant direct effects on mental HR-QoL. Social support mediated the relationship between HIV-related stigma and mental HR-QoL, accounting for 22.7% of the effect. Social support accounted for 41.4% of the effect of gender discrimination on mental HR-QoL. Economic insecurity accounted for 14.3% of the effect of HIV-related stigma, and 42.4% of the effect of racial discrimination, on physical HR-QoL. Fit indices suggest good model fit (χ 2 [1]=3.319, p=0.069; CFI=0.998; RMSEA=0.042 (90% CI: 0-0.069); SRMR=0.004). Findings reveal complex relationships between intersecting stigma and HR-QoL. Strategies that address intersecting stigma and economic insecurity among WLWH may prevent the harmful impacts of HIV-related stigma and gender discrimination on physical HR-QoL. Increasing social support may mitigate the impacts of stigma on mental health. Findings can inform multi-level interventions to promote health and wellbeing among WLWH. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups.

    Science.gov (United States)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives I Batlle, Jordi; Oughton, Deborah H; Garnier-Laplace, Jacqueline

    2016-02-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R0, asymptotic population growth rate λ, equilibrium population size Neq) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R0, λ or Neq) and the life history of the studied species. Among population endpoints, net reproductive rate R0 showed the lowest EDR10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h(-1) in the mouse Mus musculus to 38,000 μGy h(-1) in the fish Oryzias latipes. For several species, EDR10 for population endpoints were lower than the lowest EDR10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h(-1) in fish to 12,000 μGy h(-1) in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h(-1) in mammals to 1800 μGy h(-1) in

  6. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups

    International Nuclear Information System (INIS)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives i Batlle, Jordi; Oughton, Deborah H.; Garnier-Laplace, Jacqueline

    2016-01-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R_0, asymptotic population growth rate λ, equilibrium population size N_e_q) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R_0, λ or N_e_q) and the life history of the studied species. Among population endpoints, net reproductive rate R_0 showed the lowest EDR_1_0 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h"−"1 in the mouse Mus musculus to 38,000 μGy h"−"1 in the fish Oryzias latipes. For several species, EDR_1_0 for population endpoints were lower than the lowest EDR_1_0 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h"−"1 in fish to 12,000 μGy h"−"1 in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h"−"1

  7. The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2010-01-01

    OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

  8. Gender differences in clinical manifestations before AIDS diagnosis among injecting drug users

    NARCIS (Netherlands)

    Spijkerman, I. J.; Langendam, M. W.; van Ameijden, E. J.; Coutinho, R. A.; van den Hoek, A.

    1998-01-01

    We compared incidence rates of self-reported HIV-related symptoms and illnesses, verified clinical manifestations and findings on physical examination between female and male injecting drug users (IDU) stratified by HIV serostatus in the Amsterdam cohort study on the natural history of HIV

  9. A comparison of the clinical features of depression in HIV-positive ...

    African Journals Online (AJOL)

    AIDS with prevalence 2 to 3 times higher than the general population. It's still questionable whether HIV related depression is clinically different from depression in HIV-negative populations, a fact that could have treatment implications.This study ...

  10. Predicting the outcome of oral food challenges with hen's egg through skin test end-point titration.

    Science.gov (United States)

    Tripodi, S; Businco, A Di Rienzo; Alessandri, C; Panetta, V; Restani, P; Matricardi, P M

    2009-08-01

    Oral food challenge (OFC) is the diagnostic 'gold standard' of food allergies but it is laborious and time consuming. Attempts to predict a positive OFC through specific IgE assays or conventional skin tests so far gave suboptimal results. To test whether skin test with titration curves predict with enough confidence the outcome of an oral food challenge. Children (n=47; mean age 6.2 +/- 4.2 years) with suspected and diagnosed allergic reactions to hen's egg (HE) were examined through clinical history, physical examination, oral food challenge, conventional and end-point titrated skin tests with HE white extract and determination of serum specific IgE against HE white. Predictive decision points for a positive outcome of food challenges were calculated through receiver operating characteristic (ROC) analysis for HE white using IgE concentration, weal size and end-point titration (EPT). OFC was positive (Sampson's score >or=3) in 20/47 children (42.5%). The area under the ROC curve obtained with the EPT method was significantly bigger than the one obtained by measuring IgE-specific antibodies (0.99 vs. 0.83, P<0.05) and weal size (0.99 vs. 0.88, P<0.05). The extract's dilution that successfully discriminated a positive from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256, corresponding to a concentration of 5.9 microg/mL of ovotransferrin, 22.2 microg/mL of ovalbumin, and 1.4 microg/mL of lysozyme. EPT is a promising approach to optimize the use of skin prick tests and to predict the outcome of OFC with HE in children. Further studies are needed to test whether this encouraging finding can be extended to other populations and food allergens.

  11. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

    NARCIS (Netherlands)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; de Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-01-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across

  12. Comparison of audio computer assisted self-interview and face-to-face interview methods in eliciting HIV-related risks among men who have sex with men and men who inject drugs in Nigeria.

    Directory of Open Access Journals (Sweden)

    Sylvia Adebajo

    Full Text Available INTRODUCTION: Face-to-face (FTF interviews are the most frequently used means of obtaining information on sexual and drug injecting behaviours from men who have sex with men (MSM and men who inject drugs (MWID. However, accurate information on these behaviours may be difficult to elicit because of sociocultural hostility towards these populations and the criminalization associated with these behaviours. Audio computer assisted self-interview (ACASI is an interviewing technique that may mitigate social desirability bias in this context. METHODS: This study evaluated differences in the reporting of HIV-related risky behaviours by MSM and MWID using ACASI and FTF interviews. Between August and September 2010, 712 MSM and 328 MWID in Nigeria were randomized to either ACASI or FTF interview for completion of a behavioural survey that included questions on sensitive sexual and injecting risk behaviours. Data were analyzed separately for MSM and MWID. Logistic regression was run for each behaviour as a dependent variable to determine differences in reporting methods. RESULTS: MSM interviewed via ACASI reported significantly higher risky behaviours with both women (multiple female sexual partners 51% vs. 43%, p = 0.04; had unprotected anal sex with women 72% vs. 57%, p = 0.05 and men (multiple male sex partners 70% vs. 54%, p≤0.001 than through FTF. Additionally, they were more likely to self-identify as homosexual (AOR: 3.3, 95%CI:2.4-4.6 and report drug use in the past 12 months (AOR:40.0, 95%CI: 9.6-166.0. MWID interviewed with ACASI were more likely to report needle sharing (AOR:3.3, 95%CI:1.2-8.9 and re-use (AOR:2.2, 95%CI:1.2-3.9 in the past month and prior HIV testing (AOR:1.6, 95%CI 1.02-2.5. CONCLUSION: The feasibility of using ACASI in studies and clinics targeting key populations in Nigeria must be explored to increase the likelihood of obtaining more accurate data on high risk behaviours to inform improved risk reduction strategies

  13. Comparison of audio computer assisted self-interview and face-to-face interview methods in eliciting HIV-related risks among men who have sex with men and men who inject drugs in Nigeria.

    Science.gov (United States)

    Adebajo, Sylvia; Obianwu, Otibho; Eluwa, George; Vu, Lung; Oginni, Ayo; Tun, Waimar; Sheehy, Meredith; Ahonsi, Babatunde; Bashorun, Adebobola; Idogho, Omokhudu; Karlyn, Andrew

    2014-01-01

    Face-to-face (FTF) interviews are the most frequently used means of obtaining information on sexual and drug injecting behaviours from men who have sex with men (MSM) and men who inject drugs (MWID). However, accurate information on these behaviours may be difficult to elicit because of sociocultural hostility towards these populations and the criminalization associated with these behaviours. Audio computer assisted self-interview (ACASI) is an interviewing technique that may mitigate social desirability bias in this context. This study evaluated differences in the reporting of HIV-related risky behaviours by MSM and MWID using ACASI and FTF interviews. Between August and September 2010, 712 MSM and 328 MWID in Nigeria were randomized to either ACASI or FTF interview for completion of a behavioural survey that included questions on sensitive sexual and injecting risk behaviours. Data were analyzed separately for MSM and MWID. Logistic regression was run for each behaviour as a dependent variable to determine differences in reporting methods. MSM interviewed via ACASI reported significantly higher risky behaviours with both women (multiple female sexual partners 51% vs. 43%, p = 0.04; had unprotected anal sex with women 72% vs. 57%, p = 0.05) and men (multiple male sex partners 70% vs. 54%, p≤0.001) than through FTF. Additionally, they were more likely to self-identify as homosexual (AOR: 3.3, 95%CI:2.4-4.6) and report drug use in the past 12 months (AOR:40.0, 95%CI: 9.6-166.0). MWID interviewed with ACASI were more likely to report needle sharing (AOR:3.3, 95%CI:1.2-8.9) and re-use (AOR:2.2, 95%CI:1.2-3.9) in the past month and prior HIV testing (AOR:1.6, 95%CI 1.02-2.5). The feasibility of using ACASI in studies and clinics targeting key populations in Nigeria must be explored to increase the likelihood of obtaining more accurate data on high risk behaviours to inform improved risk reduction strategies that reduce HIV transmission.

  14. Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression.

    Science.gov (United States)

    Turan, Bulent; Smith, Whitney; Cohen, Mardge H; Wilson, Tracey E; Adimora, Adaora A; Merenstein, Daniel; Adedimeji, Adebola; Wentz, Eryka L; Foster, Antonina G; Metsch, Lisa; Tien, Phyllis C; Weiser, Sheri D; Turan, Janet M

    2016-06-01

    Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence. The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced. The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence. Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.

  15. Changing forms of HIV-related stigma along the HIV care and treatment continuum in sub-Saharan Africa: a temporal analysis.

    Science.gov (United States)

    Bonnington, O; Wamoyi, J; Ddaaki, W; Bukenya, D; Ondenge, K; Skovdal, M; Renju, J; Moshabela, M; Wringe, A

    2017-07-01

    Stigma remains pervasive for people living with HIV (PLHIV) in sub-Saharan Africa, undermining care engagement. Using everyday , biographical and epochal temporalities, we explored the manifestation of stigma at different stages of the HIV care continuum in seven health and demographic surveillance sites in Eastern and Southern Africa. Between 2015 and 2016, we conducted qualitative in-depth interviews with 264 PLHIV, 54 health providers and 48 family members of people who had died from HIV. Topic guides explored experiences of HIV testing, care and treatment services. Data were analysed thematically, aided by NVivo 10. In everyday time across these communities, stigma was evident in the presence of gossiping and the relative absence of supportive interpersonal discourse, which fuelled judicious disclosure. This was especially disruptive at testing, counselling and early antiretroviral therapy adherence stages of care. Biographical time framed everyday stigma events, highlighting the dilemma of disclosure in relation to sexual relationship norms, as well as the interfacing of age and healthcare continuum points. Epochal patriarchal relations gave a structural context to everyday and biographical stigma dynamics. Historical shifts to social acceptance of PLHIV within these communities, while positive, were complicated by stigma in everyday life and in respect of biographical goals like having a family. Moreover, low community-level resistance to HIV-related stigma jeopardised stigma reduction strategies. Despite improvements to HIV care services, stigma remains pervasive across the HIV care continuum in these sites. Context-specific interventions are needed to address stigma and discrimination of PLHIV within the community and in health services, and greater reflection is required to ensure policies aiming to expand HIV treatment do not exacerbate stigma and result in negative HIV outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where

  16. Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

    Science.gov (United States)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

    2013-01-01

    Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

  17. Cross-sectional study assessing HIV-related knowledge, attitudes and behavior in the Namibian truck transport sector: Readjusting HIV prevention programs in the workplace

    Directory of Open Access Journals (Sweden)

    Til R. Kiderlen

    2015-07-01

    Full Text Available Summary: The objectives of this study were to assess the current status of HIV-related knowledge, attitudes, and behavior (KAB of employees in the private transport sector in Namibia and to compare companies with established HIV workplace program (WPPs with those that have recently initiated the implementation of such programs. The study was designed as a cross-sectional questionnaire-based survey. Between January and March 2011, the survey was conducted in the Namibian truck transport sector in six companies of different sizes. The participants were selected randomly from the workforce. Data collection was based on a KAB questionnaire.The range of correct answers to the survey concerning the knowledge of HIV transmission was 67–95%. Twenty percent of the employees had never been tested for HIV. Additionally, risky sexual behaviors were quite prevalent and included having multiple concurrent partners and the use of sex for incentives. This study revealed that drivers and laborers were especially at risk for such behaviors. The employees of companies with established WPPs were tested for HIV more often than those of companies with new WPPs; however, aside from this difference, only minor differences were observed between the two groups. The findings of this study highlight the need for on-going HIV information and prevention campaigns that focus on the special needs of mobile and low-income workers. WPPs should be tailored accordingly and shift their focus to more practical approaches, such as voluntary counseling and testing (VCT, to increase their effectiveness. Keywords: HIV, Knowledge, Attitudes, Behavior, Namibia, Transport sector

  18. Cross-sectional study assessing HIV-related knowledge, attitudes and behavior in the Namibian truck transport sector: Readjusting HIV prevention programs in the workplace.

    Science.gov (United States)

    Kiderlen, Til R; Conteh, Michael; Roll, Stephanie; Seeling, Stefanie; Weinmann, Stefan

    2015-01-01

    The objectives of this study were to assess the current status of HIV-related knowledge, attitudes, and behavior (KAB) of employees in the private transport sector in Namibia and to compare companies with established HIV workplace program (WPPs) with those that have recently initiated the implementation of such programs. The study was designed as a cross-sectional questionnaire-based survey. Between January and March 2011, the survey was conducted in the Namibian truck transport sector in six companies of different sizes. The participants were selected randomly from the workforce. Data collection was based on a KAB questionnaire. The range of correct answers to the survey concerning the knowledge of HIV transmission was 67-95%. Twenty percent of the employees had never been tested for HIV. Additionally, risky sexual behaviors were quite prevalent and included having multiple concurrent partners and the use of sex for incentives. This study revealed that drivers and laborers were especially at risk for such behaviors. The employees of companies with established WPPs were tested for HIV more often than those of companies with new WPPs; however, aside from this difference, only minor differences were observed between the two groups. The findings of this study highlight the need for on-going HIV information and prevention campaigns that focus on the special needs of mobile and low-income workers. WPPs should be tailored accordingly and shift their focus to more practical approaches, such as voluntary counseling and testing (VCT), to increase their effectiveness. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  19. Hypersexual, Sexually Compulsive, or Just Highly Sexually Active? Investigating Three Distinct Groups of Gay and Bisexual Men and Their Profiles of HIV-Related Sexual Risk

    Science.gov (United States)

    Rendina, H. Jonathon; Ventuneac, Ana; Moody, Raymond L.; Grov, Christian

    2015-01-01

    Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups—Neither SC nor HD; SC only, and Both SC and HD—that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures—temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition—as well as reports of actual sexual behavior. Nearly half (48.9 %) of this highly sexually active sample was classified as Neither SC nor HD, 30 % as SC Only, and 21.1 % as Both SC and HD. While we found no significant differences between the three groups on reported number of male partners, anal sex acts, or anal sex acts with serodiscordant partners, the Both SC and HD group reported higher numbers of CAS acts and CAS acts with serodiscordant partners and also had a higher proportion of their anal sex acts without condoms compared to the SC Only group. Our findings support the validity of a three-group classification system of SC/HD severity in differentiating psychosexual and HIV-related sexual risk behavior outcomes in a sample of GBM who report similarly high levels of sexual activity. Notwithstanding the need for sex positive HIV prevention programs, interventions that attempt to help Both SC and HD men deal with distress and address their psychosexual needs specifically may derive HIV prevention benefits. PMID:25750052

  20. Parental Monitoring Among Young Men Who Have Sex With Men: Associations With Sexual Activity and HIV-Related Sexual Risk Behaviors.

    Science.gov (United States)

    Thoma, Brian C

    2017-09-01

    Young men who have sex with men (YMSM) are at disproportionate risk for HIV infection. Parental monitoring is protective against adolescent sexual risk behavior among heterosexual adolescents, yet it is unclear whether these findings generalize to YMSM. YMSM experience unique family dynamics during adolescence, including coming out to parents and parental rejection of sexual orientation. The present study examined how theoretically derived parental monitoring constructs were associated with sexual activity and sexual risk behaviors among YMSM. YMSM aged 14-18 years completed a cross-sectional online survey (n = 646). Factor analysis was completed to determine factor structure of monitoring measure. Sexual behaviors were predicted from monitoring constructs and covariates within regression models. Parental knowledge and adolescent disclosure, parental solicitation, parental control, and adolescent secret-keeping emerged as four distinct monitoring constructs among YMSM. Higher knowledge and disclosure (b = -.32, p = .022), higher control (b = -.28, p = .006), lower solicitation (b = .31, p = .008), and lower secret-keeping (b = .25, p = .015) were associated with lower odds of sexual activity with males in the past 6 months. Higher knowledge and disclosure (b = -.12, p = .016), higher control (b = -.08, p = .039), and lower secret-keeping (b = .11, p = .005) were associated with having fewer recent sexual partners. Monitoring constructs were unassociated with condomless anal intercourse instances among sexually active YMSM. YMSM disclosure is closely tied with parental knowledge, and parents should foster relationships and home environments where YMSM are comfortable disclosing information freely. Effective parental monitoring could limit YMSM's opportunities for sexual activity, but monitoring is not sufficient to protect against HIV-related sexual risk behaviors among sexually active YMSM. Copyright © 2017 Society for Adolescent Health and

  1. A multi-level modeling approach examining PTSD symptom reduction during prolonged exposure therapy: moderating effects of number of trauma types experienced, having an HIV-related index trauma, and years since HIV diagnosis among HIV-positive adults.

    Science.gov (United States)

    Junglen, Angela G; Smith, Brian C; Coleman, Jennifer A; Pacella, Maria L; Boarts, Jessica M; Jones, Tracy; Feeny, Norah C; Ciesla, Jeffrey A; Delahanty, Douglas L

    2017-11-01

    People living with HIV (PLWH) have extensive interpersonal trauma histories and higher rates of posttraumatic stress disorder (PTSD) than the general population. Prolonged exposure (PE) therapy is efficacious in reducing PTSD across a variety of trauma samples; however, research has not examined factors that influence how PTSD symptoms change during PE for PLWH. Using multi-level modeling, we examined the potential moderating effect of number of previous trauma types experienced, whether the index trauma was HIV-related or not, and years since HIV diagnosis on PTSD symptom reduction during a 10-session PE protocol in a sample of 51 PLWH. In general, PTSD symptoms decreased linearly throughout the PE sessions. Experiencing more previous types of traumatic events was associated with a slower rate of PTSD symptom change. In addition, LOCF analyses found that participants with a non-HIV-related versus HIV-related index trauma had a slower rate of change for PTSD symptoms over the course of PE. However, analyses of raw data decreased this finding to marginal. Years since HIV diagnosis did not impact PTSD symptom change. These results provide a better understanding of how to tailor PE to individual clients and aid clinicians in approximating the rate of symptom alleviation. Specifically, these findings underscore the importance of accounting for trauma history and index trauma type when implementing a treatment plan for PTSD in PLWH.

  2. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations.

    Science.gov (United States)

    Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

    2018-01-01

    Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

  3. Adaptive endpoint detection of seismic signal based on auto-correlated function

    International Nuclear Information System (INIS)

    Fan Wanchun; Shi Ren

    2000-01-01

    There are certain shortcomings for the endpoint detection by time-waveform envelope and/or by checking the travel table (both labelled as the artificial detection method). Based on the analysis of the auto-correlation function, the notion of the distance between auto-correlation functions was quoted, and the characterizations of the noise and the signal with noise were discussed by using the distance. Then, the method of auto-adaptable endpoint detection of seismic signal based on auto-correlated similarity was summed up. The steps of implementation and determining of the thresholds were presented in detail. The experimental results that were compared with the methods based on artificial detecting show that this method has higher sensitivity even in a low SNR circumstance

  4. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

    Directory of Open Access Journals (Sweden)

    Federico Fogolari

    2018-02-01

    Full Text Available Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

  5. Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption.

    Science.gov (United States)

    Inouye, Joshua M; Valero-Cuevas, Francisco J

    2016-02-01

    Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms

  6. Comparison of mammalian and fish cell line cytotoxicity: impact of endpoint and exposure duration

    International Nuclear Information System (INIS)

    Guelden, Michael; Moerchel, Sabine; Seibert, Hasso

    2005-01-01

    Comparisons of acute toxic concentrations of chemicals to fish in vivo and cytotoxic concentrations to fish cell lines in vitro reveal rather good correlations of the toxic potencies in vitro and in vivo, but a clearly lower sensitivity of the fish cells. To examine whether the low sensitivity is specific for fish cells, cytotoxic potencies of reference chemicals from the Multicenter Evaluation of In Vitro Cytotoxicity program (MEIC) reported for the fish cell lines R1 and RTG-2 were compared with those obtained with the mouse Balb/c 3T3 cell line. Cytotoxic potencies (EC 50 values) for MEIC reference chemicals were determined with exponentially growing Balb/c 3T3 cells using three different test protocols. To assess both endpoints, cell proliferation and cell survival, EC 50 values were measured for the decrease in final cell protein after 24 and 72 h of exposure and for the reduction of cell protein increase during 24 h of exposure. EC 50 values obtained with the fish cell lines R1 and RTG-2 using cell survival as endpoint were taken from the MEIC data base. The comparison of cytotoxic potencies shows that, in general, the fish cell lines and the mammalian cell line are almost equally sensitive towards the cytotoxic action of chemicals. The mammalian cell line assay, however, becomes considerably more sensitive, by factors of 3.4-8.5, than the fish cell line assays, if cell growth instead of cell survival is used as endpoint. It is concluded, that cell proliferation might be a better endpoint than cell survival and that mammalian cell lines might be suited to assess fish acute toxicity

  7. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    International Nuclear Information System (INIS)

    Xu Jinsheng; Purcell, Wendy M.

    2006-01-01

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

  8. Kinetic titration with differential thermometric determination of the end-point.

    Science.gov (United States)

    Sajó, I

    1968-06-01

    A method has been described for the determination of concentrations below 10(-4)M by applying catalytic reactions and using thermometric end-point determination. A reference solution, identical with the sample solution except for catalyst, is titrated with catalyst solution until the rates of reaction become the same, as shown by a null deflection on a galvanometer connected via bridge circuits to two opposed thermistors placed in the solutions.

  9. Quantitative 4D Transcatheter Intraarterial Perfusion MR Imaging as a Method to Standardize Angiographic Chemoembolization Endpoints

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2011-01-01

    PURPOSE We aimed to test the hypothesis that subjective angiographic endpoints during transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) exhibit consistency and correlate with objective intraprocedural reductions in tumor perfusion as determined by quantitative four dimensional (4D) transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging. MATERIALS AND METHODS This prospective study was approved by the institutional review board. Eighteen consecutive patients underwent TACE in a combined MR/interventional radiology (MR-IR) suite. Three board-certified interventional radiologists independently graded the angiographic endpoint of each procedure based on a previously described subjective angiographic chemoembolization endpoint (SACE) scale. A consensus SACE rating was established for each patient. Patients underwent quantitative 4D TRIP-MR imaging immediately before and after TACE, from which mean whole tumor perfusion (Fρ) was calculated. Consistency of SACE ratings between observers was evaluated using the intraclass correlation coefficient (ICC). The relationship between SACE ratings and intraprocedural TRIP-MR imaging perfusion changes was evaluated using Spearman’s rank correlation coefficient. RESULTS The SACE rating scale demonstrated very good consistency among all observers (ICC = 0.80). The consensus SACE rating was significantly correlated with both absolute (r = 0.54, P = 0.022) and percent (r = 0.85, P SACE rating scale demonstrates very good consistency between raters, and significantly correlates with objectively measured intraprocedural perfusion reductions during TACE. These results support the use of the SACE scale as a standardized alternative method to quantitative 4D TRIP-MR imaging to classify patients based on embolic endpoints of TACE. PMID:22021520

  10. Factors Influencing Depression Endpoints Research (FINDER: baseline results of Italian patients with depression

    Directory of Open Access Journals (Sweden)

    Grassi Luigi

    2009-05-01

    Full Text Available Abstract Background Factors Influencing Depression Endpoints Research (FINDER is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL in outpatients receiving pharmacological treatment for a first or new depressive episode. Baseline characteristics of patients enrolled in Italy are presented. Methods All treatment decisions were at the discretion of the investigator. Data were collected at baseline and after 3 and 6 months of treatment. Baseline evaluations included demographics, medical and psychiatric history, and medications used in the last 24 months and prescribed at enrolment. The Hospital Anxiety and Depression Scale (HADS, was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the Somatic Symptom Inventory (SSI and a 0 to 100 mm visual analogue scale (VAS, HRQoL via 36-item Short Form Health Survey (SF-36, and the European Quality of Life 5-Dimensions (EQ-5D instrument. Results A total of 513 patients were recruited across 38 sites. The mean ± standard deviation (SD age at first depressive episode was 38.7 ± 15.9 years, the mean duration of depression 10.6 ± 12.3 years. The most common psychiatric comorbidities in the previous 24 months were anxiety/panic (72.6% and obsessive/compulsive disorders (13.4%, while 35.9% had functional somatic syndromes. Most patients (65.1% reported pain from any cause. Monotherapy with selective serotonin reuptake inhibitors (SSRIs and tricyclic antidepressants (TCAs was prescribed at enrolment in 64.5% and 6.4% of the cases, respectively. The most commonly prescribed agents were sertraline (17.3%, escitalopram (16.2%, venlaflaxine (15.6% and paroxetine (14.8%. The mean HADS subscores for depression and anxiety were 13.3 ± 4.2 and 12.2 ± 3.9, respectively; 76.4% of patients could be defined as being 'probable cases' for depression and 66.2% for anxiety. The

  11. A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

    Science.gov (United States)

    Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

    2015-11-01

    No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping.

    Science.gov (United States)

    Erden, Mustafa Suphi; Billard, Aude

    2015-06-01

    The goal of this paper is to perform end-point impedance measurements across dominant and nondominant hands while doing airbrush painting and to use the results for developing a robotic assistance scheme. We study airbrush painting because it resembles in many ways manual welding, a standard industrial task. The experiments are performed with the 7 degrees of freedom KUKA lightweight robot arm. The robot is controlled in admittance using a force sensor attached at the end-point, so as to act as a free-mass and be passively guided by the human. For impedance measurements, a set of nine subjects perform 12 repetitions of airbrush painting, drawing a straight-line on a cartoon horizontally placed on a table, while passively moving the airbrush mounted on the robot's end-point. We measure hand impedance during the painting task by generating sudden and brief external forces with the robot. The results show that on average the dominant hand displays larger impedance than the nondominant in the directions perpendicular to the painting line. We find the most significant difference in the damping values in these directions. Based on this observation, we develop a "directional damping" scheme for robotic assistance and conduct a pilot study with 12 subjects to contrast airbrush painting with and without robotic assistance. Results show significant improvement in precision with both dominant and nondominant hands when using robotic assistance.

  13. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  14. Individuals versus organisms versus populations in the definition of ecological assessment endpoints.

    Science.gov (United States)

    Suter, Glenn W; Norton, Susan B; Fairbrother, Anne

    2005-11-01

    Discussions and applications of the policies and practices of the U.S. Environmental Protection Agency (USEPA) in ecological risk assessment will benefit from continued clarification of the concepts of assessment endpoints and of levels of biological organization. First, assessment endpoint entities and attributes can be defined at different levels of organization. Hence, an organism-level attribute, such as growth or survival, can be applied collectively to a population-level entity such as the brook trout in a stream. Second, assessment endpoints for ecological risk assessment are often mistakenly described as "individual level," which leads to the idea that such assessments are intended to protect individuals. Finally, populations play a more important role in risk assessments than is generally recognized. Organism-level attributes are used primarily for population-level assessments. In addition, the USEPA and other agencies already are basing management decisions on population or community entities and attributes such as production of fisheries, abundance of migratory bird populations, and aquatic community composition.

  15. Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

    Directory of Open Access Journals (Sweden)

    Thomas Staab

    2016-11-01

    Full Text Available Abstract Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA. Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany.

  16. HIV-related risk behaviours and the correlates among rickshaw pullers of Kamrangirchar, Dhaka, Bangladesh: a cross-sectional study using probability sampling

    Directory of Open Access Journals (Sweden)

    Ravari Shahrzad

    2009-03-01

    Full Text Available Abstract Background National HIV serological and behavioural surveillance of Bangladesh repeatedly demonstrated a very high proportion of rickshaw pullers in Dhaka city, having sex with female sex workers (FSWs and using illicit substances. However, no study has been conducted to identify the correlates of having sex with FSWs among this population. This study aimed to describe behavioural profile of rickshaw pullers in Dhaka city using probability samples and to identify the correlates for having sex with FSWs in order to focus HIV prevention intervention. Methods Six hundred rickshaw pullers were randomly selected from rickshaw garages in the Kamrangirchar area, the single largest slum cluster of Dhaka, Bangladesh, during March–April 2008 using the Proportion Probability to Size method. Participants were interviewed, with a response rate of 99.2% (n = 595, using a structured questionnaire and asked about illicit substance use, sexual behaviour and risk perception for HIV and sexually transmitted diseases. Independent predictors of having sex with FSWs were analysed by multivariate analysis. A qualitative study was subsequently conducted with 30 rickshaw pullers to supplement the findings of the initial survey. Results The proportion of survey respondents who had sex with FSWs and those who used illicit substances in the previous 12 months period were 7.9% and 24.9%, respectively, much lower than the results achieved in the 2003–04 behavioural surveillance (72.8% and 89.9%, respectively. Multivariate analysis revealed the characteristics of younger age, being never married, living alone with family remaining in other districts and using illicit substances in the previous 12 months were significantly associated with having sex with FSWs. Conclusion HIV-related risk behaviour of our study population of the rickshaw pullers was lower than what has been suggested by the results of behavioural surveillance. While this discrepancy should be

  17. Energetic endpoints provide early indicators of life history effects in a freshwater gastropod exposed to the fungicide, pyraclostrobin

    International Nuclear Information System (INIS)

    Fidder, Bridgette N.; Reátegui-Zirena, Evelyn G.; Olson, Adric D.; Salice, Christopher J.

    2016-01-01

    Organismal energetics provide important insights into the effects of environmental toxicants. We aimed to determine the effects of pyraclostrobin on Lymnaea stagnalis by examining energy allocation patterns and life history traits. Juvenile snails exposed to pyraclostrobin decreased feeding rate and increased apparent avoidance behaviors at environmentally relevant concentrations. In adults, we found that sublethal concentrations of pyraclostrobin did not affect reproductive output, however, there were significant effects on developmental endpoints with longer time to hatch and decreased hatching success in pyraclostrobin-exposed egg masses. Further, there were apparent differences in developmental effects depending on whether mothers were also exposed to pyraclostrobin suggesting this chemical can exert intergenerational effects. Pyraclostrobin also affected protein and carbohydrate content of eggs in mothers that were exposed to pyraclostrobin. Significant effects on macronutrient content of eggs occurred at lower concentrations than effects on gross endpoints such as hatching success and time to hatch suggesting potential value for these endpoints as early indicators of ecologically relevant stress. These results provide important insight into the effects of a common fungicide on important endpoints for organismal energetics and life history. - Highlights: • We exposed a freshwater snail to relevant concentrations of pyraclostrobin. • We monitored energetic and life history endpoints. • Pyraclostrobin affected feeding, hatching success and egg macronutrient content. • Energetic-based endpoints may provide valuable insight to toxic effects. - The fungicide pyraclostrobin at environmentally relevant concentrations effects a range of life history and energetic endpoints in the freshwater snail, Lymnaea stagnalis.

  18. The time-dependent "cure-death" model investigating two equally important endpoints simultaneously in trials treating high-risk patients with resistant pathogens.

    Science.gov (United States)

    Sommer, Harriet; Wolkewitz, Martin; Schumacher, Martin

    2017-07-01

    A variety of primary endpoints are used in clinical trials treating patients with severe infectious diseases, and existing guidelines do not provide a consistent recommendation. We propose to study simultaneously two primary endpoints, cure and death, in a comprehensive multistate cure-death model as starting point for a treatment comparison. This technique enables us to study the temporal dynamic of the patient-relevant probability to be cured and alive. We describe and compare traditional and innovative methods suitable for a treatment comparison based on this model. Traditional analyses using risk differences focus on one prespecified timepoint only. A restricted logrank-based test of treatment effect is sensitive to ordered categories of responses and integrates information on duration of response. The pseudo-value regression provides a direct regression model for examination of treatment effect via difference in transition probabilities. Applied to a topical real data example and simulation scenarios, we demonstrate advantages and limitations and provide an insight into how these methods can handle different kinds of treatment imbalances. The cure-death model provides a suitable framework to gain a better understanding of how a new treatment influences the time-dynamic cure and death process. This might help the future planning of randomised clinical trials, sample size calculations, and data analyses. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Automatic Identification of the Repolarization Endpoint by Computing the Dominant T-wave on a Reduced Number of Leads.

    Science.gov (United States)

    Giuliani, C; Agostinelli, A; Di Nardo, F; Fioretti, S; Burattini, L

    2016-01-01

    Electrocardiographic (ECG) T-wave endpoint (Tend) identification suffers lack of reliability due to the presence of noise and variability among leads. Tend identification can be improved by using global repolarization waveforms obtained by combining several leads. The dominant T-wave (DTW) is a global repolarization waveform that proved to improve Tend identification when computed using the 15 (I to III, aVr, aVl, aVf, V1 to V6, X, Y, Z) leads usually available in clinics, of which only 8 (I, II, V1 to V6) are independent. The aim of the present study was to evaluate if the 8 independent leads are sufficient to obtain a DTW which allows a reliable Tend identification. To this aim Tend measures automatically identified from 15-dependent-lead DTWs of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were compared with those obtained from 8-independent-lead DTWs. Results indicate that Tend distributions have not statistically different median values (CHS: 340 ms vs. 340 ms, respectively; AMIP: 325 ms vs. 320 ms, respectively), besides being strongly correlated (CHS: ρ=0.97, AMIP: 0.88; Pautomatic Tend identification from DTW, the 8 independent leads can be used without a statistically significant loss of accuracy but with a significant decrement of computational effort. The lead dependence of 7 out of 15 leads does not introduce a significant bias in the Tend determination from 15 dependent lead DTWs.

  20. Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

    Energy Technology Data Exchange (ETDEWEB)

    Deeb, Rula A.; Hawley, Elisabeth L. [ARCADIS, U.S., 2000 Powell St., 7th Floor, Emeryville, California 94608 (United States)

    2013-07-01

    The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed

  1. Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

    International Nuclear Information System (INIS)

    Deeb, Rula A.; Hawley, Elisabeth L.

    2013-01-01

    The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate

  2. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

    Science.gov (United States)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-11-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay

    International Nuclear Information System (INIS)

    Ehling, G.; Hecht, M.; Heusener, A.; Huesler, J.; Gamer, A.O.; Loveren, H. van; Maurer, Th.; Riecke, K.; Ullmann, L.; Ulrich, P.; Vandebriel, R.; Vohr, H.-W.

    2005-01-01

    The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC 3 values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme

  4. Phase II Trials for Heterogeneous Patient Populations with a Time-to-Event Endpoint.

    Science.gov (United States)

    Jung, Sin-Ho

    2017-07-01

    In this paper, we consider a single-arm phase II trial with a time-to-event end-point. We assume that the study population has multiple subpopulations with different prognosis, but the study treatment is expected to be similarly efficacious across the subpopulations. We review a stratified one-sample log-rank test and present its sample size calculation method under some practical design settings. Our sample size method requires specification of the prevalence of subpopulations. We observe that the power of the resulting sample size is not very sensitive to misspecification of the prevalence.

  5. On weighted hardy inequalities on semiaxis for functions vanishing at the endpoints

    Directory of Open Access Journals (Sweden)

    Vladimir Stepanov

    1997-01-01

    Full Text Available We study the weighted Hardy inequalities on the semiaxis of the form ‖Fu‖2≤C‖F(kv‖2  (1 for functions vanishing at the endpoints together with derivatives up to the order k−1. The case k=2 is completely characterized.

  6. Adaptive endpoint detection of seismic signal based on auto-correlated function

    International Nuclear Information System (INIS)

    Fan Wanchun; Shi Ren

    2001-01-01

    Based on the analysis of auto-correlation function, the notion of the distance between auto-correlation function was quoted, and the characterization of the noise and the signal with noise were discussed by using the distance. Then, the method of auto- adaptable endpoint detection of seismic signal based on auto-correlated similarity was summed up. The steps of implementation and determining of the thresholds were presented in detail. The experimental results that were compared with the methods based on artificial detecting show that this method has higher sensitivity even in a low signal with noise ratio circumstance

  7. Giant Magnetic Fluctuations at the Critical Endpoint in Insulating HoMnO3

    Science.gov (United States)

    Choi, Y. J.; Lee, N.; Sharma, P. A.; Kim, S. B.; Vajk, O. P.; Lynn, J. W.; Oh, Y. S.; Cheong, S.-W.

    2013-04-01

    Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP’s) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., χ''(2.05T,2.2K)/χ''(3T,2.2K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3.

  8. Does bisphenol A induce superfeminization in Marisa cornuarietis? Part I: intra- and inter-laboratory variability in test endpoints.

    Science.gov (United States)

    Forbes, Valery E; Selck, Henriette; Palmqvist, Annemette; Aufderheide, John; Warbritton, Ryan; Pounds, Nadine; Thompson, Roy; van der Hoeven, Nelly; Caspers, Norbert

    2007-03-01

    It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability in endpoints. The results highlight the importance of obtaining basic knowledge of husbandry requirements and baseline information on life-history traits of potential test species prior to designing toxicity test protocols. Understanding of the levels and sources of endpoint variability is essential so that statistically robust and ecologically relevant tests of chemicals can be conducted.

  9. An overview of techniques for linking high-dimensional molecular data to time-to-event endpoints by risk prediction models.

    Science.gov (United States)

    Binder, Harald; Porzelius, Christine; Schumacher, Martin

    2011-03-01

    Analysis of molecular data promises identification of biomarkers for improving prognostic models, thus potentially enabling better patient management. For identifying such biomarkers, risk prediction models can be employed that link high-dimensional molecular covariate data to a clinical endpoint. In low-dimensional settings, a multitude of statistical techniques already exists for building such models, e.g. allowing for variable selection or for quantifying the added value of a new biomarker. We provide an overview of techniques for regularized estimation that transfer this toward high-dimensional settings, with a focus on models for time-to-event endpoints. Techniques for incorporating specific covariate structure are discussed, as well as techniques for dealing with more complex endpoints. Employing gene expression data from patients with diffuse large B-cell lymphoma, some typical modeling issues from low-dimensional settings are illustrated in a high-dimensional application. First, the performance of classical stepwise regression is compared to stage-wise regression, as implemented by a component-wise likelihood-based boosting approach. A second issues arises, when artificially transforming the response into a binary variable. The effects of the resulting loss of efficiency and potential bias in a high-dimensional setting are illustrated, and a link to competing risks models is provided. Finally, we discuss conditions for adequately quantifying the added value of high-dimensional gene expression measurements, both at the stage of model fitting and when performing evaluation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

    Science.gov (United States)

    Kanda, Eiichiro; Usui, Tomoko; Kashihara, Naoki; Iseki, Chiho; Iseki, Kunitoshi; Nangaku, Masaomi

    2018-04-01

    Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m 2 . Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m 2 ) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

  11. Reducing HIV-related risk and mental health problems through a client-centred psychosocial intervention for vulnerable adolescents in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Jani, Nrupa; Vu, Lung; Kay, Lynnette; Habtamu, Kassahun; Kalibala, Samuel

    2016-01-01

    Ethiopia is experiencing an increasingly urban HIV epidemic, alongside a rise in urban adolescent migration. Adolescent migrants are often confronted by unique social challenges, including living in a difficult environment, abuse and mental health problems. These issues can increase adolescents' vulnerability to HIV and compromise their capacity to protect themselves and others from HIV. We piloted and assessed the effects of a targeted psychosocial intervention to reduce mental health problems and improve HIV-related outcomes among migrant adolescents in Addis Ababa. A pre- and post-comparison design was used in a cohort of 576 female and 154 male migrant adolescents aged 15 to 18 years in Addis Ababa receiving services from two service delivery organizations, Biruh Tesfa and Retrak. We implemented a three-month client-centred, counsellor-delivered psychosocial intervention, based on findings from formative research among the same target population, to address participants' increased vulnerability to HIV. The intervention package comprised individual, group and creative arts therapy counselling sessions. Key outcome indicators included anxiety, depression, aggressive behaviour, attention problems, social problems, knowledge of HIV, safer sex practices and use of sexual health services. Longitudinal data analysis (McNemar test and random effects regression) was used to assess changes over time in key indicators by gender. For females, aggressive behaviour decreased by 60% (adjusted odds ratio (AOR): 0.4 (0.25 to 0.65)) and any mental health problem decreased by 50% (AOR: 0.5 (0.36 to 0.81)) from baseline to end line. In addition, knowledge of HIV increased by 60% (AOR: 1.6 (1.08 to 2.47)), knowledge of a place to test for HIV increased by 70% (AOR: 1.7 (1.12 to 2.51)) and HIV testing increased by 80% (AOR: 1.8 (1.13 to 2.97)). For males, HIV knowledge increased by 110% (AOR: 2.1 (1.1 to 3.94)), knowledge of a place to test for HIV increased by 290% (AOR: 3.9 (1

  12. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hailay Abrha Gesesew

    Full Text Available Late presentation for human immunodeficiency virus (HIV care is a major impediment for the success of antiretroviral therapy (ART outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care.Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value.Ten studies from low- and middle- income countries met the search criteria, including six (6 and four (4 case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5 of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%.High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling

  13. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis

    Science.gov (United States)

    Gesesew, Hailay Abrha; Tesfay Gebremedhin, Amanuel; Demissie, Tariku Dejene; Kerie, Mirkuzie Woldie; Sudhakar, Morankar; Mwanri, Lillian

    2017-01-01

    Background Late presentation for human immunodeficiency virus (HIV) care is a major impediment for the success of antiretroviral therapy (ART) outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome) is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care. Methods Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: ‘late HIV testing’, ‘late HIV diagnosis’ and ‘late presentation for HIV care after testing’. Data were extracted using a standardized Joanna Briggs Institute (JBI) data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value. Results Ten studies from low- and middle- income countries met the search criteria, including six (6) and four (4) case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5) of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6–3.6, I2 = 79%). Conclusions High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should

  14. Mesoscale simulation of semiflexible chains. I. Endpoint distribution and chain dynamics

    Science.gov (United States)

    Groot, Robert D.

    2013-06-01

    The endpoint distribution and dynamics of semiflexible fibers are studied by numerical simulation. A brief overview is given over the analytical theory of flexible and semiflexible polymers. In particular, a closed expression is given for the relaxation spectrum of wormlike chains, which determines polymer diffusion and rheology. Next a simulation model for wormlike chains with full hydrodynamic interaction is described, and relations for the bending and torsion modulus are given. Two methods are introduced to include torsion stiffness into the model. The model is validated by simulating single chains in a heat bath, and comparing the endpoint distribution of the chains with established Monte Carlo results. It is concluded that torsion stiffness leads to a slightly shorter effective persistence length for a given bending stiffness. To further validate the simulation model, polymer diffusion is studied for fixed persistence length and varying polymer length N. The diffusion constant shows crossover from Rouse (D ∝ N-1) to reptation behaviour (D ∝ N-2). The terminal relaxation time obtained from the monomer displacement is consistent with the theory of wormlike chains. The probability for chain crossing has also been studied. This probability is so low that it does not influence the present results.

  15. Hairy black holes and the endpoint of AdS{sub 4} charged superradiance

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Óscar J.C.; Masachs, Ramon [STAG research centre and Mathematical Sciences, University of Southampton,Southampton (United Kingdom)

    2017-02-24

    We construct hairy black hole solutions that merge with the anti-de Sitter (AdS{sub 4}) Reissner-Nordström black hole at the onset of superradiance. These hairy black holes have, for a given mass and charge, higher entropy than the corresponding AdS{sub 4}-Reissner-Nordström black hole. Therefore, they are natural candidates for the endpoint of the charged superradiant instability. On the other hand, hairy black holes never dominate the canonical and grand-canonical ensembles. The zero-horizon radius of the hairy black holes is a soliton (i.e. a boson star under a gauge transformation). We construct our solutions perturbatively, for small mass and charge, so that the properties of hairy black holes can be used to testify and compare with the endpoint of initial value simulations. We further discuss the near-horizon scalar condensation instability which is also present in global AdS{sub 4}-Reissner-Nordström black holes. We highlight the different nature of the near-horizon and superradiant instabilities and that hairy black holes ultimately exist because of the non-linear instability of AdS.

  16. Transgenerational endpoints provide increased sensitivity and insight into multigenerational responses of Lymnaea stagnalis exposed to cadmium.

    Science.gov (United States)

    Reátegui-Zirena, Evelyn G; Fidder, Bridgette N; Olson, Adric D; Dawson, Daniel E; Bilbo, Thomas R; Salice, Christopher J

    2017-05-01

    Ecotoxicology provides data to inform environmental management. Many testing protocols do not consider offspring fitness and toxicant sensitivity. Cadmium (Cd) is a well-studied and ubiquitous toxicant but little is known about the effects on offspring of exposed parents (transgenerational effects). This study had three objectives: to identify endpoints related to offspring performance; to determine whether parental effects would manifest as a change in Cd tolerance in offspring and how parental exposure duration influenced the manifestation of parental effects. Adult snails were exposed to Cd 0, 25, 50, 100, 200 and 400 μg Cd/L for eight weeks. There were effects on adult endpoints (e.g., growth, reproduction) but only at the highest concentrations (>100 μg/L). Alternatively, we observed significant transgenerational effects at all Cd concentrations. Surprisingly, we found increased Cd tolerance in hatchlings from all parental Cd exposure concentrations even though eggs and hatchlings were in Cd-free conditions for 6 weeks. Explicit consideration of offspring performance adds value to current toxicity testing protocols. Parental exposure duration has important implications for offspring effects and that contaminant concentrations that are not directly toxic to parents can cause transgenerational changes in resistance that have significant implications for toxicity testing and adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

    Directory of Open Access Journals (Sweden)

    Astrid Yeo

    Full Text Available Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY and one in acute coronary syndrome (SOLID-TIMI 52. No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%. We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1 and identified three novel loci (TOMM5, FRMD5 and LPL using the GWAS-significance threshold P≤5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2 within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores and one common locus (minor allele frequency 0.24 with genotype by treatment interaction effect passing the GWAS

  18. A patient and community-centered approach selecting endpoints for a randomized trial of a novel advance care planning tool

    Directory of Open Access Journals (Sweden)

    Bridges JFP

    2018-02-01

    Full Text Available John FP Bridges,1,2 Norah L Crossnohere,2 Anne L Schuster,1 Judith A Miller,3 Carolyn Pastorini,3,† Rebecca A Aslakson2,4,5 1Department of Health Policy and Management, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 2Department of Health, Behavior, and Society, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 3Patient-Centered Outcomes Research Institute (PCORI Project, Baltimore, MD, 4Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, 5Armstrong Institute for Patient Safety and Quality, The Johns Hopkins School of Medicine, Baltimore, MD, USA †Carolyn Pastorini passed away on August 24, 2015 Background: Despite a movement toward patient-centered outcomes, best practices on how to gather and refine patients’ perspectives on research endpoints are limited. Advanced care planning (ACP is inherently patient centered and would benefit from patient prioritization of endpoints for ACP-related tools and studies.Objective: This investigation sought to prioritize patient-centered endpoints for the content and evaluation of an ACP video being developed for patients undergoing major surgery. We also sought to highlight an approach using complementary engagement and research strategies to document priorities and preferences of patients and other stakeholders.Materials and methods: Endpoints identified from a previously published environmental scan were operationalized following rating by a caregiver co-investigator, refinement by a patient co-investigator, review by a stakeholder committee, and validation by patients and family members. Finalized endpoints were taken to a state fair where members of the public who indicated that they or a loved one had undergone major surgery prioritized their most relevant endpoints and provided comments.Results: Of the initial 50 ACP endpoints identified from the review, 12 endpoints were selected for public

  19. Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

    Science.gov (United States)

    Saps, M; Lavigne, J V

    2015-06-01

    The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children. 80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals. There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval). Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials. © 2015 John Wiley & Sons Ltd.

  20. Towards better environmental performance of wastewater sludge treatment using endpoint approach in LCA methodology

    Directory of Open Access Journals (Sweden)

    Isam Alyaseri

    2017-03-01

    Full Text Available The aim of this study is to use the life cycle assessment method to measure the environmental performance of the sludge incineration process in a wastewater treatment plant and to propose an alternative that can reduce the environmental impact. To show the damages caused by the treatment processes, the study aimed to use an endpoint approach in evaluating impacts on human health, ecosystem quality, and resources due to the processes. A case study was taken at Bissell Point Wastewater Treatment Plant in Saint Louis, Missouri, U.S. The plant-specific data along with literature data from technical publications were used to build an inventory, and then analyzed the environmental burdens from sludge handling unit in the year 2011. The impact assessment method chosen was ReCipe 2008. The existing scenario (dewatering-multiple hearth incineration-ash to landfill was evaluated and three alternative scenarios (fluid bed incineration and anaerobic digestion with and without land application with energy recovery from heat or biogas were proposed and analyzed to find the one with the least environmental impact. The existing scenario shows that the most significant impacts are related to depletion in resources and damage to human health. These impacts mainly came from the operation phase (electricity and fuel consumption and emissions related to combustion. Alternatives showed better performance than the existing scenario. Using ReCipe endpoint methodology, and among the three alternatives tested, the anaerobic digestion had the best overall environmental performance. It is recommended to convert to fluid bed incineration if the concerns were more about human health or to anaerobic digestion if the concerns were more about depletion in resources. The endpoint approach may simplify the outcomes of this study as follows: if the plant is converted to fluid bed incineration, it could prevent an average of 43.2 DALYs in human life, save 0.059 species in the area

  1. Earlier anal sexarche and co-occurring sexual risk are associated with current HIV-related risk behaviors among an online sample of men who have sex with men in Asia

    Science.gov (United States)

    Cheung, Doug H.; Suharlim, Christian; Guadamuz, Thomas E.; Lim, Sin How; Koe, Stuart; Wei, Chongyi

    2014-01-01

    Studies of heterosexual populations across the globe and men who have sex with men (MSM) in a few developed countries showed that earlier sexual debut (sexarche) was associated with higher levels of co-occurring and subsequent HIV risk behaviors. We examined the relationships between earlier anal sexarche, unprotected earlier anal sexarche and current HIV risks among MSM from Asia. A cross-sectional online survey was conducted among MSM (N = 10,826) in Asia in 2010. Bivariate and multivariable logistic regressions were used to identify co-occurring (i.e., sexual experiences during sexarche) and current HIV-related risk factors (i.e., past six months) associated with earlier anal sexarche (before the age of 18) and unprotected earlier anal sexarche, respectively. Earlier anal sexarche was significantly associated with lack of condom use, being anal receptive or both receptive and insertive, and having a partner who were older during sexarche. It was also associated with current HIV-related risk behaviors including having multiple male sexual partners, having been paid for sex, and increased frequencies of recreational drug use. Unprotected earlier anal sexarche was significantly associated with inconsistent condom use in the past the six months. Improved and culturally sensitive sex education at schools should be included in national and regional HIV/AIDS prevention programming and policies in Asia. Such sex education programs should incorporate curriculum that address sexuality, sexual orientation, and sexual behaviors beyond those related to reproductive health. PMID:24920344

  2. The impact of exposure to mass media campaigns and social support on levels and trends of HIV-related stigma and discrimination in Nigeria: tools for enhancing effective HIV prevention programmes.

    Science.gov (United States)

    Fakolade, R; Adebayo, S B; Anyanti, J; Ankomah, A

    2010-05-01

    People living with HIV and AIDS (PLWHAs) often face stigma and discrimination, especially in developing countries. HIV-related stigma is expressed through social ostracism, personal rejection, direct and indirect discrimination, and denial from families and friends. Consequently, it is associated with reduced adoption of preventive and care behaviours, including condom use, seeking for HIV test and care-seeking behaviour subsequent to diagnosis. Ignorance about the epidemiology of the disease on modes of transmission and prevention aggravates HIV-related stigma in Nigeria. Behaviour change communication activities through mass media have been shown to be an effective approach in improving people's knowledge about the disease. This paper monitors trends in the level of accepting attitudes towards PLWHAs in Nigeria between 2003 and 2007. It also evaluates the impact of exposure to mass media and social support on the levels of accepting attitudes towards PLWHAs. A significant and positive trend was evident between 2003 and 2007 (pmedia communications on HIV and AIDS issues and social support were significantly related to the reduced stigma and discrimination against PLWHAs (p<0.0001).

  3. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Nestler, Holger; Groh, Ksenia J.; Schönenberger, René; Behra, Renata; Schirmer, Kristin; Eggen, Rik I.L.; Suter, Marc J.-F.

    2012-01-01

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  4. Root length of aquatic plant, Lemna minor L., as an optimal toxicity endpoint for biomonitoring of mining effluents.

    Science.gov (United States)

    Gopalapillai, Yamini; Vigneault, Bernard; Hale, Beverley A

    2014-10-01

    Lemna minor, a free-floating macrophyte, is used for biomonitoring of mine effluent quality under the Metal Mining Effluent Regulations (MMER) of the Environmental Effects Monitoring (EEM) program in Canada and is known to be sensitive to trace metals commonly discharged in mine effluents such as Ni. Environment Canada's standard toxicity testing protocol recommends frond count (FC) and dry weight (DW) as the 2 required toxicity endpoints-this is similar to other major protocols such as those by the US Environmental Protection Agency (USEPA) and the Organisation for Economic Co-operation and Development (OECD)-that both require frond growth or biomass endpoints. However, we suggest that similar to terrestrial plants, average root length (RL) of aquatic plants will be an optimal and relevant endpoint. As expected, results demonstrate that RL is the ideal endpoint based on the 3 criteria: accuracy (i.e., toxicological sensitivity to contaminant), precision (i.e., lowest variance), and ecological relevance (metal mining effluents). Roots are known to play a major role in nutrient uptake in conditions of low nutrient conditions-thus having ecological relevance to freshwater from mining regions. Root length was the most sensitive and precise endpoint in this study where water chemistry varied greatly (pH and varying concentrations of Ca, Mg, Na, K, dissolved organic carbon, and an anthropogenic organic contaminant, sodium isopropyl xanthates) to match mining effluent ranges. Although frond count was a close second, dry weight proved to be an unreliable endpoint. We conclude that toxicity testing for the floating macrophyte should require average RL measurement as a primary endpoint. © 2014 SETAC.

  5. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Nestler, Holger [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Groh, Ksenia J.; Schoenenberger, Rene; Behra, Renata [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); Schirmer, Kristin [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); EPF Lausanne, School of Architecture, Civil and Environmental Engineering, 1015 Lausanne (Switzerland); Eggen, Rik I.L. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Suter, Marc J.-F., E-mail: suter@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland)

    2012-04-15

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  6. On the Higher Moments of Particle Multiplicity, Chemical Freeze-Out, and QCD Critical Endpoint

    Directory of Open Access Journals (Sweden)

    A. Tawfik

    2013-01-01

    Full Text Available We calculate the first six nonnormalized moments of particle multiplicity within the framework of the hadron resonance gas model. In terms of the lower order moments and corresponding correlation functions, general expressions of higher order moments are derived. Thermal evolution of the first four normalized moments and their products (ratios are studied at different chemical potentials, so that it is possible to evaluate them at chemical freeze-out curve. It is found that a nonmonotonic behaviour reflecting the dynamical fluctuation and strong correlation of particles starts to appear from the normalized third order moment. We introduce novel conditions for describing the chemical freeze-out curve. Although the hadron resonance gas model does not contain any information on the criticality related to the chiral dynamics and singularity in the physical observables, we are able to find out the location of the QCD critical endpoint at μ ~ 350  MeV and temperature T ~ 162  MeV.

  7. Comparison endpoint study of process plasma and secondary electron beam exciter optical emission spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Stephan Thamban, P. L.; Yun, Stuart; Padron-Wells, Gabriel; Hosch, Jimmy W.; Goeckner, Matthew J. [Department of Mechanical Engineering, University of Texas at Dallas, 800W Campbell Road, Richardson, Texas 75080 (United States); Department of Electrical Engineering, University of Texas at Dallas, 800W Campbell Road, Richardson, Texas 75080 (United States); Verity Instruments, Inc., 2901 Eisenhower Street, Carrollton, Texas 75007 (United States); Department of Mathematical Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, Texas 75080 (United States)

    2012-11-15

    Traditionally process plasmas are often studied and monitored by optical emission spectroscopy. Here, the authors compare experimental measurements from a secondary electron beam excitation and direct process plasma excitation to discuss and illustrate its distinctiveness in the study of process plasmas. They present results that show excitations of etch process effluents in a SF{sub 6} discharge and endpoint detection capabilities in dark plasma process conditions. In SF{sub 6} discharges, a band around 300 nm, not visible in process emission, is observed and it can serve as a good indicator of etch product emission during polysilicon etches. Based on prior work reported in literature the authors believe this band is due to SiF{sub 4} gas phase species.

  8. Impact of copula directional specification on multi-trial evaluation of surrogate endpoints

    Science.gov (United States)

    Renfro, Lindsay A.; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of surrogate endpoints using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival versus distribution functions). We demonstrate that evenwith the “correct” copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a re-analysis of disease-free survival as a surrogate for overall survival in early stage colon cancer. PMID:24905465

  9. Simultaneous small-sample comparisons in longitudinal or multi-endpoint trials using multiple marginal models

    DEFF Research Database (Denmark)

    Pallmann, Philip; Ritz, Christian; Hothorn, Ludwig A

    2018-01-01

    , however only asymptotically. In this paper, we show how to make the approach also applicable to small-sample data problems. Specifically, we discuss the computation of adjusted P values and simultaneous confidence bounds for comparisons of randomised treatment groups as well as for levels......Simultaneous inference in longitudinal, repeated-measures, and multi-endpoint designs can be onerous, especially when trying to find a reasonable joint model from which the interesting effects and covariances are estimated. A novel statistical approach known as multiple marginal models greatly...... simplifies the modelling process: the core idea is to "marginalise" the problem and fit multiple small models to different portions of the data, and then estimate the overall covariance matrix in a subsequent, separate step. Using these estimates guarantees strong control of the family-wise error rate...

  10. Determination of the Acidity of Oils Using Paraformaldehyde as a Thermometric End-Point Indicator

    Directory of Open Access Journals (Sweden)

    Carneiro Mário J. D.

    2002-01-01

    Full Text Available The determination of the acidity of oils by catalytic thermometric titrimetry using paraformaldehyde as the thermometric end-point indicator was investigated. The sample solvent was a 1:1 (v/v mixture of toluene and 2-propanol and the titrant was 0.1 mol L-1 aqueous sodium hydroxide. Paraformaldehyde, being insoluble in the sample solvent, does not present the inconvenience of other indicators that change the properties of the solvent due to composition changes. The titration can therefore be done effectively in the same medium as the standard potentiometric and visual titration methods. The results of the application of the method to both non-refined and refined oils are presented herein. The proposed method has advantages in relation to the potentiometric method in terms of speed and simplicity.

  11. End-Point Contact Force Control with Quantitative Feedback Theory for Mobile Robots

    Directory of Open Access Journals (Sweden)

    Shuhuan Wen

    2012-12-01

    Full Text Available Robot force control is an important issue for intelligent mobile robotics. The end-point stiffness of a robot is a key and open problem in the research community. The control strategies are mostly dependent on both the specifications of the task and the environment of the robot. Due to the limited stiffness of the end-effector, we may adopt inherent torque to feedback the oscillations of the controlled force. This paper proposes an effective control strategy which contains a controller using quantitative feedback theory. The nested loop controllers take into account the physical limitation of the system's inner variables and harmful interference. The biggest advantage of the method is its simplicity in both the design process and the implementation of the control algorithm in engineering practice. Taking the one-link manipulator as an example, numerical experiments are carried out to verify the proposed control method. The results show the satisfactory performance.

  12. Elastic collisions of classical point particles on a finite frictionless linear track with perfectly reflecting endpoints

    Science.gov (United States)

    DeLuca, R.

    2006-03-01

    Repeated elastic collisions of point particles on a finite frictionless linear track with perfectly reflecting endpoints are considered. The problem is analysed by means of an elementary linear algebra approach. It is found that, starting with a state consisting of a projectile particle in motion at constant velocity and a target particle at rest in a fixed known position, the points at which collisions occur on track, when plotted versus progressive numerals, corresponding to the collisions themselves, show periodic patterns for a rather large choice of values of the initial position x(0) and on the mass ratio r. For certain values of these parameters, however, only regular behaviour over a large number of collisions is detected.

  13. Radiological impacts analysis with use of new endpoint as complementary safety indicators

    International Nuclear Information System (INIS)

    Peralta Vital, J.L.; Gil Castillo, R.; Fleitas Estevez, G.G.; Olivera Acosta, J.

    2015-01-01

    The paper shows the new safety indicators on risk assessment (safety assessment) to radioactive waste environmental management implementation (concentrations and fluxes of naturally occurring radioactive materials (NORM)). The endpoint obtained, allow the best analysis of the radiological impact associated to radioactive waste isolation system. The common safety indicators for safety assessment purpose, dose and risk, are very time dependent, increasing the uncertainties in the results for long term assessment. The complementary and new proposed endpoints are more stable and they are not affected by changes in the critical group, pathways, etc. The NORM values on facility site were obtained as result of national surveys, the natural concentrations of U, Ra, Th, K has been associated with the variation of the lithologies in 3 geographical areas of the Country (Occidental, Central and Oriental). The results obtained are related with the safety assessment topics and allowed to apply the new complementary safety indicators, by comparisons between the natural concentrations and fluxes on site and its calculated values for the conceptual repository design. In order to normalize the concentration results, the analysis was realized adopting the criteria of the Repository Equivalent Rock Volume (RERV). The preliminary comparison showed that the calculated concentrations and fluxes in the Cuban conceptual radioactive waste repository are not higher than the natural values in the host rock. According to the application of new safety indicators, the reference disposal facility does not increase the natural activity concentration and fluxes in the environment. In order to implement these new safety indicator it has been used the current 226 Ra inventory of the Repository and the 226 Ra as natural concentration on the site. (authors)

  14. Correlation of Hip Fracture with Other Fracture Types: Toward a Rational Composite Hip Fracture Endpoint

    Science.gov (United States)

    Colón-Emeric, Cathleen; Pieper, Carl F.; Grubber, Janet; Van Scoyoc, Lynn; Schnell, Merritt L; Van Houtven, Courtney Harold; Pearson, Megan; Lafleur, Joanne; Lyles, Kenneth W.; Adler, Robert A.

    2016-01-01

    Purpose With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. Methods Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between1999-2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics, were used to describe the correlation between each fracture type and hip fracture within individuals, without regards to the timing of the events. Results 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, p<0.0001), femur (0.15, p<0.0001), and shoulder (0.11, p<0.0001). Conclusions Pelvic, acetabular, femur, and shoulder fractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider use of a composite endpoint to better estimate hip fracture risk. PMID:26151123

  15. Log-gamma directed polymer with fixed endpoints via the replica Bethe Ansatz

    International Nuclear Information System (INIS)

    Thiery, Thimothée; Le Doussal, Pierre

    2014-01-01

    We study the model of a discrete directed polymer (DP) on a square lattice with homogeneous inverse gamma distribution of site random Boltzmann weights, introduced by Seppalainen (2012 Ann. Probab. 40 19–73). The integer moments of the partition sum, Z n -bar , are studied using a transfer matrix formulation, which appears as a generalization of the Lieb–Liniger quantum mechanics of bosons to discrete time and space. In the present case of the inverse gamma distribution the model is integrable in terms of a coordinate Bethe Ansatz, as discovered by Brunet. Using the Brunet-Bethe eigenstates we obtain an exact expression for the integer moments of Z n -bar for polymers of arbitrary lengths and fixed endpoint positions. Although these moments do not exist for all integer n, we are nevertheless able to construct a generating function which reproduces all existing integer moments and which takes the form of a Fredholm determinant (FD). This suggests an analytic continuation via a Mellin–Barnes transform and we thereby propose a FD ansatz representation for the probability distribution function (PDF) of Z and its Laplace transform. In the limit of a very long DP, this ansatz yields that the distribution of the free energy converges to the Gaussian unitary ensemble (GUE) Tracy-Widom distribution up to a non-trivial average and variance that we calculate. Our asymptotic predictions coincide with a result by Borodin et al (2013 Commun. Math. Phys. 324 215–32) based on a formula obtained by Corwin et al (2011 arXiv:1110.3489) using the geometric Robinson–Schensted–Knuth (gRSK) correspondence. In addition we obtain the dependence on the endpoint position and the exact elastic coefficient at a large time. We argue the equivalence between our formula and that of Borodin et al. As we will discuss, this provides a connection between quantum integrability and tropical combinatorics. (paper)

  16. Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Rosa Correa, Albertina Xavier da [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Roerig, Leonardo Rubi [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Verdinelli, Miguel A. [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Cotelle, Sylvie [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Ferard, Jean-Francois [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Radetski, Claudemir Marcos [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil)]. E-mail: radetski@univali.br

    2006-03-15

    In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd{sup 2+} that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity > biomass > germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values.

  17. Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers

    International Nuclear Information System (INIS)

    Rosa Correa, Albertina Xavier da; Roerig, Leonardo Rubi; Verdinelli, Miguel A.; Cotelle, Sylvie; Ferard, Jean-Francois; Radetski, Claudemir Marcos

    2006-01-01

    In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd 2+ that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity > biomass > germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values

  18. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

    Science.gov (United States)

    Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

    2017-09-01

    Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

  19. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Directory of Open Access Journals (Sweden)

    Amory Koch

    Full Text Available Acute radiation sickness (ARS following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS developed at the Veterinary Sciences Department (VSD of the Armed Forces Radiobiology Research Institute (AFRRI to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1, which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated, 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors. In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

  20. Constraints on grip selection in hemiparetic cerebral palsy: effects of lesional side, end-point accuracy, and context.

    Science.gov (United States)

    Steenbergen, Bert; Meulenbroek, Ruud G J; Rosenbaum, David A

    2004-04-01

    This study was concerned with selection criteria used for grip planning in adolescents with left or right hemiparetic cerebral palsy. In the first experiment, we asked participants to pick up a pencil and place the tip in a pre-defined target region. We varied the size of the target to test the hypothesis that increased end-point precision demands would favour the use of a grip that affords end-state comfort. In the second experiment, we studied grip planning in three task contexts that were chosen to let us test the hypothesis that a more functional task context would likewise promote the end-state comfort effect. When movements were performed with the impaired hand, we found that participants with right hemiparesis (i.e., left brain damage) aimed for postural comfort at the start rather than at the end of the object-manipulation phase in both experiments. By contrast, participants with left hemiparesis (i.e., right brain damage) did not favour a particular selection criterion with the impaired hand in the first experiment, but aimed for postural comfort at the start in the second experiment. When movements were performed with the unimpaired hand, grip selection criteria again differed for right and left hemiparetic participants. Participants with right hemiparesis did not favour a particular selection criterion with the unimpaired hand in the first experiment and only showed the end-state comfort effect in the most functional tasks of the second experiment. By contrast, participants with left hemiparesis showed the end-state comfort effect in all conditions of both experiments. These data suggest that the left hemisphere plays a special role in action planning, as has been recognized before, and that one of the deficits accompanying left brain damage is a deficit in forward movement planning, which has not been recognized before. Our findings have both theoretical and clinical implications.