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Sample records for cap-1 trial stepwise

  1. [Effects of a stepwise approach to behavioural problems in dementia: a cluster randomised controlled trial].

    Science.gov (United States)

    Pieper, M J C; Francke, A L; van der Steen, J T; Scherder, E J A; Twisk, J W R; Kovach, C R; Achterberg, W P

    2016-01-01

    To investigate whether implementation of a stepwise multidisciplinary intervention ('STA OP!' ['STAND UP!']) is effective in reducing behavioural problems and depressive symptoms in nursing home residents with advanced dementia. Cluster randomised controlled trial. We implemented the STA OP! protocol on the intervention units by training the entire multidisciplinary team. This team was trained in all 6 steps of the protocol during five 3-hour sessions. Professionals working on the control unit received training on general technical nursing skills, dementia management and pain, but then without the stepwise component. All elderly care physicians were given additional training in pain management in patients with dementia, based on the guidelines on pain in vulnerable older people. Measurements were taken at baseline, and after 3 and 6 months. We used longitudinal 'multilevel' techniques to correct for clustering of data (e.g. at unit level) for statistical analysis (Dutch Trial Register: NTR1967). A total of 288 residents with dementia were included, from 12 nursing homes (21 units): 148 in the intervention group in 11 units and 140 in the control group in 10 units. On the units where the STA OP! protocol was used there was a significant decline in agitation, neuropsychiatric symptoms and depression compared with the control units at 6 months. Furthermore, use of anti-depressive medication was significantly lower on the intervention units (odds ratio: 0.32; 95% CI: 0.10-0.98). This cluster RCT revealed that the stepwise multidisciplinary intervention STA OP! is effective in reducing behavioural problems and use of psycho-pharmaceuticals in nursing home residents with dementia.

  2. Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy.

    Science.gov (United States)

    Bjørndal, Lars; Reit, Claes; Bruun, Gitte; Markvart, Merete; Kjaeldgaard, Marianne; Näsman, Peggy; Thordrup, Marianne; Dige, Irene; Nyvad, Bente; Fransson, Helena; Lager, Anders; Ericson, Dan; Petersson, Kerstin; Olsson, Jadranka; Santimano, Eva M; Wennström, Anette; Winkel, Per; Gluud, Christian

    2010-06-01

    Less invasive excavation methods have been suggested for deep caries lesions. We tested the effects of stepwise vs. direct complete excavation, 1 yr after the procedure had been carried out, in 314 adults (from six centres) who had received treatment of a tooth with deep caries. The teeth had caries lesions involving 75% or more of the dentin and were centrally randomized to stepwise or direct complete excavation. Stepwise excavation resulted in fewer pulp exposures compared with direct complete excavation [difference: 11.4%, 95% confidence interval (CI) (1.2; 21.3)]. At 1 yr of follow-up, there was a statistically significantly higher success rate with stepwise excavation, with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [difference: 11.7%, 95% CI (0.5; 22.5)]. In a subsequent nested trial, 58 patients with exposed pulps were randomized to direct capping or partial pulpotomy. We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [31.8% and 34.5%; difference: 2.7%, 95% CI (-22.7; 26.6)]. In conclusion, stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation. In view of the poor prognosis of vital pulp treatment, a stepwise excavation approach for managing deep caries lesions is recommended.

  3. A Proficiency Based Stepwise Endovascular Curricular Training (PROSPECT) Program Enhances Operative Performance in Real Life: A Randomised Controlled Trial.

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    Maertens, H; Aggarwal, R; Moreels, N; Vermassen, F; Van Herzeele, I

    2017-09-01

    Healthcare evolution requires optimisation of surgical training to provide safe patient care. Operating room performance after completion of proficiency based training in vascular surgery has not been investigated. A randomised controlled trial evaluated the impact of a Proficiency based Stepwise Endovascular Curricular Training program (PROSPECT) on the acquisition of endovascular skills and the transferability of these skills to real life interventions. All subjects performed two endovascular interventions treating patients with symptomatic iliac and/or superficial femoral artery stenosis under supervision. Primary outcomes were technical performances (Global Rating Scale [GRS]; Examiner Checklist), operative metrics, and patient outcomes, adjusted for case difficulty and trainee experience. Secondary outcomes included knowledge and technical performance after 6 weeks and 3 months. Thirty-two general surgical trainees were randomised into three groups. Besides traditional training, the first group (n = 11) received e-learning and simulation training (PROSPECT), the second group (n = 10) only had access to e-learning, while controls (n = 11) did not receive supplementary training. Twenty-nine trainees (3 dropouts) performed 58 procedures. Trainees who completed PROSPECT showed superior technical performance (GRS 39.36 ± 2.05; Checklist 63.51 ± 3.18) in real life with significantly fewer supervisor takeovers compared with trainees receiving e-learning alone (GRS 28.42 ± 2.15; p = .001; Checklist 53.63 ± 3.34; p = .027) or traditional education (GRS 23.09 ± 2.18; p = .001; Checklist 38.72 ± 3.38; p = .001). Supervisors felt more confident in allowing PROSPECT trained physicians to perform basic (p = .006) and complex (p = .003) procedures. No differences were detected in procedural parameters (such as fluoroscopy time, DAP, procedure time, etc.) or complications. Proficiency levels were maintained up to 3 months. A structured

  4. CAP1 expression is developmentally regulated in Xenopus.

    Science.gov (United States)

    KhosrowShahian, F; Hubberstey, A V; Crawford, M J

    2002-05-01

    We have cloned and characterized a Xenopus member of the cyclase associated protein (CAP) gene family. xCAP1 is expressed as a maternal transcript, but is up-regulated prior to gastrulation and subsequently localizes to head mesenchyme, lens, otic vesicle, and trunk mesoderm including the pronephros. At different stages, the gene also appears to differentiate surface from deep (sensorial) ectoderm. As in Drosophila, Xenopus CAP1 is expressed in the developing eye, specifically in the differentiating lens. However, in distinction to Drosophila, Xenopus CAP1 does not express in periodically arrayed neural bands.

  5. Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial.

    Science.gov (United States)

    Skuginna, Veronika; Nguyen, Daniel P; Seiler, Roland; Kiss, Bernhard; Thalmann, George N; Roth, Beat

    2016-02-01

    Renal damage is more frequent with new-generation lithotripters. However, animal studies suggest that voltage ramping minimizes the risk of complications following extracorporeal shock wave lithotripsy (SWL). In the clinical setting, the optimal voltage strategy remains unclear. To evaluate whether stepwise voltage ramping can protect the kidney from damage during SWL. A total of 418 patients with solitary or multiple unilateral kidney stones were randomized to receive SWL using a Modulith SLX-F2 lithotripter with either stepwise voltage ramping (n=213) or a fixed maximal voltage (n=205). SWL. The primary outcome was sonographic evidence of renal hematomas. Secondary outcomes included levels of urinary markers of renal damage, stone disintegration, stone-free rate, and rates of secondary interventions within 3 mo of SWL. Descriptive statistics were used to compare clinical outcomes between the two groups. A logistic regression model was generated to assess predictors of hematomas. Significantly fewer hematomas occurred in the ramping group(12/213, 5.6%) than in the fixed group (27/205, 13%; p=0.008). There was some evidence that the fixed group had higher urinary β2-microglobulin levels after SWL compared to the ramping group (p=0.06). Urinary microalbumin levels, stone disintegration, stone-free rate, and rates of secondary interventions did not significantly differ between the groups. The logistic regression model showed a significantly higher risk of renal hematomas in older patients (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05; p=0.04). Stepwise voltage ramping was associated with a lower risk of hematomas (OR 0.39, 95% CI 0.19-0.80; p=0.01). The study was limited by the use of ultrasound to detect hematomas. In this prospective randomized study, stepwise voltage ramping during SWL was associated with a lower risk of renal damage compared to a fixed maximal voltage without compromising treatment effectiveness. Lithotripsy is a noninvasive

  6. CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis.

    Science.gov (United States)

    Miyake, Kotaro; Ohta, Toshio; Nakayama, Hisako; Doe, Nobutaka; Terao, Yuri; Oiki, Eiji; Nagatomo, Izumi; Yamashita, Yui; Abe, Takaya; Nishikura, Kazuko; Kumanogoh, Atsushi; Hashimoto, Kouichi; Kawahara, Yukio

    2016-11-15

    Calcium-dependent activator protein for secretion 1 (CAPS1) plays a distinct role in the priming step of dense core vesicle (DCV) exocytosis. CAPS1 pre-mRNA is known to undergo adenosine-to-inosine RNA editing in its coding region, which results in a glutamate-to-glycine conversion at a site in its C-terminal region. However, the physiological significance of CAPS1 RNA editing remains elusive. Here, we created mutant mice in which edited CAPS1 was solely expressed. These mice were lean due to increased energy expenditure caused by physical hyperactivity. Electrophysiological and biochemical analyses demonstrated that the exocytosis of DCVs was upregulated in the chromaffin cells and neurons of these mice. Furthermore, we showed that edited CAPS1 bound preferentially to the activated form of syntaxin-1A, a component of the exocytotic fusion complex. These findings suggest that RNA editing regulates DCV exocytosis in vivo, affecting physical activity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy

    DEFF Research Database (Denmark)

    Bjørndal, Lars; Reit, Claes; Bruun, Gitte Hoffmann

    2010-01-01

    Less invasive excavation methods have been suggested for deep caries lesions. We tested the effects of stepwise vs. direct complete excavation, 1 yr after the procedure had been carried out, in 314 adults (from six centres) who had received treatment of a tooth with deep caries. The teeth had car...

  8. A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD): Results of an Observer-Blinded, Multicenter, Randomized Trial in Depressed Patients With Coronary Artery Disease.

    Science.gov (United States)

    Herrmann-Lingen, Christoph; Beutel, Manfred E; Bosbach, Alexandra; Deter, Hans-Christian; Fritzsche, Kurt; Hellmich, Martin; Jordan, Jochen; Jünger, Jana; Ladwig, Karl-Heinz; Michal, Matthias; Petrowski, Katja; Pieske, Burkert; Ronel, Joram; Söllner, Wolfgang; Stöhr, Andreas; Weber, Cora; de Zwaan, Martina; Albus, Christian

    2016-01-01

    Depression predicts adverse prognosis in patients with coronary artery disease (CAD), but previous treatment trials yielded mixed results. We tested the hypothesis that stepwise psychotherapy improves depressive symptoms more than simple information. In a multicenter trial, we randomized 570 CAD patients scoring higher than 7 on the Hospital Anxiety and Depression Scale-depression subscale to usual care plus either one information session (UC-IS) or stepwise psychotherapy (UC-PT). UC-PT patients received three individual psychotherapy sessions. Those still depressed were offered group psychotherapy (25 sessions). The primary outcome was changed in the Hospital Anxiety and Depression Scale-depression scores from baseline to 18 months. Preplanned subgroup analyses examined whether treatment responses differed by patients' sex and personality factors (Type D). The mean (standard deviation) depression scores declined from 10.4 (2.5) to 8.7 (4.1) at 18 months in UC-PT and from 10.4 (2.5) to 8.9 (3.9) in UC-IS (both p < .001). There was no significant group difference in change of depressive symptoms (group-by-time effect, p = .90). Preplanned subgroup analyses revealed no differences in treatment effects between men versus women (ptreatment-by-sex interaction = .799) but a significant treatment-by-Type D interaction on change in depressive symptoms (p = .026) with a trend for stronger improvement with UC-PT than UC-IS in Type D patients (n = 341, p = .057) and no such difference in improvement in patients without Type D (n = 227, p = .54). Stepwise psychotherapy failed to improve depressive symptoms in CAD patients more than UC-IS. The intervention might be beneficial for depressed CAD patients with Type D personality. However, this finding requires further study. www.clinicaltrials.gov NCT00705965; www.isrctn.com ISRCTN76240576.

  9. Cap +1 mutation; an unsuspected cause of beta thalassaemia transmission in Pakistan

    Directory of Open Access Journals (Sweden)

    Sadia Usman Babar

    2009-12-01

    Full Text Available Objective: Thalassemia is one of the most common genetic disorders worldwide. Cap +1 mutation which causes ‘silent beta thalassemia’ is present around all ethnic groups of Pakistan. This study was designed to detect the frequency of Cap+1 mutation in Pakistani Population.Materials and Methods: Molecular genetic for Cap+1 beta thalassemic mutation was done by extracting DNA from whole blood by using Genomic DNA Purification Kit (Gentra system USA. Amplification Refractory Mutation System (ARMS primers were designed for detection of normal and mutant DNA.Basic hematological parameters were performed by using automated analyzer (Sysmex KX-21. Cellulose acetate hemoglobin electrophoresis was done by using semi-automated technique (INTERLAB Roma Microtech Series Electrophoresis system 4.23. Results: The frequency of Cap+1 mutation was observed 5% (10/200 in targeted thalassemic families (having patients with beta-thalassemia intermedia while its frequency was observed 2% (12/600 in total thalassemic genes in Pakistani population. Conclusion: Cap+1 (A-C is a silent mutation and it has very minimum effect on beta globin synthesis because of which it produces very less clinical severity and certain important laboratory diagnostic tests like basic hematological parameters and Hb A2 levels are also remain in normal range. Therefore individuals with Cap+1 mutation may produce children with beta-thalassemia intermedia if they marry an individual with beta-thalassemia minor. Cap+1 (A-C mutation is an unsuspected cause of beta thalassemia transmission in Pakistani population. This mutation can identify at molecular level. As this molecular defect is difficult to diagnose in Laboratory with routine laboratory tests because of that it has become a serious hindrance for thalassemia prevention program in Pakistan.

  10. Stepwise strategy to improve Cervical Cancer Screening Adherence (SCAN-CC): automated text messages, phone calls and face-to-face interviews: protocol of a population-based randomised controlled trial

    Science.gov (United States)

    Mendes, Romeu; Moreira, Amélia; Lunet, Nuno

    2017-01-01

    Introduction Screening is highly effective for cervical cancer prevention and control. Population-based screening programmes are widely implemented in high-income countries, although adherence is often low. In Portugal, just over half of the women adhere to cervical cancer screening, contributing for greater mortality rates than in other European countries. The most effective adherence raising strategies are based on patient reminders, small/mass media and face-to-face educational programmes, but sequential interventions targeting the general population have seldom been evaluated. The aim of this study is to assess the effectiveness of a stepwise approach, with increasing complexity and cost, to improve adherence to organised cervical cancer screening: step 1a—customised text message invitation; step 1b—customised automated phone call invitation; step 2—secretary phone call; step 3—family health professional phone call and face-to-face appointment. Methods A population-based randomised controlled trial will be implemented in Portuguese urban and rural areas. Women eligible for cervical cancer screening will be randomised (1:1) to intervention and control. In the intervention group, women will be invited for screening through text messages, automated phone calls, manual phone calls and health professional appointments, to be applied sequentially to participants remaining non-adherent after each step. Control will be the standard of care (written letter). The primary outcome is the proportion of women adherent to screening after step 1 or sequences of steps from 1 to 3. The secondary outcomes are: proportion of women screened after each step (1a, 2 and 3); proportion of text messages/phone calls delivered; proportion of women previously screened in a private health institution who change to organised screening. The intervention and control groups will be compared based on intention-to-treat and per-protocol analyses. Ethics and dissemination The study was

  11. A Matlab program for stepwise regression

    Directory of Open Access Journals (Sweden)

    Yanhong Qi

    2016-03-01

    Full Text Available The stepwise linear regression is a multi-variable regression for identifying statistically significant variables in the linear regression equation. In present study, we presented the Matlab program of stepwise regression.

  12. Stepwise strategy to improve Cervical Cancer Screening Adherence (SCAN-CC): automated text messages, phone calls and face-to-face interviews: protocol of a population-based randomised controlled trial.

    Science.gov (United States)

    Firmino-Machado, João; Mendes, Romeu; Moreira, Amélia; Lunet, Nuno

    2017-10-05

    Screening is highly effective for cervical cancer prevention and control. Population-based screening programmes are widely implemented in high-income countries, although adherence is often low. In Portugal, just over half of the women adhere to cervical cancer screening, contributing for greater mortality rates than in other European countries. The most effective adherence raising strategies are based on patient reminders, small/mass media and face-to-face educational programmes, but sequential interventions targeting the general population have seldom been evaluated. The aim of this study is to assess the effectiveness of a stepwise approach, with increasing complexity and cost, to improve adherence to organised cervical cancer screening: step 1a-customised text message invitation; step 1b-customised automated phone call invitation; step 2-secretary phone call; step 3-family health professional phone call and face-to-face appointment. A population-based randomised controlled trial will be implemented in Portuguese urban and rural areas. Women eligible for cervical cancer screening will be randomised (1:1) to intervention and control. In the intervention group, women will be invited for screening through text messages, automated phone calls, manual phone calls and health professional appointments, to be applied sequentially to participants remaining non-adherent after each step. Control will be the standard of care (written letter). The primary outcome is the proportion of women adherent to screening after step 1 or sequences of steps from 1 to 3. The secondary outcomes are: proportion of women screened after each step (1a, 2 and 3); proportion of text messages/phone calls delivered; proportion of women previously screened in a private health institution who change to organised screening. The intervention and control groups will be compared based on intention-to-treat and per-protocol analyses. The study was approved by the Ethics Committee of the Northern Health

  13. The Cyclase-associated protein Cap1 is important for proper regulation of infection-related morphogenesis in Magnaporthe oryzae.

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    Xiaoying Zhou

    2012-09-01

    Full Text Available Surface recognition and penetration are critical steps in the infection cycle of many plant pathogenic fungi. In Magnaporthe oryzae, cAMP signaling is involved in surface recognition and pathogenesis. Deletion of the MAC1 adenylate cyclase gene affected appressorium formation and plant infection. In this study, we used the affinity purification approach to identify proteins that are associated with Mac1 in vivo. One of the Mac1-interacting proteins is the adenylate cyclase-associated protein named Cap1. CAP genes are well-conserved in phytopathogenic fungi but none of them have been functionally characterized. Deletion of CAP1 blocked the effects of a dominant RAS2 allele and resulted in defects in invasive growth and a reduced intracellular cAMP level. The Δcap1 mutant was defective in germ tube growth, appressorium formation, and formation of typical blast lesions. Cap1-GFP had an actin-like localization pattern, localizing to the apical regions in vegetative hyphae, at the periphery of developing appressoria, and in circular structures at the base of mature appressoria. Interestingly, Cap1, similar to LifeAct, did not localize to the apical regions in invasive hyphae, suggesting that the apical actin cytoskeleton differs between vegetative and invasive hyphae. Domain deletion analysis indicated that the proline-rich region P2 but not the actin-binding domain (AB of Cap1 was responsible for its subcellular localization. Nevertheless, the AB domain of Cap1 must be important for its function because CAP1(ΔAB only partially rescued the Δcap1 mutant. Furthermore, exogenous cAMP induced the formation of appressorium-like structures in non-germinated conidia in CAP1(ΔAB transformants. This novel observation suggested that AB domain deletion may result in overstimulation of appressorium formation by cAMP treatment. Overall, our results indicated that CAP1 is important for the activation of adenylate cyclase, appressorium morphogenesis, and plant

  14. Step-Wise Migration : Evidence from Indonesia

    NARCIS (Netherlands)

    Pardede, Elda; McCann, Philip; Venhorst, Viktor

    2016-01-01

    The objective of this paper is to study multiple internal migration trajectories in Indonesia, with special attention to step-wise migration. Step-wise migration involves moves with smaller steps from village to nearby small town, to larger town, and then to big cities rather than a direct move from

  15. Understanding the Biocompatibility of Sintered Calcium Phosphate with Ratio of [Ca]/[P] = 1.50

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    Feng-Lin Yen

    2012-01-01

    Full Text Available Biocompatibility of sintered calcium phosphate pellets with [Ca]/[P] = 1.50 was determined in this study. Calcium pyrophosphate (CPP phase formed on the sintered pellets immersed in a normal saline solution for 14 d at 37∘C. The intensities of hydroxyapatite (HA reflections in the X-ray diffraction (XRD patterns of the pellets were retrieved to as-sintered state. The pellet surface morphology shows that CPP crystallites were clearly present and make an amorphous calcium phosphate (ACP to discriminate against become to the area of slice join together. In addition, the intensities of the CPP reflections in the XRD patterns were the highest when the pellets were immersed for 28 d. When the CPP powders were extracted from the pellets after immersion in the solution for 14 d, the viability of 3T3 cells remained above 90% for culture times from 1 to 4 d. The pellet surface morphology observed using optical microscopy showed that the cells did not adhere to the bottom of the sintered pellets when cultured for 4 d; however, some CPP phase precipitates were formed, as confirmed by XRD. In consequence, the results suggest that the sintered HA powders are good materials for use in biomedical applications because of their good biocompatibility.

  16. Stepwise Investment and Capacity Sizing under Uncertainty

    OpenAIRE

    Chronopoulos, Michail; Hagspiel, Verena; Fleten, Stein-Erik

    2015-01-01

    The relationship between uncertainty and managerial flexibility is particularly crucial in addressing capital projects. We consider a firm that can invest in a project in either a single (lumpy investment) or multiple stages (stepwise investment) under price uncertainty and has discretion over not only the time of investment but also the size of the project. We confirm that, if the capacity of a project is fixed, then lumpy investment becomes more valuable than a stepwise inves...

  17. Stepwise investment and capacity sizing under uncertainty

    OpenAIRE

    Chronopoulos, Michail; Hagspiel, Verena; Fleten, Stein-Erik

    2016-01-01

    The relationship between uncertainty and managerial flexibility is particularly crucial in addressing capital projects. We consider a firm that can invest in a project in either a single (lumpy investment) or multiple stages (stepwise investment) under price uncertainty and has discretion over not only the time of investment but also the size of the project. We confirm that if the capacity of a project is fixed and the investment premium associated with stepwise investment is positive, then l...

  18. Technology-derived storage solutions for stabilizing insulin in extreme weather conditions I: the ViViCap-1 device.

    Science.gov (United States)

    Pfützner, Andreas; Pesach, Gidi; Nagar, Ron

    2017-06-01

    Injectable life-saving drugs should not be exposed to temperatures 30°C/86°F. Frequently, weather conditions exceed these temperature thresholds in many countries. Insulin is to be kept at 4-8°C/~ 39-47°F until use and once opened, is supposed to be stable for up to 31 days at room temperature (exception: 42 days for insulin levemir). Extremely hot or cold external temperature can lead to insulin degradation in a very short time with loss of its glucose-lowering efficacy. Combined chemical and engineering solutions for heat protection are employed in ViViCap-1 for disposable insulin pens. The device works based on vacuum insulation and heat consumption by phase-change material. Laboratory studies with exposure of ViViCap-1 to hot outside conditions were performed to evaluate the device performance. ViViCap-1 keeps insulin at an internal temperature change process and 'recharges' the device for further use. ViViCap-1 performed within its specifications. The small and convenient device maintains the efficacy and safety of using insulin even when carried under hot weather conditions.

  19. Stepwise Regression as an Exploratory Data Analysis Procedure.

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    Thayer, Jerome D.

    This paper identifies specific problems with stepwise regression, notes criticisms of stepwise methods by statisticians, suggests appropriate ways in which stepwise procedures can be used, and gives examples of how this can be done. Although the stepwise method has been routinely criticized by statisticians, it is still frequently used in the…

  20. Improved parental attitudes and beliefs through stepwise perinatal vaccination education.

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    Saitoh, Aya; Saitoh, Akihiko; Sato, Isamu; Shinozaki, Tomohiro; Kamiya, Hajime; Nagata, Satoko

    2017-11-02

    This study examined the effects of providing vaccination education during the perinatal period on Japanese parents' knowledge, attitudes, and beliefs about childhood vaccination. A cluster-randomized controlled-trial method was used on a sample of 160 pregnant women recruited from 9 obstetrical sites in Niigata, Japan. The treatment group received a stepwise interactive education intervention, while the control group received a general vaccination leaflet. Changes in parental attitudes toward and beliefs about infant vaccination were assessed on the child's one-month and 6-month birthdays using paper questionnaires. Of the initial 188 participants, 160 (90.4%) completed the final post-survey questionnaire. Scores on injunctive social norms (a morally neutral perception of the behavior of the majority) and descriptive social norms (a moral perception of what individuals should do) significantly increased in the treatment group (p = .02 and p = .01, respectively). There was a significant difference between the 2 groups over time in terms of perceived benefit (efficacy of available preventive actions) (p = .03), but no significant differences in perceived severity (seriousness of a disease outcome), perceived susceptibility (likelihood of getting a disease), perceived benefits, perceived behavioral control, or descriptive social norms between the groups at any time point or in the patterns of change over time (p > .31). Thus, stepwise perinatal vaccination education was found to positively influence maternal attitudes and beliefs about infant vaccination. This study suggests the importance of vaccination education during the perinatal period.

  1. Ways of enhancing pulp preservation by stepwise excavation--a systematic review.

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    Hayashi, Mikako; Fujitani, Morioki; Yamaki, Chinami; Momoi, Yasuko

    2011-02-01

    The best possible methods and materials in stepwise excavation for deep caries in permanent teeth were investigated. The review considers the questions from many aspects including clinical success, effects of reducing cariogenic bacteria, possibility of hardening softened dentin, and likelihood of generating tertiary dentin. This systematic review includes the use of data from randomized controlled trials, controlled clinical trials as well as from case series in which pulp exposure resulted following the treatment and removal of deep caries. Only studies of caries in permanent teeth were considered. Those involving treatment of primary teeth were excluded. An electronic search was conducted in the databases of MEDLINE and Igaku Chuo Zasshi (Japanese) from 1970 to 2008. The electronic search was supplemented by a manual search of the references lists of all the relevant studies. The electronic and manual searches of journals retrieved a total of 266 English and 130 Japanese papers. According to the inclusion and exclusion criteria, 10 English and 3 Japanese studies were finally identified. Our research suggests that stepwise excavation is effective for pulp preservation in extremely deep caries that do not show clinical symptoms of irreversible pulpitis. Calcium hydroxide, as well as antimicrobials and polycarboxylate cement combined with tannin-fluoride preparation, is effective in reducing bacteria and promoting remineralization of the carious dentin that remained after stepwise excavation. Further clinical trials with a high level of study design should be conducted to identify the best methods of removing carious dentin using stepwise excavation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Stepwise excavation in a permanent molar

    DEFF Research Database (Denmark)

    Lima, Fernanda Ferruzzi; Pascotto, Renata Corrêa; Benetti, Ana Raquel

    2010-01-01

    The current study presents a 17-year clinical report of stepwise excavation and indirect pulp capping in a lower right first molar, with great dentin destruction and a lack of dentin support of the cusps. At the first appointment, indirect pulp capping with calcium hydroxide and a temporary filling...... with zinc oxide cement were performed to minimize the risk of pulp exposure during excavation. After 45 days, the remaining carious tissue was removed and a restoration with glass-ionomer lining (Vitrebond) and resin composite (P-50) was performed. Satisfactory morphology and function of the restoration...

  3. Stepwise Synthesis of Metal-Organic Frameworks.

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    Bosch, Mathieu; Yuan, Shuai; Rutledge, William; Zhou, Hong-Cai

    2017-04-18

    Metal-organic frameworks (MOFs) are a category of porous materials that offer unparalleled control over their surface areas (demonstrated as higher than for any other material), pore characteristics, and functionalization. This allows them to be customized for exceptional performance in a wide variety of applications, most commonly including gas storage and separation, drug delivery, luminescence, or heterogeneous catalysis. In order to optimize biomimicry, controlled separations and storage of small molecules, and detailed testing of structure-property relationships, one major goal of MOF research is "rational design" or "pore engineering", or precise control of the placement of multiple functional groups in pores of chosen sizes and shapes. MOF crystal growth can be controlled through judicious design of stepwise synthetic routes, which can also allow functionalization of MOFs in ways that were previously synthetically inaccessible. Organic chemists have developed a library of powerful techniques over the last century, allowing the total synthesis and detailed customization of complex molecules. Our hypothesis is that total synthesis is also possible for customized porous materials, through the development of similar multistep techniques. This will enable the rational design of MOFs, which is a major goal of many researchers in the field. We have begun developing a library of stepwise synthetic techniques for MOFs, allowing the synthesis of ultrastable MOFs with multiple crystallographically ordered and customizable functional groups at controlled locations within the pores. In order to design MOFs with precise control over pore size and shape, stability, and the placement of multiple different functional groups within the pores at tunable distances from one another, we have concentrated on methods which allow us to circumvent the lack of control inherent to one-pot MOF crystallization. Kinetically tuned dimensional augmentation (KTDA) is an approach using

  4. Concerted versus stepwise mechanism in thymidylate synthase.

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    Islam, Zahidul; Strutzenberg, Timothy S; Gurevic, Ilya; Kohen, Amnon

    2014-07-16

    Thymidylate synthase (TSase) catalyzes the intracellular de novo formation of thymidylate (a DNA building block) in most living organisms, making it a common target for chemotherapeutic and antibiotic drugs. Two mechanisms have been proposed for the rate-limiting hydride transfer step in TSase catalysis: a stepwise mechanism in which the hydride transfer precedes the cleavage of the covalent bond between the enzymatic cysteine and the product and a mechanism where both happen concertedly. Striking similarities between the enzyme-bound enolate intermediates formed in the initial and final step of the reaction supported the first mechanism, while QM/MM calculations favored the concerted mechanism. Here, we experimentally test these two possibilities using secondary kinetic isotope effect (KIE), mutagenesis study, and primary KIEs. The findings support the concerted mechanism and demonstrate the critical role of an active site arginine in substrate binding, activation of enzymatic nucleophile, and the hydride transfer studied here. The elucidation of this reduction/substitution sheds light on the critical catalytic step in TSase and may aid future drug or biomimetic catalyst design.

  5. Identifying secondary series for stepwise common singular spectrum ...

    African Journals Online (AJOL)

    Section 6 contains concluding remarks and ideas for further research. In the next section background information on MSSA as well as stepwise CSSA is given. 2 MSSA and stepwise CSSA. Consider two time series of equal length N, y1t and y2t, where t = 1,...,N. A signal- plus-noise structure is assumed for both series, i.e..

  6. CAPS-1 requires its C2, PH, MHD1 and DCV domains for dense core vesicle exocytosis in mammalian CNS neurons

    NARCIS (Netherlands)

    van Keimpema, Linda; Kooistra, Robbelien; Toonen, Ruud F; Verhage, Matthijs

    2017-01-01

    CAPS (calcium-dependent activator protein for secretion) are multi-domain proteins involved in regulated exocytosis of synaptic vesicles (SVs) and dense core vesicles (DCVs). Here, we assessed the contribution of different CAPS-1 domains to its subcellular localization and DCV exocytosis by

  7. FPGA Implementation of the stepwise shutdown system

    Energy Technology Data Exchange (ETDEWEB)

    Lotjonen, L.

    2012-07-01

    This report elaborates the design process of applications for field-programmable gate array (FPGA) devices. Brief introductions to EPGA technology and the design process are first given and then the design phases are walked through with the aid of a case study. FPGA is a programmable logic device that is programmed by the customer rather than the manufacturer. They are also usually re-programmable which enables updating their programming and otherwise modifying the design. There are also one-time programmable FPGAs that can be used when security issues require it. FPGA is said to be 'hardware designed like software', which means that the design process resembles software development but the end-product is considered a hardware application because the execution of the functions is entirely different from a microprocessor. This duality can give both the flexibility of software and the reliability of hardware. The FPGA design and verification and validation (V and V) methods for NPP safety systems have not yet matured because the technology is rather new in the field. Software development methods and stanfards can be used to some extent but the hardware aspects bring new challenges that cannot be tacled using purely software methods. International efforts are being made to development formal and consistent design and V and V methodology regulations for FPGA devices. A preventive safety function called Stepwise Shutdown System (SWS) was implemented on an Actel M1 IGLOO field-programmable gate array (FPGA) device. SWS is used to drive a process into a normal state if the process measurements deviate from the desired operating values. This can happen in case of process disturbances. The SWS implementation processfrom the reguirements to the functional device is elaborated. The design is tested via simulation and hardware testing. The case study is to be further expanded as a part of a master's thesis. (orig.)

  8. Stepwise iterative maximum likelihood clustering approach.

    Science.gov (United States)

    Sharma, Alok; Shigemizu, Daichi; Boroevich, Keith A; López, Yosvany; Kamatani, Yoichiro; Kubo, Michiaki; Tsunoda, Tatsuhiko

    2016-08-24

    Biological/genetic data is a complex mix of various forms or topologies which makes it quite difficult to analyze. An abundance of such data in this modern era requires the development of sophisticated statistical methods to analyze it in a reasonable amount of time. In many biological/genetic analyses, such as genome-wide association study (GWAS) analysis or multi-omics data analysis, it is required to cluster the plethora of data into sub-categories to understand the subtypes of populations, cancers or any other diseases. Traditionally, the k-means clustering algorithm is a dominant clustering method. This is due to its simplicity and reasonable level of accuracy. Many other clustering methods, including support vector clustering, have been developed in the past, but do not perform well with the biological data, either due to computational reasons or failure to identify clusters. The proposed SIML clustering algorithm has been tested on microarray datasets and SNP datasets. It has been compared with a number of clustering algorithms. On MLL datasets, SIML achieved highest clustering accuracy and rand score on 4/9 cases; similarly on SRBCT dataset, it got for 3/5 cases; on ALL subtype it got highest clustering accuracy for 5/7 cases and highest rand score for 4/7 cases. In addition, SIML overall clustering accuracy on a 3 cluster problem using SNP data were 97.3, 94.7 and 100 %, respectively, for each of the clusters. In this paper, considering the nature of biological data, we proposed a maximum likelihood clustering approach using a stepwise iterative procedure. The advantage of this proposed method is that it not only uses the distance information, but also incorporate variance information for clustering. This method is able to cluster when data appeared in overlapping and complex forms. The experimental results illustrate its performance and usefulness over other clustering methods. A Matlab package of this method (SIML) is provided at the web-link http://www.riken.jp/en/research/labs/ims/med_sci_math/ .

  9. Estimation of transport airplane aerodynamics using multiple stepwise regression

    Science.gov (United States)

    Keskar, D. A.; Klein, V.; Batterson, J. G.

    1985-01-01

    This paper presents an application of multiple stepwise regression to the flight test data of a typical transport airplane. The flight test data was carefully preprocessed to eliminate aliasing, time skews and high frequency noise. The data consisted both of basic certification maneuvers, such as wind-up-turns and maneuvers suitable for parameter estimation, such as responses to elevator pulses and doublets. It is shown that the results of multiple stepwise regression techniques compare favorably with the results obtained from maximum likelihood estimation. Finally, it is concluded that multiple stepwise regression could be a fast economical way to estimate transport airplane aerodynamics.

  10. An Original Stepwise Multilevel Logistic Regression Analysis of Discriminatory Accuracy

    DEFF Research Database (Denmark)

    Merlo, Juan; Wagner, Philippe; Ghith, Nermin

    2016-01-01

    BACKGROUND AND AIM: Many multilevel logistic regression analyses of "neighbourhood and health" focus on interpreting measures of associations (e.g., odds ratio, OR). In contrast, multilevel analysis of variance is rarely considered. We propose an original stepwise analytical approach that disting......BACKGROUND AND AIM: Many multilevel logistic regression analyses of "neighbourhood and health" focus on interpreting measures of associations (e.g., odds ratio, OR). In contrast, multilevel analysis of variance is rarely considered. We propose an original stepwise analytical approach...

  11. Stepwise hydrolysis to improve carbon releasing efficiency from sludge.

    Science.gov (United States)

    Liu, Hongbo; Wang, Yuanyuan; Wang, Ling; Yu, Tiantian; Fu, Bo; Liu, He

    2017-08-01

    Based on thermal alkaline hydrolysis (TAH), a novel strategy of stepwise hydrolysis was developed to improve carbon releasing efficiency from waste activated sludge (WAS). By stepwise increasing hydrolysis intensity, conventional sludge hydrolysis (the control) was divided into four stages for separately recovering sludge carbon sources with different bonding strengths, namely stage 1 (60 °C, pH 6.0-8.0), stage 2 (80 °C, pH 6.0-8.0), stage 3 (80 °C, pH 10.0) and stage 4 (90 °C, pH 12.0). Results indicate stepwise hydrolysis could enhance the amount of released soluble chemical oxygen demand (SCOD) for almost 2 times, from 7200 to 14,693 mg/L, and the released carbon presented better biodegradability, with BOD/COD of 0.47 and volatile fatty acids (VFAs) yield of 0.37 g VFAs/g SCOD via anaerobic fermentation. Moreover, stepwise hydrolysis also improved the dewaterability of hydrolyzed sludge, capillary suction time (CST) reducing from 2500 to 1600 s. Economic assessment indicates stepwise hydrolysis shows less alkali demand and lower thermal energy consumption than those of the control. Furthermore, results of this study help support the concepts of improving carbon recovery in wastewater by manipulating WAS composition and the idea of classifiably recovering the nutrients in WAS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Melanin fluorescence spectra by step-wise three photon excitation

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; DiMarzio, Charles A.

    2012-03-01

    Melanin is the characteristic chromophore of human skin with various potential biological functions. Kerimo discovered enhanced melanin fluorescence by stepwise three-photon excitation in 2011. In this article, step-wise three-photon excited fluorescence (STPEF) spectrum between 450 nm -700 nm of melanin is reported. The melanin STPEF spectrum exhibited an exponential increase with wavelength. However, there was a probability of about 33% that another kind of step-wise multi-photon excited fluorescence (SMPEF) that peaks at 525 nm, shown by previous research, could also be generated using the same process. Using an excitation source at 920 nm as opposed to 830 nm increased the potential for generating SMPEF peaks at 525 nm. The SMPEF spectrum peaks at 525 nm photo-bleached faster than STPEF spectrum.

  13. Synthesis of 5′ cap-0 and cap-1 RNAs using solid-phase chemistry coupled with enzymatic methylation by human (guanine-N7)-methyl transferase

    Science.gov (United States)

    Thillier, Yann; Decroly, Etienne; Morvan, François; Canard, Bruno; Vasseur, Jean-Jacques; Debart, Françoise

    2012-01-01

    The 5′ end of eukaryotic mRNA carries a N7-methylguanosine residue linked by a 5′-5′ triphosphate bond. This cap moiety (7mGpppN) is an essential RNA structural modification allowing its efficient translation, limiting its degradation by cellular 5′ exonucleases and avoiding its recognition as “nonself” by the innate immunity machinery. In vitro synthesis of capped RNA is an important bottleneck for many biological studies. Moreover, the lack of methods allowing the synthesis of large amounts of RNA starting with a specific 5′-end sequence have hampered biological and structural studies of proteins recognizing the cap structure or involved in the capping pathway. Due to the chemical nature of N7-methylguanosine, the synthesis of RNAs possessing a cap structure at the 5′ end is still a significant challenge. In the present work, we combined a chemical synthesis method and an enzymatic methylation assay in order to produce large amounts of RNA oligonucleotides carrying a cap-0 or cap-1. Short RNAs were synthesized on solid support by the phosphoramidite 2′-O-pivaloyloxymethyl chemistry. The cap structure was then coupled by the addition of GDP after phosphorylation of the terminal 5′-OH and activation by imidazole. After deprotection and release from the support, GpppN-RNAs or GpppN2′-Om-RNAs were purified before the N7-methyl group was added by enzymatic means using the human (guanine-N7)-methyl transferase to yield 7mGpppN-RNAs (cap-0) or 7mGpppN2′-Om-RNAs (cap-1). The RNAs carrying different cap structures (cap, cap-0 or, cap-1) act as bona fide substrates mimicking cellular capped RNAs and can be used for biochemical and structural studies. PMID:22334760

  14. Synthesis of 5' cap-0 and cap-1 RNAs using solid-phase chemistry coupled with enzymatic methylation by human (guanine-N⁷)-methyl transferase.

    Science.gov (United States)

    Thillier, Yann; Decroly, Etienne; Morvan, François; Canard, Bruno; Vasseur, Jean-Jacques; Debart, Françoise

    2012-04-01

    The 5' end of eukaryotic mRNA carries a N(7)-methylguanosine residue linked by a 5'-5' triphosphate bond. This cap moiety ((7m)GpppN) is an essential RNA structural modification allowing its efficient translation, limiting its degradation by cellular 5' exonucleases and avoiding its recognition as "nonself" by the innate immunity machinery. In vitro synthesis of capped RNA is an important bottleneck for many biological studies. Moreover, the lack of methods allowing the synthesis of large amounts of RNA starting with a specific 5'-end sequence have hampered biological and structural studies of proteins recognizing the cap structure or involved in the capping pathway. Due to the chemical nature of N(7)-methylguanosine, the synthesis of RNAs possessing a cap structure at the 5' end is still a significant challenge. In the present work, we combined a chemical synthesis method and an enzymatic methylation assay in order to produce large amounts of RNA oligonucleotides carrying a cap-0 or cap-1. Short RNAs were synthesized on solid support by the phosphoramidite 2'-O-pivaloyloxymethyl chemistry. The cap structure was then coupled by the addition of GDP after phosphorylation of the terminal 5'-OH and activation by imidazole. After deprotection and release from the support, GpppN-RNAs or GpppN(2'-Om)-RNAs were purified before the N(7)-methyl group was added by enzymatic means using the human (guanine-N(7))-methyl transferase to yield (7m)GpppN-RNAs (cap-0) or (7m)GpppN(2'-Om)-RNAs (cap-1). The RNAs carrying different cap structures (cap, cap-0 or, cap-1) act as bona fide substrates mimicking cellular capped RNAs and can be used for biochemical and structural studies.

  15. Reduced autonomic activity during stepwise exposure to high altitude

    NARCIS (Netherlands)

    Sevre, K; Bendz, B; Hanko, E; Nakstad, AR; Hauge, A; Kasin, JI; Lefrandt, JD; Smit, AJ; Eide, [No Value; Rostrup, M

    2001-01-01

    Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in

  16. Stepwise innovation adoption : a neglected concept in innovation research

    NARCIS (Netherlands)

    Huizingh, K.R.E.; Brand, M.J.

    2009-01-01

    Most innovation researchers tend to consider innovation adoption as a binary process, implying that companies have either adopted an innovation or not. In this paper we focus on e-commerce as an innovation that can be adopted stepwise. We distinguish between two levels of e-commerce, basic and

  17. Stepwise commissioning of a steam boiler with stability guarantees

    DEFF Research Database (Denmark)

    Johansen, Simon Vestergaard; Kallesøe, Carsten Skovmose; Bendtsen, Jan Dimon

    2016-01-01

    This paper aims to make the commissioning of an industrial MIMO controller more straightforward by gradually commissioning it from a set of SISO controllers, after the system has been started. For this purpose a stepwise commissioning strategy based on the Youla-Kucera parametrization has been...

  18. COPD: A stepwise or a hit hard approach?

    Directory of Open Access Journals (Sweden)

    A.J. Ferreira

    2016-07-01

    Full Text Available Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or “hit hard” approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS are recommended, a step-up or “hit hard” approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications.This paper discusses and proposes stepwise, “hit hard”, step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach. Keywords: COPD, Stepwise, Hit hard, Step-up, ICS withdrawal, Bronchodilators, ICS

  19. Controlling the Type I Error Rate in Stepwise Regression Analysis.

    Science.gov (United States)

    Pohlmann, John T.

    1979-01-01

    The type I error rate in stepwise regression analysis deserves serious consideration by researchers. The problem-wide error rate is the probability of selecting any variable when all variables have population regression weights of zero. Appropriate significance tests are presented and a Monte Carlo experiment is described. (Author/CTM)

  20. MULGRES: a computer program for stepwise multiple regression analysis

    Science.gov (United States)

    A. Jeff Martin

    1971-01-01

    MULGRES is a computer program source deck that is designed for multiple regression analysis employing the technique of stepwise deletion in the search for most significant variables. The features of the program, along with inputs and outputs, are briefly described, with a note on machine compatibility.

  1. Stepwise biometric procedures for managing student attendance in ...

    African Journals Online (AJOL)

    Stepwise biometric procedures for managing student attendance in higher institutions of learning. ... Large numbers of higher academic institutions in the developing countries are still using the process of manual attendance for both lecture and examination for students' authentication and authorization, hence, the need for ...

  2. A Stepwise Discriminant Analysis of Eight Selected Basketball Skill Tests.

    Science.gov (United States)

    Hopkins, David R.

    The purpose of this study was to determine the discriminatory ability of eight selected skill tests in evaluating the abilities of a group of male basketball players. The raw scores of the skill tests for each participant were analyzed by a stepwise discriminant analysis procedure. The results of this study indicate that a test battery comprised…

  3. A Stepwise Regression Analysis On Under-Five Diarrhoael ...

    African Journals Online (AJOL)

    The data were entered into a computer, edited and analyzed using SPSS for windows version 12.01. Stepwise logistic regression model was used to calculate the Odds ratios and 95% confidence interval for the different risk factors was considered. Results: From 477, 461 were participated in the study giving a response ...

  4. Microbiological Evaluation of Ozone on Dentinal Lesions in Young Permanent Molars using the Stepwise Excavation.

    Science.gov (United States)

    Safwat, Osama; Elkateb, Mona; Dowidar, Karin; Salam, Hala Abdel; El Meligy, Omar

    2017-09-22

    To assess the microbial effect of ozone gas on dentinal lesions in young permanent molars using the stepwise excavation. An experimental, controlled clinical trial was performed. The sample included 80 immature first permanent molars, showing deep occlusal carious cavities that were indicated for stepwise excavation. Following first step of dentin excavation, the sample was divided into test (ozone gas) and control (calcium hydroxide (Ca(OH)2) base material) groups. One half of the cases in each group were evaluated for microbiological changes after 6 months, and the other half after 12 months. Mutans streptococci (MS), Lactobacilli, and Candida counts were significantly reduced immediately after ozone application in the test group (P ≤0.05). At the final assessment period, MS and Lactobacilli were significantly reduced in the test group (P ≤0.05). Meanwhile, the Candida counts were significantly reduced only in the test group of the 6 and 12 month-cases (P ≤0.05). Regarding the control group, the significant reduction in microbial count was observed with MS after 6 and 12 months (P ≤0.05). No significant differences were observed between test and control groups at different evaluation periods (P >0.05). Ozone gas had a significant antimicrobial effect in deep class I carious lesions.

  5. Comparison of step-wise and ramp-wise incremental rowing exercise tests and 2000-m rowing ergometer performance.

    Science.gov (United States)

    Ingham, Stephen A; Pringle, Jamie S; Hardman, Sarah L; Fudge, Barry W; Richmond, Victoria L

    2013-03-01

    This study examined parameters derived from both an incremental step-wise and a ramp-wise graded rowing exercise test in relation to rowing performance. Discontinuous step-wise incremental rowing to exhaustion established lactate threshold (LT), maximum oxygen consumption (VO(2maxSTEP)), and power associated with VO(2max) (W VO(2max)). A further continuous ramp-wise test was undertaken to derive ventilatory threshold (VT), maximum oxygen consumption (VO(2maxRAMP)), and maximum minute power (MMW). Results were compared with maximal 2000-m ergometer time-trial power. The strongest correlation with 2000-m power was observed for MMW (r = .98, P rowing performance and thus may have potential as an influential monitoring tool for rowing athletes.

  6. A stepwise framework for the normalization of array CGH data

    Directory of Open Access Journals (Sweden)

    Lam Wan L

    2005-11-01

    Full Text Available Abstract Background In two-channel competitive genomic hybridization microarray experiments, the ratio of the two fluorescent signal intensities at each spot on the microarray is commonly used to infer the relative amounts of the test and reference sample DNA levels. This ratio may be influenced by systematic measurement effects from non-biological sources that can introduce biases in the estimated ratios. These biases should be removed before drawing conclusions about the relative levels of DNA. The performance of existing gene expression microarray normalization strategies has not been evaluated for removing systematic biases encountered in array-based comparative genomic hybridization (CGH, which aims to detect single copy gains and losses typically in samples with heterogeneous cell populations resulting in only slight shifts in signal ratios. The purpose of this work is to establish a framework for correcting the systematic sources of variation in high density CGH array images, while maintaining the true biological variations. Results After an investigation of the systematic variations in the data from two array CGH platforms, SMRT (Sub Mega base Resolution Tiling BAC arrays and cDNA arrays of Pollack et al., we have developed a stepwise normalization framework integrating novel and existing normalization methods in order to reduce intensity, spatial, plate and background biases. We used stringent measures to quantify the performance of this stepwise normalization using data derived from 5 sets of experiments representing self-self hybridizations, replicated experiments, detection of single copy changes, array CGH experiments which mimic cell population heterogeneity, and array CGH experiments simulating different levels of gene amplifications and deletions. Our results demonstrate that the three-step normalization procedure provides significant improvement in the sensitivity of detection of single copy changes compared to conventional

  7. Stepwise Nanopore Evolution in One-Dimensional Nanostructures

    KAUST Repository

    Choi, Jang Wook

    2010-04-14

    We report that established simple lithium (Li) ion battery cycles can be used to produce nanopores inside various useful one-dimensional (1D) nanostructures such as zinc oxide, silicon, and silver nanowires. Moreover, porosities of these 1D nanomaterials can be controlled in a stepwise manner by the number of Li-battery cycles. Subsequent pore characterization at the end of each cycle allows us to obtain detailed snapshots of the distinct pore evolution properties in each material due to their different atomic diffusion rates and types of chemical bonds. Also, this stepwise characterization led us to the first observation of pore size increases during cycling, which can be interpreted as a similar phenomenon to Ostwald ripening in analogous nanoparticle cases. Finally, we take advantage of the unique combination of nanoporosity and 1D materials and demonstrate nanoporous silicon nanowires (poSiNWs) as excellent supercapacitor (SC) electrodes in high power operations compared to existing devices with activated carbon. © 2010 American Chemical Society.

  8. Efficacy of stepwise application of orthosis and kinesiology tape for treating thumb metacarpophalangeal joint hyperextension injury.

    Science.gov (United States)

    Lee, Sun-Min; Lee, Jung-Hoon

    2015-08-01

    [Purpose] The purpose of this study was to investigate on the effects of the stepwise application of orthosis and kinesiology tape on a patient with thumb metacarpophalangeal joint hyperextension injury. [Subject] The patient was a 43-year-old man with severe thumb MCP pain and extremely limited thumb movement. [Methods] Stepwise application of orthosis and kinesiology taping were performed for 3 weeks and 4 weeks, respectively. [Results] After stepwise treatment, the patient was able to power grip, precision pinch, turn a key, and hold a pen without pain. [Conclusion] Stepwise application of thumb orthosis and kinesiology tape is a safe and effective treatment for thumb MCP joint hyperextension injury.

  9. Stepwise calibration procedure for regional coupled hydrological-hydrogeological models

    Science.gov (United States)

    Labarthe, Baptiste; Abasq, Lena; de Fouquet, Chantal; Flipo, Nicolas

    2014-05-01

    Stream-aquifer interaction is a complex process depending on regional and local processes. Indeed, the groundwater component of hydrosystem and large scale heterogeneities control the regional flows towards the alluvial plains and the rivers. In second instance, the local distribution of the stream bed permeabilities controls the dynamics of stream-aquifer water fluxes within the alluvial plain, and therefore the near-river piezometric head distribution. In order to better understand the water circulation and pollutant transport in watersheds, the integration of these multi-dimensional processes in modelling platform has to be performed. Thus, the nested interfaces concept in continental hydrosystem modelling (where regional fluxes, simulated by large scale models, are imposed at local stream-aquifer interfaces) has been presented in Flipo et al (2014). This concept has been implemented in EauDyssée modelling platform for a large alluvial plain model (900km2) part of a 11000km2 multi-layer aquifer system, located in the Seine basin (France). The hydrosystem modelling platform is composed of four spatially distributed modules (Surface, Sub-surface, River and Groundwater), corresponding to four components of the terrestrial water cycle. Considering the large number of parameters to be inferred simultaneously, the calibration process of coupled models is highly computationally demanding and therefore hardly applicable to a real case study of 10000km2. In order to improve the efficiency of the calibration process, a stepwise calibration procedure is proposed. The stepwise methodology involves determining optimal parameters of all components of the coupled model, to provide a near optimum prior information for the global calibration. It starts with the surface component parameters calibration. The surface parameters are optimised based on the comparison between simulated and observed discharges (or filtered discharges) at various locations. Once the surface parameters

  10. Stepwise advancement versus maximum jumping with headgear activator.

    Science.gov (United States)

    Wey, Mang Chek; Bendeus, Margareta; Peng, Li; Hägg, Urban; Rabie, A Bakr M; Robinson, Wayne

    2007-06-01

    The aim of this study was to compare the effects of stepwise mandibular advancement versus maximum jumping and extended treatment versus early retention. The material was obtained prospectively and consisted of lateral cephalograms taken at the start (T0), after initial (T1), and at the end (T2) of treatment, from two groups of consecutively treated skeletal Class II patients who had undergone therapy with headgear activators. The first headgear activator group, HGA-S (n=24; mean age 11.9 +/- 1.2 years), was treated for 13 months and had 4-mm mandibular advancement every 3 months. The second headgear activator group, HGA-M (n=31; mean age 11.2 +/- 1.5 years), had maximum jumping, 6-8 mm interincisal opening, for a total of 15.4 months, and with reduced wear for the last 6.9 months. The dropout over 12 months was 41 and 46 per cent, respectively. Pre-treatment growth changes were obtained as a reference. An independent t-test was used to determine differences in baseline dentofacial morphology between the groups, a paired t-test for intra-group comparisons, and an independent t-test to evaluate differences between the groups. The results, in both groups, showed enhanced mandibular prognathism during the initial phase (T0-T1), followed by normal growth (T1-T2), and lower face height enhancement throughout treatment (T0-T2). For both groups, the mandibular plane and occlusal angle increased, possibly enhanced by 'extrusion' of the lower molars. For both groups, maxillary forward growth was restrained only during the initial phase, but the effect remained significant at T2 for the HGA-S group. In the HGA-M group, the lower incisors were protruded, while in the HGA-S group, they were unaffected. The findings indicate that both modes of mandibular jumping resulted in skeletal and dental effects. The length of active treatment seemed to be decisive in maintaining the treatment effects; stepwise advancement had less dental effects.

  11. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  12. Stepwise extraction of proteins and carbohydrates from soybean seed.

    Science.gov (United States)

    Kasai, Naoya; Ikehara, Hiroko

    2005-05-18

    The stepwise hot water extraction of soybeans, which were extractions in a series of procedures of whole soybean seeds, dehulled and sliced ones, and pressed ones carried out by autoclaving, was investigated to study the localization in the seed and their characteristics. The characteristics of each extraction were studied by HPLC, SDS-PAGE, components analysis, microscopic observation, and effect for some enzymes. Carbohydrates were easier to extract than protein. In the extractions, the ratio of uronic acid per total sugar was constantly about 0.3. A comparison of these extracts, soybean milk, extraction from defatted soybean meal, and soybean milk residues was also carried out, and the characteristics and the localization were investigated. Mid-sized proteins in soybean milk were easy to extract. However, hardly any high molecular weight proteins or high molecular weight carbohydrates were extracted. The proteins and carbohydrates were considered to be localized in the middle lamella and in the protein and/or oil bodies of the cell, and the proteins and carbohydrates were gradually extracted through seed and cell breaking. Gelation was observed only in the boiled extracts from whole seeds. Pepsin and trypsin digests of the high molecular weight protein had inhibitory activity against the angiotensin I converting enzyme.

  13. A stepwise procedure for science communication in the field

    Science.gov (United States)

    Nisancioglu, Kerim; Paasche, Øyvind

    2017-04-01

    Communicating and disseminating earth science to laypersons, high-school students and their teachers are becoming increasingly important considering the overwhelming impact human civilization have on the planet. One of the main challenges with this type of dissemination arises from the cross-disciplinary nature of the Earth system as it encompasses anything from cloud physics to the geological evidence of ice ages being played out on millennial time scales. During the last four years we have tested and developed an approach referred to as «Turspor» which can be translated to 'Trail Tracks'. The ambition with "Turspor" is to inspire participants to seek in-depth knowledge relating to observations of features made in the field (glacial moraines, active permafrost, clouds, winds and so forth) as we have come to learn that observations made in the field enhances students capability to grasp the bare essentials related to the phenomena in question. By engaging master and PhD students in the process we create a platform where students can improve their teaching and communicative skills through a stepwise procedure. The initial concept was tested on 35 high school students during the summer of 2012 in the mountainous area of Snøheim on Dovre, Southern Norway. Before the arrival of the high school students, the university students prepared one page written summaries describing relevant geological or meteorological features and trained on how to best disseminate a basic scientific understanding of these. Specific examples were patterned ground caused by permafrost, glacier flour, katabatic winds, and equilibrium line altitude of glaciers. Based on the success of the program over the past 4 years with field trips together with local schools, we are in the process of developing the concept to be offered as a course at the master and PhD level, including a week of training in didactics applied to topics in the geosciences as well as practical training in the field. The

  14. Stepwise group sparse regression (SGSR): gene-set-based pharmacogenomic predictive models with stepwise selection of functional priors.

    Science.gov (United States)

    Jang, In Sock; Dienstmann, Rodrigo; Margolin, Adam A; Guinney, Justin

    2015-01-01

    Complex mechanisms involving genomic aberrations in numerous proteins and pathways are believed to be a key cause of many diseases such as cancer. With recent advances in genomics, elucidating the molecular basis of cancer at a patient level is now feasible, and has led to personalized treatment strategies whereby a patient is treated according to his or her genomic profile. However, there is growing recognition that existing treatment modalities are overly simplistic, and do not fully account for the deep genomic complexity associated with sensitivity or resistance to cancer therapies. To overcome these limitations, large-scale pharmacogenomic screens of cancer cell lines--in conjunction with modern statistical learning approaches--have been used to explore the genetic underpinnings of drug response. While these analyses have demonstrated the ability to infer genetic predictors of compound sensitivity, to date most modeling approaches have been data-driven, i.e. they do not explicitly incorporate domain-specific knowledge (priors) in the process of learning a model. While a purely data-driven approach offers an unbiased perspective of the data--and may yield unexpected or novel insights--this strategy introduces challenges for both model interpretability and accuracy. In this study, we propose a novel prior-incorporated sparse regression model in which the choice of informative predictor sets is carried out by knowledge-driven priors (gene sets) in a stepwise fashion. Under regularization in a linear regression model, our algorithm is able to incorporate prior biological knowledge across the predictive variables thereby improving the interpretability of the final model with no loss--and often an improvement--in predictive performance. We evaluate the performance of our algorithm compared to well-known regularization methods such as LASSO, Ridge and Elastic net regression in the Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (Sanger

  15. Stepwise kinetic equilibrium models of quantitative polymerase chain reaction.

    Science.gov (United States)

    Cobbs, Gary

    2012-08-16

    Numerous models for use in interpreting quantitative PCR (qPCR) data are present in recent literature. The most commonly used models assume the amplification in qPCR is exponential and fit an exponential model with a constant rate of increase to a select part of the curve. Kinetic theory may be used to model the annealing phase and does not assume constant efficiency of amplification. Mechanistic models describing the annealing phase with kinetic theory offer the most potential for accurate interpretation of qPCR data. Even so, they have not been thoroughly investigated and are rarely used for interpretation of qPCR data. New results for kinetic modeling of qPCR are presented. Two models are presented in which the efficiency of amplification is based on equilibrium solutions for the annealing phase of the qPCR process. Model 1 assumes annealing of complementary targets strands and annealing of target and primers are both reversible reactions and reach a dynamic equilibrium. Model 2 assumes all annealing reactions are nonreversible and equilibrium is static. Both models include the effect of primer concentration during the annealing phase. Analytic formulae are given for the equilibrium values of all single and double stranded molecules at the end of the annealing step. The equilibrium values are then used in a stepwise method to describe the whole qPCR process. Rate constants of kinetic models are the same for solutions that are identical except for possibly having different initial target concentrations. Analysis of qPCR curves from such solutions are thus analyzed by simultaneous non-linear curve fitting with the same rate constant values applying to all curves and each curve having a unique value for initial target concentration. The models were fit to two data sets for which the true initial target concentrations are known. Both models give better fit to observed qPCR data than other kinetic models present in the literature. They also give better estimates of

  16. Stepwise kinetic equilibrium models of quantitative polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Cobbs Gary

    2012-08-01

    Full Text Available Abstract Background Numerous models for use in interpreting quantitative PCR (qPCR data are present in recent literature. The most commonly used models assume the amplification in qPCR is exponential and fit an exponential model with a constant rate of increase to a select part of the curve. Kinetic theory may be used to model the annealing phase and does not assume constant efficiency of amplification. Mechanistic models describing the annealing phase with kinetic theory offer the most potential for accurate interpretation of qPCR data. Even so, they have not been thoroughly investigated and are rarely used for interpretation of qPCR data. New results for kinetic modeling of qPCR are presented. Results Two models are presented in which the efficiency of amplification is based on equilibrium solutions for the annealing phase of the qPCR process. Model 1 assumes annealing of complementary targets strands and annealing of target and primers are both reversible reactions and reach a dynamic equilibrium. Model 2 assumes all annealing reactions are nonreversible and equilibrium is static. Both models include the effect of primer concentration during the annealing phase. Analytic formulae are given for the equilibrium values of all single and double stranded molecules at the end of the annealing step. The equilibrium values are then used in a stepwise method to describe the whole qPCR process. Rate constants of kinetic models are the same for solutions that are identical except for possibly having different initial target concentrations. Analysis of qPCR curves from such solutions are thus analyzed by simultaneous non-linear curve fitting with the same rate constant values applying to all curves and each curve having a unique value for initial target concentration. The models were fit to two data sets for which the true initial target concentrations are known. Both models give better fit to observed qPCR data than other kinetic models present in the

  17. Laboratory quality stepwise implementation tool: National reference TB laboratory of Iran

    Directory of Open Access Journals (Sweden)

    Ali Naghi Kebriaee

    2015-01-01

    Conclusions: As the internal score of NRL reaches 5, an international evaluation of accreditation scheme is sought. This is the first investigation that used the quality stepwise implementation tool in Iran.

  18. Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways.

    Science.gov (United States)

    Schlitter, Anna Melissa; Born, Diana; Bettstetter, Marcus; Specht, Katja; Kim-Fuchs, Corina; Riener, Marc-Oliver; Jeliazkova, Petia; Sipos, Bence; Siveke, Jens T; Terris, Benoit; Zen, Yoh; Schuster, Tibor; Höfler, Heinz; Perren, Aurel; Klöppel, Günter; Esposito, Irene

    2014-01-01

    Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, β-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.

  19. Integrated Approach to Construction of Benchmarking Network in DEA-Based Stepwise Benchmark Target Selection

    Directory of Open Access Journals (Sweden)

    Jaehun Park

    2016-06-01

    Full Text Available Stepwise benchmark target selection in data envelopment analysis (DEA is a realistic and effective method by which inefficient decision-making units (DMUs can choose benchmarks in a stepwise manner. We propose, for the construction of a benchmarking network (i.e., a network structure consisting of an alternative sequence of benchmark targets, an approach that integrates the cross-efficiency DEA, K-means clustering and context-dependent DEA methods to minimize resource improvement pattern inconsistency in the selection of the intermediate benchmark targets (IBTs of an inefficient DMU. The specific advantages and overall effectiveness of the proposed method were demonstrated by application to a case study of 34 actual container terminal ports and the successful determination of the stepwise benchmarking path of an inefficient DMU.

  20. Improvement of the Performance of Scheduled Stepwise Power Programme Changes within the European Power System

    DEFF Research Database (Denmark)

    Welfonder, E.; Weissbach, T.; Schulz, U.

    2008-01-01

    the corresponding power generating units and increases the mechanical wear of respective actuators. Therefore, the Uni Stuttgart has investigated the origins of the power imbalances within the framework of a research project on behalf of the VGB Powertech. One main reason for the occurrence of the described power...... imbalances is the non-uniform conversion of scheduled stepwise power programme changes as rampwise changes of the actual power outputs with different ramp durations and gradients respectively, such as fast power output decreases of hydro power plants and slow power output increases of inert steam power plant......Since the deregulation of the electrical energy market, the technical realisation of power transactions based on energy market contracts often effects large stepwise power programme changes – especially at the change of the hour. Due to mainly economic reasons these stepwise power programme changes...

  1. Technique of ICP monitored stepwise intracranial decompression effectively reduces postoperative complications of severe bifrontal contusion

    Directory of Open Access Journals (Sweden)

    Guan eSun

    2016-04-01

    Full Text Available Background Bifrontal contusion is a common clinical brain injury. In the early stage, it is often mild, but it progresses rapidly and frequently worsens suddenly. This condition can become life threatening and therefore requires surgery. Conventional decompression craniectomy is the commonly used treatment method. In this study, the effect of ICP monitored stepwise intracranial decompression surgery on the prognosis of patients with acute severe bifrontal contusion was investigated. Method A total of 136 patients with severe bifrontal contusion combined with deteriorated intracranial hypertension admitted from March 2001 to March 2014 in our hospital were selected and randomly divided into two groups, i.e., a conventional decompression group and an intracranial pressure (ICP monitored stepwise intracranial decompression group (68 patients each, to conduct a retrospective study. The incidence rates of acute intraoperative encephalocele, delayed hematomas, and postoperative cerebral infarctions and the Glasgow outcome scores (GOSs 6 months after the surgery were compared between the two groups.Results (1 The incidence rates of acute encephalocele and contralateral delayed epidural hematoma in the stepwise decompression surgery group were significantly lower than those in the conventional decompression group; the differences were statistically significant (P < 0.05; (2 6 months after the surgery, the incidence of vegetative state and mortality in the stepwise decompression group were significantly lower than those in the conventional decompression group (P < 0.05; the rate of favorable prognosis in the stepwise decompression group was also significantly higher than that in the conventional decompression group (P < 0.05.Conclusions The ICP monitored stepwise intracranial decompression technique reduced the perioperative complications of traumatic brain injury through the gradual release of intracranial pressure and was beneficial to the prognosis of

  2. Step-Wise Group Screening Designs with Unequal A-Priori Probabilities and Errors in Observations

    Directory of Open Access Journals (Sweden)

    M.M. Manene

    2003-06-01

    Full Text Available The performance of step-wise group screening with unequal a-priori probabilities in terms of the expected number of runs and the expected maximum number of incorrect decisions is considered. A method of obtaining optimal step-wise designs with unequal a-priori probabilities is presented for the case in which the direction of each defective factor is assumed to be known a -priori and observations are subject to error. An appropriate cost function is introduced and the value of the group size which minimizes the expected total cost is obtained.

  3. Stepwise Excavation Allows Apexogenesis in Permanent Molars with Deep Carious Lesions and Incomplete Root Formation.

    Science.gov (United States)

    Hernandéz-Gatón, Patrícia; Serrano, César Ruiz; Nelson Filho, Paulo; De Castañeda, Esther Ruiz; Lucisano, Marília P; Silva, Raquel A B da; Silva, Léa A B da

    2015-01-01

    This study evaluated the stepwise excavation technique in 138 permanent molars with deep carious lesions and incomplete root formation within a 24-month clinical and radiographic follow-up period. In 96.7% of the cases, success was observed (no pain, integrity of restoration margins, absence of radiographic alterations and apexogenesis). The cases of failure (3.3%) were due to the loss of the temporary restoration. In conclusion, the stepwise excavation is a promising technique for permanent teeth with deep carious lesions and incomplete root formation as a minimally invasive approach because it allows the preservation of pulp vitality and occurrence of apexogenesis. © 2015 S. Karger AG, Basel.

  4. Photon absorption in step-wise multi-photon activation fluorescence (SMPAF) of Sepia melanin

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; DiMarzio, Charles

    2013-02-01

    Previous research has shown that melanin goes through a step-wise three-photon absorption process when the fluorescence is activated with high laser intensity. We have conducted further research using even higher laser intensity for the activation, and have shown the possibility of observing power dependence other than third-order. This article discusses the possible energy states of Sepia melanin by studying the power dependence curves of the step-wise multi-photon activated fluorescence signal. Three different excitation channels are activated. Possible reasons causing the three channels are discussed.

  5. Stepwise compensation waveform generation by using Josephson voltage standards for joule balance

    Science.gov (United States)

    Wang, Gang; Xu, Jinxin; You, Qiang; Li, Zhengkun; Zhang, Zhonghua

    2017-01-01

    Flux linkage difference in the new joule balance can be obtained by the time integration of the induced voltage u(t) from the suspended coil relative to a moving magnet driven by a dc motor translation platform. Due to the finite acceleration of the dc motor, the transition and waveform of u(t) are finite and not regular. To accurately measure the time integration of u(t), a compensation waveform with precision time integration should be synthesized. In this paper, a stepwise compensation waveform is synthesized by a programmable Josephson voltage standard (PJVS) according to u(t). The accuracy of measuring the stepwise waveform with multiple transitions can be improved by reducing the ratio of the time integrated value of the total transitions to the total waveform less than one part in 102 in the joule balance. The time integration of the rise/fall transition is measured by a synchronized reference square wave generated by another PJVS system. With the total time integration more than 20 Vs, the uncertainty of the generated stepwise waveform is within 5.2  ×  10-8 VsV-1s-1. The result confirms that the PJVS has the capability to generate a stepwise compensation voltage for flux linkage difference measurement.

  6. Stepwise Inquiry into Hard Water in a High School Chemistry Laboratory

    Science.gov (United States)

    Kakisako, Mami; Nishikawa, Kazuyuki; Nakano, Masayoshi; Harada, Kana S.; Tatsuoka, Tomoyuki; Koga, Nobuyoshi

    2016-01-01

    This study focuses on the design of a learning program to introduce complexometric titration as a method for determining water hardness in a high school chemistry laboratory. Students are introduced to the different properties and reactions of hard water in a stepwise manner so that they gain the necessary chemical knowledge and conceptual…

  7. Effects of stepwise dry/wet-aging and freezing on meat quality of beef loins.

    Science.gov (United States)

    Kim, Yuan H Brad; Meyers, Brandon; Kim, Hyun-Wook; Liceaga, Andrea M; Lemenager, Ronald P

    2017-01-01

    The objective of this study was to evaluate the effects of stepwise dry/wet-aging and freezing method on quality attributes of beef loins. Paired loins (M. Longissimus lumborum) from eight carcasses were assigned to either stepwise dry/wet-aging (carcass dry-aging for 10days then further wet-aging for 7days in vacuum bags) or carcass dry-aging only for 17days. Then, each loin was divided into three sections for freezing (never-frozen, blast or cryogenic freezing). Stepwise dry/wet-aged loin had lower purge/drip loss and shear force than conventionally dry-aged loin (P0.05). The cryogenic freezing resulted in a significant decrease in shear force values and a significant improvement in water-holding capacity (WHC). These findings indicate that the stepwise dry/wet-aging coupled with cryogenic freezing could provide beneficial impacts to the local meat industry by providing equivalent quality attributes as conventional dry-aging and improving WHC of frozen/thawed meat, while reducing the time needed for dry-aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Protein Oleogels from Protein Hydrogels via a Stepwise Solvent Exchange Route

    NARCIS (Netherlands)

    Vries, De Auke; Hendriks, Jasper; Linden, Van Der Erik; Scholten, Elke

    2015-01-01

    We investigated the use of whey protein isolate (WPI) as oleogelator in liquid oil. First, heat-set WPI hydrogels were prepared varying in microstructure and network density. Then, by applying a stepwise solvent exchange procedure via an intermediate solvent, full replacement of the internal

  9. Confinement effect in diffusion-controlled stepwise polymerization by Monte Carlo simulation

    NARCIS (Netherlands)

    Malvaldi, M; Bruzzone, S; Picchioni, F

    2006-01-01

    Diffusion-controlled stepwise polymerization of a linear polymer confined in nanoscopic slits is simulated through a Monte Carlo approach. A noticeable influence of the confinement on the kinetics is found. The confinement modifies both the spatial pair distribution function and the diffusive

  10. an online model for assessing st for assessing st stepwise solving of ...

    African Journals Online (AJOL)

    User

    AN ONLINE MODEL FOR ASSESSING ST. FOR ASSESSING ST. STEPWISE SOLVING OF CA. DEPARTMENT OF COMPUTER SCIENCE. E-mail address: mail address: Abstract. Information Technology (IT) is a pivot of new phas of learning on the part of learners from passiveness. In all learning, one of the ways to ...

  11. Stepwise or concerted? DFT study on the mechanism of ionic Diels-Alder reaction of chromanes

    Directory of Open Access Journals (Sweden)

    Haghdadi Mina

    2016-01-01

    Full Text Available The stepwise and concerted Ionic Diels-Alder reaction between phenyl (pyridin-2-ylmethylene oxonium and styrene derivatives are explored using theoretical method. The results support using computational method via persistent intermediates. The DFT method was essential to reproduce a reasonable potential energy surface for these challenging systems.

  12. Stepwise excavation may enhance pulp preservation in permanent teeth affected by dental caries

    DEFF Research Database (Denmark)

    Bjørndal, Lars

    2011-01-01

    ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Ways of enhancing pulp preservation by stepwise excavation-a systematic review. Hayashi M, Fujitani M, Yamaki C, Momoi Y. J Dent 2011;39(2):95-107. Epub 2010 Dec 3. REVIEWER: Lars Bjørndal, DDS, PhD, Dr Odont PURPOSE/QUESTION: To determine the clinical...

  13. Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion

    NARCIS (Netherlands)

    de Groot, Daphne; Grundmann, Sebastian; Timmers, Leo; Pasterkamp, Gerard; Hoefer, Imo E.

    de Groot D, Grundmann S, Timmers L, Pasterkamp G, Hoefer IE. Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion. Am J Physiol Heart Circ Physiol 300: H408-H414, 2011. First published October 15, 2010; doi: 10.1152/ajpheart.00070.2010.-Therapeutic

  14. Efficacy of the genetic sonogram in a stepwise sequential protocol for down syndrome screening.

    Science.gov (United States)

    Shamshirsaz, Alireza A; Ravangard, Samadh F; Turner, Garry; Borgida, Adam; Janicki, Mary Beth; Campbell, Winston A; Zelop, Carolyn; Shamshirsaz, Amirhoushang A; Spiel, Melissa; Prabulos, Anne Marie; Feldman, Deborah; Rodis, John; Ingardia, Charles J; Gurram, Padmalatha; Fuller, Kisti; Fang, Yu M; Benn, Peter; Egan, James F X

    2013-09-01

    The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.

  15. An electromagnetism-like mechanism for the single machine total stepwise tardiness problem with release dates

    Science.gov (United States)

    Tseng, Chao-Tang; Chen, Kuan-Han

    2013-12-01

    In recent years, a new type of tardiness cost, called stepwise tardiness, has received attention. To the authors' knowledge, only a few studies have investigated this type of tardiness in the scheduling problem. This study considered the single machine total stepwise tardiness problem with release dates, which is strongly NP hard. Because of the essential complexity of the problem, heuristics were first developed to quickly generate initial solutions. Subsequently, a new electromagnetism-like mechanism (EM), which is a novel metaheuristic, was proposed to improve the solution quality. The new EM includes a natural encoding scheme, a new distance measure between solutions, and effective attraction and repulsion operators. Comparisons with a current EM and other metaheuristics were performed to verify the proposed EM. The computational results show that the proposed EM exhibits good performance for the considered problem.

  16. An Inter-Networking Mechanism with Stepwise Synchronization for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Masayuki Murata

    2011-08-01

    Full Text Available To realize the ambient information society, multiple wireless networks deployed in the region and devices carried by users are required to cooperate with each other. Since duty cycles and operational frequencies are different among networks, we need a mechanism to allow networks to efficiently exchange messages. For this purpose, we propose a novel inter-networking mechanism where two networks are synchronized with each other in a moderate manner, which we call stepwise synchronization. With our proposal, to bridge the gap between intrinsic operational frequencies, nodes near the border of networks adjust their operational frequencies in a stepwise fashion based on the pulse-coupled oscillator model as a fundamental theory of synchronization. Through simulation experiments, we show that the communication delay and the energy consumption of border nodes are reduced, which enables wireless sensor networks to communicate longer with each other.

  17. An inter-networking mechanism with stepwise synchronization for wireless sensor networks.

    Science.gov (United States)

    Yamamoto, Hiroshi; Wakamiya, Naoki; Murata, Masayuki

    2011-01-01

    To realize the ambient information society, multiple wireless networks deployed in the region and devices carried by users are required to cooperate with each other. Since duty cycles and operational frequencies are different among networks, we need a mechanism to allow networks to efficiently exchange messages. For this purpose, we propose a novel inter-networking mechanism where two networks are synchronized with each other in a moderate manner, which we call stepwise synchronization. With our proposal, to bridge the gap between intrinsic operational frequencies, nodes near the border of networks adjust their operational frequencies in a stepwise fashion based on the pulse-coupled oscillator model as a fundamental theory of synchronization. Through simulation experiments, we show that the communication delay and the energy consumption of border nodes are reduced, which enables wireless sensor networks to communicate longer with each other.

  18. Application of stepwise multiple regression techniques to inversion of Nimbus 'IRIS' observations.

    Science.gov (United States)

    Ohring, G.

    1972-01-01

    Exploratory studies with Nimbus-3 infrared interferometer-spectrometer (IRIS) data indicate that, in addition to temperature, such meteorological parameters as geopotential heights of pressure surfaces, tropopause pressure, and tropopause temperature can be inferred from the observed spectra with the use of simple regression equations. The technique of screening the IRIS spectral data by means of stepwise regression to obtain the best radiation predictors of meteorological parameters is validated. The simplicity of application of the technique and the simplicity of the derived linear regression equations - which contain only a few terms - suggest usefulness for this approach. Based upon the results obtained, suggestions are made for further development and exploitation of the stepwise regression analysis technique.

  19. Problems with step-wise regression in research on aging and recommended alternatives.

    Science.gov (United States)

    Scialfa, C T; Games, P A

    1987-11-01

    The use of step-wise regression techniques in aging research brings with it certain interpretative difficulties. Both geometric and algebraic approaches are used to demonstrate that although step-wise procedures pose little difficulty if predictors are orthogonal, these same procedures, when used with correlated predictors, can lead to poor tests of the predictor regression weights. Techniques that are useful in the detection of multicollinearity are discussed. Principal components regression, ridge regression, and hierarchical regression are evaluated as potential techniques for assessing the relative importance of predictors when these variables are correlated, as is common in aging research. Hierarchical regression is the most recommended technique in that it is theory-driven rather than dependent on empirical relations that may be sample-specific and unstable.

  20. Improvement of the Performance of Scheduled Stepwise Power Programme Changes within the European Power System

    DEFF Research Database (Denmark)

    Welfonder, E.; Weissbach, T.; Schulz, U.

    2008-01-01

    Since the deregulation of the electrical energy market, the technical realisation of power transactions based on energy market contracts often effects large stepwise power programme changes – especially at the change of the hour. Due to mainly economic reasons these stepwise power programme changes...... lead to remarkable power imbalances within the European Power System causing large unintended frequency deviations. In case of these – mostly negative – frequency deviations up to Δf = -150 mHz, considerably more than half of the primary control reserve is activated needlessly, which highly stresses...... the corresponding power generating units and increases the mechanical wear of respective actuators. Therefore, the Uni Stuttgart has investigated the origins of the power imbalances within the framework of a research project on behalf of the VGB Powertech. One main reason for the occurrence of the described power...

  1. FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner.

    Science.gov (United States)

    Shimokawa, Koya; Ishihara, Kai; Grainge, Ian; Sherratt, David J; Vazquez, Mariel

    2013-12-24

    In Escherichia coli, complete unlinking of newly replicated sister chromosomes is required to ensure their proper segregation at cell division. Whereas replication links are removed primarily by topoisomerase IV, XerC/XerD-dif site-specific recombination can mediate sister chromosome unlinking in Topoisomerase IV-deficient cells. This reaction is activated at the division septum by the DNA translocase FtsK, which coordinates the last stages of chromosome segregation with cell division. It has been proposed that, after being activated by FtsK, XerC/XerD-dif recombination removes DNA links in a stepwise manner. Here, we provide a mathematically rigorous characterization of this topological mechanism of DNA unlinking. We show that stepwise unlinking is the only possible pathway that strictly reduces the complexity of the substrates at each step. Finally, we propose a topological mechanism for this unlinking reaction.

  2. Stepwise bioprocess for exopolysaccharide production using potato starch as carbon source.

    Science.gov (United States)

    Bhatia, Shashi Kant; Kumar, Narinder; Bhatia, Ravi Kant

    2015-10-01

    Xanthan gum is a biopolymer produced by Xanthomonas sp. XC6. In this study, xanthan gum is produced from potato starch using a stepwise bioprocess design. Potato starch is hydrolyzed using Bacillus sp. having amylase activity and 30.2 g/L reducing sugar was released, while Xanthomonas sp. XC6 can release only 14.5 g/L. Bacillus sp. hydrolyzed potato starch extract was further used as a carbon source for xanthan gum biosynthesis using Xanthomonas sp. XC6. Yeast extract acts as the best nitrogen source, and 10.0 g/L xanthan gum was recovered. Downstreaming process after stepwise bioprocess resulted in 17.4 g/L xanthan gum production, which is 2.8 times higher as compared to single step process.

  3. Stepwise synthesis and characterization of germa[4], [5], [8], and [10]pericyclynes.

    Science.gov (United States)

    Tanimoto, Hiroki; Nagao, Tomohiko; Fujiwara, Taro; Nishiyama, Yasuhiro; Morimoto, Tsumoru; Suzuka, Toshimasa; Tsutsumi, Ken; Kakiuchi, Kiyomi

    2015-07-14

    The stepwise syntheses of germa[N]pericyclynes, including [5]pericyclynes, and their characterization are described. The yields of germa[4] and [8]pericyclynes were improved significantly compared to those obtained in previous studies. The routes reported herein afforded the novel germa[5] and [10]pericyclynes, which were characterized by X-ray crystallography, UV-Vis spectroscopy, and fluorescence emission spectroscopy. A unique fluorescence emission was observed for the large germa[10]pericyclyne ring.

  4. Stepwise method based on Wiener estimation for spectral reconstruction in spectroscopic Raman imaging.

    Science.gov (United States)

    Chen, Shuo; Wang, Gang; Cui, Xiaoyu; Liu, Quan

    2017-01-23

    Raman spectroscopy has demonstrated great potential in biomedical applications. However, spectroscopic Raman imaging is limited in the investigation of fast changing phenomena because of slow data acquisition. Our previous studies have indicated that spectroscopic Raman imaging can be significantly sped up using the approach of narrow-band imaging followed by spectral reconstruction. A multi-channel system was built to demonstrate the feasibility of fast wide-field spectroscopic Raman imaging using the approach of simultaneous narrow-band image acquisition followed by spectral reconstruction based on Wiener estimation in phantoms. To further improve the accuracy of reconstructed Raman spectra, we propose a stepwise spectral reconstruction method in this study, which can be combined with the earlier developed sequential weighted Wiener estimation to improve spectral reconstruction accuracy. The stepwise spectral reconstruction method first reconstructs the fluorescence background spectrum from narrow-band measurements and then the pure Raman narrow-band measurements can be estimated by subtracting the estimated fluorescence background from the overall narrow-band measurements. Thereafter, the pure Raman spectrum can be reconstructed from the estimated pure Raman narrow-band measurements. The result indicates that the stepwise spectral reconstruction method can improve spectral reconstruction accuracy significantly when combined with sequential weighted Wiener estimation, compared with the traditional Wiener estimation. In addition, qualitatively accurate cell Raman spectra were successfully reconstructed using the stepwise spectral reconstruction method from the narrow-band measurements acquired by a four-channel wide-field Raman spectroscopic imaging system. This method can potentially facilitate the adoption of spectroscopic Raman imaging to the investigation of fast changing phenomena.

  5. Efficacy of stepwise sodium profile versus individualized dialysate sodium in blood pressure control among hemodialysis patients.

    Science.gov (United States)

    Shahgholian, Nahid; Hashemi, Maryam Sadat; Shahidi, Shahrzade

    2015-01-01

    Hypertension is very common in patients with end-stage renal disease and accelerates cardiovascular morbidity and mortality. The most important factor in achieving normal blood pressure in these patients is reaching dry weight. Sodium and extracellular fluid balance play a vital role in this regard. Considering the lack of consensus about the efficacy of stepwise sodium profile and individualized dialysate sodium, this study aimed to determine the superior method for blood pressure control in hemodialysis patients. In a quasi-experimental study, patients satisfying the inclusion criteria were enrolled through convenience sampling. The patients were randomly assigned to two groups of stepwise sodium profile and individualized dialysate sodium. Information record form was used for data collection. Data were analyzed with paired and independent t-test and descriptive statistics using SPSS for Windows 20.0. Patients in the two groups were similar in qualitative and quantitative background variables. While systolic blood pressure significantly decreased following hemodialysis with individualized dialysate sodium (P profile (P = 0.060). Individualized dialysate sodium caused greater change in the mean systolic blood pressure than stepwise sodium profile did (P = 0.040). Pre- and post-dialysis diastolic blood pressure values showed significant differences in both groups (P profile). However, the mean changes in diastolic blood pressure of the two groups were not significantly different (P = 0.295). We found no significant difference in interdialytic weight gain and blood pressure control by the two methods. The change in systolic blood pressure was lower in the stepwise profile method than in the individualized dialysate sodium method, and this method did not cause interdialytic hypertension. So, by adjusting the dialysis solution with regard to plasma sodium levels, lead to more blood pressure control. Meanwhile, the two groups were not significantly different in the

  6. Impact of Antibiotic Shortage on H. Pylori Treatment: A Step-Wise Approach for Pharmacist Management

    Directory of Open Access Journals (Sweden)

    Ann Lloyd, Pharm.D., BCPS

    2013-01-01

    Full Text Available The current drug shortage crisis involving multiple oral antibiotics has significantly impacted preferred therapeutic options for treatment of H.pylori infection. Pharmacists may help alleviate the impact of this shortage through a proposed step-wise approach which includes proper inventory management, verification of indication, evaluation of regimen, therapeutic monitoring, and communication with patients and providers regarding alternative therapy or symptomatic relief.

  7. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli

    OpenAIRE

    Nakagawa, Akira; Matsumura, Eitaro; Koyanagi, Takashi; Katayama, Takane; Kawano, Noriaki; Yoshimatsu, Kayo; Yamamoto, Kenji; Kumagai, Hidehiko; Sato, Fumihiko; Minami, Hiromichi

    2016-01-01

    Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four ...

  8. An Inter-Networking Mechanism with Stepwise Synchronization for Wireless Sensor Networks

    OpenAIRE

    Masayuki Murata; Naoki Wakamiya; Hiroshi Yamamoto

    2011-01-01

    To realize the ambient information society, multiple wireless networks deployed in the region and devices carried by users are required to cooperate with each other. Since duty cycles and operational frequencies are different among networks, we need a mechanism to allow networks to efficiently exchange messages. For this purpose, we propose a novel inter-networking mechanism where two networks are synchronized with each other in a moderate manner, which we call stepwise synchronization. With ...

  9. Individual stepwise intensification of insulin analogue therapy in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Aleksandr Sergeevich Ametov

    2012-12-01

    Full Text Available Article reviews basic steps and regimens of insulin analogue therapy intensification in patients with type 2 diabetes mellitus (T2DM. Intensification of insulin therapy is commonly implemented by supplementation of basal insulin with prandial before breakfast, lunch and dinner. Updated EASD/ADA guidelines (August 2012 recommend individual stepwise intensification of T2DM insulin therapy. Application of insulin analogues simplifies diabetes training and patient self-monitoring.

  10. Renewable platform chemicals from directional microwave-assisted liquefaction coupling stepwise extraction of waste biomass

    Science.gov (United States)

    Junfeng Feng; Chungyun Hse; Zhongzhi Yang; Kui Wang; Jianchun Jiang; Junming Xu

    2017-01-01

    Directional microwave-assisted liquefaction and stepwise extraction are introduced for producing platform chemicals: aromatics and monosaccharides. When sulfuric acid was used as a catalyst, a 45% monosaccharides yield and a 29% aromatics yield were obtained from bamboo with 0.3 g catalyst per 18 g methanol and 2 g bamboo at 160 °C with 10 min. Approximately 78–86 wt%...

  11. Stepwise cyanation of naphthalene diimide for n-channel field-effect transistors

    KAUST Repository

    Chang, Jingjing

    2012-06-15

    Stepwise cyanation of tetrabromonaphthalenediimide (NDI) 1 gave a series of cyanated NDIs 2-5 with the monocyanated NDI 2 and dicyanated NDI 3 isolated. The tri- and tetracyano- NDIs 4 and 5 show intrinsic instability toward moisture because of their extremely low-lying LUMO energy levels. The partially cyanated intermediates can be utilized as air-stable n-type semiconductors with OFET electron mobility up to 0.05 cm 2 V -1 s -1. © 2012 American Chemical Society.

  12. In vitro production of buffalo embryos from stepwise vitrified immature oocytes

    Directory of Open Access Journals (Sweden)

    Saber Mohammed Abd-Allah

    2009-09-01

    Full Text Available This study was conducted to produce buffalo embryos in vitro from stepwise vitrified immature oocytes. Cumulus oocyte complexes (COCs were obtained from the ovaries of slaughtered buffalo and were collected from the local abattoir. Selected COCs were exposed to a vitrification solution consisting of 40% ethylene glycol (EG plus 0.3 M trehalose and 20% polyvinyl pyrrolidone (PVP for 1 min and loaded in 0.25 ml plastic mini-straws containing 100 µl of 10% sucrose. The loaded cryostraws were cryopreserved by stepwise vitrification and were stored in liquid nitrogen for 4 to 6 months. Data analysis revealed a high percentage of post-thawing morphologically normal immature oocytes (80.7% with a low percentage of damaged oocytes. There were no significant differences in the maturation (82.1%, cleavage (47.6% and buffalo embryo development (15.4% produced by the stepwise vitrified immature oocytes in comparison to the three observations in fresh oocytes (88.3%, 50.4% and 19.4%, respectively, p<0.05.

  13. In vitro production of buffalo embryos from stepwise vitrified immature oocytes.

    Science.gov (United States)

    Abd-Allah, Saber Mohammed

    2009-01-01

    This study was conducted to produce buffalo embryos in vitro from stepwise vitrified immature oocytes. Cumulus oocyte complexes (COCs) were obtained from the ovaries of slaughtered buffalo and were collected from the local abattoir. Selected COCs were exposed to a vitrification solution consisting of 40% ethylene glycol (EG) plus 0.3 M trehalose and 20% polyvinyl pyrrolidone (PVP) for 1 min and loaded in 0.25 ml plastic mini-straws containing 100 microl of 10% sucrose. The loaded cryostraws were cryopreserved by stepwise vitrification and were stored in liquid nitrogen for 4 to 6 months. Data analysis revealed a high percentage of post-thawing morphologically normal immature oocytes (80.7%) with a low percentage of damaged oocytes. There were no significant differences in the maturation (82.1%), cleavage (47.6%) and buffalo embryo development (15.4%) produced by the stepwise vitrified immature oocytes in comparison to the three observations in fresh oocytes (88.3%, 50.4% and 19.4%, respectively, p<0.05).

  14. Fourth-order Perturbed Eigenvalue Equation for Stepwise Damage Detection of Aeroplane Wing

    Directory of Open Access Journals (Sweden)

    Wong Chun Nam

    2016-01-01

    Full Text Available Perturbed eigenvalue equations up to fourth-order are established to detect structural damage in aeroplane wing. Complete set of perturbation terms including orthogonal and non-orthogonal coefficients are computed using perturbed eigenvalue and orthonormal equations. Then the perturbed eigenparameters are optimized using BFGS approach. Finite element model with small to large stepwise damage is used to represent actual aeroplane wing. In small damaged level, termination number is the same for both approaches, while rms errors and termination d-norms are very close. For medium damaged level, termination number is larger for third-order perturbation with lower d-norm and smaller rms error. In large damaged level, termination number is much larger for third-order perturbation with same d-norm and larger rms error. These trends are more significant as the damaged level increases. As the stepwise damage effect increases with damage level, the increase in stepwise effect leads to the increase in model order. Hence, fourth-order perturbation is more accurate to estimate the model solution.

  15. Improved model of the retardance in citric acid coated ferrofluids using stepwise regression

    Science.gov (United States)

    Lin, J. F.; Qiu, X. R.

    2017-06-01

    Citric acid (CA) coated Fe3O4 ferrofluids (FFs) have been conducted for biomedical application. The magneto-optical retardance of CA coated FFs was measured by a Stokes polarimeter. Optimization and multiple regression of retardance in FFs were executed by Taguchi method and Microsoft Excel previously, and the F value of regression model was large enough. However, the model executed by Excel was not systematic. Instead we adopted the stepwise regression to model the retardance of CA coated FFs. From the results of stepwise regression by MATLAB, the developed model had highly predictable ability owing to F of 2.55897e+7 and correlation coefficient of one. The average absolute error of predicted retardances to measured retardances was just 0.0044%. Using the genetic algorithm (GA) in MATLAB, the optimized parametric combination was determined as [4.709 0.12 39.998 70.006] corresponding to the pH of suspension, molar ratio of CA to Fe3O4, CA volume, and coating temperature. The maximum retardance was found as 31.712°, close to that obtained by evolutionary solver in Excel and a relative error of -0.013%. Above all, the stepwise regression method was successfully used to model the retardance of CA coated FFs, and the maximum global retardance was determined by the use of GA.

  16. Stepwise dehydrogenation of ammonia on Fcc-Co surfaces: A DFT study

    Energy Technology Data Exchange (ETDEWEB)

    Ma, F.F.; Ma, S.H., E-mail: mash.phy@htu.edu.cn; Jiao, Z.Y.; Dai, X.Q.

    2017-05-31

    Highlights: • On Co surfaces, oxygen atom not only strengthens ammonia-substrate interaction but also facilitates ammonia dissociation on the Co surfaces. • Pre-adsorbed O atom significantly promotes the stepwise dehydrogenation of ammonia on Co(110), giving rise to N atom strongly binding with the surface. • The dissociation of NH appears to be the rate-determining step on O-covered Co(111) and Co(100) surfaces. • The species N and NH produced in ammonia dehydrogenation are likely responsible for cobalt catalyst deactivation in the excess of oxygen atom. - Abstract: The stepwise dehydrogenation of ammonia on clean and O-covered Co surfaces have been studied by performing density functional theory (DFT) calculations. It is found that the interaction of species NH{sub x} (x = 0–3) with the Co surfaces become stronger with its further dehydrogenation, and oxygen atom not only strengthens ammonia-substrate interaction but also facilitates ammonia dissociation. Specifically, pre-adsorbed O atom significantly promotes the stepwise dehydrogenation of ammonia on Co(110), giving rise to N atom strongly binding with the surface. In contrast, the dissociation of NH appears to be the rate-determining step on O-covered Co(111) and Co(100) surfaces, due to the high energy barriers. And present results demonstrate that the species N and NH produced in ammonia dehydrogenation are likely responsible for cobalt catalyst deactivation in the excess of oxygen atom.

  17. Step-wise and punctuated genome evolution drive phenotype changes of tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Stepanenko, Aleksei, E-mail: a.a.stepanenko@gmail.com [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine); Andreieva, Svitlana; Korets, Kateryna; Mykytenko, Dmytro [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine); Huleyuk, Nataliya [Institute of Hereditary Pathology, National Academy of Medical Sciences of Ukraine, Lviv 79008 (Ukraine); Vassetzky, Yegor [CNRS UMR8126, Université Paris-Sud 11, Institut de Cancérologie Gustave Roussy, Villejuif 94805 (France); Kavsan, Vadym [Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680 (Ukraine)

    2015-01-15

    Highlights: • There are the step-wise continuous and punctuated phases of cancer genome evolution. • The system stresses during the different phases may lead to very different responses. • Stable transfection of an empty vector can result in genome and phenotype changes. • Functions of a (trans)gene can be opposite/versatile in cells with different genomes. • Contextually, temozolomide can both promote and suppress tumor cell aggressiveness. - Abstract: The pattern of genome evolution can be divided into two phases: the step-wise continuous phase (step-wise clonal evolution, stable dominant clonal chromosome aberrations (CCAs), and low frequency of non-CCAs, NCCAs) and punctuated phase (marked by elevated NCCAs and transitional CCAs). Depending on the phase, system stresses (the diverse CIN promoting factors) may lead to the very different phenotype responses. To address the contribution of chromosome instability (CIN) to phenotype changes of tumor cells, we characterized CCAs/NCCAs of HeLa and HEK293 cells, and their derivatives after genotoxic stresses (a stable plasmid transfection, ectopic expression of cancer-associated CHI3L1 gene or treatment with temozolomide) by conventional cytogenetics, copy number alterations (CNAs) by array comparative genome hybridization, and phenotype changes by cell viability and soft agar assays. Transfection of either the empty vector pcDNA3.1 or pcDNA3.1-CHI3L1 into 293 cells initiated the punctuated genome changes. In contrast, HeLa-CHI3L1 cells demonstrated the step-wise genome changes. Increased CIN correlated with lower viability of 293-pcDNA3.1 cells but higher colony formation efficiency (CFE). Artificial CHI3L1 production in 293-CHI3L1 cells increased viability and further contributed to CFE. The opposite growth characteristics of 293-CHI3L1 and HeLa-CHI3L1 cells were revealed. The effect and function of a (trans)gene can be opposite and versatile in cells with different genetic network, which is defined by

  18. Is there a step-wise migration in Nigeria? A case study of the migrational histories of migrants in Lagos.

    Science.gov (United States)

    Afolayan, A A

    1985-09-01

    "The paper sets out to test whether or not the movement pattern of people in Nigeria is step-wise. It examines the spatial order in the country and the movement pattern of people. It then analyzes the survey data and tests for the validity of step-wise migration in the country. The findings show that step-wise migration cannot adequately describe all the patterns observed." The presence of large-scale circulatory migration between rural and urban areas is noted. Ways to decrease the pressure on Lagos by developing intermediate urban areas are considered. excerpt

  19. Stepwise radical endoscopic resection of the complete Barrett's esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities

    NARCIS (Netherlands)

    Peters, Femke P.; Krishnadath, K. K.; Rygiel, Agnieszka M.; Curvers, Wouter L.; Rosmolen, Wilda D.

    2007-01-01

    OBJECTIVES: Malignant transformation of Barrett's mucosa is associated with the accumulation of genetic alterations. Stepwise radical endoscopic resection of the Barrett's segment with early neoplasia is a promising new treatment resulting in complete re-epithelialization of the esophagus with

  20. Stepwise Percutaneous Leverage Technique to Avoid Posterior Interosseous Nerve Injury in Pediatric Radial Neck Fracture.

    Science.gov (United States)

    Choi, Wan-Sun; Han, Kyeong-Jin; Lee, Doo-Hyung; Lee, Ga-Eun; Kweon, Heon-Ju; Cho, Jae-Ho

    2017-05-01

    To introduce a stepwise percutaneous leverage technique to avoid posterior interosseous nerve (PIN) injury in pediatric patients with radial neck fractures and to evaluate the clinical outcome and the predisposing factors affecting the outcome. Retrospective case series study. University level 1 trauma center. Thirty-four children with a radial neck fracture, who were treated using a stepwise percutaneous leverage technique, were included in the study. The radial head fragment was reduced by pulling the first Steinmann pin proximally as a lever. Then, the kinked soft tissue was released by removal of the Steinmann pin with buttressing the radial head by the operator's thumb. The second Steinmann pin was inserted into relaxed soft tissue for fixation of the radial head. We used the Métaizeau classification as a radiologic result and Mayo Elbow Performance Score (MEPS) as a clinical outcome. Regression analysis was performed to identify the predisposing factors affecting the outcome. There was no occurrence of PIN palsy. According to the Métaizeau classification, 23 cases were classified as excellent, 9 as good, 1 as fair, and 1 as poor. The average MEPS was 97.6 points. Based on the regression analysis, only the postoperative Métaizeau classification was confirmed as a risk factor of a relatively poor outcome. The stepwise percutaneous leverage technique can be considered a good option in the treatment of pediatric radial neck fractures, because it ensures excellent results by avoiding injury to soft tissues including the PIN. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  1. An investigation of correlation between pilot scanning behavior and workload using stepwise regression analysis

    Science.gov (United States)

    Waller, M. C.

    1976-01-01

    An electro-optical device called an oculometer which tracks a subject's lookpoint as a time function has been used to collect data in a real-time simulation study of instrument landing system (ILS) approaches. The data describing the scanning behavior of a pilot during the instrument approaches have been analyzed by use of a stepwise regression analysis technique. A statistically significant correlation between pilot workload, as indicated by pilot ratings, and scanning behavior has been established. In addition, it was demonstrated that parameters derived from the scanning behavior data can be combined in a mathematical equation to provide a good representation of pilot workload.

  2. A neon-E rich phase in Orgueil - Results of stepwise heating experiments

    Science.gov (United States)

    Eberhardt, P.

    1978-01-01

    A Ne-E rich phase was separated from the Orgeuil carbonaceous chondrite. He and Ne were analyzed in this phase and in an Orgueil residual bulk silicate sample using the stepwise heating technique. Ne-E was found to be released from the Ne-E rich phase at temperatures as low as 500 C; however, gas richest in Ne-E is observed at the highest temperatures (1230 C). The following limits for the isotopic composition of Ne-E were obtained: Ne-20/Ne-22 less than 1.52; Ne-21/Ne-22 less than 0.0244.

  3. Factors related to patients' general satisfaction with removable partial dentures: a stepwise multiple regression analysis.

    Science.gov (United States)

    Zlatarić, Dubravka Knezović; Celebić, Asja

    2008-01-01

    This study aimed to analyze factors related to patients' general satisfaction with removable partial dentures (RPDs), such as esthetics, retention, speech, chewing, and comfort. A total of 103 patients with Kennedy Class I RPDs (34 to 82 years old; mean age: 63; 35 men, 68 women) assessed their satisfaction with dentures. Stepwise multiple regression analysis was used to evaluate the relationship among the factors. Significant correlations were found between general satisfaction and each of the individual components (P < .05). The patients' assessment of esthetics explained almost 50% of general satisfaction in both arches (P < .05). Esthetics, chewing, and speech had significant effects on the patients' general satisfaction with dentures.

  4. Stepwise aggregation of dimethyl-di-n-octylammonium chloride in aqueous solutions: from dimers to vesicles.

    Science.gov (United States)

    Leclercq, Loïc; Nardello-Rataj, Véronique; Turmine, Mireille; Azaroual, Nathalie; Aubry, Jean-Marie

    2010-02-02

    The self-aggregation of dimethyl-di-n-octylammonium chloride, in diluted aqueous solutions, was studied with various experimental and theoretical techniques: zetametry, conductimetry, dimethyl-di-n-octylammonium and chloride-selective electrodes, tensiometry, NMR spectroscopy ((1)H and DOSY), and molecular modeling (PM3 and molecular dynamic). The combination of the data obtained by these techniques led us to propose a stepwise aggregation process with increasing concentration: dimers (0.2-10 mM), bilayers (10-30 mM), and finally vesicles (>30 mM).

  5. In vivo stepwise multi-photon activation fluorescence imaging of melanin in human skin

    Science.gov (United States)

    Lai, Zhenhua; Gu, Zetong; Abbas, Saleh; Lowe, Jared; Sierra, Heidy; Rajadhyaksha, Milind; DiMarzio, Charles

    2014-03-01

    The stepwise multi-photon activated fluorescence (SMPAF) of melanin is a low cost and reliable method of detecting melanin because the activation and excitation can be a continuous-wave (CW) mode near infrared (NIR) laser. Our previous work has demonstrated the melanin SMPAF images in sepia melanin, mouse hair, and mouse skin. In this study, we show the feasibility of using SMPAF to detect melanin in vivo. in vivo melanin SMPAF images of normal skin and benign nevus are demonstrated. SMPAF images add specificity for melanin detection than MPFM images and CRM images. Melanin SMPAF is a promising technology to enable early detection of melanoma for dermatologists.

  6. Step-wise and punctuated genome evolution drive phenotype changes of tumor cells.

    Science.gov (United States)

    Stepanenko, Aleksei; Andreieva, Svitlana; Korets, Kateryna; Mykytenko, Dmytro; Huleyuk, Nataliya; Vassetzky, Yegor; Kavsan, Vadym

    2015-01-01

    The pattern of genome evolution can be divided into two phases: the step-wise continuous phase (step-wise clonal evolution, stable dominant clonal chromosome aberrations (CCAs), and low frequency of non-CCAs, NCCAs) and punctuated phase (marked by elevated NCCAs and transitional CCAs). Depending on the phase, system stresses (the diverse CIN promoting factors) may lead to the very different phenotype responses. To address the contribution of chromosome instability (CIN) to phenotype changes of tumor cells, we characterized CCAs/NCCAs of HeLa and HEK293 cells, and their derivatives after genotoxic stresses (a stable plasmid transfection, ectopic expression of cancer-associated CHI3L1 gene or treatment with temozolomide) by conventional cytogenetics, copy number alterations (CNAs) by array comparative genome hybridization, and phenotype changes by cell viability and soft agar assays. Transfection of either the empty vector pcDNA3.1 or pcDNA3.1_CHI3L1 into 293 cells initiated the punctuated genome changes. In contrast, HeLa_CHI3L1 cells demonstrated the step-wise genome changes. Increased CIN correlated with lower viability of 293_pcDNA3.1 cells but higher colony formation efficiency (CFE). Artificial CHI3L1 production in 293_CHI3L1 cells increased viability and further contributed to CFE. The opposite growth characteristics of 293_CHI3L1 and HeLa_CHI3L1 cells were revealed. The effect and function of a (trans)gene can be opposite and versatile in cells with different genetic network, which is defined by genome context. Temozolomide treatment of 293_pcDNA3.1 cells intensified the stochastic punctuated genome changes and CNAs, and significantly reduced viability and CFE. In contrast, temozolomide treatment of HeLa_CHI3L1 cells promoted the step-wise genome changes, CNAs, and increased viability and CFE, which did not correlate with the ectopic CHI3L1 production. Thus, consistent coevolution of karyotypes and phenotypes was observed. CIN as a driving force of genome

  7. Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Watz, Henrik; Kirsten, Anne

    2014-01-01

    Long-acting bronchodilators in combination with inhaled corticosteroids (ICS) are recommended to decrease the risk of recurrent exacerbations in patients with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3-4 chronic obstructive pulmonary disease (COPD). There is increasing......-controlled fashion, one group of patients continues to receive tiotropium, salmeterol and fluticasone, while the second group initiates stepwise withdrawal of fluticasone. The primary end point is time to first moderate or severe exacerbation following randomized treatment over 52 weeks. Lung function, symptoms...

  8. The step-wise pathway of septin hetero-octamer assembly in budding yeast

    OpenAIRE

    Weems, Andrew; McMurray, Michael

    2017-01-01

    Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1?Cdc12?Cdc3?Cdc10?Cdc10?Cdc3?Cdc12?Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended...

  9. Vapor permeation-stepwise injection simultaneous determination of methanol and ethanol in biodiesel with voltammetric detection.

    Science.gov (United States)

    Shishov, Andrey; Penkova, Anastasia; Zabrodin, Andrey; Nikolaev, Konstantin; Dmitrenko, Maria; Ermakov, Sergey; Bulatov, Andrey

    2016-02-01

    A novel vapor permeation-stepwise injection (VP-SWI) method for the determination of methanol and ethanol in biodiesel samples is discussed. In the current study, stepwise injection analysis was successfully combined with voltammetric detection and vapor permeation. This method is based on the separation of methanol and ethanol from a sample using a vapor permeation module (VPM) with a selective polymer membrane based on poly(phenylene isophtalamide) (PA) containing high amounts of a residual solvent. After the evaporation into the headspace of the VPM, methanol and ethanol were transported, by gas bubbling, through a PA membrane to a mixing chamber equipped with a voltammetric detector. Ethanol was selectively detected at +0.19 V, and both compounds were detected at +1.20 V. Current subtractions (using a correction factor) were used for the selective determination of methanol. A linear range between 0.05 and 0.5% (m/m) was established for each analyte. The limits of detection were estimated at 0.02% (m/m) for ethanol and methanol. The sample throughput was 5 samples h(-1). The method was successfully applied to the analysis of biodiesel samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. A deformation analysis method of stepwise regression for bridge deflection prediction

    Science.gov (United States)

    Shen, Yueqian; Zeng, Ying; Zhu, Lei; Huang, Teng

    2015-12-01

    Large-scale bridges are among the most important infrastructures whose safe conditions concern people's daily activities and life safety. Monitoring of large-scale bridges is crucial since deformation might have occurred. How to obtain the deformation information and then judge the safe conditions are the key and difficult problems in bridge deformation monitoring field. Deflection is the important index for evaluation of bridge safety. This paper proposes a forecasting modeling of stepwise regression analysis. Based on the deflection monitoring data of Yangtze River Bridge, the main factors influenced deflection deformation is chiefly studied. Authors use the monitoring data to forecast the deformation value of a bridge deflection at different time from the perspective of non-bridge structure, and compared to the forecasting of gray relational analysis based on linear regression. The result show that the accuracy and reliability of stepwise regression analysis is high, which provides the scientific basis to the bridge operation management. And above all, the ideas of this research provide and effective method for bridge deformation analysis.

  11. Renewable platform chemicals from directional microwave-assisted liquefaction coupling stepwise extraction of waste biomass.

    Science.gov (United States)

    Feng, Junfeng; Hse, Chungyun; Yang, Zhongzhi; Wang, Kui; Jiang, Jianchun; Xu, Junming

    2017-11-01

    Directional microwave-assisted liquefaction and stepwise extraction are introduced for producing platform chemicals: aromatics and monosaccharides. When sulfuric acid was used as a catalyst, a 45% monosaccharides yield and a 29% aromatics yield were obtained from bamboo with 0.3g catalyst per 18g methanol and 2g bamboo at 160°C with 10min. Approximately 78-86wt% of the six biomass materials were converted into liquid products. After the stepwise extraction and precipitation process, the yields of monosaccharide derivatives and three phenolic compound fractions were 39-45% and 28-32%, respectively. Monosaccharides from holocellulose collected with a high purity of methyl glycosides were higher than 90%. Aromatic derivatives with different weight-molecular distributions were separated into three fractions with more than 80% phenolics. As their similar chemical properties within each fraction, platform chemicals have great commercial potential for producing high-quality chemicals and biofuels using mild upgrading conditions. Copyright © 2017. Published by Elsevier Ltd.

  12. A modified GFP facilitates counting membrane protein subunits by step-wise photobleaching in Arabidopsis.

    Science.gov (United States)

    Song, Kai; Xue, Yiqun; Wang, Xiaohua; Wan, Yinglang; Deng, Xin; Lin, Jinxing

    2017-06-01

    Membrane proteins exert functions by forming oligomers or molecular complexes. Currently, step-wise photobleaching has been applied to count the fluorescently labelled subunits in plant cells, for which an accurate and reliable control is required to distinguish individual subunits and define the basal fluorescence. However, the common procedure using immobilized GFP molecules is obviously not applicable for analysis in living plant cells. Using the spatial intensity distribution analysis (SpIDA), we found that the A206K mutation reduced the dimerization of GFP molecules. Further ectopic expression of Myristoyl-GFPA206K driven by the endogenous AtCLC2 promoter allowed imaging of individual molecules at a low expression level. As a result, the percentage of dimers in the transgenic pCLC2::Myristoyl-mGFPA206K line was significantly reduced in comparison to that of the pCLC2::Myristoyl-GFP line, confirming its application in defining the basal fluorescence intensity of GFP. Taken together, our results demonstrated that pCLC2::Myristoyl-mGFPA206K can be used as a standard control for monomer GFP, facilitating the analysis of the step-wise photobleaching of membrane proteins in Arabidopsis thaliana. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Clinical Evaluation of Ozone on Dentinal Lesions in Young Permanent Molars using the Stepwise Excavation.

    Science.gov (United States)

    Safwat, Osama; Elkateb, Mona; Dowidar, Karin; El Meligy, Omar

    To evaluate the clinical changes in dentin of deep carious lesions in young permanent molars, following ozone application with and without the use of a remineralizing solution, using the stepwise excavation. The sample included 162 first permanent immature molars, showing deep occlusal carious cavities that were indicated for indirect pulp capping. Teeth were divided into 2 main groups according to the method of ozone treatment. Each group was further subdivided equally into test and control subgroups. Following caries excavation, color, consistency and DIAGNOdent assessments of dentin were evaluated after 6 and 12 months. Regarding dentin color and consistency, no significant differences were observed following ozone application, with and without a remineralizing solution. There were no significant differences between ozone treatment, and calcium hydroxide during the different evaluation periods, except in group I cases after 6 months, concerning the dentin color. The DIAGNOdent values were significantly reduced following ozone application, with or without a remineralizing solution, as well as between test and control cases in group I after 6 months. Ozone application through the stepwise excavation had no significant effect on dentin color and consistency in young permanent molars. DIAGNOdent was unreliable in monitoring caries activity.

  14. Stepwise Versus Concerted Mechanisms in General-Base Catalysis by Serine Proteases.

    Science.gov (United States)

    Uritsky, Neta; Shokhen, Michael; Albeck, Amnon

    2016-01-26

    General-base catalysis in serine proteases still poses mechanistic challenges despite decades of research. Whether proton transfer from the catalytic Ser to His and nucleophilic attack on the substrate are concerted or stepwise is still under debate, even for the classical Asp-His-Ser catalytic triad. To address these key catalytic steps, the transformation of the Michaelis complex to tetrahedral complex in the covalent inhibition of two prototype serine proteases was studied: chymotrypsin (with the catalytic triad) inhibition by a peptidyl trifluoromethane and GlpG rhomboid (with Ser-His dyad) inhibition by an isocoumarin derivative. The sampled MD trajectories of averaged pKa  values of catalytic residues were QM calculated by the MD-QM/SCRF(VS) method on molecular clusters simulating the active site. Differences between concerted and stepwise mechanisms are controlled by the dynamically changing pKa  values of the catalytic residues as a function of their progressively reduced water exposure, caused by the incoming ligand. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Screening for type 2 diabetes in primary care using a stepwise protocol: the Diabscreen study.

    Science.gov (United States)

    Klein Woolthuis, Erwin P; de Grauw, Wim J C; van Gerwen, Willem H E M; van den Hoogen, Henk J M; van de Lisdonk, Eloy H; Metsemakers, Job F M; van Weel, Chris

    2007-12-01

    To evaluate a stepwise protocol in opportunistic screening for type 2 diabetes. From 2000 to 2001, in 11 Dutch general practices (n=49,229) we invited at-risk patients during usual care for a capillary fasting plasma glucose (cFPG1) measurement. If >6.0 mmol/l, a second sample (cFPG2) was taken on another day, followed by a venous sample (vFPG) if cFPG2>6.0 mmol/l and cFPG1 or 2> or =7.0 mmol/l. Of 3724 at-risk patients invited for a cFPG1, 3335 (90%) returned for the measurement. Ultimately, in 125 (4%) of them a vFPG was measured. In 101 out of 125 patients the vFPG was > or =7.0 mmol/l, giving a positive predictive value of our protocol of 81%. A stepwise screening protocol including two subsequent capillary blood glucose measurements from a portable blood glucose meter is well applicable in screening for type 2 diabetes in primary care.

  16. Hyperspectral Image Classification via Multitask Joint Sparse Representation and Stepwise MRF Optimization.

    Science.gov (United States)

    Yuan, Yuan; Lin, Jianzhe; Wang, Qi

    2016-12-01

    Hyperspectral image (HSI) classification is a crucial issue in remote sensing. Accurate classification benefits a large number of applications such as land use analysis and marine resource utilization. But high data correlation brings difficulty to reliable classification, especially for HSI with abundant spectral information. Furthermore, the traditional methods often fail to well consider the spatial coherency of HSI that also limits the classification performance. To address these inherent obstacles, a novel spectral-spatial classification scheme is proposed in this paper. The proposed method mainly focuses on multitask joint sparse representation (MJSR) and a stepwise Markov random filed framework, which are claimed to be two main contributions in this procedure. First, the MJSR not only reduces the spectral redundancy, but also retains necessary correlation in spectral field during classification. Second, the stepwise optimization further explores the spatial correlation that significantly enhances the classification accuracy and robustness. As far as several universal quality evaluation indexes are concerned, the experimental results on Indian Pines and Pavia University demonstrate the superiority of our method compared with the state-of-the-art competitors.

  17. Estimating stepwise debromination pathways of polybrominated diphenyl ethers with an analogue Markov Chain Monte Carlo algorithm.

    Science.gov (United States)

    Zou, Yonghong; Christensen, Erik R; Zheng, Wei; Wei, Hua; Li, An

    2014-11-01

    A stochastic process was developed to simulate the stepwise debromination pathways for polybrominated diphenyl ethers (PBDEs). The stochastic process uses an analogue Markov Chain Monte Carlo (AMCMC) algorithm to generate PBDE debromination profiles. The acceptance or rejection of the randomly drawn stepwise debromination reactions was determined by a maximum likelihood function. The experimental observations at certain time points were used as target profiles; therefore, the stochastic processes are capable of presenting the effects of reaction conditions on the selection of debromination pathways. The application of the model is illustrated by adopting the experimental results of decabromodiphenyl ether (BDE209) in hexane exposed to sunlight. Inferences that were not obvious from experimental data were suggested by model simulations. For example, BDE206 has much higher accumulation at the first 30 min of sunlight exposure. By contrast, model simulation suggests that, BDE206 and BDE207 had comparable yields from BDE209. The reason for the higher BDE206 level is that BDE207 has the highest depletion in producing octa products. Compared to a previous version of the stochastic model based on stochastic reaction sequences (SRS), the AMCMC approach was determined to be more efficient and robust. Due to the feature of only requiring experimental observations as input, the AMCMC model is expected to be applicable to a wide range of PBDE debromination processes, e.g. microbial, photolytic, or joint effects in natural environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Stepwise shock compression with relation to phase diagram of C70 fullerite

    Science.gov (United States)

    Borodina, Tatiana; Khishchenko, Konstantin; Milyavskiy, Vladimir

    2009-06-01

    Phase transitions of C70 fullerite with different initial phase compositions under stepwise shock compression are experimentally studied to pressure of 52 GPa and temperature of about 1700 K. The crystalline phase of fullerite C70 with a hexagonal close-packed structure remain practically unchanged under stepwise shock loading up to pressure of 8 GPa. Shock-induced transformation of the hexagonal phase into the face centered cubic phase is observed at pressures in the range 9 to 23.5 GPa. The amount of transformed material increases with the shock intensity. Upon further increase of the shock pressure, the destruction of C70 molecules occurs. This destruction is accompanied by a formation of the graphite phase of carbon. Pressure--temperature history of C70 specimens is estimated with the use of equation of state C60 fullerite [K.V. Khishchenko et al. Diamond and Relat. Mat. 2007 (16) 1204]. Analyzing this pressure-temperature history along with the tentative phase diagram of C70 [B. Sundqvist. Advances in Phys. 1999 (48) 1], we conclude that the observed conversion of the hexagonal to the cubic phase can not be described in the framework of this diagram.

  19. Stepwise drying of medicinal plants as alternative to reduce time and energy processing

    Science.gov (United States)

    Cuervo-Andrade, S. P.; Hensel, O.

    2016-07-01

    The objective of drying medicinal plants is to extend the shelf life and conserving the fresh characteristics. This is achieved by reducing the water activity (aw) of the product to a value which will inhibit the growth and development of pathogenic and spoilage microorganisms, significantly reducing enzyme activity and the rate at which undesirable chemical reactions occur. The technical drying process requires an enormous amount of thermal and electrical energy. An improvement in the quality of the product to be dried and at the same time a decrease in the drying cost and time are achieved through the utilization of a controlled conventional drying method, which is based on a good utilization of the renewable energy or looking for other alternatives which achieve lower processing times without sacrificing the final product quality. In this work the method of stepwise drying of medicinal plants is presented as an alternative to the conventional drying that uses a constant temperature during the whole process. The objective of stepwise drying is the decrease of drying time and reduction in energy consumption. In this process, apart from observing the effects on decreases the effective drying process time and energy, the influence of the different combinations of drying phases on several characteristics of the product are considered. The tests were carried out with Melissa officinalis L. variety citronella, sowed in greenhouse. For the stepwise drying process different combinations of initial and final temperature, 40/50°C, are evaluated, with different transition points associated to different moisture contents (20, 30, 40% and 50%) of the product during the process. Final quality of dried foods is another important issue in food drying. Drying process has effect in quality attributes drying products. This study was determining the color changes and essential oil loses by reference the measurement of the color and essential oil content of the fresh product was

  20. A Stepwise Optimal Design of a Dynamic Vibration Absorber with Tunable Resonant Frequency

    Directory of Open Access Journals (Sweden)

    Jiejian DI

    2014-08-01

    Full Text Available A new kind of dynamic vibration absorber (DVA with tunable resonant frequency is presented. The kinematics differential equation about it is built and the stepwise optimization is performed. Firstly, four main system parameters involving the ratios of mass m, natural frequency f, vibration frequency g and damping z are solved by small-step-search method to obtain optimal steady state amplitude. Secondly, the sizing optimization of the dynamic vibration absorber is proceeded to search an optimal damping effect based on the optimal parameters (g, m, z, f. And such the damping effect is simulated in a flat structure, and the results show that the working frequency band and damping effect of the DVA after optimization won 20 % of the effect of ascension compared with that before optimization.

  1. Examples of Nearly Net Zero Energy Buildings Through One-Step and Stepwise Retrofits

    DEFF Research Database (Denmark)

    Galiotto, Nicolas; Heiselberg, Per; Knudstrup, Mary-Ann

    2012-01-01

    -step or stepwise retrofit process. The review work is part of a more global Ph.D. project and is used as one of the basement of the future research work. The considered approaches have been sorted in two categories. The first approach has a very high use of energy conservation measures and low use of renewable...... energy production measures. The second approach has a lower use of energy conservation measures (but still high compared to a traditional renovation) and a higher use of renewable energy production measures. A third approach to nearly net zero energy building renovation exists but has not been considered......: a very low use of energy conservation measures and very high use of renewable energy production measures. While the projects from the first category have still a possibility to improve considerably their carbon footprint during an ulterior upgrade, the projects part of the second category seem to have...

  2. Stepwise oxygenations of toluene and 4-nitrotoluene by a fungal peroxygenase.

    Science.gov (United States)

    Kinne, Matthias; Zeisig, Christian; Ullrich, René; Kayser, Gernot; Hammel, Kenneth E; Hofrichter, Martin

    2010-06-18

    Fungal peroxygenases have recently been shown to catalyze remarkable oxidation reactions. The present study addresses the mechanism of benzylic oxygenations catalyzed by the extracellular peroxygenase of the agaric basidiomycete Agrocybe aegerita. The peroxygenase oxidized toluene and 4-nitrotoluene via the corresponding alcohols and aldehydes to give benzoic acids. The reactions proceeded stepwise with total conversions of 93% for toluene and 12% for 4-nitrotoluene. Using H(2)(18)O(2) as the co-substrate, we show here that H(2)O(2) is the source of the oxygen introduced at each reaction step. A. aegerita peroxygenase resembles cytochromes P450 and heme chloroperoxidase in catalyzing benzylic hydroxylations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. Order Selection for General Expression of Nonlinear Autoregressive Model Based on Multivariate Stepwise Regression

    Science.gov (United States)

    Shi, Jinfei; Zhu, Songqing; Chen, Ruwen

    2017-12-01

    An order selection method based on multiple stepwise regressions is proposed for General Expression of Nonlinear Autoregressive model which converts the model order problem into the variable selection of multiple linear regression equation. The partial autocorrelation function is adopted to define the linear term in GNAR model. The result is set as the initial model, and then the nonlinear terms are introduced gradually. Statistics are chosen to study the improvements of both the new introduced and originally existed variables for the model characteristics, which are adopted to determine the model variables to retain or eliminate. So the optimal model is obtained through data fitting effect measurement or significance test. The simulation and classic time-series data experiment results show that the method proposed is simple, reliable and can be applied to practical engineering.

  4. Assessment of exposure of Korean consumers to acesulfame K and sucralose using a stepwise approach.

    Science.gov (United States)

    Ha, Mi-Sun; Ha, Sang-Do; Choi, Sung-Hee; Bae, Dong-Ho

    2013-09-01

    Using a stepwise assessment of the exposure of Korean consumers to acesulfame K and sucralose, theoretical maximum daily intakes of the sweeteners were calculated using the Budget screening method, which resulted in values greater than the acceptable daily intakes (ADIs). Accordingly, the daily intakes of the sweeteners based on food consumption data and concentrations determined by instrumental analysis of 605 food samples were estimated for the more refined approach. The estimated daily intakes (EDIs) of all ordinary consumers were lower than the ADI, which was considered safe. However, for infants and 95th percentile high-level consumers (especially those who choose sucralose-containing foods), the EDIs of sucralose were very close to and higher than the ADI. Therefore, the sucralose concentration in sweetened beverages should be reduced; this would benefit the health of both high-level consumers and infants.

  5. Solid structures of the stepwise self-assembled copillar[5]arene-based supramolecular polymers

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yeon Sil; Hwang, Seong Min; Shin, Jae Yeon; Paek, Kyung Soo [Dept. of Chemistry, Soongsil University, Seoul (Korea, Republic of)

    2016-10-15

    Development of supramolecular polymer has attracted much interest because of their interesting properties such as stimuli-responsiveness, recycling, self-healing and degradability, and their consequential applications. The essential feature of this class of polymers is the self-assembly of discrete monomeric subunits via non-covalent interactions or dynamic covalent bonds. Among the many monomeric subunits, pillar[n]arenes have been ideal building blocks for the fabrication of polymeric supramolecules because of their intrinsic characteristics. The ring-shaped morphologies in supramolecular polymer P are probably due to the tendency of the end-to-end connection in the solid state of long flexible supramolecular chains. The size increase of nano-rings as the stepwise addition increases might be due to the fact that the linear supramolecular polymer P in solution seems to be maintained until the nano-ring formation by solidification.

  6. The stepwise multi-photon activation fluorescence guided ablation of melanin

    Science.gov (United States)

    Lai, Zhenhua; Gu, Zetong; DiMarzio, Charles

    2015-02-01

    Previous research has shown that the stepwise multi-photon activation fluorescence (SMPAF) of melanin, activated and excited by a continuous-wave (CW) mode near infrared (NIR) laser, is a low-cost and reliable method for detecting melanin. We have developed a device utilizing the melanin SMPAF to guide the ablation of melanin with a 975 nm CW laser. This method provides the ability of targeting individual melanin particles with micrometer resolution, and enables localized melanin ablation to be performed without collateral damage. Compared to the traditional selective photothermolysis, which uses pulsed lasers for melanin ablation, this method demonstrates higher precision and lower cost. Therefore, the SMPAF guided selective ablation of melanin is a promising tool of melanin ablation for both medical and cosmetic purposes.

  7. Retrieval of Airborne Lidar Misalignments Based on the Stepwise Geometric Method

    DEFF Research Database (Denmark)

    Zhang, Xiaohong; Forsberg, René

    2010-01-01

    In this paper, a new simple method for airborne LIDAR system misalignment calibration is described in detail. The method is especially designed for environmental surveys, such as beach mapping or glacier surveys. The proposed method, termed stepwise geometric misalignment determination is based...... on the relationship between the point clouds on a regular object, e.g. a flat top building, and the ground truth of the objects used for calibration. In order to extract the footprints on the objects, filtering is implemented before the calibration. The tests verify that the proposed method is feasible, and very...... effective. The calibration flight should be designed beforehand to ensure the accuracy of the retrieved boresight corrections. We outline some examples of application of the method by using airborne laser scanning data from Greenland, acquired by a Riegl laser scanning system....

  8. A Stepwise ISO-Based TQM Implementation Approach Using ISO 9001:2015

    Directory of Open Access Journals (Sweden)

    Chen Chi-kuang

    2016-12-01

    Full Text Available The lack of an implementation roadmap always deters enterprises from choosing Total Quality Management (TQM as its major management approach. This paper proposes a stepwise ISO-based TQM implementation approach which is based on the notion of the new three-dimensional overall business excellence framework developed by Dahlgaard et al. [1]. The proposed approach consists of nine steps comprising three categories: “TQM faith building”, “TQM tools and techniques learning”, and “system development”. The steps in each of the three categories are arranged to span across the proposed nine-step approach. The ISO 9001:2015 standard is used as a case study to demonstrate the proposed approach. The ideas and benefits of the proposed approach are further discussed in relation to this illustration.

  9. Acquisition of thermotolerant yeast Saccharomyces cerevisiae by breeding via stepwise adaptation.

    Science.gov (United States)

    Satomura, Atsushi; Katsuyama, Yoshiaki; Miura, Natsuko; Kuroda, Kouichi; Tomio, Ayako; Bamba, Takeshi; Fukusaki, Eiichiro; Ueda, Mitsuyoshi

    2013-01-01

    A thermotolerant Saccharomyces cerevisiae yeast strain, YK60-1, was bred from a parental strain, MT8-1, via stepwise adaptation. YK60-1 grew at 40°C, a temperature at which MT8-1 could not grow at all. YK60-1 exhibited faster growth than MT8-1 at 30°C. To investigate the mechanisms how MT8-1 acquired thermotolerance, DNA microarray analysis was performed. The analysis revealed the induction of stress-responsive genes such as those encoding heat shock proteins and trehalose biosynthetic enzymes in YK60-1. Furthermore, nontargeting metabolome analysis showed that YK60-1 accumulated more trehalose, a metabolite that contributes to stress tolerance in yeast, than MT8-1. In conclusion, S. cerevisiae MT8-1 acquired thermotolerance by induction of specific stress-responsive genes and enhanced intracellular trehalose levels. © 2013 American Institute of Chemical Engineers.

  10. A stepwise approach for defining the applicability domain of SAR and QSAR models

    DEFF Research Database (Denmark)

    Dimitrov, Sabcho; Dimitrova, Gergana; Pavlov, Todor

    2005-01-01

    by the model. The structural neighborhood of atom-centered fragments is used to determine this similarity. The third stage in defining the domain is based on a mechanistic understanding of the modeled phenomenon. Here, the model domain combines the reliability of specific reactive groups hypothesized to cause......A stepwise approach for determining the model applicability domain is proposed. Four stages are applied to account for the diversity and complexity of the current SAR/QSAR models, reflecting their mechanistic rationality (including metabolic activation of chemicals) and transparency. General......, if metabolic activation of chemicals is a part of the (Q)SAR model. Some of the stages of the proposed approach for defining the model domain can be eliminated depending on the availability and quality of the experimental data used to derive the model, the specificity of (Q)SARs, and the goals...

  11. Stepwise Splitting Growth and Pseudocapacitive Properties of Hierarchical Three-Dimensional Co3O4 Nanobooks

    Directory of Open Access Journals (Sweden)

    Huilong Chen

    2017-04-01

    Full Text Available Three-dimensional hierarchical Co3O4 nanobooks have been synthesized successfully on a large scale by calcining orthorhombic Co(CO30.5(OH·0.11H2O precursors with identical morphologies. Based on the influence of reaction time and urea concentration on the nanostructures of the precursors, a stepwise splitting growth mechanism can be proposed to understand the formation of the 3D nanobooks. The 3D Co3O4 nanobooks exhibit excellent pseudocapacitive performances with specific capacitances of 590, 539, 476, 453, and 421 F/g at current densities of 0.5, 1, 2, 4, and 8 A/g, respectively. The devices can retain ca. 97.4% of the original specific capacitances after undergoing charge–discharge cycle tests 1000 times continuously at 4 A/g.

  12. A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

    Science.gov (United States)

    Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

    2017-09-01

    Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

  13. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida

    2016-01-01

    Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...... concentrations of docetaxel. Whole exome sequencing performed at five successive stages during this process was used to identify single point mutational events, insertions/deletions and copy number alterations associated with the acquisition of docetaxel resistance. Acquired coding variation undergoing positive...

  14. Dynamically concerted and stepwise trajectories of the Cope rearrangement of 1,5-hexadiene

    Science.gov (United States)

    Mackey, Joel L.; Yang, Zhongyue; Houk, K. N.

    2017-09-01

    Molecular dynamics of the [3,3]-sigmatropic (Cope) rearrangement of 1,5-hexadiene were performed with the B3LYP/6-31G(d) density functional theory method. We found that the forming or breaking bond lengths of sampled transition state geometries are 1.97 Å ± 0.15 Å, which is defined as the transition zone. Two hundred and thirty trajectories were propagated. Ninety-five percent of the trajectories connect reactant to product. Five percent of the trajectories involved recrossing. For the reactive trajectories, the time to traverse the transition zone was 35 ± 16 fs. Ninety-four percent of these trajectories are dynamically concerted, while the remaining six percent are dynamically stepwise.

  15. Stepwise dynamics of an anionic micellar film - Formation of crown lenses.

    Science.gov (United States)

    Lee, Jongju; Nikolov, Alex; Wasan, Darsh

    2017-06-15

    We studied the stepwise thinning of a microscopic circular foam film formed from an anionic micellar solution of sodium dodecyl sulfate (SDS). The foam film formed from the SDS micellar solution thins in a stepwise manner by the formation and expansion of a dark spot(s) of one layer less than the film thickness. During the last stages of film thinning (e.g., a film with one micellar layer), the dark spot expansion occurs via two steps. Initially, a small dark circular spot inside a film of several microns in size is formed, which expands at a constant rate. Then, a ridge along the expanding spot is formed. As the ridge grows, it becomes unstable and breaks into regular crown lenses, which are seen as white spots in the reflected light at the border of the dark spot with the surrounding thicker film. The Rayleigh type of instability contributes to the formation of the lenses, which results in the increase of the dark spot expansion rate with time. We applied the two-dimensional micellar-vacancy diffusion model and took into consideration the effects of the micellar layering and film volume on the rate of the dark spot expansion [Lee et al., 2016] to predict the rate of the dark spot expansion for a 0.06M SDS film in the presence of lenses. We briefly discuss the Rayleigh type of instability in the case of a 0.06M SDS foam film. The goals of this study are to reveal why the crown lenses are formed during the foam film stratification and to elucidate their effect on the rate of spot expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Stepwise expansion of evidence-based care is needed for mental health reform.

    Science.gov (United States)

    McGorry, Patrick D; Hamilton, Matthew P

    2016-05-16

    Mortality from mental illnesses is increasing and, because they frequently occur early in the life cycle, they are the largest source of disability and reduced economic productivity of all non-communicable diseases. Successful mental health reform can reduce the mortality, morbidity, growing welfare costs and losses in economic productivity caused by mental illness. The government has largely adopted the recommendations of the National Mental Health Commission focusing on early intervention and stepwise care and will implement a reform plan that involves devolving commissioning of federally funded mental health services to primary health networks, along with a greater emphasis on e-mental health. Stepwise expanded investment in and structural support (data collection, evaluation, model fidelity, workforce training) for evidence-based care that rectifies high levels of undertreatment are essential for these reforms to succeed. However, the reforms are currently constrained by a cost-containment policy framework that envisages no additional funding. The early intervention reform aim requires financing for the next stage of development of Australia's youth mental health system, rather than redirecting funds from existing evidence-based programs. People with complex, enduring mental disorders need more comprehensive care. In the context of the National Disability Insurance Scheme, there is a risk that these already seriously underserved patients may paradoxically receive a reduction in coverage. E-health has a key role to play at all stages of illness but must be integrated in a complementary way, rather than as a barrier to access. Research and evaluation are the keys to cost-effective, sustainable reform.

  17. Stepwise quantitative risk assessment as a tool for characterization of microbiological food safety.

    Science.gov (United States)

    van Gerwen, S J; te Giffel, M C; van't Riet, K; Beumer, R R; Zwietering, M H

    2000-06-01

    This paper describes a system for the microbiological quantitative risk assessment for food products and their production processes. The system applies a stepwise risk assessment, allowing the main problems to be addressed before focusing on less important problems. First, risks are assessed broadly, using order of magnitude estimates. Characteristic numbers are used to quantitatively characterize microbial behaviour during the production process. These numbers help to highlight the major risk-determining phenomena, and to find negligible aspects. Second, the risk-determining phenomena are studied in more detail. Both general and/or specific models can be used for this and varying situations can be simulated to quantitatively describe the risk-determining phenomena. Third, even more detailed studies can be performed where necessary, for instance by using stochastic variables. The system for quantitative risk assessment has been implemented as a decision supporting expert system called SIEFE: Stepwise and Interactive Evaluation of Food safety by an Expert System. SIEFE performs bacterial risk assessments in a structured manner, using various information sources. Because all steps are transparent, every step can easily be scrutinized. In the current study the effectiveness of SIEFE is shown for a cheese spread. With this product, quantitative data concerning the major risk-determining factors were not completely available to carry out a full detailed assessment. However, this did not necessarily hamper adequate risk estimation. Using ranges of values instead helped identifying the quantitatively most important parameters and the magnitude of their impact. This example shows that SIEFE provides quantitative insights into production processes and their risk-determining factors to both risk assessors and decision makers, and highlights critical gaps in knowledge.

  18. Surgical technique: Lateral retinaculum release in knee arthroplasty using a stepwise, outside-in technique.

    Science.gov (United States)

    Maniar, Rajesh N; Singhi, Tushar; Rathi, Suyog Shashimohan; Baviskar, Jayesh Vinod; Nayak, Ravi Mohan

    2012-10-01

    Lateral release of a tight lateral retinaculum in a TKA is intended to correct patellar maltracking but the widely used inside-out technique has associated risks. We describe an alternate stepwise outside-in technique, with titrated release intended to maximize the chance of preserving the superior lateral genicular artery (SLGA). Patellar maltracking was judged by a no-thumb technique and graded as I and Ia: normal and near normal tracking; II: patella tilted; III: patella subluxed; or IV: patella dislocated. Outside-in release was performed in three progressive steps. Step-1 release was from the midpatella to the upper tibial border, Step-2 release was from the midpatella to the proximal pole of the patella, and Step-3 release was proximal to the superior pole of the patella with sectioning of the SLGA. We retrospectively reviewed records of 1884 patients operated on between 2002 to 2008. Two hundred five patients (11%) had lateral release performed, and 177 of those 205 patients (86%) were reviewed. Patellofemoral function was assessed clinically by The Knee Society score. Radiographs were examined for patellar tilt, shift, and avascular necrosis. The minimum followup was 22 months (median 48 months; range, 22-105 months). The SLGA was preserved in 155 (76%) patients. At last followup, no patient had patellar maltracking, patellar fracture, or avascular necrosis. Six of 177 (3%) patients had anterior knee pain. Female patients and high-flex components had a higher incidence of release and midvastus arthrotomy had a lower incidence of release. Stepwise release of the lateral retinaculum by an outside-in technique allowed minimum necessary retinacular release, preserving the SLGA in 76% of patients. No complications were seen at followup with functional and radiographic examinations. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  19. Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

    Science.gov (United States)

    Golriz, Mohammad; Abbasi, Sepehr; Fathi, Parham; Majlesara, Ali; Brenner, Thorsten; Mehrabi, Arianeb

    2017-10-01

    Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco 2 values increased after 75% resection in the jugular vein. In contrast, arterial Po 2 increased after every resection, whereas the venous Po 2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco 2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation. NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow

  20. A broadly applicable surgical teaching method: evaluation of a stepwise introduction to cataract surgery.

    Science.gov (United States)

    Kloek, Carolyn E; Borboli-Gerogiannis, Sheila; Chang, Kenneth; Kuperwaser, Mark; Newman, Lori R; Lane, Anne Marie; Loewenstein, John I

    2014-01-01

    Although cataract surgery is one of the most commonly performed surgeries in the country, it is a microsurgical procedure that is difficult to learn and to teach. This study aims to assess the effectiveness of a new method for introducing postgraduate year (PGY)-3 ophthalmology residents to cataract surgery. Hospital-based ophthalmology residency program. Retrospective cohort study. PGY-3 and PGY-4 residents of the Harvard Medical School Ophthalmology Residency from graduating years 2010 to 2012. In July 2009, a new method of teaching PGY-3 ophthalmology residents cataract surgery was introduced, which was termed "the stepwise introduction to cataract surgery." This curriculum aimed to train residents to perform steps of cataract surgery by deliberately practicing each of the steps of surgery under a structured curriculum with faculty feedback. Assessment methods included surveys administered to the PGY-4 residents who graduated before the implementation of these measures (n = 7), the residents who participated in the first and second years of the new curriculum (n = 16), faculty who teach PGY-4 residents cataract surgery (n = 8), and review of resident Accreditation Council for Graduate Medical Education surgical logs. Resident survey response rate was 100%. Residents who participated in the new curriculum performed more of each step of cataract surgery in the operating room, spent more time practicing each step of cataract surgery on a cataract surgery simulator during the PGY-3 year, and performed more primary cataract surgeries during the PGY-3 year than those who did not. Faculty survey response rate was 63%. Faculty noted an increase in resident preparedness following implementation of the new curriculum. There was no statistical difference between the precurriculum and postcurriculum groups in the percentage turnover of cataracts for the first 2 cataract surgery rotations of the PGY-4 year of training. The introduction of cataract surgery to PGY-3 residents

  1. Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jing, E-mail: zhangjing@zjut.edu.cn; Li, Mengfei [Zhejiang University of Technology, College of Materials Science and Engineering (China); Yuan, Zhefan [Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering (China); Wu, Dan; Chen, Jia-da; Feng, Jie, E-mail: fengjie@zjut.edu.cn [Zhejiang University of Technology, College of Materials Science and Engineering (China)

    2016-10-15

    A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K{sub 10}), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K{sub 10}, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.Graphical abstractA novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for selective drug delivery in cancerous cells. MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would

  2. Stepwise magnetic-geochemical approach for efficient assessment of heavy metal polluted sites

    Science.gov (United States)

    Appel, E.; Rösler, W.; Ojha, G.

    2012-04-01

    Previous studies have shown that magnetometry can outline the distribution of fly ash deposition in the surroundings of coal-burning power plants and steel industries. Especially the easy-to-measure magnetic susceptibility (MS) is capable to act as a proxy for heavy metal (HM) pollution caused by such kind of point source pollution. Here we present a demonstration project around the coal-burning power plant complex "Schwarze Pumpe" in eastern Germany. Before reunification of West and East Germany huge amounts of HM pollutants were emitted from the "Schwarze Pumpe" into the environment by both fly ash emission and dumped clinker. The project has been conducted as part of the TASK Centre of Competence which aims at bringing new innovative techniques closer to the market. Our project combines in situ and laboratory MS measurements and HM analyses in order to demonstrate the efficiency of a stepwise approach for site assessment of HM pollution around point sources of fly-ash emission and deposition into soil. The following scenario is played through: We assume that the "true" spatial distribution of HM pollution (given by the pollution load index PLI comprising Fe, Zn, Pb, and Cu) is represented by our entire set of 85 measured samples (XRF analyses) from forest sites around the "Schwarze Pumpe". Surface MS data (collected with a Bartington MS2D) and in situ vertical MS sections (logged by an SM400 instrument) are used to determine a qualitative overview of potentially higher and lower polluted areas. A suite of spatial HM distribution maps obtained by random selections of 30 out of the 85 analysed sites is compared to the HM map obtained from a targeted 30-sites-selection based on pre-information from the MS results. The PLI distribution map obtained from the targeted 30-sites-selection shows all essential details of the "true" pollution map, while the different random 30-sites-selections miss important features. This comparison shows that, for the same cost

  3. Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients

    NARCIS (Netherlands)

    Pouw, R.E.; Seewald, S.; Gondrie, J.J.; Deprez, P.H.; Piessevaux, H.; Pohl, H.; Rösch, T.; Soehendra, N.; Bergman, J.J.

    2010-01-01

    Background and Aims Endoscopic resection is safe and effective to remove early neoplasia (ie, high-grade intra-epithelial neoplasia/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical

  4. Stepwise Swelling of a Thin Film of Lamellae-Forming Poly(styrene-b-butadiene) in Cyclohexane Vapor

    DEFF Research Database (Denmark)

    Di, Zhenyu; Posselt, Dorthe; Smilgies, Detlef-M.

    2012-01-01

    We investigated the swelling of a thin film of lamellae-forming poly(styrene-b-butadiene) in cyclohexane vapor. The vapor pressure and thus the degree of swelling of the film are increased in a stepwise manner using a custom-built sample cell. The resulting structural changes during and after eac...

  5. Staying put in moving sands. The stepwise migration process of sub-Saharan African migrants heading north

    NARCIS (Netherlands)

    Schapendonk, J.

    2010-01-01

    This chapter focuses on the stepwise migration process of sub-Saharan African migrants heading North with a strong actor-centred approach. It aims to gain more insights into the migration processes by investigating migrant's flexibility and dependency. The chapter examines the way sub-Saharan

  6. Effects of constant and stepwise changes in temperature on the species abundance dynamics of four cladocera species

    Directory of Open Access Journals (Sweden)

    Verbitsky V. B.

    2011-09-01

    Full Text Available Laboratory experiments with natural zooplankton communities were carried out to study the effects of two contrasting temperature regimes: constant temperature (15, 20, and 25 °C and graded changes in temperature. The graded regime consisted of repeated sustained (three weeks controlled stepwise temperature changes of 5 or 10 °C within 15–25 °C on the population dynamics of four dominant species of lake littoral zooplankton, Daphnia longispina (Müller, 1785, Diaphanosoma brachyurum (Lievin, 1848, Simocephalus vetulus (Müller, 1776 and Chydorus sphaericus (Müller, 1785. The results show that controlled stepwise changes (positive or negative in temperature within the ranges of 15–20, 20–25, and 15–25 °C can exert either stimulating or inhibitory effect (direct or delayed on the development of D. longispina and S. vetulus populations. The development of D. brachyurum and Ch. sphaericus, both more steno-thermophile, was only stimulated by a stable elevated temperature (25 °C. These results support the previously formulated hypothesis that, in determining the ecological temperature optimum of a species within a natural community, it is not enough to define its optimum from constant, cyclic or random temperature fluctuations, but also from unidirectional stepwise changes in temperature. These stepwise changes may also induce prolonged or delayed effects.

  7. A step-wise approach to find a valid and feasible method to detect non-adherence to tuberculosis drugs.

    NARCIS (Netherlands)

    Ruslami, R.; Crevel, R. van; Berge, E van de; Alisjahbana, B.; Aarnoutse, R.E.

    2008-01-01

    A step-wise approach to identify valid and feasible methods to detect non-adherence to tuberculosis drugs was evaluated in a prospective study among pulmonary tuberculosis patients in an outpatient clinic in Indonesia. First, adherence was measured by self-reporting with the standardized Morisky

  8. Comparison of different stepwise screening strategies for type 2 diabetes: Finding from Danish general practice, Addition-DK

    DEFF Research Database (Denmark)

    Dalsgaard, Else-Marie; Christensen, Jesper O; Skriver, Mette Vinter

    2010-01-01

    AIM: To examine attendance, number of people with T2DM and costs of three different stepwise screening strategies for T2DM in general practice (GP). METHODS: Diabetes risk questionnaires were mailed to individuals aged 40-69 years from 45 general practices in 2001-2002 and individuals at high risk...

  9. A Step-Wise Approach to Total Laparoscopic Gastrectomy with Jejunal Pouch Reconstruction : How and Why We Do It

    NARCIS (Netherlands)

    Brenkman, Hylke J F; Correa-Cote, Juan; Ruurda, Jelle P; van Hillegersberg, Richard

    2016-01-01

    Laparoscopic gastrectomy (LG) is a safe alternative compared to open gastrectomy for cancer. To increase the uptake of minimally invasive approaches and facilitate their analysis and improvement a stepwise approach is warranted. This study describes our technique and experiences total laparoscopic

  10. Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin.

    Science.gov (United States)

    Chen, Wei-Liang; Li, Fang; Tang, Yan; Yang, Shu-di; Li, Ji-Zhao; Yuan, Zhi-Qiang; Liu, Yang; Zhou, Xiao-Feng; Liu, Chun; Zhang, Xue-Nong

    2017-01-01

    Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.

  11. Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions

    Directory of Open Access Journals (Sweden)

    Sang-Man Jin

    2017-06-01

    Full Text Available Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.

  12. Stepwise transformation of the molecular building blocks in a porphyrin-encapsulating metal-organic material

    KAUST Repository

    Zhang, ZhenJie

    2013-04-24

    When immersed in solutions containing Cu(II) cations, the microporous metal-organic material P11 ([Cd4(BPT)4]·[Cd(C 44H36N8)(S)]·[S], BPT = biphenyl-3,4′,5-tricarboxylate) undergoes a transformation of its [Cd 2(COO)6]2- molecular building blocks (MBBs) into novel tetranuclear [Cu4X2(COO)6(S) 2] MBBs to form P11-Cu. The transformation occurs in single-crystal to single-crystal fashion, and its stepwise mechanism was studied by varying the Cd2+/Cu2+ ratio of the solution in which crystals of P11 were immersed. P11-16/1 (Cd in framework retained, Cd in encapsulated porphyrins exchanged) and other intermediate phases were thereby isolated and structurally characterized. P11-16/1 and P11-Cu retain the microporosity of P11, and the relatively larger MBBs in P11-Cu permit a 20% unit cell expansion and afford a higher surface area and a larger pore size. © 2013 American Chemical Society.

  13. Stepwise functionalization of SiN{sub x} surfaces for covalent immobilization of antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Dauphas, Stephanie [Universite de Rennes 1, UMR-CNRS 6226, Laboratoire des Sciences Chimiques de Rennes, Equipe catalyse et organometalliques, Campus de Beaulieu, 35042 Rennes cedex (France); Ababou-Girard, Soraya [Universite de Rennes 1, UMR-CNRS 6251, Institut de Physique de Rennes, Equipe Physique des surfaces et interfaces, Campus de Beaulieu, 35042 Rennes cedex (France); Girard, Aurelie; Le Bihan, France; Mohammed-Brahim, Tayeb [Universite de Rennes 1, UMR-CNRS 6164, Institut d' Electronique et Telecommunications de Rennes, Groupe de Microelectronique, Campus de Beaulieu, 35042 Rennes cedex (France); Vie, Veronique [Universite de Rennes 1, UMR-CNRS 6251, Institut de Physique de Rennes, Equipe Biophysique, Campus Beaulieu, 35042 Rennes (France); Corlu, Anne; Guguen-Guillouzo, Christiane [Universite de Rennes 1, INSERM U522, IFR 140, Campus de Villejean, 35042 Rennes cedex (France); Lavastre, Olivier [Universite de Rennes 1, UMR-CNRS 6226, Laboratoire des Sciences Chimiques de Rennes, Equipe catalyse et organometalliques, Campus de Beaulieu, 35042 Rennes cedex (France); Geneste, Florence, E-mail: Florence.Geneste@univ-rennes1.f [Universite de Rennes 1, UMR-CNRS 6226, Laboratoire des Sciences Chimiques de Rennes, Equipe catalyse et organometalliques, Campus de Beaulieu, 35042 Rennes cedex (France)

    2009-09-01

    A stepwise functionalization of silicon nitride surfaces is followed by X-ray photoelectron spectroscopy (XPS). The first step involves a silanization reaction leading to the formation of a silane film with a thickness estimated by XPS of one or two molecular layers. A monoprotected homobifunctionalized linker is then used to avoid the formation of bridge structures on the surface. The linker reacts quantitatively with the amino groups of the surface as outlined by the absence of residual unreacted CNH{sub 2}/CNH{sub 3}{sup +} groups in XPS analyses. Deprotection of the ester groups of the immobilized linker and subsequent reaction with N-hydroxysuccinimid lead to N-hydroxysuccinimid activated surfaces able to react with biological species. These surfaces were then incubated with anti-transferrin antibodies. As seen by XPS and atomic force microscopy analyses, the concentration and incubation conditions of antibodies are important to obtain a compact layer of antibodies on the surface. All chemical steps of the procedure are compatible with microelectronic process on silicon. Moreover, antibodies introduced under native conditions at physiological pH, in the last step of the immobilization process, recognized specifically antigens, as shown by fluorescence competitive assay.

  14. Interior-architectured ZnO nanostructure for enhanced electrical conductivity via stepwise fabrication process.

    Science.gov (United States)

    Chong, Eugene; Kim, Sarah; Choi, Jun-Hyuk; Choi, Dae-Geun; Jung, Joo-Yun; Jeong, Jun-Ho; Lee, Eung-Sug; Lee, Jaewhan; Park, Inkyu; Lee, Jihye

    2014-01-01

    Fabrication of ZnO nanostructure via direct patterning based on sol-gel process has advantages of low-cost, vacuum-free, and rapid process and producibility on flexible or non-uniform substrates. Recently, it has been applied in light-emitting devices and advanced nanopatterning. However, application as an electrically conducting layer processed at low temperature has been limited by its high resistivity due to interior structure. In this paper, we report interior-architecturing of sol-gel-based ZnO nanostructure for the enhanced electrical conductivity. Stepwise fabrication process combining the nanoimprint lithography (NIL) process with an additional growth process was newly applied. Changes in morphology, interior structure, and electrical characteristics of the fabricated ZnO nanolines were analyzed. It was shown that filling structural voids in ZnO nanolines with nanocrystalline ZnO contributed to reducing electrical resistivity. Both rigid and flexible substrates were adopted for the device implementation, and the robustness of ZnO nanostructure on flexible substrate was verified. Interior-architecturing of ZnO nanostructure lends itself well to the tunability of morphological, electrical, and optical characteristics of nanopatterned inorganic materials with the large-area, low-cost, and low-temperature producibility.

  15. Stepwise extraction of valuable components from red mud based on reductive roasting with sodium salts.

    Science.gov (United States)

    Li, Guanghui; Liu, Mingxia; Rao, Mingjun; Jiang, Tao; Zhuang, Jinqiang; Zhang, Yuanbo

    2014-09-15

    The feasibility of an integrated technological route for comprehensive utilization of red mud was verified in this study. Valuable components in the mud, including Fe2O3, Al2O3 and SiO2 were stepwise extracted by magnetic separation and sulfuric acid leaching from reduced red mud, and meanwhile TiO2 was enriched in the leaching residue. Sodium salts were proved to be favorable for the magnetic separation of metallic iron and the subsequent acid leaching of Al and Si, through facilitating the reduction of iron oxides and the growth of metallic iron grains, together with enhancing the activation of Al and Si components during the roasting process. After reductive roasting in the presence of 6% Na2CO3 and 6% Na2SO4, a magnetic concentrate containing 90.2% iron with iron recovery of 95.0% was achieved from the red mud by magnetic separation. Subsequently, 94.7% Fe, 98.6% Al and 95.9% Si were extracted by dilute sulfuric acid leaching from the upper-stream non-magnetic material, yielding a TiO2-rich material with 37.8% TiO2. Furthermore, value-added products of silica gel and Al(OH)3 were prepared from the leachate by ripening and neutralizing. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Laparoscopic stepwise-cut double initial stay suture pyeloplasty: our novel surgical technique.

    Science.gov (United States)

    Ates, Mutlu; Ozgok, Yasar; Akin, Yigit; Arslan, Murat; Akand, Murat; Hoscan, Mustafa Burak

    2015-03-01

    To describe a novel surgical technique, laparoscopic stepwise-cut double initial stay suture (LASDISS) pyeloplasty for ureteropelvic junction obstruction (UPJO). Additionally, we evaluated the safety and short-term results. This was a nonrandomized study with a series of 6 patients with UPJO, operated on between March 2012 and August 2013. Perioperative and short-term outcomes were evaluated. In brief, a "T shape cut" was performed from the dilated pelvis to the ureter. The initial stay suture was placed between the lower edge of the pelvis and the distal end of the spatulated anterolateral part of the ureter. The pelvis was closed with a continuous suture starting from the opened upper edge of the pelvis that was secured after leaving enough space for ureteral anastomosis. The second initial stay suture was placed after passing the ureter and pelvis two times. The dilated part of the renal pelvis and the stenotic segment were excised. A double-J stent was inserted. The remaining space between the two initial sutures was closed with these continuous sutures. We performed the LASDISS pyeloplasty technique in all cases. Median operation time was 177 minutes (range, 100-290 minutes). Mean follow-up was 7.5 months (range, 3-18 months). The mean pre- and postoperative split renal function on diuretic renography was 33% (range, 25%-56%) and 42% (range, 30%-52%), respectively. The LASDISS pyeloplasty surgical technique represents a safe and effective option in surgical treatment of UPJO.

  17. A highly integrated vertical SU8 valve for stepwise in-series reactions

    Science.gov (United States)

    Calvo, V.; Ezkerra, A.; Elizalde, J.; Fernández, L. J.; Berganzo, J.; Mayora, K.; Ruano-López, J. M.

    2011-06-01

    Stepwise performance of reactions demands highly integrated microfluidic control. The vertical valve presented in this work allows performing reactions in cascade with reduced control requirements, by controlling the rupture of an SU8 wall that separates a chamber from an adjacent evacuation channel. Owing to its vertical construction, the valve can be readily integrated into any geometry with a low increase in footprint. Two valve approaches are presented, which differ in the location of the rupture region, the breaking pressures and the size of the fluidic path open. Breaking the wall about its upper end has proven to be more limited in terms of geometry and resulting gap size, whereas breaking the wall about its root opens a wider fluidic path that allows smooth filling of downstream chambers. Following these conclusions, a sequence of two reactions has been demonstrated, using a wall-valve-regulated double-chamber device. The chosen protocol, DNA concentration, elution and transport, has been successfully accomplished, as evidenced by positive on-chip polymerase chain reaction in a second double-chamber device.

  18. SOLAR DRYING KINETICS OF DATE PALM FRUITS ASSUMING A STEP-WISE AIR TEMPERATURE CHANGE

    Directory of Open Access Journals (Sweden)

    ABDELGHANI BOUBEKRI

    2009-09-01

    Full Text Available The effect of drying using a step-wise temperature change was studied considering the case of indirect solar drying of the date palm fruit (Phoenix dactylifera L.. The followed procedure consists of building drying kinetics by stages of temperatures resulting from drying, in constant conditions, of the same variety of dates from Algerian and Tunisian origin. A law of daily temperature variation prevailed by 60°C, was deduced from a statement of temperature collected on a laboratory solar dryer prototype. Two drying curve equation models were used and some comparisons were discussed. The results obtained for dates from the two origins highlighted different response times by changing the air temperature and showed the possibility of reaching a fruit with standard moisture content in only one day of drying on the basis of initial water contents ranging from 0.40 to 0.65. This moisture range is in practice allotted to rehydrated dates by water immersion in order to enhance their quality. Experiments conducted in a laboratory solar drier under temperatures oscillating around 50°C and 60°C led to the same end up regarding the drying time ensuring a visually appreciable fruit quality. Results obtained by a simple sensorial test revealed a better quality of date fruits treated by solar drying comparing to those issued from industrial heat treatment units.

  19. Stepwise inversion of a groundwater flow model with multi-scale observation data

    Science.gov (United States)

    Dai, Zhenxue; Keating, Elizabeth; Gable, Carl; Levitt, Daniel; Heikoop, Jeff; Simmons, Ardyth

    2010-05-01

    Based on the regional hydrogeology and the stratigraphy beneath the Los Alamos National Laboratory (LANL) site, New Mexico (USA), a site-scale groundwater model has been built with more than 20 stratified hydrofacies. A stepwise inverse method was developed to estimate permeabilities for these hydrofacies by coupling observation data from different sources and at various spatial scales including single-well test, multiple-well pumping test and regional aquifer monitoring data. Statistical analyses of outcrop permeability measurements and single-well test results were used to define the prior distributions of the parameters. These distributions were used to define the parameter initial values and the lower and upper bounds for inverse modeling. A number of inverse modeling steps were performed including the use of drawdown data from the pump tests at two wells (PM-2 and PM-4) separately, and a joint inversion coupling PM-2 and PM-4 pump test data and head data from regional aquifer monitoring. Parameter sensitivity coefficients for different data sets were computed to analyze if the model parameters can be estimated accurately with the data provided at different steps. The joint inversion offers a reasonable fit to all data sets. The uncertainty of estimated parameters for the hydrofacies is addressed with the parameter confidence intervals.

  20. Stepwise isolation of human peripheral erythrocytes, T lymphocytes, and monocytes for blood cell proteomics.

    Science.gov (United States)

    Brosseron, Frederic; May, Caroline; Schoenebeck, Bodo; Tippler, Bettina; Woitalla, Dirk; Kauth, Marion; Brockmann, Kathrin; Meyer, Helmut E; Berg, Daniela; Bufe, Albrecht; Marcus, Katrin

    2012-10-01

    Density gradient centrifugation and magnetic- or fluorescence-activated cell sorting are common and robust techniques for the isolation of different types of blood cells. In this article, we give detailed description of a stepwise application of these methods as one isolation strategy for enrichment of different cell types from one blood sample. The workflow targeted erythrocytes, monocytes, and T lymphocytes. Pancoll® density gradient centrifugation was used together with subsequent MACS™ isolation. Purity of monocytes and T lymphocytes was controlled by fluorescence-activated cell sorting analysis, and cells were used for carrier-ampholine-based 2D-PAGE to confirm compatibility of the procedure to standard proteomic applications. Gradient centrifugation resulted in an average of 125 μL of packed erythrocytes per milliliter blood. MACS™ sorting reached purities of 90 ± 2% (monocytes) and 93 ± 2% (T lymphocytes), with an average yield of 12 × 10(4) monocytes or T lymphocytes. 2D-PAGE of isolated cells showed well-separated spot patterns. A combined isolation holds substantial advantages especially in clinical studies, as it allows for the comparison of findings not only between individuals, but also between different cell types derived from one donor. Our approach ensured high reproducibility, yields, and purities of cells as required for reliable proteome analysis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Mapping wildfire vulnerability in Mediterranean Europe. Testing a stepwise approach for operational purposes.

    Science.gov (United States)

    Oliveira, Sandra; Félix, Fernando; Nunes, Adélia; Lourenço, Luciano; Laneve, Giovanni; Sebastián-López, Ana

    2017-10-20

    Vulnerability assessment is a vital component of wildfire management. This research focused on the development of a framework to measure and map vulnerability levels in several areas within Mediterranean Europe, where wildfires are a major concern. The framework followed a stepwise approach to evaluate its main components, expressed by exposure, sensitivity and coping capacity. Data on population density, fuel types, protected areas location, roads infrastructure and surveillance activities, among others, were integrated to create composite indices, representing each component and articulated in multiple dimensions. Maps were created for several test areas, in northwest Portugal, southwest Sardinia in Italy and northeast Corsica in France, with the contribution of local participants from civil protection institutions and forest services. Results showed the influence of fuel sensitivity levels, population distribution and protected areas coverage for the overall vulnerability classes. Reasonable levels of accuracy were found on the maps provided through the validation procedure, with an overall match above 72% for the several sites. The systematic and flexible approach applied allowed for adjustments to local circumstances with regards to data availability and fire management procedures, without compromising its consistency and with substantial operational capabilities. The results obtained and the positive feedback of end-users encourage its further application, as a means to improve wildfire management strategies at multiple levels with the latest scientific outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

    Directory of Open Access Journals (Sweden)

    Götz Bucher

    2013-08-01

    Full Text Available Coarctate reactions are defined as reactions that include atoms at which two bonds are made and two bonds are broken simultaneously. In the pursuit of the discovery of new coarctate reactions we investigate the fragmentation reactions of cyclic ketals. Three ketals with different ring sizes derived from indan-2-one were decomposed by photolysis and pyrolysis. Particularly clean is the photolysis of the indan-2-one ketal 1, which gives o-quinodimethane, carbon dioxide and ethylene. The mechanism formally corresponds to a photochemically allowed coarctate fragmentation. Pyrolysis of the five-ring ketal yields a number of products. This is in agreement with the fact that coarctate fragmentation observed upon irradiation would be thermochemically forbidden, although this exclusion principle does not hold for chelotropic reactions. In contrast, fragmentation of the seven-ring ketal 3 is thermochemically allowed and photochemically forbidden. Upon pyrolysis of 3 several products were isolated that could be explained by a coarctate fragmentation. However, the reaction is less clean and stepwise mechanisms may compete.

  3. Step-wise evolution of complex chemical defenses in millipedes: a phylogenomic approach.

    Science.gov (United States)

    Rodriguez, Juanita; Jones, Tappey H; Sierwald, Petra; Marek, Paul E; Shear, William A; Brewer, Michael S; Kocot, Kevin M; Bond, Jason E

    2018-02-16

    With fossil representatives from the Silurian capable of respiring atmospheric oxygen, millipedes are among the oldest terrestrial animals, and likely the first to acquire diverse and complex chemical defenses against predators. Exploring the origin of complex adaptive traits is critical for understanding the evolution of Earth's biological complexity, and chemical defense evolution serves as an ideal study system. The classic explanation for the evolution of complexity is by gradual increase from simple to complex, passing through intermediate "stepping stone" states. Here we present the first phylogenetic-based study of the evolution of complex chemical defenses in millipedes by generating the largest genomic-based phylogenetic dataset ever assembled for the group. Our phylogenomic results demonstrate that chemical complexity shows a clear pattern of escalation through time. New pathways are added in a stepwise pattern, leading to greater chemical complexity, independently in a number of derived lineages. This complexity gradually increased through time, leading to the advent of three distantly related chemically complex evolutionary lineages, each uniquely characteristic of each of the respective millipede groups.

  4. Preserving the Facial Nerve During Orbitozygomatic Craniotomy: Surgical Anatomy Assessment and Stepwise Illustration.

    Science.gov (United States)

    Tayebi Meybodi, Ali; Lawton, Michael T; Yousef, Sonia; Sánchez, J J González; Benet, Arnau

    2017-09-01

    Surgical safety and efficiency during an orbitozygomatic (OZ) osteotomy rely on thorough knowledge of the surgical anatomy of the facial nerve. Although the anatomy of the facial nerve and its relation to the pterional craniotomy are described, a thorough assessment of facial nerve preservation techniques during the OZ approach and its variations is lacking. We assessed the surgical anatomy of the facial nerve related to the OZ approach and provided a thorough stepwise description on how to preserve it. The OZ approach was performed bilaterally in 15 cadaveric heads. The interfascial and subfascial techniques were performed to study their nuances in preserving the facial nerve. We compared the 2 techniques and provided a thorough description on how to preserve the facial nerve during each step of the OZ approach. At the zygomatic arch, the facial nerve was found between the galea and the superficial temporal fascia. A cut in the fascia at the posterior end of the zygomatic arch did not cross any facial nerve branches. The subfascial technique was simpler, more efficient, and provided more structural protection of the facial nerve branches than the interfascial technique. The frontal division of the facial nerve is related directly to dissection over the zygomatic bone and may be injured during fascial dissection or osteotomies. Both interfascial and subfascial techniques are feasible to use during the OZ craniotomy and provide ample exposure of the OZ unit. Regarding the preservation of the facial nerve branches, we favor the subfascial method. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Impact of stepwise hyperventilation on cerebral tissue oxygen saturation in anesthetized patients: a mechanistic study.

    Science.gov (United States)

    Alexander, B S; Gelb, A W; Mantulin, W W; Cerussi, A E; Tromberg, B J; Yu, Z; Lee, C; Meng, L

    2013-05-01

    While the decrease in blood carbon dioxide (CO2 ) secondary to hyperventilation is generally accepted to play a major role in the decrease of cerebral tissue oxygen saturation (SctO2 ), it remains unclear if the associated systemic hemodynamic changes are also accountable. Twenty-six patients (American Society of Anesthesiologists I-II) undergoing nonneurosurgical procedures were anesthetized with either propofol-remifentanil (n = 13) or sevoflurane (n = 13). During a stable intraoperative period, ventilation was adjusted stepwise from hypoventilation to hyperventilation to achieve a progressive change in end-tidal CO2 (ETCO2 ) from 55 to 25 mmHg. Minute ventilation, SctO2 , ETCO2 , mean arterial pressure (MAP), and cardiac output (CO) were recorded. Hyperventilation led to a SctO2 decrease from 78 ± 4% to 69 ± 5% (Δ = -9 ± 4%, P hyperventilation-induced decrease in SctO2 is hypocapnia during both propofol-remifentanil and sevoflurane anesthesia. Hyperventilation-associated increase in MAP and decrease in CO during propofol-remifentanil, but not sevoflurane, anesthesia may also contribute to the decrease in SctO2 but to a much smaller degree. © 2013 The Acta Anaesthesiologica Scandinavica Foundation.

  6. Urbanization and noncommunicable disease (NCD) risk factors: WHO STEPwise Iranian NCD risk factors surveillance in 2011.

    Science.gov (United States)

    Khorrami, Zahra; Etemad, Koorosh; Yarahmadi, Shahin; Khodakarim, Soheila; Kameli, Mohammadesmail; Hezaveh, Alireza Mahdavi; Rahimi, Ebrahim

    2017-08-27

    This study was conducted to examine the relationship between urbanization and risk factors of noncommunicable diseases (NCDs) according to the World Health Organization stepwise approach to surveillance of NCDs. This study is part of a NCD risk factor surveillance of 10 069 individuals in all provinces of the Islamic Republic of Iran, aged over 20 years, during 2011. By utilizing 2011 census data, urbanization levels were determined in all provinces and logistics regression was used to examine the relationship between urbanization and risk factors. Among males, urbanization had a positive correlation with low physical activity (OR=1.7; 95% CI: 1.42-2.09), low fruit and vegetable consumption (OR=1.8; 95% CI: 1.09-2.96), and high BMI (OR=1.4; 95% CI: 1.20-1.70). Among females there was a positive and significant correlation with low physical activity (OR=1.2; 95% CI: 1.08-1.49), low fruit and vegetable consumption (OR=1.22; 95% CI: 0.78-1.91) and high BMI (OR=1.3; 95% CI: 1.14-1.53). Thus, urbanization has a significant correlation with increases in NCD factors in the Islamic Republic of Iran.

  7. Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting.

    Science.gov (United States)

    Yang, Dan; Yang, Guixin; Gai, Shili; He, Fei; Li, Chunxia; Yang, Piaoping

    2017-03-01

    Combined therapy using multiple approaches has been demonstrated to be a promising route for cancer therapy. To achieve enhanced antiproliferation efficacy under hypoxic condition, here we report a novel hybrid system by integrating dual-model photodynamic therapies (dual-PDT) in one system. First, we attached core-shell structured up-conversion nanoparticles (UCNPs, NaGdF4:Yb,Tm@NaGdF4) on graphitic-phase carbon nitride (g-C3N4) nanosheets (one photosensitizer). Then, the as-fabricated nanocomposite and carbon dots (another photosensitizer) were assembled in ZIF-8 metal-organic frameworks through an in situ growth process, realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting. In this system, the UCNPs can convert deep-penetration and low-energy near-infrared light to higher-energy ultraviolet-visible emission, which matches well with the absorption range of the photosensitizers for reactive oxygen species (ROS) generation without sacrificing its efficacy under ZIF-8 shell protection. Furthermore, the UV light emitted from UCNPs allows successive activation of g-C3N4 and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate g-C3N4 to produce ROS, which keeps the principle of energy conservation thus achieving maximized use of the light. This dual-PDT system exhibits excellent antitumor efficiency superior to any single modality, verified vividly by in vitro and in vivo assay.

  8. Gene conversion violates the stepwise mutation model for microsatellites in y-chromosomal palindromic repeats.

    Science.gov (United States)

    Balaresque, Patricia; King, Turi E; Parkin, Emma J; Heyer, Evelyne; Carvalho-Silva, Denise; Kraaijenbrink, Thirsa; de Knijff, Peter; Tyler-Smith, Chris; Jobling, Mark A

    2014-05-01

    The male-specific region of the human Y chromosome (MSY) contains eight large inverted repeats (palindromes), in which high-sequence similarity between repeat arms is maintained by gene conversion. These palindromes also harbor microsatellites, considered to evolve via a stepwise mutation model (SMM). Here, we ask whether gene conversion between palindrome microsatellites contributes to their mutational dynamics. First, we study the duplicated tetranucleotide microsatellite DYS385a,b lying in palindrome P4. We show, by comparing observed data with simulated data under a SMM within haplogroups, that observed heteroallelic combinations in which the modal repeat number difference between copies was large, can give rise to homoallelic combinations with zero-repeats difference, equivalent to many single-step mutations. These are unlikely to be generated under a strict SMM, suggesting the action of gene conversion. Second, we show that the intercopy repeat number difference for a large set of duplicated microsatellites in all palindromes in the MSY reference sequence is significantly reduced compared with that for nonpalindrome-duplicated microsatellites, suggesting that the former are characterized by unusual evolutionary dynamics. These observations indicate that gene conversion violates the SMM for microsatellites in palindromes, homogenizing copies within individual Y chromosomes, but increasing overall haplotype diversity among chromosomes within related groups. © 2014 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

  9. Medication safety and knowledge-based functions: a stepwise approach against information overload.

    Science.gov (United States)

    Patapovas, Andrius; Dormann, Harald; Sedlmayr, Brita; Kirchner, Melanie; Sonst, Anja; Müller, Fabian; Pfistermeister, Barbara; Plank-Kiegele, Bettina; Vogler, Renate; Maas, Renke; Criegee-Rieck, Manfred; Prokosch, Hans-Ulrich; Bürkle, Thomas

    2013-09-01

    The aim was to improve medication safety in an emergency department (ED) by enhancing the integration and presentation of safety information for drug therapy. Based on an evaluation of safety of drug therapy issues in the ED and a review of computer-assisted intervention technologies we redesigned an electronic case sheet and implemented computer-assisted interventions into the routine work flow. We devised a four step system of alerts, and facilitated access to different levels of drug information. System use was analyzed over a period of 6 months. In addition, physicians answered a survey based on the technology acceptance model TAM2. The new application was implemented in an informal manner to avoid work flow disruption. Log files demonstrated that step I, 'valid indication' was utilized for 3% of the recorded drugs and step II 'tooltip for well-known drug risks' for 48% of the drugs. In the questionnaire, the computer-assisted interventions were rated better than previous paper based measures (checklists, posters) with regard to usefulness, support of work and information quality. A stepwise assisting intervention received positive user acceptance. Some intervention steps have been seldom used, others quite often. We think that we were able to avoid over-alerting and work flow intrusion in a critical ED environment. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

  10. IDENTIFIKASI FAKTOR PREDIKSI DIAGNOSIS TINGKAT KEGANASAN KANKER PAYUDARA METODE STEPWISE BINARY LOGISTIC REGRESSION

    Directory of Open Access Journals (Sweden)

    Retno Aulia Vinarti

    2014-01-01

    Full Text Available The World Health Organization (WHO reported that deaths caused by cancer in the world these last four years has increased significantly. The data also reflected in the increase in breast cancer cases. In Indonesia, two cases also the highest cases of adult female deaths. Based on Hospital Information System, the number of breast cancer patients either inpatient or outpatient care amounted to 28.7%. This fact revealed more than 40% of all cancers can be prevented with early detection cancer. Role of Information Technology can implemented by data mining techniques to shorten the diagnosing time, accuracy and selection of factors early detection of breast cancer. Stepwise binary logistic regression method has the advantage to add and subtract the independent variables in accordance with level of significance of the model. Based on the analysis of weighting method, the highest four variables that should be more aware is the area of cancer (area, fineness (smoothness, the number of dots (concave points or the nucleus of cancer and grayish level of cancer (texture. So the accuracy and processing speed of diagnosis of the severity of breast cancer can be improved through this method.

  11. Stepwise multiphoton activation fluorescence reveals a new method of melanin detection

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; Mega, Yair; DiMarzio, Charles A.

    2013-06-01

    The stepwise multiphoton activated fluorescence (SMPAF) of melanin, activated by a continuous-wave mode near infrared (NIR) laser, reveals a broad spectrum extending from the visible spectra to the NIR and has potential application for a low-cost, reliable method of detecting melanin. SMPAF images of melanin in mouse hair and skin are compared with conventional multiphoton fluorescence microscopy and confocal reflectance microscopy (CRM). By combining CRM with SMPAF, we can locate melanin reliably. However, we have the added benefit of eliminating background interference from other components inside mouse hair and skin. The melanin SMPAF signal from the mouse hair is a mixture of a two-photon process and a third-order process. The melanin SMPAF emission spectrum is activated by a 1505.9-nm laser light, and the resulting spectrum has a peak at 960 nm. The discovery of the emission peak may lead to a more energy-efficient method of background-free melanin detection with less photo-bleaching.

  12. Research on the shortwave infrared hyperspectral imaging technology based on Integrated Stepwise filter

    Science.gov (United States)

    Wei, Liqing; Xiao, Xizhong; Wang, Yueming; Zhuang, Xiaoqiong; Wang, Jianyu

    2017-11-01

    Space-borne hyperspectral imagery is an important tool for earth sciences and industrial applications. Higher spatial and spectral resolutions have been sought persistently, although this results in more power, larger volume and weight during a space-borne spectral imager design. For miniaturization of hyperspectral imager and optimization of spectral splitting methods, several methods are compared in this paper. Spectral time delay integration (TDI) method with high transmittance Integrated Stepwise Filter (ISF) is proposed.With the method, an ISF imaging spectrometer with TDI could achieve higher system sensitivity than the traditional prism/grating imaging spectrometer. In addition, the ISF imaging spectrometer performs well in suppressing infrared background radiation produced by instrument. A compact shortwave infrared (SWIR) hyperspectral imager prototype based on HgCdTe covering the spectral range of 2.0-2.5 μm with 6 TDI stages was designed and integrated. To investigate the performance of ISF spectrometer, a method to derive the optimal blocking band curve of the ISF is introduced, along with known error characteristics. To assess spectral performance of the ISF system, a new spectral calibration based on blackbody radiation with temperature scanning is proposed. The results of the imaging experiment showed the merits of ISF. ISF has great application prospects in the field of high sensitivity and high resolution space-borne hyperspectral imagery.

  13. Distinct kinetic determinants for the stepwise CCA addition to tRNA.

    Science.gov (United States)

    Kim, Sangbumn; Liu, Cuiping; Halkidis, Konstantine; Gamper, Howard B; Hou, Ya-Ming

    2009-10-01

    The universally conserved CCA sequence is present at the 3' terminal 74-76 positions of all active tRNA molecules as a functional tag to participate in ribosome protein synthesis. The CCA enzyme catalyzes CCA synthesis in three sequential steps of nucleotide addition at rapid and identical rates. However, the kinetic determinant of each addition is unknown, thus limiting the insights into the kinetic basis of CCA addition. Using our recently developed single turnover kinetics of Escherichia coli CCA enzyme as a model, we show here that the identical rate of the stepwise CCA addition is determined by distinct kinetic parameters. Specifically, the kinetics of C74 and C75 addition is controlled by the chemistry of nucleotidyl transfer, whereas the kinetics of A76 addition is controlled by a prechemistry conformational transition of the active site. In multiple turnover condition, all three steps are controlled by slow product release, indicating enzyme processivity from one addition to the next. However, the processivity decreases as the enzyme progresses to complete the CCA synthesis. Together, these results suggest the existence of a network of diverse kinetic parameters that determines the overall rate of CCA addition for tRNA maturation.

  14. Free Vibration of a Perfectly Clamped-Free Beam with Stepwise Eccentric Distributed Masses

    Directory of Open Access Journals (Sweden)

    Gilbert-Rainer Gillich

    2016-01-01

    Full Text Available A direct approach for the calculation of the natural frequencies and vibration mode shapes of a perfectly clamped-free beam with additional stepwise eccentric distributed masses is developed, along with its corresponding equations. Firstly there is contrived influence of a mass, located on a given position along the beam, upon the modal energies, via an energy analysis method. Secondly, the mass participation coefficient is defined as a function of the mass location and the bending vibration mode number. The proposed coefficient is employed to deduce the mathematical relation for the frequencies of beams with supplementary eccentric loads, generally available for any boundary conditions. The accuracy of the obtained mathematical relation was examined in comparison with the numerical simulation and experimental results for a cantilever beam. For this aim, several finite element models have been developed, individualized by the disturbance extent and the mass increase or decrease. Also, one real system was tested. The comparisons between the analytically achieved results and those obtained from experiments proved the accuracy of the developed mathematical relation.

  15. Stepwise inertial control of a wind turbine generator to minimize a second frequency dip

    Directory of Open Access Journals (Sweden)

    Dejian Yang

    2016-01-01

    Full Text Available Wind turbine generators (WTGs in power systems with high wind penetration levels are encouraged or forced to participate in frequency control. A stepwise inertial control (SIC scheme instantly increases WTG output to arrest the frequency drop for a preset period upon detecting a disturbance. After arresting the frequency drop, the output is rapidly reduced to recover the rotor speed. The reduction could cause a power deficit to the power system, which in turn results in a second frequency dip (SFD. This paper proposes an SIC scheme that can improve the frequency nadir (FN and maximum rate of change of frequency (ROCOF while minimizing an SFD. To achieve this, a reference function is separately defined prior to and after the FN. To improve the FN and maximum ROCOF, the output is instantly increased by adding a constant, which is proportional to the rotor speed, and maintaining it until the FN is reached. To minimize an SFD, the output is slowly reduced with the rotor speed. This reduction ensures a slow output reduction rate. The performance of the proposed scheme is investigated using an EMTP-RV simulator under different wind speeds and wind power penetration levels. Results clearly demonstrate that the proposed scheme can improve the FN and maximum ROCOF while ensuring a quick frequency recovery.

  16. Modelling of volunteer satisfaction and intention to remain in community service: A stepwise approach

    Science.gov (United States)

    Hasan, Hazlin; Wahid, Sharifah Norhuda Syed; Jais, Mohammad; Ridzuan, Arifi

    2017-05-01

    The purpose of this study is to obtain the most significant model of volunteer satisfaction and intention to remain in community service by using a stepwise approach. Currently, Malaysians, young and old are showing more interests in involving themselves in community service projects, either locally or internationally. This positive movement of serving the needy is somehow being halted by the lack of human and financial resources. Therefore, the trend today sees organizers of such projects depend heavily on voluntary supports as they enable project managers to add and to expand the quantity and diversity of services offered without exhausting the minimal budget available. Volunteers are considered a valuable commodity as the available pool of volunteers may be declining due to various reasons which include the volunteer satisfaction. In tandem with the existing situation, a selected sample of 215 diploma students from one of the public universities in Malaysia, who have been involved in at least one community service project, agreed that everybody should have a volunteering intention in helping others. The findings revealed that the most significant model obtained contains two factors that contributed towards intention to remain in community service; work assignment and organizational support, with work assignment becoming the most significant factor. Further research on the differences of intention to remain in community service between students' stream and gender would be conducted to contribute to the body of knowledge.

  17. Prevalence and characteristics of asthma–COPD overlap syndrome identified by a stepwise approach

    Directory of Open Access Journals (Sweden)

    Inoue H

    2017-06-01

    Full Text Available Hiromasa Inoue,1 Takahide Nagase,2 Satoshi Morita,3 Atsushi Yoshida,4 Tatsunori Jinnai,4 Masakazu Ichinose5 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 3Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 4Medical Department, AstraZeneca K.K., Osaka, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background and objective: There is increasing recognition of asthma–COPD overlap syndrome (ACOS, which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood. The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA and the Global Initiative for Chronic Obstructive Lung Disease (GOLD. Methods: This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD. Clinical data, including spirometry results, were retrieved from medical records. For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire. Results: Of the 1,008 patients analyzed, 167 (16.6% had syndromic features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2% also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1, respectively, and therefore were identified as having ACOS. Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability, and 328 patients (32.5%, ≥12%/≥400 m

  18. Expanding the scope of replicable unnatural DNA: stepwise optimization of a predominantly hydrophobic base pair.

    Science.gov (United States)

    Lavergne, Thomas; Degardin, Mélissa; Malyshev, Denis A; Quach, Henry T; Dhami, Kirandeep; Ordoukhanian, Phillip; Romesberg, Floyd E

    2013-04-10

    As part of an ongoing effort to expand the genetic alphabet for in vitro and eventually in vivo applications, we have synthesized a wide variety of predominantly hydrophobic unnatural base pairs exemplified by d5SICS-dMMO2 and d5SICS-dNaM. When incorporated into DNA, the latter is replicated and transcribed with greater efficiency and fidelity than the former; however, previous optimization efforts identified the para and methoxy-distal meta positions of dMMO2 as particularly promising for further optimization. Here, we report the stepwise optimization of dMMO2 via the synthesis and evaluation of 18 novel para-derivatized analogs of dMMO2, followed by further derivatization and evaluation of the most promising analogs with meta substituents. Subject to size constraints, we find that para substituents can optimize replication via both steric and electronic effects and that meta methoxy groups are unfavorable, while fluoro substituents can be beneficial or deleterious depending on the para substituent. In addition, we find that improvements in the efficiency of unnatural triphosphate insertion translate most directly into higher fidelity replication. Importantly, we identify multiple, unique base pair derivatives that when incorporated into DNA are well replicated. The most promising, d5SICS-dFEMO, is replicated under some conditions with greater efficiency and fidelity than d5SICS-dNaM. These results clearly demonstrate the generality of hydrophobic forces for the control of base pairing within DNA, provide a wealth of new SAR data, and importantly identify multiple new candidates for eventual in vivo evaluation.

  19. A novel, stepwise approach combining conventional and endobronchial ultrasound needle aspiration for mediastinal lymph node sampling.

    Science.gov (United States)

    Liran, Levy; Rottem, Kuint; Gregorio, Fridlender Zvi; Avi, Abutbul; Neville, Berkman

    2017-09-07

    Since the introduction of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), most pulmonary centers use this technique exclusively for mediastinal lymph node (LN) sampling. Conventional "blind" TBNA (cTBNA), however, is cheaper, more accessible, provides more tissue, and requires less training. We evaluated whether sampling of mediastinal LN using EBUS-TBNA or cTBNA according to a predefined set of criteria provides acceptable diagnostic yield. Sampling method was determined prospectively according to a predefined set of criteria based on LN station, LN size, and presumed diagnosis. Sensitivity, specificity, positive, and negative predictive value were evaluated for each modality. One hundred and eighty-six biopsies were carried out over a 3-year period (86 cTBNA, 100 EBUS-TBNA). Seventy-seven percent of LN biopsied by EBUS-TBNA were <20 mm, while 83% of cTBNA biopsies were ≥20 mm. Most common sites of cTBNA sampling were station 7, 4R, and 11R as opposed to 7, 11R, 4R, and 4 L in the case of EBUS-TBNA. Most common EBUS-TBNA diagnosis was malignancy versus sarcoidosis in cTBNA. EBUS-TBNA and cTBNA both had a true positive yield of 65%, but EBUS-TBNA had a higher true negative rate (21% vs. 2% for cTBNA) and a lower false negative rate (7% vs. 28%). Sensitivity, specificity, positive predictive value, and negative predictive value for EBUS-TBNA were 90%, 100%, 100%, and 75%, respectively, and for cTBNA were 68%, 100%, 100%, and 7%, respectively. A stepwise approach based on LN size, station, and presumed diagnosis may be a reasonable, cost-effective approach in choosing between cTBNA and EBUS-TBNA.

  20. Base-CP proteasome can serve as a platform for stepwise lid formation.

    Science.gov (United States)

    Yu, Zanlin; Livnat-Levanon, Nurit; Kleifeld, Oded; Mansour, Wissam; Nakasone, Mark A; Castaneda, Carlos A; Dixon, Emma K; Fushman, David; Reis, Noa; Pick, Elah; Glickman, Michael H

    2015-01-27

    26S proteasome, a major regulatory protease in eukaryotes, consists of a 20S proteolytic core particle (CP) capped by a 19S regulatory particle (RP). The 19S RP is divisible into base and lid sub-complexes. Even within the lid, subunits have been demarcated into two modules: module 1 (Rpn5, Rpn6, Rpn8, Rpn9 and Rpn11), which interacts with both CP and base sub-complexes and module 2 (Rpn3, Rpn7, Rpn12 and Rpn15) that is attached mainly to module 1. We now show that suppression of RPN11 expression halted lid assembly yet enabled the base and 20S CP to pre-assemble and form a base-CP. A key role for Regulatory particle non-ATPase 11 (Rpn11) in bridging lid module 1 and module 2 subunits together is inferred from observing defective proteasomes in rpn11-m1, a mutant expressing a truncated form of Rpn11 and displaying mitochondrial phenotypes. An incomplete lid made up of five module 1 subunits attached to base-CP was identified in proteasomes isolated from this mutant. Re-introducing the C-terminal portion of Rpn11 enabled recruitment of missing module 2 subunits. In vitro, module 1 was reconstituted stepwise, initiated by Rpn11-Rpn8 heterodimerization. Upon recruitment of Rpn6, the module 1 intermediate was competent to lock into base-CP and reconstitute an incomplete 26S proteasome. Thus, base-CP can serve as a platform for gradual incorporation of lid, along a proteasome assembly pathway. Identification of proteasome intermediates and reconstitution of minimal functional units should clarify aspects of the inner workings of this machine and how multiple catalytic processes are synchronized within the 26S proteasome holoenzymes. © 2015 The Author(s).

  1. Estimating leaf photosynthetic pigments information by stepwise multiple linear regression analysis and a leaf optical model

    Science.gov (United States)

    Liu, Pudong; Shi, Runhe; Wang, Hong; Bai, Kaixu; Gao, Wei

    2014-10-01

    Leaf pigments are key elements for plant photosynthesis and growth. Traditional manual sampling of these pigments is labor-intensive and costly, which also has the difficulty in capturing their temporal and spatial characteristics. The aim of this work is to estimate photosynthetic pigments at large scale by remote sensing. For this purpose, inverse model were proposed with the aid of stepwise multiple linear regression (SMLR) analysis. Furthermore, a leaf radiative transfer model (i.e. PROSPECT model) was employed to simulate the leaf reflectance where wavelength varies from 400 to 780 nm at 1 nm interval, and then these values were treated as the data from remote sensing observations. Meanwhile, simulated chlorophyll concentration (Cab), carotenoid concentration (Car) and their ratio (Cab/Car) were taken as target to build the regression model respectively. In this study, a total of 4000 samples were simulated via PROSPECT with different Cab, Car and leaf mesophyll structures as 70% of these samples were applied for training while the last 30% for model validation. Reflectance (r) and its mathematic transformations (1/r and log (1/r)) were all employed to build regression model respectively. Results showed fair agreements between pigments and simulated reflectance with all adjusted coefficients of determination (R2) larger than 0.8 as 6 wavebands were selected to build the SMLR model. The largest value of R2 for Cab, Car and Cab/Car are 0.8845, 0.876 and 0.8765, respectively. Meanwhile, mathematic transformations of reflectance showed little influence on regression accuracy. We concluded that it was feasible to estimate the chlorophyll and carotenoids and their ratio based on statistical model with leaf reflectance data.

  2. Stepwise evolution of two giant composite LTR-retrotransposon-like elements DA and Xiao

    Directory of Open Access Journals (Sweden)

    Li Xuanyang

    2009-06-01

    Full Text Available Abstract Background We recently discovered two composite long terminal repeat (LTR-retrotransposon-like elements which we named DA (~300 kb and Xiao (~30 kb, meaning big and small in Chinese respectively. Xiao and DA (three types of DA identified were found to have been derived from several donor sites and have spread to 30 loci in the human genome, totaling to 5 Mb. Our bioinformatics analyses with the released human, chimp, rhesus macaque, orangutan, and marmoset genomic sequences indicate that DA and Xiao emerged ~25 million years (Myr ago. Results To better understand the evolution of these two complex elements, we investigated various internal junctions of DA and Xiao as well as orthologous genomic sites of the 30 DA/Xiao loci in non-human primates including great apes, lesser apes, Old World monkeys, New World monkeys, and a prosimian. We found that Xiao and type I DA first emerged in the genome between 25 and 18 Myr ago, whereas type II and Type III DAs emerged between 14 and 7 Myr ago. Xiao and DA were most active in great apes, with their amplification peaking during 25-14 and 14-7 Myr ago, respectively. Neither DA nor Xiao seem to have been active in the human and chimp genomes during last 6 Myr. Conclusion The study has led to a more accurate age determination of the DA and Xiao elements than our previous bioinformatics analyses, and indicates that the amplification activity of the elements coincided with that of group I HERV-Es during evolution. It has also illustrated an evolutionary path with stepwise structural changes for the elements during past 25 Myr, and in doing so has shed more light on these two intriguing and complex elements that have reshaped our genome.

  3. Inferring transcriptional compensation interactions in yeast via stepwise structure equation modeling

    Directory of Open Access Journals (Sweden)

    Wang Woei-Fuh

    2008-03-01

    Full Text Available Abstract Background With the abundant information produced by microarray technology, various approaches have been proposed to infer transcriptional regulatory networks. However, few approaches have studied subtle and indirect interaction such as genetic compensation, the existence of which is widely recognized although its mechanism has yet to be clarified. Furthermore, when inferring gene networks most models include only observed variables whereas latent factors, such as proteins and mRNA degradation that are not measured by microarrays, do participate in networks in reality. Results Motivated by inferring transcriptional compensation (TC interactions in yeast, a stepwise structural equation modeling algorithm (SSEM is developed. In addition to observed variables, SSEM also incorporates hidden variables to capture interactions (or regulations from latent factors. Simulated gene networks are used to determine with which of six possible model selection criteria (MSC SSEM works best. SSEM with Bayesian information criterion (BIC results in the highest true positive rates, the largest percentage of correctly predicted interactions from all existing interactions, and the highest true negative (non-existing interactions rates. Next, we apply SSEM using real microarray data to infer TC interactions among (1 small groups of genes that are synthetic sick or lethal (SSL to SGS1, and (2 a group of SSL pairs of 51 yeast genes involved in DNA synthesis and repair that are of interest. For (1, SSEM with BIC is shown to outperform three Bayesian network algorithms and a multivariate autoregressive model, checked against the results of qRT-PCR experiments. The predictions for (2 are shown to coincide with several known pathways of Sgs1 and its partners that are involved in DNA replication, recombination and repair. In addition, experimentally testable interactions of Rad27 are predicted. Conclusion SSEM is a useful tool for inferring genetic networks, and the

  4. Population structure, stepwise mutations, heterozygote deficiency and their implications in DNA forensics.

    Science.gov (United States)

    Jin, L; Chakraborty, R

    1995-03-01

    In a substructured population the overall heterozygote deficiency can be predicted from the number of subpopulations (s), their time of divergence (t), and the nature of the mutations. At present the true mutational mechanisms at the hypervariable DNA loci are not known. However, the two existing mutation models (the infinite allele model (IAM) and the stepwise mutation model (SMM)) provide some guides to predictions from which the possible effect of population substructuring may be evaluated, assuming that the subpopulations do not exchange any genes among them during evolution. The theory predicts that the loci with larger mutation rate, and consequently showing greater heterozygosity within subpopulations, should exhibit a smaller proportional heterozygote deficiency (GST) and, hence, the effects of population substructuring should be minimal at the hypervariable DNA loci (an order of magnitude smaller than that at the blood group and protein loci). Applications of this theory to data on six Variable Number of Tandem Repeat (VNTR) loci and five short tandem repeat (STR) loci in the major cosmopolitan populations of the USA show that while the VNTR loci often exhibit a large significant heterozygote deficiency, the STR loci do not show a similar tendency. This discordant finding may be ascribed to the limitations, coalescence and nondetectability of alleles associated with the restriction fragment length polymorphism (RFLP) analysis through which the VNTR loci are scored. Such limitations do not apply to the polymerase chain reaction (PCR) method, through which the STR loci are scored. The implications of these results are discussed in the context of the forensic use of DNA typing data.

  5. QSAR analysis for some diaryl-substituted pyrazoles as CCR2 inhibitors by GA-stepwise MLR.

    Science.gov (United States)

    Saghaie, Lotfollah; Shahlaei, Mohsen; Fassihi, Afshin; Madadkar-Sobhani, Armin; Gholivand, Mohammad B; Pourhossein, Alireza

    2011-01-01

    Quantitative relationships between calculated molecular structure and 26 diaryl-substituted pyrazoles CCR2 inhibitors were investigated by GA-stepwise multiple linear regression. In multiple linear regression analysis, the quantitative structure-activity relationship models were constructed by grouping descriptors and also dual selection of variables using genetic algorithm and stepwise selection methods from each group of the pool of all calculated descriptors. The accuracy of the proposed multiple linear regression model was demonstrated using the following evaluation techniques: cross-validation, validation through an external test set, and Y-randomization. Furthermore, the domain of applicability that shows the area of reliable predictions was defined. The prediction results were in good agreement with the experimental values. © 2010 John Wiley & Sons A/S.

  6. Population-based stepwise screening for unrecognised Type 2 diabetes is ineffective in general practice despite reliable algorithms

    DEFF Research Database (Denmark)

    Christensen, J.O.; Sandbæk, Annelli; Lauritzen, Torsten

    2004-01-01

    Aims/hypothesis. The yield of screening programmes for Type 2 diabetes in the existing healthcare setting might be lower than anticipated from tests of screening algorithms in data from epidemiological surveys. Our aims were to evaluate the reliability of the algorithms and the effectiveness...... published prevalence estimate. This was due to a large dropout rate among high-risk individuals prior to entry into the programme. Conclusions/interpretation. Population-based mail-distributed stepwise screening for Type 2 diabetes in general practice is ineffective, despite reliable screening algorithms...... of a proposed stepwise screening programme for Type 2 diabetes in general practice. Methods. The screening programme had four steps: (i) mail-distributed self-administered risk-chart; (ii) screening tests: random blood glucose (RBG) and HbA1c; (iii) diagnostic procedure 1 for fasting blood glucose (FBG) (if RBG...

  7. Characterizing and estimating rice brown spot disease severity using stepwise regression, principal component regression and partial least-square regression*

    OpenAIRE

    Liu, Zhan-yu; Huang, Jing-feng; Shi, Jing-jing; Tao, Rong-xiang; Zhou, Wan; Zhang, Li-li

    2007-01-01

    Detecting plant health conditions plays a key role in farm pest management and crop protection. In this study, measurement of hyperspectral leaf reflectance in rice crop (Oryzasativa L.) was conducted on groups of healthy and infected leaves by the fungus Bipolaris oryzae (Helminthosporium oryzae Breda. de Hann) through the wavelength range from 350 to 2 500 nm. The percentage of leaf surface lesions was estimated and defined as the disease severity. Statistical methods like multiple stepwise...

  8. Analysis and selection of a regression model for the Use Case Points method using a stepwise approach

    OpenAIRE

    Silhavy, Radek; Silhavy, Petr; Prokopova, Zdenka

    2017-01-01

    This study investigates the significance of use case points (UCP) variables and the influence of the complexity of multiple linear regression models on software size estimation and accuracy. Stepwise multiple linear regression models and residual analysis were used to analyse the impact of model complexity. The impact of each variable was studied using correlation analysis. The estimated size of software depends mainly on the values of the weights of unadjusted UCP, which represent a number o...

  9. Driven Factors Analysis of China’s Irrigation Water Use Efficiency by Stepwise Regression and Principal Component Analysis

    OpenAIRE

    Jia, Renfu; Fang, Shibiao; Tu, Wenrong; Sun, Zhilin

    2016-01-01

    This paper introduces an integrated approach to find out the major factors influencing efficiency of irrigation water use in China. It combines multiple stepwise regression (MSR) and principal component analysis (PCA) to obtain more realistic results. In real world case studies, classical linear regression model often involves too many explanatory variables and the linear correlation issue among variables cannot be eliminated. Linearly correlated variables will cause the invalidity of the fac...

  10. A COMPARISON OF STEPWISE AND FUZZY MULTIPLE REGRESSION ANALYSIS TECHNIQUES FOR MANAGING SOFTWARE PROJECT RISKS: ANALYSIS PHASE

    OpenAIRE

    Abdelrafe Elzamly; Burairah Hussin

    2014-01-01

    Risk is not always avoidable, but it is controllable. The aim of this study is to identify whether those techniques are effective in reducing software failure. This motivates the authors to continue the effort to enrich the managing software project risks with consider mining and quantitative approach with large data set. In this study, two new techniques are introduced namely stepwise multiple regression analysis and fuzzy multiple regression to manage the software risks. Two evaluation proc...

  11. Effects of constant and stepwise changes in temperature on the species abundance dynamics of four cladocera species

    OpenAIRE

    Verbitsky V. B.; Verbitskaya T. I.

    2011-01-01

    Laboratory experiments with natural zooplankton communities were carried out to study the effects of two contrasting temperature regimes: constant temperature (15, 20, and 25 °C) and graded changes in temperature. The graded regime consisted of repeated sustained (three weeks) controlled stepwise temperature changes of 5 or 10 °C within 15–25 °C on the population dynamics of four dominant species of lake littoral zooplankton, Daphnia longispina (Müller, 1785), Diaphanosoma brachyurum (Lievin,...

  12. Finding Structure in Diversity: A Stepwise Small-N/Medium-N Qualitative Comparative Analysis Approach for Water Resources Management Research

    Directory of Open Access Journals (Sweden)

    Peter P. Mollinga

    2014-02-01

    Full Text Available Drawing particularly on recent debates on, and development of, comparative methods in the field of comparative politics, the paper argues that stepwise small-N/medium-N qualitative comparative analysis (QCA is a particularly suitable methodological approach for water resources studies because it can make use of the rich but fragmented water resources studies literature for accumulation of knowledge and development of theory. It is suggested that taking an explicit critical realist ontological and epistemological stance allows expansion of the scope of stepwise small-N/medium-N QCA beyond what is claimed for it in Ragin’s 'configurational comparative methods (CCM' perspective for analysing the complexity of causality as 'multiple conjunctural causation'. In addition to explanation of certain sets of 'outcomes' as in CCM’s combinatorial, set-theoretic approach, embedding stepwise small-N/medium-N QCA in a critical realist ontology allows the method to contribute to development of theory on (qualitative differences between the structures in society that shape water resources use, management and governance.

  13. Relationships between the structure of wheat gluten and ACE inhibitory activity of hydrolysate: stepwise multiple linear regression analysis.

    Science.gov (United States)

    Zhang, Yanyan; Ma, Haile; Wang, Bei; Qu, Wenjuan; Wali, Asif; Zhou, Cunshan

    2016-08-01

    Ultrasound pretreatment of wheat gluten (WG) before enzymolysis can improve the angiotensin converting enzyme (ACE) inhibitory activity of the hydrolysates by alerting the structure of substrate proteins. Establishment of a relationship between the structure of WG and ACE inhibitory activity of the hydrolysates to judge the end point of the ultrasonic pretreatment is vital. The results of stepwise multiple linear regression (MLR) showed that the contents of free sulfhydryl, α-helix, disulfide bond, surface hydrophobicity and random coil were significantly correlated to ACE Inhibitory activity of the hydrolysate, with the standard partial regression coefficients were 3.729, -0.676, -0.252, 0.022 and 0.156, respectively. The R(2) of this model was 0.970. External validation showed that the stepwise MLR model could well predict the ACE inhibitory activity of hydrolysate based on the content of free sulfhydryl, α-helix, disulfide bond, surface hydrophobicity and random coil of WG before hydrolysis. A stepwise multiple linear regression model describing the quantitative relationships between the structure of WG and the ACE Inhibitory activity of the hydrolysates was established. This model can be used to predict the endpoint of the ultrasonic pretreatment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  14. Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process.

    Science.gov (United States)

    Akita, Hidetaka; Kudo, Asako; Minoura, Arisa; Yamaguti, Masaya; Khalil, Ikramy A; Moriguchi, Rumiko; Masuda, Tomoya; Danev, Radostin; Nagayama, Kuniaki; Kogure, Kentaro; Harashima, Hideyoshi

    2009-05-01

    Efficient targeting of DNA to the nucleus is a prerequisite for effective gene therapy. The gene-delivery vehicle must penetrate through the plasma membrane, and the DNA-impermeable double-membraned nuclear envelope, and deposit its DNA cargo in a form ready for transcription. Here we introduce a concept for overcoming intracellular membrane barriers that involves step-wise membrane fusion. To achieve this, a nanotechnology was developed that creates a multi-layered nanoparticle, which we refer to as a Tetra-lamellar Multi-functional Envelope-type Nano Device (T-MEND). The critical structural elements of the T-MEND are a DNA-polycation condensed core coated with two nuclear membrane-fusogenic inner envelopes and two endosome-fusogenic outer envelopes, which are shed in stepwise fashion. A double-lamellar membrane structure is required for nuclear delivery via the stepwise fusion of double layered nuclear membrane structure. Intracellular membrane fusions to endosomes and nuclear membranes were verified by spectral imaging of fluorescence resonance energy transfer (FRET) between donor and acceptor fluorophores that had been dually labeled on the liposome surface. Coating the core with the minimum number of nucleus-fusogenic lipid envelopes (i.e., 2) is essential to facilitate transcription. As a result, the T-MEND achieves dramatic levels of transgene expression in non-dividing cells.

  15. Reducing bias in parameter estimates from stepwise regression in proportional hazards regression with right-censored data.

    Science.gov (United States)

    Soh, Chang-Heok; Harrington, David P; Zaslavsky, Alan M

    2008-03-01

    When variable selection with stepwise regression and model fitting are conducted on the same data set, competition for inclusion in the model induces a selection bias in coefficient estimators away from zero. In proportional hazards regression with right-censored data, selection bias inflates the absolute value of parameter estimate of selected parameters, while the omission of other variables may shrink coefficients toward zero. This paper explores the extent of the bias in parameter estimates from stepwise proportional hazards regression and proposes a bootstrap method, similar to those proposed by Miller (Subset Selection in Regression, 2nd edn. Chapman & Hall/CRC, 2002) for linear regression, to correct for selection bias. We also use bootstrap methods to estimate the standard error of the adjusted estimators. Simulation results show that substantial biases could be present in uncorrected stepwise estimators and, for binary covariates, could exceed 250% of the true parameter value. The simulations also show that the conditional mean of the proposed bootstrap bias-corrected parameter estimator, given that a variable is selected, is moved closer to the unconditional mean of the standard partial likelihood estimator in the chosen model, and to the population value of the parameter. We also explore the effect of the adjustment on estimates of log relative risk, given the values of the covariates in a selected model. The proposed method is illustrated with data sets in primary biliary cirrhosis and in multiple myeloma from the Eastern Cooperative Oncology Group.

  16. Mo-MuLV nucleotide sequence exhibits three levels of oligomeric repetitions, suggesting a stepwise molecular evolution.

    Science.gov (United States)

    Laprevotte, I

    1992-11-01

    An exhaustive computer-assisted analysis of the Moloney murine leukemia virus nucleotide sequence shows numerous deviations in the oligomeric distribution, suggesting three overlapping levels of a stepwise duplicative evolution. (1) The sequence fits the universal rule of TG/CT excess which has been proposed as the construction principle of all sequences, and maintains some degree of symmetry between the two complementary strands. (2) Oligomeric repeating units share a core consensus regularly scattered throughout the sequence. This consensus is not merely predictable from the doublet frequencies and codon usage, but could correspond to an intermediary stage in a so-called periodic-to-chaotic transition. (3) Probable stepwise local duplications could be accounted for by slippagelike mechanisms. Comparison with the human spumaretrovirus (HSRV) shows similar segments in the overrepresented oligomers of the two sequences. The intermediary stage of transition oligomeric repeating units is not so clearly suggested in HSRV, perhaps because of numerous stepwise local duplications. In any case, a common evolutionary origin for the two viruses is not ruled out.

  17. Can a stepwise steady flow computational fluid dynamics model reproduce unsteady particulate matter separation for common unit operations?

    Science.gov (United States)

    Pathapati, Subbu-Srikanth; Sansalone, John J

    2011-07-01

    Computational fluid dynamics (CFD) is emerging as a model for resolving the fate of particulate matter (PM) by unit operations subject to rainfall-runoff loadings. However, compared to steady flow CFD models, there are greater computational requirements for unsteady hydrodynamics and PM loading models. Therefore this study examines if integrating a stepwise steady flow CFD model can reproduce PM separation by common unit operations loaded by unsteady flow and PM loadings, thereby reducing computational effort. Utilizing monitored unit operation data from unsteady events as a metric, this study compares the two CFD modeling approaches for a hydrodynamic separator (HS), a primary clarifier (PC) tank, and a volumetric clarifying filtration system (VCF). Results indicate that while unsteady CFD models reproduce PM separation of each unit operation, stepwise steady CFD models result in significant deviation for HS and PC models as compared to monitored data; overestimating the physical size requirements of each unit required to reproduce monitored PM separation results. In contrast, the stepwise steady flow approach reproduces PM separation by the VCF, a combined gravitational sedimentation and media filtration unit operation that provides attenuation of turbulent energy and flow velocity.

  18. Statistical analysis on activation and photo-bleaching of step-wise multi-photon activation fluorescence of melanin

    Science.gov (United States)

    Gu, Zetong; Lai, Zhenhua; Zhang, Xi; Yin, Jihao; DiMarzio, Charles A.

    2015-03-01

    Melanin is regarded as the most enigmatic pigments/biopolymers found in most organisms. We have shown previously that melanin goes through a step-wise multi-photon absorption process after the fluorescence has been activated with high laser intensity. No melanin step-wise multi-photon activation fluorescence (SMPAF) can be obtained without the activation process. The step-wise multi-photon activation fluorescence has been observed to require less laser power than what would be expected from a non-linear optical process. In this paper, we examined the power dependence of the activation process of melanin SMPAF at 830nm and 920nm wavelengths. We have conducted research using varying the laser power to activate the melanin in a point-scanning mode for multi-photon microscopy. We recorded the fluorescence signals and position. A sequence of experiments indicates the relationship of activation to power, energy and time so that we can optimize the power level. Also we explored regional analysis of melanin to study the spatial relationship in SMPAF and define three types of regions which exhibit differences in the activation process.

  19. Development and implementation of the Caribbean Laboratory Quality Management Systems Stepwise Improvement Process (LQMS-SIP) Towards Accreditation

    Science.gov (United States)

    Alemnji, George; Edghill, Lisa; Wallace-Sankarsingh, Sacha; Albalak, Rachel; Cognat, Sebastien; Nkengasong, John; Gabastou, Jean-Marc

    2017-01-01

    Background Implementing quality management systems and accrediting laboratories in the Caribbean has been a challenge. Objectives We report the development of a stepwise process for quality systems improvement in the Caribbean Region. Methods The Caribbean Laboratory Stakeholders met under a joint Pan American Health Organization/US Centers for Disease Control and Prevention initiative and developed a user-friendly framework called ‘Laboratory Quality Management System – Stepwise Improvement Process (LQMS-SIP) Towards Accreditation’ to support countries in strengthening laboratory services through a stepwise approach toward fulfilling the ISO 15189: 2012 requirements. Results This approach consists of a three-tiered framework. Tier 1 represents the minimum requirements corresponding to the mandatory criteria for obtaining a licence from the Ministry of Health of the participating country. The next two tiers are quality improvement milestones that are achieved through the implementation of specific quality management system requirements. Laboratories that meet the requirements of the three tiers will be encouraged to apply for accreditation. The Caribbean Regional Organisation for Standards and Quality hosts the LQMS-SIP Secretariat and will work with countries, including the Ministry of Health and stakeholders, including laboratory staff, to coordinate and implement LQMS-SIP activities. The Caribbean Public Health Agency will coordinate and advocate for the LQMS-SIP implementation. Conclusion This article presents the Caribbean LQMS-SIP framework and describes how it will be implemented among various countries in the region to achieve quality improvement. PMID:28879149

  20. Development and implementation of the Caribbean Laboratory Quality Management Systems Stepwise Improvement Process (LQMS-SIP Towards Accreditation

    Directory of Open Access Journals (Sweden)

    George Alemnji

    2017-02-01

    Full Text Available Background: Implementing quality management systems and accrediting laboratories in the Caribbean has been a challenge.Objectives: We report the development of a stepwise process for quality systems improvement in the Caribbean Region.Methods: The Caribbean Laboratory Stakeholders met under a joint Pan American Health Organization/US Centers for Disease Control and Prevention initiative and developed a user-friendly framework called ‘Laboratory Quality Management System – Stepwise Improvement Process (LQMS-SIP Towards Accreditation’ to support countries in strengthening laboratory services through a stepwise approach toward fulfilling the ISO 15189: 2012 requirements.Results: This approach consists of a three-tiered framework. Tier 1 represents the minimum requirements corresponding to the mandatory criteria for obtaining a licence from the Ministry of Health of the participating country. The next two tiers are quality improvement milestones that are achieved through the implementation of specific quality management system requirements. Laboratories that meet the requirements of the three tiers will be encouraged to apply for accreditation. The Caribbean Regional Organisation for Standards and Quality hosts the LQMS-SIP Secretariat and will work with countries, including the Ministry of Health and stakeholders, including laboratory staff, to coordinate and implement LQMS-SIP activities. The Caribbean Public Health Agency will coordinate and advocate for the LQMS-SIP implementation.Conclusion: This article presents the Caribbean LQMS-SIP framework and describes how it will be implemented among various countries in the region to achieve quality improvement.

  1. Randomized Clinical Trials on Deep Carious Lesions

    DEFF Research Database (Denmark)

    Bjørndal, Lars; Fransson, Helena; Bruun, Gitte

    2017-01-01

    nonselective carious removal to hard dentin with or without pulp exposure. The aim of this article was to report the 5-y outcome on these previously treated patients having radiographically well-defined carious lesions extending into the pulpal quarter of the dentin but with a well-defined radiodense zone...... between the carious lesion and the pulp. In this long-term study, 239 of 314 (76.2%) patients were analyzed. The stepwise removal group had a significantly higher proportion of success (60.2%) at 5-y follow-up compared with the nonselective carious removal to hard dentin group (46.3%) (P = 0.031) when......) in deep carious lesions in adults. In conclusion, the stepwise carious removal group had a significantly higher proportion of pulps with sustained vitality without apical radiolucency versus nonselective carious removal of deep carious lesions in adult teeth at 5-y follow-up (ClinicalTrials.gov NCT...

  2. [Who benefits from stepwise occupational reintegration provided under the statutory pension insurance scheme?].

    Science.gov (United States)

    Bürger, W; Streibelt, M

    2011-06-01

    Stepwise occupational reintegration (SOR) - since law amendments in April 2004 also provided under the German pension insurance scheme (Deutsche Rentenversicherung, DRV) - is an instrument intended to support insurants on sick-leave in reintegrating into work step by step after long-term illness. In 2008, the effectiveness of SOR regarding return to work was affirmed for the first time in a comprehensive study. However, in view of the growing amount of SOR, the question of differential effects of SOR in special subgroups is raised. This paper presents a re-analysis of data collected in the 2008 study. A total of 696 patients after medical rehabilitation were included in the analyses, 348 with SOR provided by the DRV, and a control group of 348 patients without SOR matched on a multitude of different variables using the Propensity Scores. Successful outcome was measured using a combined criterion "Return to work in good health", that is, patients returning to gainful activity and with sick leave of under 6 weeks and no intention to retire within a one-year follow-period after medical rehabilitation. Differentiating criteria are age gender, rehab indication, periods of sick leave in the year before medical rehabilitation, kind of and access to medical rehabilitation. The data indicate especially good results of SOR for patients with mental disorders (OR=2.49), patients who were requested to participate in medical rehabilitation by a health insurance fund because of long-term sick leave (OR=2.71), and patients with longer periods of sick leave before medical rehabilitation (3 to <6 months: OR=2.41, 6 months and more: OR=2.23). In contrast, there are only minimal effects (statistically not significant) of SOR in patients with medical rehabilitation directly after a hospital stay ("Anschlussheilbehandlung"), patients with cardiac or oncological diseases, and in younger (age 19-34) and older patients (age 55-60). In-depth analyses show that SOR success is more marked in

  3. Multimodal microscopy and the stepwise multi-photon activation fluorescence of melanin

    Science.gov (United States)

    Lai, Zhenhua

    The author's work is divided into three aspects: multimodal microscopy, stepwise multi-photon activation fluorescence (SMPAF) of melanin, and customized-profile lenses (CPL) for on-axis laser scanners, which will be introduced respectively. A multimodal microscope provides the ability to image samples with multiple modalities on the same stage, which incorporates the benefits of all modalities. The multimodal microscopes developed in this dissertation are the Keck 3D fusion multimodal microscope 2.0 (3DFM 2.0), upgraded from the old 3DFM with improved performance and flexibility, and the multimodal microscope for targeting small particles (the "Target" system). The control systems developed for both microscopes are low-cost and easy-to-build, with all components off-the-shelf. The control system have not only significantly decreased the complexity and size of the microscope, but also increased the pixel resolution and flexibility. The SMPAF of melanin, activated by a continuous-wave (CW) mode near-infrared (NIR) laser, has potential applications for a low-cost and reliable method of detecting melanin. The photophysics of melanin SMPAF has been studied by theoretical analysis of the excitation process and investigation of the spectra, activation threshold, and photon number absorption of melanin SMPAF. SMPAF images of melanin in mouse hair and skin, mouse melanoma, and human black and white hairs are compared with images taken by conventional multi-photon fluorescence microscopy (MPFM) and confocal reflectance microscopy (CRM). SMPAF images significantly increase specificity and demonstrate the potential to increase sensitivity for melanin detection compared to MPFM images and CRM images. Employing melanin SMPAF imaging to detect melanin inside human skin in vivo has been demonstrated, which proves the effectiveness of melanin detection using SMPAF for medical purposes. Selective melanin ablation with micrometer resolution has been presented using the Target system

  4. Occurrence and Minimization of Cysteine Racemization during Stepwise Solid-Phase Peptide Synthesis(1)(,)(2).

    Science.gov (United States)

    Han, Yongxin; Albericio, Fernando; Barany, George

    1997-06-27

    Contrary to the conventional wisdom of the peptide synthesis field, N,S-protected derivatives of cysteine can undergo substantial levels of racemization with widely-used reagents and protocols for stepwise incorporation. A systematic study of this problem has been carried out as a function of coupling conditions and beta-thiol protecting groups, i.e., S-acetamidomethyl (Acm), S-triphenylmethyl (trityl or Trt), S-2,4,6-trimethoxybenzyl (Tmob), and S-9H-xanthen-9-yl (Xan), taking advantage of a convenient and quantitative model system assay involving HPLC resolution of H-Gly-L-Cys-Phe-NH(2) from H-Gly-D-Cys-Phe-NH(2). For example, standard protocols for couplings mediated by phosphonium and aminium salts, e.g., (benzotriazolyloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HBTU), N-[[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl]methylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU), and (7-azabenzotriazol-1-yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP), typically involve 5-min preactivation times and are conducted in the presence of suitable additives such as 1-hydroxybenzotriazole (HOBt) or 7-aza-1-hydroxybenzotriazole (HOAt) plus a tertiary amine base such as N,N-diisopropylethylamine (DIEA) or N-methylmorpholine (NMM). Under such conditions, the levels of racemization in the model peptide, expressed as the ratio of D:L peptide formed, were in the entirely unacceptable range of 5-33%. However, these levels were in general reduced by a factor of 6- or 7-fold by avoiding the preactivation step. Additional strategies to reduce racemization involved change to a weaker base, with 2,4,6-trimethylpyridine (TMP, collidine) being substantially better than DIEA or NMM; 2-fold reduction in the amount of base; and change in solvent from neat N,N-dimethylformamide (DMF) to the less polar CH(2)Cl(2)-DMF (1:1). Coupling methods

  5. Regressão múltipla stepwise e hierárquica em Psicologia Organizacional: aplicações, problemas e soluções Stepwise and hierarchical multiple regression in organizational psychology: Applications, problemas and solutions

    Directory of Open Access Journals (Sweden)

    Gardênia Abbad

    2002-01-01

    Full Text Available Este artigo discute algumas aplicações das técnicas de análise de regressão múltipla stepwise e hierárquica, as quais são muito utilizadas em pesquisas da área de Psicologia Organizacional. São discutidas algumas estratégias de identificação e de solução de problemas relativos à ocorrência de erros do Tipo I e II e aos fenômenos de supressão, complementaridade e redundância nas equações de regressão múltipla. São apresentados alguns exemplos de pesquisas nas quais esses padrões de associação entre variáveis estiveram presentes e descritas as estratégias utilizadas pelos pesquisadores para interpretá-los. São discutidas as aplicações dessas análises no estudo de interação entre variáveis e na realização de testes para avaliação da linearidade do relacionamento entre variáveis. Finalmente, são apresentadas sugestões para lidar com as limitações das análises de regressão múltipla (stepwise e hierárquica.This article discusses applications of stepwise and hierarchical multiple regression analyses to research in organizational psychology. Strategies for identifying type I and II errors, and solutions to potential problems that may arise from such errors are proposed. In addition, phenomena such as suppression, complementarity, and redundancy are reviewed. The article presents examples of research where these phenomena occurred, and the manner in which they were explained by researchers. Some applications of multiple regression analyses to studies involving between-variable interactions are presented, along with tests used to analyze the presence of linearity among variables. Finally, some suggestions are provided for dealing with limitations implicit in multiple regression analyses (stepwise and hierarchical.

  6. Characterization of a stepwise approach in cavotricuspid isthmus ablation for typical atrial flutter: A randomized study comparing three catheters.

    Science.gov (United States)

    Rubín, José Manuel; Calvo, David; Pérez, Diego; Fidalgo, Ana; de la Hera, Jesús María; Martínez, Lidia; Capín, Esmeralda; Arrizabalaga, Haritz; Carballeira, Lidia; García, Daniel; Morís, Cesar

    2017-10-01

    Our aim was to characterize a stepwise approach in cavotricuspid isthmus ablation for typical atrial flutter in a prospective, noncrossover randomized study. One hundred and fifty patients referred for cavotricuspid isthmus (CTI)-dependent atrial flutter ablation were randomized to undergo an ablation with an 8-mm-tip catheter (group 1), a 3.5-mm open irrigation-tip catheter (group 2), and a 3.5-mm open irrigation porous-tip catheter (group 3). A stepwise approach was performed, changing the ablation site from medial to septal aspects of the CTI, in case it was not effective without crossover between catheters. CTI block was achieved in all the patients using only one catheter. There was a 68% efficacy in group 1, 40% in group 2, and 28% in group 3 to achieve CTI block within 10 minutes (P  =  0.001) and 96%, 70%, and 70% in groups 1, 2, and 3, respectively, within 20 minutes (P  =  0.002) of radiofrequency ablation. The 8-mm catheter was also faster in fluoroscopy time and CTI block time. There were no differences in efficiency in the both irrigated catheters. There were no significant differences in complications among three catheters. With this stepwise approach, it is possible to achieve CTI block in all cases, using a single catheter without crossover, with good times of procedure and with a low complication rate. The 8-mm solid catheter is faster than the other irrigated-tip catheters. The 3.5-mm open irrigation porous-tip catheter is as effective and safe as the conventional irrigated-tip catheter. © 2017 Wiley Periodicals, Inc.

  7. Stepwise vs concerted excited state tautomerization of 2-hydroxypyridine: Ammonia dimer wire mediated hydrogen/proton transfer

    Energy Technology Data Exchange (ETDEWEB)

    Esboui, Mounir, E-mail: mounir.esboui@fst.rnu.tn [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications, Département de Physique, Faculté des Sciences de Tunis, 2092 Tunis (Tunisia); Technical and Vocational Training Corporation, Hail College of Technology, P.O. Box 1960, Hail 81441 (Saudi Arabia)

    2015-07-21

    The stepwise and concerted excited state intermolecular proton transfer (PT) and hydrogen transfer (HT) reactions in 2-hydroxypyridine-(NH{sub 3}){sub 2} complex in the gas phase under Cs symmetry constraint and without any symmetry constraints were performed using quantum chemical calculations. It shows that upon excitation, the hydrogen bonded in 2HP-(NH{sub 3}){sub 2} cluster facilitates the releasing of both hydrogen and proton transfer reactions along ammonia wire leading to the formation of the 2-pyridone tautomer. For the stepwise mechanism, it has been found that the proton and the hydrogen may transfer consecutively. These processes are distinguished from each other through charge translocation analysis and the coupling between the motion of the proton and the electron density distribution along ammonia wire. For the complex under Cs symmetry, the excited state HT occurs on the A″({sup 1}πσ{sup ∗}) and A′({sup 1}nσ{sup ∗}) states over two accessible energy barriers along reaction coordinates, and excited state PT proceeds mainly through the A′({sup 1}ππ{sup ∗}) and A″({sup 1}nπ{sup ∗}) potential energy surfaces. For the unconstrained complex, potential energy profiles show two {sup 1}ππ{sup ∗}-{sup 1}πσ{sup ∗} conical intersections along enol → keto reaction path indicating that proton and H atom are localized, respectively, on the first and second ammonia of the wire. Moreover, the concerted excited state PT is competitive to take place with the stepwise process, because it proceeds over low barriers of 0.14 eV and 0.11 eV with respect to the Franck-Condon excitation of enol tautomer, respectively, under Cs symmetry and without any symmetry constraints. These barriers can be probably overcome through tunneling effect.

  8. Step-Wise Velocity of an Air Bubble Rising in a Vertical Tube Filled with a Liquid Dispersion of Nanoparticles.

    Science.gov (United States)

    Cho, Heon Ki; Nikolov, Alex D; Wasan, Darsh T

    2017-03-21

    The motion of air bubbles in tubes filled with aqueous suspensions of nanoparticles (nanofluids) is of practical interest for bubble jets, lab-on-a-chip, and transporting media. Therefore, the focus of this study is the dynamics of air bubbles rising in a tube in a nanofluid. Many authors experimentally and analytically proposed that the velocity of rising air bubbles is constant for long air bubbles suspended in a vertical tube in common liquids (e.g. an aqueous glycerol solution) when the capillary number is larger than 10-4. For the first time, we report here a systematic study of an air bubble rising in a vertical tube in a nanofluid (e.g. an aqueous silica dioxide nanoparticle suspension, nominal particle size, 19 nm). We varied the bubble length scaled by the diameter of the tubes (L/D), the concentration of the nanofluid (10 and 12.5 v %), and the tube diameter (0.45, 0.47, and 0.50 cm). The presence of the nanoparticles creates a significant change in the bubble velocity compared with the bubble rising in the common liquid with the same bulk viscosity. We observed a novel phenomenon of a step-wise increase in the air bubble rising velocity versus bubble length for small capillary numbers less than 10-7. This step-wise velocity increase versus the bubble length was not observed in a common fluid. The step-wise velocity increase is attributed to the nanoparticle self-layering phenomenon in the film adjacent to the tube wall. To elucidate the role of the nanoparticle film self-layering on the bubble rising velocity, the effect of the capillary number, the tube diameter (e.g. the capillary pressure), and nanofilm viscosity are investigated. We propose a model that takes into consideration the nanoparticle layering in the film confinement to explain the step-wise velocity phenomenon versus the length of the bubble. The oscillatory film interaction energy isotherm is calculated and the Frenkel approach is used to estimate the film viscosity.

  9. The Determination of Polyethlylene Glycol and Water in Archaeological Wood using Infrared Spectroscopy and Stepwise Multiple Linear Regression

    Directory of Open Access Journals (Sweden)

    Rohan PATEL

    2012-03-01

    Full Text Available Polyethylene glycol (PEG is the most common preservative in use for bulking and maintaining structural integrity in waterlogged wood. Conservators therefore have a need to be able to determine PEG concentrations in wood in a non-destructive manner. We present a study highlighting the application of infrared spectroscopy coupled with multivariate analysis techniques to predict the concentration of polyethylene glycol 400 (PEG-400 and water simultaneously. This technique uses attenuated total reflectance (ATR spectroscopy andunconstrained stepwise multiple linear regression (SMLR analysis for prediction of multiple components in archaeological wood. Using this model we have calculated the concentration of PEG-400 and water in treated archaeological waterlogged wood samples.

  10. QSAR Analysis for Some 1, 2-Benzisothiazol-3-one Derivatives as Caspase-3 Inhibitors by Stepwise MLR Method

    OpenAIRE

    Hajimahdi, Zahra; Safizadeh, Fatemeh; Zarghi, Afshin

    2016-01-01

    Caspase-3 inhibitory activities of some 1, 2-benzisothiazol-3-one derivatives were modeled by quantitative structure?activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R2) of 0.91 and 0.59 for training and test groups, respectively. The quality of the model was evaluated by leave-one out (LOO) cross validation (LOO correlation coefficient, Q2) of 0.80). The results indicate that the de...

  11. Stepwise formation of 1,3-diazolium-4-thiolates by münchnone cycloadditions: promising candidates for nonlinear optics.

    Science.gov (United States)

    Cantillo, David; Ávalos, Martín; Babiano, Reyes; Cintas, Pedro; Jiménez, José L; Light, Mark E; Palacios, Juan C; Porro, Rocío

    2014-05-02

    An improved preparation of mesoionic heterocycles 1,3-diazolium-4-thiolates by [3 + 2] cycloadditions of münchnones with aryl isothiocyanates is reported. The process takes place with high or complete regioselectivity, and fast and clean transformations are observed under microwave heating in DMF. DFT calculations support that this cycloaddition proceeds preferably through a stepwise mechanism. Given the pattern substitution around the mesoionic ring resulting in a push-pull system, theoretical estimations predict large hyperpolarizabilities in some cases, which is typical of molecules exhibiting nonlinear optical responses.

  12. Step-wise changes in glacier flow speed coincide with calving and glacial earthquakes at Helheim Glacier, Greenland

    DEFF Research Database (Denmark)

    Nettles, M.; Larsen, T. B.; Elósegui, P.

    2008-01-01

    Geodetic observations show several large, sudden increases in flow speed at Helheim Glacier, one of Greenland's largest outlet glaciers, during summer, 2007. These step-like accelerations, detected along the length of the glacier, coincide with teleseismically detected glacial earthquakes and major...... at Greenland's largest outlet glaciers, on timescales as short as minutes to hours, and clarify the mechanism by which glacial earthquakes occur. Citation: Nettles, M., et al. (2008), Step-wise changes in glacier flow speed coincide with calving and glacial earthquakes at Helheim Glacier, Greenland....

  13. Clinical Trials

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    Full Text Available ... under way. For example, some trials are stopped early if benefits from a strategy or treatment are ... stop a trial, or part of a trial, early if the strategy or treatment is having harmful ...

  14. Clinical Trials

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    Full Text Available ... criteria differ from trial to trial. They include factors such as a patient's age and gender, the ... bias. "Bias" means that human choices or other factors not related to the protocol affect the trial's ...

  15. Monitoring during the stepwise implementation of the Swedish deep repository for spent fuel

    Energy Technology Data Exchange (ETDEWEB)

    Baeckblom, Goeran [Conrox (Sweden); Almen, Karl-Erik [KEA Geokonsult AB (Sweden)

    2004-03-01

    Monitoring in this report is defined as 'Continuous or repeated observations or measurements of parameters to increase the scientific understanding of the site and the repository, to show compliance with requirements or for adaptation of plans in light of the monitoring results.' The international outlook from IAEA, OECD/NEA, CEC and some country-specific reviews presented in the report forms a necessary background to the Swedish monitoring framework. The implementation of the deep repository in Sweden is executed in phases where monitoring is an inherently integrated activity in the programme. The first phase is the site investigations when Primary Baseline conditions are established. During the following construction phase of the repository, detailed site characterisation continues in conjunction with construction of the access to the deposition area, construction of parts of the deposition area and the central service area. Monitoring is then used to track the changes to the previously established Primary Baseline conditions and distinguishing these imposed changes from natural variations or from other man-made influences. During the initial operation phase, around 200-400 canisters of spent fuel is emplaced and deposition tunnels backfilled. After up-dated evaluations, the phase of regular operation begin, where detailed characterisation, construction of the repository and waste emplacement are concurrent activities. The closure of the repository will take place when all spent fuel has been emplaced, i.e. in the latter part of this century. Monitoring during the stepwise implementation of the repository is executed of several reasons mainly to: describe the Primary Baseline conditions of the repository site, develop and demonstrate understanding of the repository site and the behaviour of engineered barriers, assist in the decision-making process, show compliance with international and national guidelines and regulations. Specific rationales for

  16. High-intensity stepwise conditioning programme for improved exercise responses and agility performance of a badminton player with knee pain.

    Science.gov (United States)

    Chen, Bob; Mok, Damon; Lee, Winson C C; Lam, Wing Kai

    2015-02-01

    To examine the effect of a high-intensity stepwise conditioning programme combined with multiple recovery measures on physical fitness, agility, and knee pain symptoms of an injured player. A single case study. University-based conditioning training laboratory. One 26-year-old male world-class badminton player (height, 190.0 cm; weight, 79.3 kg; left dominant hand; playing experience, 16 years; former world champion) with patellar tendinosis and calcification of his left knee. The player received seven conditioning sessions over three weeks. During the programme, there was a gradual increase in training duration and load across sessions while cold therapy, manual stretches and massage were administered after each session to minimise inflammation. The training outcome was evaluated with three different testing methods: standard step test, badminton-specific agility test, and tension-pain rating. The conditioning programme reduced knee pain symptoms and improved actual performance and cardiopulmonary fitness during the agility task. The player was able to return to sport and compete within a month. A high-intensity stepwise conditioning programme improved the physical fitness while sufficient recovery measures minimised any possible undesirable effects and promoted faster return to elite level competition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Excited singlet (S1) state interactions of calixarenes with chloroalkanes: A combination of concerted and stepwise dissociative electron transfer mechanism

    Science.gov (United States)

    Mohanty, J.; Pal, H.; Nayak, S. K.; Chattopadhyay, S.; Sapre, A. V.

    2002-12-01

    Both steady-state and time-resolved studies in acetonitrile (ACN) solutions show that the excited singlet (S1) states of calixarenes (CX) undergo quenching by chloroalkanes (CA). It has been revealed by characterizing the Cl ions in the photolyzed CX-CA systems in ACN solutions that the quenching occurs due to dissociative electron transfer (DET) mechanism, whereby a C-Cl bond of the CAs undergoes dissociation on acceptance of an electron from excited CX. The bimolecular quenching constants (kq) in the present systems were correlated with the free energy changes for the concerted DET reactions based on a suitable DET theory. Such a correlation results in the recovery of an intramolecular reorganization energy, which is substantially lower to account for the C-Cl bond dissociation energy of the CAs. Comparing present results with those of an another donor-acceptor system (e.g., biphenyldiol-CA systems) where a concerted DET mechanism is applicable, it is inferred that in CX-CA systems both concerted and stepwise DET mechanisms operate simultaneously. It is proposed that the interaction of excited CXs with encaged CAs follows the stepwise mechanism whereas that with the out of cage CAs follows the concerted mechanism.

  18. Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Boram [Korea University, Seoul (Korea, Republic of); Sun Medical Center, Daejeon (Korea, Republic of); Lee, Sunyoung [Sun Medical Center, Daejeon (Korea, Republic of); Yang, Injeong [Seoul National University Hospital Medical Center, Seoul (Korea, Republic of); Yoon, Myeonggeun [Korea University, Seoul (Korea, Republic of)

    2014-05-15

    The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

  19. The "STEP-wise" future of adenovirus-based HIV vaccines.

    Science.gov (United States)

    Patterson, L J

    2011-01-01

    The HIV pandemic continues to be a public health crisis with over 30 million people currently living with the disease and, depending on the estimate, another 2 - 2.8 million infected annually. The disappointing results of the first Phase II study of a highly immunogenic adenovirus-vectored vaccine, named the STEP trial, was a wake up call to both the clinical and preclinical HIV vaccine fields. A vaccine designed only to elicit T cells and including a single HIV gene insert, will not be sufficient to reduce transmission or lower viremia in people. Additionally, future use of adenovirus-based vectored vaccines needs to be carefully planned with respect to vector type, gene inserts, route of immunization and risk factors among subject volunteers. The initial observation of a transient, increased risk of infection in Ad5 seropositive, uncircumcised men who have sex with men (MSM) is still unexplained, and may yet be considered simply a random event. The vaccine field has not given up on adenoviruses and there is continued interest in pursuing these highly immunogenic vectors, either in combination approaches with DNA, use of rare serotypes with low seroprevalence, or those derived from simian origin. Finally, evaluation of replicating adenovirus vectors known to be capable of inducing potent cellular, humoral, and mucosal immunity will be vital to meeting our future goal of an effective HIV vaccine.

  20. A Bayesian Stepwise Discriminant Model for Predicting Risk Factors of Preterm Premature Rupture of Membranes: A Case-control Study.

    Science.gov (United States)

    Zhang, Li-Xia; Sun, Yang; Zhao, Hai; Zhu, Na; Sun, Xing-De; Jin, Xing; Zou, Ai-Min; Mi, Yang; Xu, Ji-Ru

    2017-10-20

    Preterm premature rupture of membrane (PPROM) can lead to serious consequences such as intrauterine infection, prolapse of the umbilical cord, and neonatal respiratory distress syndrome. Genital infection is a very important risk which closely related with PPROM. The preliminary study only made qualitative research on genital infection, but there was no deep and clear judgment about the effects of pathogenic bacteria. This study was to analyze the association of infections with PPROM in pregnant women in Shaanxi, China, and to establish Bayesian stepwise discriminant analysis to predict the incidence of PPROM. In training group, the 112 pregnant women with PPROM were enrolled in the case subgroup, and 108 normal pregnant women in the control subgroup using an unmatched case-control method. The sociodemographic characteristics of these participants were collected by face-to-face interviews. Vaginal excretions from each participant were sampled at 28-36+6 weeks of pregnancy using a sterile swab. DNA corresponding to Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Candida albicans, group B streptococci (GBS), herpes simplex virus-1 (HSV-1), and HSV-2 were detected in each participant by real-time polymerase chain reaction. A model of Bayesian discriminant analysis was established and then verified by a multicenter validation group that included 500 participants in the case subgroup and 500 participants in the control subgroup from five different hospitals in the Shaanxi province, respectively. The sociological characteristics were not significantly different between the case and control subgroups in both training and validation groups (all P > 0.05). In training group, the infection rates of UU (11.6% vs. 3.7%), CT (17.0% vs. 5.6%), and GBS (22.3% vs. 6.5%) showed statistically different between the case and control subgroups (all P case and control subgroups (P case and control subgroup were 84.1% and 86.8% in the training and validation groups, respectively

  1. Stepwise transition of a topological defect from the smectic film to the boundary of a dipolar inclusion

    Science.gov (United States)

    Dolganov, P. V.; Kats, E. I.; Cluzeau, P.

    2010-03-01

    Cholesteric droplets accompanied by a topological defect are studied in free standing smectic C∗ films. We observed a transition between two droplet-defect configurations with the defect in the film and on the droplet boundary. We found that the distance between the droplet surface and the topological defect decreases continuously with increasing temperature and above a certain critical temperature the defect jumps to the droplet boundary. We relate this stepwise change in the defect position to the change in the anchoring on the droplet boundary. This transformation leads to a decrease in the interparticle distances in self-organized chains from droplets. Our simple theory allows us to estimate the value of the anchoring energy.

  2. Modified precision lingual bonding technique: A step-wise approach with torque angulation device-bracket positioning device

    Directory of Open Access Journals (Sweden)

    Rosaline Tina Paul

    2017-01-01

    Full Text Available Objectives: Contemporary preadjusted edgewise appliance is all about the precision in bracket design, prescription and positioning in addition to the orthodontist's skill and training. However, achieving it is a bigger challenge as the anatomy of the lingual surface of a tooth is uneven, dissimilar, and moreover the tooth alignment on the lingual surface is variant. Thus, the need for an accurate method of bracket positioning with predetermined torque and angulation incorporated in the brackets according to the patients' need is of key importance. Materials and Methods: A TAD-BPD machine used to enhance the accuracy of bracket positioning and bioplast accurate tray transfer technique was used. Results: A step-wise procedures in bracket positioning and fabricating an indirect bonding tray for lingual orthodontics using the torque angulation device-bracket positioning device. Conclusions: This technique facilitated unhindered bonding even in severely crowded cases and easy rebonding during mid-treatment stages.

  3. Smoothing effect of the thermal interface material on the temperature distribution in a stepwise varying width microchannel cooling device

    Science.gov (United States)

    Riera, Sara; Barrau, Jérôme; Rosell, Joan I.; Fréchette, Luc G.; Omri, Mohamed; Vilarrubí, Montse; Laguna, Gerard

    2017-09-01

    The impact of the thermal interface material (TIM) layer on the performance of a stepwise varying width microchannel cooling device is analysed. A numerical model shows that the TIM layer, besides its well known negative impact on the temperature, also generates a smoothing effect on the temperature distribution. In this study, an analytical model is used to define a nondimensional parameter, called Smoothing Resistance ratio, as the quotient between the origin of the temperature non uniformities and the TIM thermal resistance that flatten the temperature distribution. The relationship between the temperature uniformity of the cooled device, expressed through the temperature standard deviation, and the Smoothing Resistance ratio is shown to be linear. These results lead to the definition of a new design procedure for this kind of cooling device, which aims to reduce the Smoothing Resistance ratio. Two solutions are identified and their drawbacks are analysed.

  4. A Hybrid Approach of Stepwise Regression, Logistic Regression, Support Vector Machine, and Decision Tree for Forecasting Fraudulent Financial Statements

    Science.gov (United States)

    Goo, Yeong-Jia James; Shen, Zone-De

    2014-01-01

    As the fraudulent financial statement of an enterprise is increasingly serious with each passing day, establishing a valid forecasting fraudulent financial statement model of an enterprise has become an important question for academic research and financial practice. After screening the important variables using the stepwise regression, the study also matches the logistic regression, support vector machine, and decision tree to construct the classification models to make a comparison. The study adopts financial and nonfinancial variables to assist in establishment of the forecasting fraudulent financial statement model. Research objects are the companies to which the fraudulent and nonfraudulent financial statement happened between years 1998 to 2012. The findings are that financial and nonfinancial information are effectively used to distinguish the fraudulent financial statement, and decision tree C5.0 has the best classification effect 85.71%. PMID:25302338

  5. Cracking behavior of thin gold strip deposited on polycarbonate plate under Cyclic and stepwisely-increased tension

    Directory of Open Access Journals (Sweden)

    Tada Naoya

    2017-01-01

    Full Text Available Thin metal films deposited on polymers have been attracting much attention in flexible electronics. Various combinations of film and polymer substrate are expected to be developed. In this paper, deformation and fracture of thin metal film on polymer substrate was briefly analysed and the influencing factors were summarized. After that, focusing on the shape and thickness of thin metal film on polymer substrate, cracking behavior of small rounded-rectangular thin gold films called “strips” with a thickness less than one micrometer was observed under cyclic and stepwisely-increased trapezoidal tensions. The strips were deposited on a polycarbonate plate specimen, and wide and narrow strips with different thickness were prepared for the tests. The cracking behaviour was successfully observed and the increasing rate of crack number with the load or strain was examined. Since most cracks were initiated from the small defects, the crack initiation behavior was correlated with the distribution of defects.

  6. A Hybrid Approach of Stepwise Regression, Logistic Regression, Support Vector Machine, and Decision Tree for Forecasting Fraudulent Financial Statements

    Directory of Open Access Journals (Sweden)

    Suduan Chen

    2014-01-01

    Full Text Available As the fraudulent financial statement of an enterprise is increasingly serious with each passing day, establishing a valid forecasting fraudulent financial statement model of an enterprise has become an important question for academic research and financial practice. After screening the important variables using the stepwise regression, the study also matches the logistic regression, support vector machine, and decision tree to construct the classification models to make a comparison. The study adopts financial and nonfinancial variables to assist in establishment of the forecasting fraudulent financial statement model. Research objects are the companies to which the fraudulent and nonfraudulent financial statement happened between years 1998 to 2012. The findings are that financial and nonfinancial information are effectively used to distinguish the fraudulent financial statement, and decision tree C5.0 has the best classification effect 85.71%.

  7. QSAR Analysis for Some 1, 2-Benzisothiazol-3-one Derivatives as Caspase-3 Inhibitors by Stepwise MLR Method.

    Science.gov (United States)

    Hajimahdi, Zahra; Safizadeh, Fatemeh; Zarghi, Afshin

    2016-01-01

    Caspase-3 inhibitory activities of some 1, 2-benzisothiazol-3-one derivatives were modeled by quantitative structure-activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R(2)) of 0.91 and 0.59 for training and test groups, respectively. The quality of the model was evaluated by leave-one out (LOO) cross validation (LOO correlation coefficient, Q(2)) of 0.80). The results indicate that the descriptors related to the electronegativity, the atomic masses, the atomic van der Waals volumes and R--CX--R Atom-centered fragments play a more significant role in caspase-3 inhibitory activity.

  8. Driven Factors Analysis of China’s Irrigation Water Use Efficiency by Stepwise Regression and Principal Component Analysis

    Directory of Open Access Journals (Sweden)

    Renfu Jia

    2016-01-01

    Full Text Available This paper introduces an integrated approach to find out the major factors influencing efficiency of irrigation water use in China. It combines multiple stepwise regression (MSR and principal component analysis (PCA to obtain more realistic results. In real world case studies, classical linear regression model often involves too many explanatory variables and the linear correlation issue among variables cannot be eliminated. Linearly correlated variables will cause the invalidity of the factor analysis results. To overcome this issue and reduce the number of the variables, PCA technique has been used combining with MSR. As such, the irrigation water use status in China was analyzed to find out the five major factors that have significant impacts on irrigation water use efficiency. To illustrate the performance of the proposed approach, the calculation based on real data was conducted and the results were shown in this paper.

  9. Descriptive Epidemiology of Hypertension and Its Association With Obesity: Based on the WHO STEPwise Approach to Surveillance in Palau.

    Science.gov (United States)

    Wang, Chaochen; Chiang, Chifa; Yatsuya, Hiroshi; Hilawe, Esayas Haregot; Ikerdeu, Edolem; Honjo, Kaori; Mita, Takashi; Cui, Renzhe; Hirakawa, Yoshihisa; Madraisau, Sherilynn; Iso, Hiroyasu; Aoyama, Atsuko

    2017-05-01

    The rise of noncommunicable diseases is a serious health burden for Palau. This study described the prevalence of hypertension, and assessed its association with obesity. Surveys following the WHO STEPwise approach to surveillance were conducted in 2529 adults. Multivariate prevalence ratios (PR) of hypertension for body mass index (BMI) categories were calculated by logistic regression models using conditional standardization procedure. Age- and sex-specified analyses were performed. Overall prevalence of obesity and hypertension were 40.4% and 46.8%, respectively. Prevalence of hypertension was positively associated with BMI. However, overweight men had as high prevalence of hypertension as the obese (multivariable-adjusted PR was 1.84 for overweight and 1.91 for obese compared with nonoverweight). The association between hypertension and BMI was similar across age groups. The prevalence of hypertension in women increased gradually with the increase of BMI whereas that in men reached a plateau already in the overweight.

  10. A Gastrointestinal Stromal Tumor of the Stomach Demonstrating a Stepwise Progression from Low- to High-Grade Malignancy

    Directory of Open Access Journals (Sweden)

    Takahiko Nakajima

    2012-01-01

    Full Text Available We report a case of a gastrointestinal stromal tumor (GIST of the stomach that demonstrated a stepwise progression from low- to high-grade malignancy. The patient had been followed for a small gastric submucosal tumor that had turned malignant after 8 years of indolence, manifested by tarry stools. The tumor was enucleated, and gastric GIST was diagnosed. The most significant histological finding was that the tumor comprised two clearly demarcated areas, one with less aggressive characteristics and the other with highly aggressive characteristics. The patient exhibited multiple liver metastases 24 months after surgery. Imatinib mesylate was not administered throughout the clinical course because it was not available for clinical use at that time. The patient followed an unfavorable clinical course and died of liver dysfunction 55 months after surgery. Autopsy was performed. By comparing the immunohistochemical profiles of primary and metastatic tumors, it was established that only the tumor cells with highly aggressive characteristics had metastasized.

  11. Characterizing and estimating rice brown spot disease severity using stepwise regression, principal component regression and partial least-square regression.

    Science.gov (United States)

    Liu, Zhan-yu; Huang, Jing-feng; Shi, Jing-jing; Tao, Rong-xiang; Zhou, Wan; Zhang, Li-Li

    2007-10-01

    Detecting plant health conditions plays a key role in farm pest management and crop protection. In this study, measurement of hyperspectral leaf reflectance in rice crop (Oryzasativa L.) was conducted on groups of healthy and infected leaves by the fungus Bipolaris oryzae (Helminthosporium oryzae Breda. de Hann) through the wavelength range from 350 to 2,500 nm. The percentage of leaf surface lesions was estimated and defined as the disease severity. Statistical methods like multiple stepwise regression, principal component analysis and partial least-square regression were utilized to calculate and estimate the disease severity of rice brown spot at the leaf level. Our results revealed that multiple stepwise linear regressions could efficiently estimate disease severity with three wavebands in seven steps. The root mean square errors (RMSEs) for training (n=210) and testing (n=53) dataset were 6.5% and 5.8%, respectively. Principal component analysis showed that the first principal component could explain approximately 80% of the variance of the original hyperspectral reflectance. The regression model with the first two principal components predicted a disease severity with RMSEs of 16.3% and 13.9% for the training and testing dataset, respectively. Partial least-square regression with seven extracted factors could most effectively predict disease severity compared with other statistical methods with RMSEs of 4.1% and 2.0% for the training and testing dataset, respectively. Our research demonstrates that it is feasible to estimate the disease severity of rice brown spot using hyperspectral reflectance data at the leaf level.

  12. A novel technique for ultrasound-guided central venous catheterization under short-axis out-of-plane approach: "stepwise flashing with triangulation".

    Science.gov (United States)

    Horiuchi, Toshinori; Okuda, Chie; Kurita, Naoko; Yamaguchi, Ayako; Kitagawa, Kazuhiko; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

    2017-10-01

    In ultrasound-guided central venous catheterization, there is no standard technique either for the needle tip visualization or for the adequate needle angle and entry to the skin with short-axis view under out-of-plane technique. In the present study, we propose a novel technique named "stepwise flashing with triangulation", and the efficacy of this technique is assessed. Before and after a didactic session in which the technique was explained, 12 novice residents were asked to position the needle tip on or into the imitation vessels and to avoid deeper penetration by using an agar tissue phantom with ultrasound guidance. "Stepwise flashing" technique was for stepwise visualization of the needle tip, and "triangulation" technique was for adequate needle angle and entry to the skin. After the session, the success rate was increased and a deeper penetration rate was decreased. This technique will help us to facilitate vascular access and to avoid complications in clinical settings.

  13. Clinical Trials

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    Full Text Available ... help produce reliable study results. Clinical trials are one of the final stages of a long and ... trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of lowering ...

  14. Clinical Trials

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    Full Text Available ... they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. The NIH may partner ... the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing ...

  15. Clinical Trials

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    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  16. Clinical Trials

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    Full Text Available ... comparison groups by chance, rather than choice. This method helps ensure that any differences observed during a ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

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    Full Text Available ... are research studies that explore whether a medical strategy, treatment, or device is safe and effective for ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

  18. Clinical Trials

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    Full Text Available ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers ( ...

  19. Clinical Trials

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    Full Text Available ... treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ... are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and ...

  20. Clinical Trials

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    Full Text Available ... and groups sponsor clinical trials that test the safety of products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ...

  1. Clinical Trials

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    Full Text Available ... research—that is, who is eligible. Each trial must include only people who fit the patient traits ... to take part in the study. Each trial must include only people who fit the patient traits ...

  2. Clinical Trials

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    Full Text Available ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ... lung, and blood disorders. By engaging the research community and a broad group of stakeholders and advisory ...

  3. Clinical Trials

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    Full Text Available ... also requires DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs for some earlier phase trials that involve high-risk procedures (such as gene therapy) or ...

  4. Clinical Trials

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... care providers might be part of your treatment team. They will monitor your health closely. You may ...

  5. Quantity and quality of food losses along the Swiss potato supply chain: Stepwise investigation and the influence of quality standards on losses.

    Science.gov (United States)

    Willersinn, Christian; Mack, Gabriele; Mouron, Patrik; Keiser, Andreas; Siegrist, Michael

    2015-12-01

    This paper presents the results of a stepwise investigation of the quantity and quality of food losses along the Swiss potato supply chain. Quantitative data were collected from field trials, from structured interviews with wholesalers, processors and retailers, and from consumer surveys in combination with a 30-day diary study. The "Swiss trade customs for potatoes" pose the basis for the qualitative evaluation of losses. The influences of technological, institutional (business and economy; legislation and policy), and social drivers on the generation of fresh potato and processed potato products losses were assessed. Losses due to quality standards driven by food safety and consumer preferences for certain aesthetic standards have been evaluated too. Across the entire potato value chain, approximately 53-55% of the initial fresh potato production and 41-46% of the initial processing potato production are finally lost. Losses between organic and non-organic supply chains differ from 2% to 5%. From the total initial fresh potato production, 15-24% gets lost during agricultural production, a further 12-24% at wholesalers, 1-3% at retailers, and 15% at private households. In comparison, 5-11% of the initial production gets lost at wholesalers, a further 14-15% during processing, 0% at retailers, and 2% at private households. Losses during agricultural production do not vary much (13-25%) between fresh and processing potatoes. Approximately half of total potato losses occur because potatoes do not meet quality standards. 25-34% of these quality-driven losses are caused by food safety reasons, and the remainder are caused by consumer preferences or suitability for storage. In total, social drivers (e.g., consumer preferences, behavior, or socio-demographical factors) are responsible for two-thirds to three-fourths of all fresh potato losses and 40-45% of all processing potato losses. Technological drivers cause circa one-third of the total processing potato losses. The

  6. Effect and prognosis of peri-pancreatic stepwise minimally invasive treatment in patients with severe acute pancreatitis

    Directory of Open Access Journals (Sweden)

    XIONG Yong

    2016-03-01

    Full Text Available ObjectiveTo investigate the clinical effect and prognosis of peri-pancreatic stepwise minimally invasive treatment in patients with severe acute pancreatitis (SAP. MethodsThe clinical data of 110 patients with SAP who were treated in Panzhihua Central Hospital from January 2013 to December 2014 were analyzed retrospectively, and these patients were divided into two groups (55 patients in each group according to the treatment regimen. The patients in the control group were treated with laparotomy, and those in the study group received peri-pancreatic stepwise minimally invasive treatment. The postoperative short-term treatment outcome, Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ score, laboratory markers [serum amylase (AMS, white blood cell (WBC, and C-reactive protein (CRP], time to intestinal recovery, incidence of complications, and mortality were compared between the two groups. The t-test was applied for comparison of continuous data between the two groups, and the chi-square test was applied for comparison of categorical data between the two groups. ResultsCompared with the control group, the study group had significantly higher short-term marked response rate, response rate, and overall response rate(χ2=5.1665, 4.9865 and 5.6357, all P<0.05. There were significant differences in AMS, WBC, pulse oxygen saturation (SpO2, CRP, and APACHE Ⅱ score between the two groups at 1 week after surgery and at discharge (t=13.6585, 13.4698, 12.0566, 14.6856, and 13.8869 for 1 week after surgery, t=12.8946, 14.2683, 13.8963, 14.8989, and 13.0986 for discharge, all P<0.05; there was a significant difference in WBC count on day 1 after surgery between the two groups (χ2=12.6984, P<005; both groups showed significant improvements in AMS, WBC, SpO2, CRP, and APACHE Ⅱ score at 1 week after surgery and at discharge compared with the values on day 1 after surgery, and there were significant changes in these values within

  7. Insulin degludec once-daily in type 2 diabetes: simple or step-wise titration (BEGIN: once simple use).

    Science.gov (United States)

    Philis-Tsimikas, Athena; Brod, Meryl; Niemeyer, Marcus; Ocampo Francisco, Ann Marie; Rothman, Jeffrey

    2013-06-01

    Insulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins. This 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a "Simple" algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a "Step-wise" algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch® insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups. Glycosylated hemoglobin (HbA1c) decreased from baseline to week 26 in both groups (-1.09%, IDegSimple; -0.93%, IDegStep-wise). IDegSimple was non-inferior to IDegStep-wise in lowering HbA1c [estimated treatment difference (IDegSimple - IDegStep-wise): -0.16% points (-0.39; 0.07)95% CI]. Fasting plasma glucose was reduced (-3.27 mmol/L, IDegSimple; -2.68 mmol/L, IDegStep-wise) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDegSimple; 1.17, IDegStep-wise events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDegSimple; 0.10, IDegStep-wise events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDegSimple) and 0.50 U/kg (IDegStep-wise). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDegSimple; +1.1 kg, IDegStep-wise), and there were no clinically relevant differences in adverse event profiles. IDeg was effective and well tolerated using either the Simple or Step-wise titration

  8. Field Analysis of Stepwise Effective Thermal Conductivity along a Borehole Heat Exchanger under Artificial Conditions of Groundwater Flow

    Directory of Open Access Journals (Sweden)

    Yoshitaka Sakata

    2017-03-01

    Full Text Available Heat advection caused by groundwater flow can potentially improve the performance of a borehole heat exchanger. However, the required flow velocity is not achieved under most natural conditions. This study focuses on artificial groundwater flow generated by pumping and investigates the associated effect in a lowland area near the Toyohira River alluvial fan, Sapporo, Japan. Thermal response test results are compared under natural and artificial groundwater flow conditions. A pumping well is constructed one meter from the borehole. Temperature profiles are measured in the U-tube during testing, using a pair of optic fiber distributed temperature sensors. The effective thermal conductivity is calculated from the profiles obtained in each 10-m sub-layer; this thermal conductivity is termed the stepwise thermal conductivity. Additionally, the upward flow velocity in the pumping well is measured to estimate the mean groundwater flow velocity at the borehole. The results show that effective thermal conductivity increases at depths less than 50 m, where the pumping creates mean velocities greater than 0.1 m d−1 in each sub-layer (1.5 md−1 on average. Thus, a borehole length of 50 m is more reasonable at the test site for its efficiency in a ground source heat pump system coupled with the pumping well than that used.

  9. Self-assembly versus stepwise synthesis: heterometal-organic frameworks based on metalloligands with tunable luminescence properties.

    Science.gov (United States)

    Zhang, Shu-Ran; Du, Dong-Ying; Tan, Ke; Qin, Jun-Sheng; Dong, Hui-Qing; Li, Shun-Li; He, Wen-Wen; Lan, Ya-Qian; Shen, Ping; Su, Zhong-Min

    2013-08-19

    A new family of heterometal-organic frameworks has been prepared by two synthesis strategies, in which IFMC-26 and IFMC-27 are constructed by self-assembly and IFMC-28 is obtained by stepwise synthesis based on the metalloligand (IFMC=Institute of Functional Material Chemistry). IFMC-26 is a (3,6)-connected net and IFMC-27 is a (4,8)-connected 3D framework. The metalloligands {Ni(H4 L)}(NO3 )2 are connected by binuclear lanthanide clusters giving rise to a 2D sheet structure in IFMC-28. Notably, IFMC-26-Eux Tby and IFMC-28-Eux Tby have been obtained by changing the molar ratios of raw materials. Owing to the porosity of IFMC-26, Tb(3+) @IFMC-26-Eu and Eu(3+) @IFMC-26-Tb are obtained by postencapsulating Tb(III) and Eu(III) ions into the pores, respectively. Tunable luminescence in metal-organic frameworks is achieved by the two kinds of doping methods. In particular, the quantum yields of heterometal-organic frameworks are apparently enhanced by postencapsulation of Ln(III) ions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The World Health Organization STEPwise Approach to Noncommunicable Disease Risk-Factor Surveillance: Methods, Challenges, and Opportunities.

    Science.gov (United States)

    Riley, Leanne; Guthold, Regina; Cowan, Melanie; Savin, Stefan; Bhatti, Lubna; Armstrong, Timothy; Bonita, Ruth

    2016-01-01

    We sought to outline the framework and methods used by the World Health Organization (WHO) STEPwise approach to noncommunicable disease (NCD) surveillance (STEPS), describe the development and current status, and discuss strengths, limitations, and future directions of STEPS surveillance. STEPS is a WHO-developed, standardized but flexible framework for countries to monitor the main NCD risk factors through questionnaire assessment and physical and biochemical measurements. It is coordinated by national authorities of the implementing country. The STEPS surveys are generally household-based and interviewer-administered, with scientifically selected samples of around 5000 participants. To date, 122 countries across all 6 WHO regions have completed data collection for STEPS or STEPS-aligned surveys. STEPS data are being used to inform NCD policies and track risk-factor trends. Future priorities include strengthening these linkages from data to action on NCDs at the country level, and continuing to develop STEPS' capacities to enable a regular and continuous cycle of risk-factor surveillance worldwide.

  11. Mapping multiple linked quantitative trait loci in non-obese diabetic mice using a stepwise regression strategy.

    Science.gov (United States)

    Cordell, H J; Todd, J A; Lathrop, G M

    1998-02-01

    A simple regression strategy for mapping multiple linked quantitative trait loci (QTLs) in inbred populations is proposed and applied to data from a non-obese diabetic (NOD) mouse backcross. The method involves adding and deleting markers from a linear model in a stepwise manner, allowing the association with a particular marker to be examined once associations with other (in particular neighbouring) markers have been taken into account. This approach has the advantage of using programs available in standard statistical packages while still allowing adequate separation of possible multiple linked effects. For the mouse backcross, using these methods, at least two and possibly three diabetogenic loci are detected on each of chromosomes 1 and 3. Some evidence for epistasis is seen between the loci on chromosome 1, with a possible additional epistatic interaction between the loci on chromosome 3. Congenic strain analysis of the chromosome regions in NOD diabetes suggests that although the true type I error rate may be larger than that suggested by the nominal P values, our results nevertheless correspond well with those disease loci and interactions detected using a congenic approach, indicating that the regression method may be a powerful strategy for the detection and characterization of QTLs in inbred populations.

  12. Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion.

    Directory of Open Access Journals (Sweden)

    Olga Rechkoblit

    2006-01-01

    Full Text Available 7,8-dihydro-8-oxoguanine (oxoG, the predominant lesion formed following oxidative damage of DNA by reactive oxygen species, is processed differently by replicative and bypass polymerases. Our kinetic primer extension studies demonstrate that the bypass polymerase Dpo4 preferentially inserts C opposite oxoG, and also preferentially extends from the oxoG*C base pair, thus achieving error-free bypass of this lesion. We have determined the crystal structures of preinsertion binary, insertion ternary, and postinsertion binary complexes of oxoG-modified template-primer DNA and Dpo4. These structures provide insights into the translocation mechanics of the bypass polymerase during a complete cycle of nucleotide incorporation. Specifically, during noncovalent dCTP insertion opposite oxoG (or G, the little-finger domain-DNA phosphate contacts translocate by one nucleotide step, while the thumb domain-DNA phosphate contacts remain fixed. By contrast, during the nucleotidyl transfer reaction that covalently incorporates C opposite oxoG, the thumb-domain-phosphate contacts are translocated by one nucleotide step, while the little-finger contacts with phosphate groups remain fixed. These stepwise conformational transitions accompanying nucleoside triphosphate binding and covalent nucleobase incorporation during a full replication cycle of Dpo4-catalyzed bypass of the oxoG lesion are distinct from the translocation events in replicative polymerases.

  13. Stepwise Translocation of Dpo4 Polymerase during Error-Free Bypass of an oxoG Lesion.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available 7,8-dihydro-8-oxoguanine (oxoG, the predominant lesion formed following oxidative damage of DNA by reactive oxygen species, is processed differently by replicative and bypass polymerases. Our kinetic primer extension studies demonstrate that the bypass polymerase Dpo4 preferentially inserts C opposite oxoG, and also preferentially extends from the oxoG*C base pair, thus achieving error-free bypass of this lesion. We have determined the crystal structures of preinsertion binary, insertion ternary, and postinsertion binary complexes of oxoG-modified template-primer DNA and Dpo4. These structures provide insights into the translocation mechanics of the bypass polymerase during a complete cycle of nucleotide incorporation. Specifically, during noncovalent dCTP insertion opposite oxoG (or G, the little-finger domain-DNA phosphate contacts translocate by one nucleotide step, while the thumb domain-DNA phosphate contacts remain fixed. By contrast, during the nucleotidyl transfer reaction that covalently incorporates C opposite oxoG, the thumb-domain-phosphate contacts are translocated by one nucleotide step, while the little-finger contacts with phosphate groups remain fixed. These stepwise conformational transitions accompanying nucleoside triphosphate binding and covalent nucleobase incorporation during a full replication cycle of Dpo4-catalyzed bypass of the oxoG lesion are distinct from the translocation events in replicative polymerases.

  14. Stepwise inhibition of T cell recruitment at post-capillary venules by orally active desulfated heparins in inflammatory arthritis.

    Science.gov (United States)

    Al Faruque, Hasan; Kang, Jin Hee; Hwang, Seung Rim; Sung, Shijin; Alam, Md Mahmudul; Sa, Keum Hee; Nam, Eon Jeong; Byun, Young Ro; Kang, Young Mo

    2017-01-01

    Identification of the structure-function relationship of heparin, particularly between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory activities, is critical in order to evaluate the biological effects of heparin, especially in conjunction with modifications for oral formulation. In this study, we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic modifications have differential effects on the blocking of interactions between sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH to interfere with T cell adhesion via selectin-sLeX interactions. Furthermore, 6DSHbD coated on the apical surface of inflamed endothelium directly blocked the adhesive interactions of circulating T cells, which was confirmed in vivo by suppressing T cell adhesion at post-capillary venular endothelium. Thus, in series with our previous study demonstrating inhibition of transendothelial migration, oral delivery of low anticoagulant LMWH to venular endothelium of inflamed joint tissues ameliorated arthritis by the stepwise inhibition of T cell recruitment and provides a rationale for the development of modified oral heparins as innovative agents for the treatment of chronic inflammatory arthritis.

  15. Stepwise swelling of a thin film of lamellae-forming poly(styrene-b- butadiene) in cyclohexane vapor

    KAUST Repository

    Di, Zhenyu

    2012-06-26

    We investigated the swelling of a thin film of lamellae-forming poly(styrene-b-butadiene) in cyclohexane vapor. The vapor pressure and thus the degree of swelling of the film are increased in a stepwise manner using a custom-built sample cell. The resulting structural changes during and after each step were followed in situ using time-resolved grazing-incidence small-angle X-ray scattering (GISAXS). During the first step, the lamellar thickness increases strongly, before it decreases again. At the same time, the full width at half-maximum (FWHM) of the diffuse Bragg reflection along the film normal has a sharp maximum. These observations point to the formation of new lamellae. During the subsequent swelling steps, the lamellar thickness overshoots only weakly. The behavior thus resembles qualitatively our previous results on a similar thin film during swelling in saturated vapor of cyclohexane; however, it deviates from earlier theoretical predictions. We propose a theory that is quantitatively correct for the description of the dependence of the lamellar thickness on the polymer volume fraction in the late stage of the swelling steps. © 2012 American Chemical Society.

  16. Relationships between each part of the spinal curves and upright posture using Multiple stepwise linear regression analysis.

    Science.gov (United States)

    Boulet, Sebastien; Boudot, Elsa; Houel, Nicolas

    2016-05-03

    Back pain is a common reason for consultation in primary healthcare clinical practice, and has effects on daily activities and posture. Relationships between the whole spine and upright posture, however, remain unknown. The aim of this study was to identify the relationship between each spinal curve and centre of pressure position as well as velocity for healthy subjects. Twenty-one male subjects performed quiet stance in natural position. Each upright posture was then recorded using an optoelectronics system (Vicon Nexus) synchronized with two force plates. At each moment, polynomial interpolations of markers attached on the spine segment were used to compute cervical lordosis, thoracic kyphosis and lumbar lordosis angle curves. Mean of centre of pressure position and velocity was then computed. Multiple stepwise linear regression analysis showed that the position and velocity of centre of pressure associated with each part of the spinal curves were defined as best predictors of the lumbar lordosis angle (R(2)=0.45; p=1.65*10-10) and the thoracic kyphosis angle (R(2)=0.54; p=4.89*10-13) of healthy subjects in quiet stance. This study showed the relationships between each of cervical, thoracic, lumbar curvatures, and centre of pressure's fluctuation during free quiet standing using non-invasive full spinal curve exploration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A Collaborative Step-Wise Process to Implementing an Innovative Clinic for Adult Survivors of Childhood Cancer.

    Science.gov (United States)

    McClellan, Wendy; Fulbright, Joy M; Doolittle, Gary C; Alsman, Kyla; Klemp, Jennifer R; Ryan, Robin; Nelson, Eve-Lynn; Stegenga, Kristin; Krebill, Hope; Al-hihi, Eyad M; Schuetz, Nik; Heiman, Ashley; Lowry, Becky

    2015-01-01

    With a 5 year survival rate of approximately 80%, there is an increasing number of childhood cancer survivors in the United States. Childhood cancer survivors are at an increased risk for physical and psychosocial health problems many years after treatment. Long-term follow-up care should include education, development of individualized follow up plans and screening for health problems in accordance with the Children's Oncology Group survivor guidelines. Due to survivor, provider and healthcare system related barriers, adult survivors of childhood cancer (ASCC) infrequently are receiving care in accordance to these guidelines. In this paper we describe the stepwise process and collaboration between a children's hospital and an adult academic medical center that was implemented to develop the Survivorship Transition Clinic and address the needs of ASCC in our region. In the clinic model that we designed ASCC follow-up with a primary care physician in the adult setting who is knowledgeable about late effects of childhood cancer treatment and are provided transition support and education by a transition nurse navigator. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The Stepwise Behavioral Responses: Behavioral Adjustment of the Chinese Rare Minnow (Gobiocypris rarus in the Exposure of Carbamate Pesticides

    Directory of Open Access Journals (Sweden)

    Zongming Ren

    2013-01-01

    Full Text Available In order to illustrate the behavioral regulation in environmental stress, the behavioral responses of the Chinese rare minnow (Gobiocypris rarus to arprocarb, carbofuran, and oxamyl were analyzed with an online monitoring system. The Self-Organizing Map (SOM was used to define the patterns of the behavioral data obtained from treatments at concentrations of 0.1 toxic unit (TU, 1 TU, 2 TU, 5 TU, 10 TU, and 20 TU and a control. In certain cases, differences among the carbamate pesticides (CPs tested were observed. The profiles of behavioral strength (BS in SOM varied according to the concentration used. The time of the first significant decrease of the BS varied inversely with the CP concentrations. The results suggested that the behavioral regulation in the stepwise behavioral responses (SBR was evident. The primary movement behaviors shown by the SBR model included no effect, stimulation, acclimation, adjustment (readjustment, and toxic effect, especially at the lower concentrations. However, higher stress (10 TU and 20 TU might limit the function of the behavioral adjustment produced by the intrinsic response mechanisms. It was concluded that SBR, which were affected by both the concentration and the exposure time, could be used as a suitable indicator in the ecotoxicological risk assessment of CPs.

  19. Retroviral oligonucleotide distributions correlate with biased nucleotide compositions of retrovirus sequences, suggesting a duplicative stepwise molecular evolution.

    Science.gov (United States)

    Laprevotte, I; Brouillet, S; Terzian, C; Hénaut, A

    1997-02-01

    A computer-assisted analysis was made of 24 complete nucleotide sequences selected from the vertebrate retroviruses to represent the ten viral groups. The conclusions of this analysis extend and strengthen the previously made hypothesis on the Moloney murine leukemia virus: The evolution of the nucleotide sequence appears to have occurred mainly through at least three overlapping levels of duplication: (1) The distributions of overrepresented (3-6)-mers are consistent with the universal rule of a trend toward TG/CT excess and with the persistence of a certain degree of symmetry between the two strands of DNA. This suggests one or several original tandemly repeated sequences and some inverted duplications. (2) The existence of two general core consensuses at the level of these (3-6)-mers supports the hypothesis of a common evolutionary origin of vertebrate retroviruses. Consensuses more specific to certain sequences are compatible with phylogenetic trees established independently. The consensuses could correspond to intermediary evolutionary stages. (3) Most of the (3-6)-mers with a significantly higher than average frequency appear to be internally repeated (with monomeric or oligomeric internal iterations) and seem to be at least partly the cause of the bias observed by other researchers at the level of retroviral nucleotide composition. They suggest a third evolutionary stage by slippage-like stepwise local duplications.

  20. Stepwise intervention including 1-on-1 counseling is highly effective in increasing influenza vaccination among health care workers.

    Science.gov (United States)

    Jung, Younghee; Kwon, Mihye; Song, Jeongmi

    2017-06-01

    The influenza vaccination rate among health care workers (HCWs) remains suboptimal. We attempted to increase vaccine uptake in HCWs by nonmandatory measures, including 1-on-1 counseling. In 2015 we used a stepwise approach including (1) text messaging on the last day of the vaccination period, (2) extending the vaccination period by 3 days, (3) education for the low uptake group, and (4) 1-on-1 counseling for unvaccinated HCWs after the 3 interventions. There were 1,433 HCWs included. By the end of the initial 3 days, the uptake rate was 80.0% (1,146/1,433). During an extension for a further 3 days, 33 additional HCWs received the vaccine. One month after starting the vaccination, 90.1% (1,291/1,433) of the HCWs were vaccinated, but this included only 76.1% (210/276) of the doctors (lowest among HCWs). After 3 educational presentations targeted at the unvaccinated doctors, no additional individuals were vaccinated in the following 2 weeks. After 1-on-1 counseling for unvaccinated HCWs, the overall vaccination rate increased to 94.7% (1,357/1,433) in 2015, higher than in the previous year (82.5%, P vaccinated, therefore achieving 92.4% (255/276) compliance, higher than the 56.5% in the previous year (152/269, P vaccination rates among HCWs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Continuous enhancement of iturin A production by Bacillus subtilis with a stepwise two-stage glucose feeding strategy.

    Science.gov (United States)

    Jin, Hu; Li, Kunpeng; Niu, Yanxing; Guo, Mian; Hu, Chuanjiong; Chen, Shouwen; Huang, Fenghong

    2015-06-09

    The lipopeptide antibiotic iturin A is an attractive biopesticide with the potential to replace chemical-based pesticides for controlling plant pathogens. However, its industrial fermentation has not been realized due to the high production costs and low product concentrations. This study aims to enhance iturin A production by performing a novel fermentation process with effective glucose feeding control using rapeseed meal as a low-cost nitrogen source. We demonstrated that continuous and significant enhancement of iturin A production could be achieved by a novel two-stage glucose-feeding strategy with a stepwise decrease in feeding rate. Using this strategy, the ratio of spores to total cells could be maintained at a desirable/stable level of 0.80-0.86, and the reducing sugar concentration could be controlled at a low level of 2-3 g/L so that optimal substrate balance could be maintained throughout the feeding phase. As a result, the maximum iturin A concentration reached 1.12 g/L, which was two-fold higher than that of batch culture. This is the first report which uses control of the glucose supply to improve iturin A production by fed-batch fermentation and identifies some important factors necessary to realize industrial iturin A production. This approach may also enhance the production of other useful secondary metabolites by Bacillus subtilis.

  2. [Prediction of psychosis by stepwise multilevel assessment--the Basel FePsy (Early Recognition of Psychosis)-Project].

    Science.gov (United States)

    Riecher-Rössler, A; Aston, J; Borgwardt, S; Bugra, H; Fuhr, P; Gschwandtner, U; Koutsouleris, N; Pflueger, M; Tamagni, C; Radü, E-W; Rapp, C; Smieskova, R; Studerus, E; Walter, A; Zimmermann, R

    2013-05-01

    We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Früherkennung von Psychosen, FePsy). From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc. Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6%) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81% by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction. The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre. © Georg Thieme Verlag KG Stuttgart · New York.

  3. A stepwise model of reaction-diffusion and positional information governs self-organized human peri-gastrulation-like patterning.

    Science.gov (United States)

    Tewary, Mukul; Ostblom, Joel; Prochazka, Laura; Zulueta-Coarasa, Teresa; Shakiba, Nika; Fernandez-Gonzalez, Rodrigo; Zandstra, Peter W

    2017-12-01

    How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a reaction-diffusion (RD)-based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle. Consequent fate acquisition occurred as a function of both pSMAD1 signaling strength and duration of induction, consistent with the positional-information (PI) paradigm. We propose that the self-organized peri-gastrulation-like fate patterning in BMP4-treated geometrically confined hPSC colonies arises via a stepwise model of RD followed by PI. This two-step model predicted experimental responses to perturbations of key parameters such as colony size and BMP4 dose. Furthermore, it also predicted experimental conditions that resulted in RD-like periodic patterning in large hPSC colonies, and rescued peri-gastrulation-like patterning in colony sizes previously thought to be reticent to this behavior. © 2017. Published by The Company of Biologists Ltd.

  4. Stepwise Synthesis of Mesoporous Carbon Nitride Functionalized by Melamine Based Dendrimer Amines for Adsorption of CO2 and CH4

    Directory of Open Access Journals (Sweden)

    Mansoor Anbia

    2016-12-01

    Full Text Available In this study, a novel solid dendrimer amine (hyperbranched polymers was prepared using mesoporous carbon nitride functionalized by melamine based dendrimer amines. This adsorbent was denoted MDA-MCN-1. The process was stepwise synthesis and hard-templating method using mesoporous silica SBA-15 as a template. Cyanuric chloride and N,N-diisopropylethylamine (DIPEA, Merck were used for functionalization of the MCN-1. Fourier transform infrared spectroscopy (FT-IR, Nitrogen adsorption-desorption analysis, Small Angle X-ray Scattering (SAXS, X-ray diffraction (XRD and thermogravimetric analysis (TGA were used for characterization of the adsorbent. This material was used for carbon dioxide gas (CO2 and methane gas (CH4 adsorption at high pressure (up to 20 bar and room temperature. The volumetric method was used for the tests of the gas adsorption. The CO2 adsorption capacity of modified mesoporous carbon nitrides was about 4 mmol CO2 per g adsorbent. The methane adsorption capacity of this material was less than that CO2. Modified Mesoporous Carbon Nitride adsorbed about 3.52 mmol CH4 /g adsorbent. The increment of melamine based dendrimer generation on mesoporous surface increased adsorption capacity of both carbon dioxide and methane gases. According to the results obtained, the solid dendrimer amines, (MDA-MCN-1, performs excellently for CO2 and CH4 capture from flow gases and CO2 and CH4 storage.

  5. Predicting the Enzymatic Hydrolysis Half-lives of New Chemicals Using Support Vector Regression Models Based on Stepwise Feature Elimination.

    Science.gov (United States)

    Shen, Wanxiang; Xiao, Tao; Chen, Shangying; Liu, Feng; Chen, Yu Zong; Jiang, Yuyang

    2017-11-01

    The enzymatic hydrolysis of chemicals, which is important for in vitro drug metabolism assays, is an important indicator of drug stability profiles during drug discovery and development. Herein, we employed a stepwise feature elimination (SFE) method with nonlinear support vector machine regression (SVR) models to predict the in vitro half-lives in human plasma/blood of various esters. The SVR model was developed using public databases and literature-reported data on the half-lives of esters in human plasma/blood. In particular, the SFE method was developed to prevent over fitting and under fitting in the nonlinear model, and it provided a novel and efficient method of realizing feature combinations and selections to enhance the prediction accuracy. Our final developed model with 24 features effectively predicted an external validation set using the time-split method and presented reasonably good R2 values (0.6) and also predicted two completely independent validation datasets with R2 values of 0.62 and 0.54; thus, this model performed much better than other prediction models. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Treatment of posttraumatic stress disorder at the end-of-life: application of the Stepwise Psychosocial Palliative Care model.

    Science.gov (United States)

    Feldman, David B; Sorocco, Kristen H; Bratkovich, Kristi L

    2014-06-01

    Feldman (2011) has proposed a new approach to the treatment of posttraumatic stress disorder (PTSD) in individuals at the end-of-life known as Stepwise Psychosocial Palliative Care (SPPC). This approach helps to compensate for the disadvantages of existing PTSD interventions with regard to treating patients with life-limiting and terminal illnesses by employing a palliative care philosophy. The model relies on cognitive and behavioral techniques drawn from evidence-based approaches to PTSD, deploying them in a stage-wise manner designed to allow for interventions to track with patents' needs and prognoses. Because this model is relatively new, we seek to explore issues related to its implementation in the complex settings in which providers encounter patients at the end-of-life. We also seek to provide concrete guidance to providers regarding the management of PTSD at the end-of-life in diverse palliative care settings. We examine three specific cases in which the SPPC model was utilized, highlighting particular treatment challenges and strategies. These case studies provide information regarding the SPPC model's application to patients in two distinct palliative care settings-a palliative care consult team and an inpatient palliative care unit. The SPPC model's stage-wise approach allows for its flexible use given a variety of constraints related to setting and patient issues. The SPPC model provides an alternative to existing psychosocial treatments for PTSD that may be more appropriate for patients at the end of life.

  7. Discrimination of Chinese teas with different fermentation degrees by stepwise linear discriminant analysis (S-LDA) of the chemical compounds.

    Science.gov (United States)

    Wu, Quan-Jin; Dong, Qing-Hua; Sun, Wei-Jiang; Huang, Yan; Wang, Qiong-Qiong; Zhou, Wei-Long

    2014-09-24

    This study aimed to construct objective and accurate analytical models of tea categories based on their polyphenols and caffeine. A total of 522 tea samples of 4 commonly consumed teas with different fermentation degrees (green tea, white tea, oolong tea, and black tea) were analyzed by high-performance liquid chromatography (HPLC) coupled with spectrophotometry, utilizing ISO 14502, as analytical tools. The content of polyphenols and caffeine varied significantly according to differently fermented teas, indicating that these active constituents may discriminate fermentation degrees effectively. By principal component analysis (PCA) and stepwise linear discriminant analysis (S-LDA), the vast majority of tea samples could be successfully differentiated according to their chemical markers. This study yielded three discriminant functions with the capacity to simultaneously discriminate the four tea categories with a 97.8% correct rate. In classification of oolong and other teas, there were one discriminant function and two equations with best discriminant capacity. Furthermore, the classification of different degrees of fermentation of oolong and external validation achieved the desired results. It is suggested that polyphenols and caffeine are the distinct variables to establish internationally recognized models of teas.

  8. Towards a short questionnaire for stepwise assessment of upper limb function, pain and stiffness in Duchenne muscular dystrophy.

    Science.gov (United States)

    Janssen, Mariska M H P; Geurts, Alexander C H; de Groot, Imelda J M

    2018-04-01

    Duchenne muscular dystrophy can lead to upper extremity limitations, pain and stiffness. In a previous study, these domains have been investigated using extensive questionnaires, which are too time-consuming for clinical practice. This study aimed at gaining insight into the underlying dimensions of these questionnaires, and to construct a short questionnaire that can be used for clinical assessment. Exploratory factor analysis was performed on the responses of 213 participants to a web-based survey to find the underlying dimensions in the Capabilities of Upper Extremity questionnaire, the ABILHAND questionnaire, and questionnaires regarding pain and stiffness. Based on these underlying dimensions, a stepwise approach was formulated. In addition, construct validity of the factors was investigated. In total, 14 factors were identified. All had high internal consistency (Cronbach's alpha >0.89) and explained 80-88% of the variance of the original questionnaires. Construct validity was supported, because participants in the early ambulatory stage performed significantly better (pDuchenne muscular dystrophy. Based on the factor commonalities, the Upper Limb Short Questionnaire was formulated. Implications for Rehabilitation New insights into the underlying dimensions of upper extremity function, pain and stiffness in Duchenne muscular dystrophy are gained. Fourteen factors, with good internal consistency and construct validity, are identified regarding upper extremity function, pain and stiffness in Duchenne muscular dystrophy. Based on these factors, the Upper Limb Short Questionnaire is presented. The Upper Limb Short Questionnaire can be used as an identifier of arm-hand limitations and the start of more thorough clinical investigation.

  9. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2009-04-20

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.

  10. A systematic search for SNPs/haplotypes associated with disease phenotypes using a haplotype-based stepwise procedure.

    Science.gov (United States)

    Yang, Yin; Li, Shuying Sue; Chien, Jason W; Andriesen, Jessica; Zhao, Lue Ping

    2008-12-22

    Genotyping technologies enable us to genotype multiple Single Nucleotide Polymorphisms (SNPs) within selected genes/regions, providing data for haplotype association analysis. While haplotype-based association analysis is powerful for detecting untyped causal alleles in linkage-disequilibrium (LD) with neighboring SNPs/haplotypes, the inclusion of extraneous SNPs could reduce its power by increasing the number of haplotypes with each additional SNP. Here, we propose a haplotype-based stepwise procedure (HBSP) to eliminate extraneous SNPs. To evaluate its properties, we applied HBSP to both simulated and real data, generated from a study of genetic associations of the bactericidal/permeability-increasing (BPI) gene with pulmonary function in a cohort of patients following bone marrow transplantation. Under the null hypothesis, use of the HBSP gave results that retained the desired false positive error rates when multiple comparisons were considered. Under various alternative hypotheses, HBSP had adequate power to detect modest genetic associations in case-control studies with 500, 1,000 or 2,000 subjects. In the current application, HBSP led to the identification of two specific SNPs with a positive validation. These results demonstrate that HBSP retains the essence of haplotype-based association analysis while improving analytic power by excluding extraneous SNPs. Minimizing the number of SNPs also enables simpler interpretation and more cost-effective applications.

  11. High-quality fuel from food waste - investigation of a stepwise process from the perspective of technology development.

    Science.gov (United States)

    Yin, Ke; Li, Ling; Giannis, Apostolos; Weerachanchai, Piyarat; Ng, Bernard J H; Wang, Jing-Yuan

    2017-07-01

    A stepwise process (SP) was developed for sustainable energy production from food waste (FW). The process comprised of hydrothermal treatment followed by oil upgrading. Synthetic food waste was primarily used as feedstock in the hydrothermal reactor under subcritical water conditions. The produced hydrochars were analyzed for calorific value (17.0-33.7 MJ/kg) and elemental composition indicating high-quality fuel comparable to coal. Hydrothermal carbonization (e.g. 180°C) would be efficient for oil recovery (>90%) from FW, as compared to hydrothermal liquefaction (320°C) whereby lipid degradation may take place. The recovered oil was upgraded to biodiesel in a catalytic refinery process. Selected biodiesels, that is, B3 and B4 were characterized for density (872.7 and 895.5 kg/m3), kinematic viscosity (3.115 and 8.243 cSt), flash and pour point (30°C and >126°C), micro carbon (0.03% and 0.04%), sulfur (both biofuel and hydrochar production.

  12. Mobile Phone Apps to Improve Medication Adherence: A Systematic Stepwise Process to Identify High-Quality Apps.

    Science.gov (United States)

    Santo, Karla; Richtering, Sarah S; Chalmers, John; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

    2016-12-02

    There are a growing number of mobile phone apps available to support people in taking their medications and to improve medication adherence. However, little is known about how these apps differ in terms of features, quality, and effectiveness. We aimed to systematically review the medication reminder apps available in the Australian iTunes store and Google Play to assess their features and their quality in order to identify high-quality apps. This review was conducted in a similar manner to a systematic review by using a stepwise approach that included (1) a search strategy; (2) eligibility assessment; (3) app selection process through an initial screening of all retrieved apps and full app review of the included apps; (4) data extraction using a predefined set of features considered important or desirable in medication reminder apps; (5) analysis by classifying the apps as basic and advanced medication reminder apps and scoring and ranking them; and (6) a quality assessment by using the Mobile App Rating Scale (MARS), a reliable tool to assess mobile health apps. We identified 272 medication reminder apps, of which 152 were found only in Google Play, 87 only in iTunes, and 33 in both app stores. Apps found in Google Play had more customer reviews, higher star ratings, and lower cost compared with apps in iTunes. Only 109 apps were available for free and 124 were recently updated in 2015 or 2016. Overall, the median number of features per app was 3.0 (interquartile range 4.0) and only 18 apps had ≥9 of the 17 desirable features. The most common features were flexible scheduling that was present in 56.3% (153/272) of the included apps, medication tracking history in 54.8% (149/272), snooze option in 34.9% (95/272), and visual aids in 32.4% (88/272). We classified 54.8% (149/272) of the included apps as advanced medication reminder apps and 45.2% (123/272) as basic medication reminder apps. The advanced apps had a higher number of features per app compared with the

  13. Mobile Phone Apps to Improve Medication Adherence: A Systematic Stepwise Process to Identify High-Quality Apps

    Science.gov (United States)

    Richtering, Sarah S; Chalmers, John; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

    2016-01-01

    Background There are a growing number of mobile phone apps available to support people in taking their medications and to improve medication adherence. However, little is known about how these apps differ in terms of features, quality, and effectiveness. Objective We aimed to systematically review the medication reminder apps available in the Australian iTunes store and Google Play to assess their features and their quality in order to identify high-quality apps. Methods This review was conducted in a similar manner to a systematic review by using a stepwise approach that included (1) a search strategy; (2) eligibility assessment; (3) app selection process through an initial screening of all retrieved apps and full app review of the included apps; (4) data extraction using a predefined set of features considered important or desirable in medication reminder apps; (5) analysis by classifying the apps as basic and advanced medication reminder apps and scoring and ranking them; and (6) a quality assessment by using the Mobile App Rating Scale (MARS), a reliable tool to assess mobile health apps. Results We identified 272 medication reminder apps, of which 152 were found only in Google Play, 87 only in iTunes, and 33 in both app stores. Apps found in Google Play had more customer reviews, higher star ratings, and lower cost compared with apps in iTunes. Only 109 apps were available for free and 124 were recently updated in 2015 or 2016. Overall, the median number of features per app was 3.0 (interquartile range 4.0) and only 18 apps had ≥9 of the 17 desirable features. The most common features were flexible scheduling that was present in 56.3% (153/272) of the included apps, medication tracking history in 54.8% (149/272), snooze option in 34.9% (95/272), and visual aids in 32.4% (88/272). We classified 54.8% (149/272) of the included apps as advanced medication reminder apps and 45.2% (123/272) as basic medication reminder apps. The advanced apps had a higher number

  14. Spectroscopic determination of leaf biochemistry using band-depth analysis of absorption features and stepwise multiple linear regression

    Science.gov (United States)

    Kokaly, R.F.; Clark, R.N.

    1999-01-01

    We develop a new method for estimating the biochemistry of plant material using spectroscopy. Normalized band depths calculated from the continuum-removed reflectance spectra of dried and ground leaves were used to estimate their concentrations of nitrogen, lignin, and cellulose. Stepwise multiple linear regression was used to select wavelengths in the broad absorption features centered at 1.73 ??m, 2.10 ??m, and 2.30 ??m that were highly correlated with the chemistry of samples from eastern U.S. forests. Band depths of absorption features at these wavelengths were found to also be highly correlated with the chemistry of four other sites. A subset of data from the eastern U.S. forest sites was used to derive linear equations that were applied to the remaining data to successfully estimate their nitrogen, lignin, and cellulose concentrations. Correlations were highest for nitrogen (R2 from 0.75 to 0.94). The consistent results indicate the possibility of establishing a single equation capable of estimating the chemical concentrations in a wide variety of species from the reflectance spectra of dried leaves. The extension of this method to remote sensing was investigated. The effects of leaf water content, sensor signal-to-noise and bandpass, atmospheric effects, and background soil exposure were examined. Leaf water was found to be the greatest challenge to extending this empirical method to the analysis of fresh whole leaves and complete vegetation canopies. The influence of leaf water on reflectance spectra must be removed to within 10%. Other effects were reduced by continuum removal and normalization of band depths. If the effects of leaf water can be compensated for, it might be possible to extend this method to remote sensing data acquired by imaging spectrometers to give estimates of nitrogen, lignin, and cellulose concentrations over large areas for use in ecosystem studies.We develop a new method for estimating the biochemistry of plant material using

  15. Clinical Trials

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    Full Text Available ... trial's potential risks are greater than minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older ... trial's potential risks are greater than minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older ...

  16. Clinical Trials

    Medline Plus

    Full Text Available ... The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in postmenopausal women. (When the trial began, HT was already in common ...

  17. Clinical Trials

    Medline Plus

    Full Text Available ... for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health ... trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A DSMB's ...

  18. Comparison of different stepwise screening strategies for type 2 diabetes: Finding from Danish general practice, Addition-DK.

    Science.gov (United States)

    Dalsgaard, Else-Marie; Christensen, Jesper O; Skriver, Mette Vinter; Borch-Johnsen, Knut; Lauritzen, Torsten; Sandbaek, Annelli

    2010-12-01

    To examine attendance, number of people with T2DM and costs of three different stepwise screening strategies for T2DM in general practice (GP). Diabetes risk questionnaires were mailed to individuals aged 40-69 years from 45 general practices in 2001-2002 and individuals at high risk for T2DM, were asked to contact their GP to arrange a screening test. In 2005-2006, 26 general practices were randomised into two different opportunistic screening programmes (OP-direct and OP-subsequent) and risk questionnaires were distributed to individuals aged 40-69 years during GP consultations. In the OP-direct approach, high-risk individuals were offered to start the screening during the actual consultation while high-risk individuals in the OP-subsequent approach, were invited to a screening test at a later date. We report attendance, number of people with T2DM and costs of each screening approach. The mail-distributed approach identified 0.8% of the target population with T2DM, the OP-direct approach and the OP-subsequent approach, 0.9% and 0.5% respectively. Cost per person with T2DM was in the mail-distributed approach: € 1058, OP-direct approach: € 707 and the OP-subsequent approach: € 727. This study indicates that opportunistic screening identifies the same level of unknown diabetes as a mail-distributed approach but with lower costs. Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  19. Stepwise colonization of the Andes by ruddy ducks and the evolution of novel β-globin variants.

    Science.gov (United States)

    Muñoz-Fuentes, V; Cortázar-Chinarro, M; Lozano-Jaramillo, M; McCracken, K G

    2013-03-01

    Andean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high-altitude environments remain little understood. Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff-tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes. We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (α(A), α(D), β(A)) and used isolation-with-migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes. Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes. While no nonsynonymous substitutions were found in either α globin gene, three amino acid substitutions were observed in the β(A) globin. Based on phylogenetic reconstruction and power analysis, the first β(A) substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes. This stepwise colonization pattern accompanied by polarized β(A) globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands. In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America. © 2013 Blackwell Publishing Ltd.

  20. The 'Densitometric Image Analysis Software' and its application to determine stepwise equilibrium constants from electrophoretic mobility shift assays.

    Directory of Open Access Journals (Sweden)

    Liesbeth van Oeffelen

    Full Text Available Current software applications for densitometric analysis, such as ImageJ, QuantityOne (BioRad and the Intelligent or Advanced Quantifier (Bio Image do not allow to take the non-linearity of autoradiographic films into account during calibration. As a consequence, quantification of autoradiographs is often regarded as problematic, and phosphorimaging is the preferred alternative. However, the non-linear behaviour of autoradiographs can be described mathematically, so it can be accounted for. Therefore, the 'Densitometric Image Analysis Software' has been developed, which allows to quantify electrophoretic bands in autoradiographs, as well as in gels and phosphorimages, while providing optimized band selection support to the user. Moreover, the program can determine protein-DNA binding constants from Electrophoretic Mobility Shift Assays (EMSAs. For this purpose, the software calculates a chosen stepwise equilibrium constant for each migration lane within the EMSA, and estimates the errors due to non-uniformity of the background noise, smear caused by complex dissociation or denaturation of double-stranded DNA, and technical errors such as pipetting inaccuracies. Thereby, the program helps the user to optimize experimental parameters and to choose the best lanes for estimating an average equilibrium constant. This process can reduce the inaccuracy of equilibrium constants from the usual factor of 2 to about 20%, which is particularly useful when determining position weight matrices and cooperative binding constants to predict genomic binding sites. The MATLAB source code, platform-dependent software and installation instructions are available via the website http://micr.vub.ac.be.

  1. Step-wise DNA methylation changes are linked to escape from defined proliferation barriers and mammary epithelial cell immortalization

    Science.gov (United States)

    Novak, P; Jensen, TJ; Garbe, JC; Stampfer, MR; Futscher, BW

    2009-01-01

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16 INK4A expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending upon how stasis was overcome. A second step coincides with immortalization, and results in hundreds of additional DNA methylation changes, regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that may prove useful in breast cancer risk assessment. PMID:19509227

  2. Lack of correlation between cerebral vasomotor reactivity and dynamic cerebral autoregulation during stepwise increases in inspired CO2 concentration.

    Science.gov (United States)

    Jeong, Sung-Moon; Kim, Seon-Ok; DeLorey, Darren S; Babb, Tony G; Levine, Benjamin D; Zhang, Rong

    2016-06-15

    Cerebral vasomotor reactivity (CVMR) and dynamic cerebral autoregulation (CA) are measured extensively in clinical and research studies. However, the relationship between these measurements of cerebrovascular function is not well understood. In this study, we measured changes in cerebral blood flow velocity (CBFV) and arterial blood pressure (BP) in response to stepwise increases in inspired CO2 concentrations of 3 and 6% to assess CVMR and dynamic CA in 13 healthy young adults [2 women, 32 ± 9 (SD) yr]. CVMR was assessed as percentage changes in CBFV (CVMRCBFV) or cerebrovascular conductance index (CVCi, CVMRCVCi) in response to hypercapnia. Dynamic CA was estimated by performing transfer function analysis between spontaneous oscillations in BP and CBFV. Steady-state CBFV and CVCi both increased exponentially during hypercapnia; CVMRCBFV and CVMRCVCi were greater at 6% (3.85 ± 0.90 and 2.45 ± 0.79%/mmHg) than at 3% CO2 (2.09 ± 1.47 and 0.21 ± 1.56%/mmHg, P = 0.009 and 0.005, respectively). Furthermore, CVMRCBFV was greater than CVMRCVCi during either 3 or 6% CO2 (P = 0.017 and P < 0.001, respectively). Transfer function gain and coherence increased in the very low frequency range (0.02-0.07 Hz), and phase decreased in the low-frequency range (0.07-0.20 Hz) when breathing 6%, but not 3% CO2 There were no correlations between the measurements of CVMR and dynamic CA. These findings demonstrated influences of inspired CO2 concentrations on assessment of CVMR and dynamic CA. The lack of correlation between CVMR and dynamic CA suggests that cerebrovascular responses to changes in arterial CO2 and BP are mediated by distinct regulatory mechanisms. Copyright © 2016 the American Physiological Society.

  3. Stepwise discriminant function analysis for rapid identification of acute promyelocytic leukemia from acute myeloid leukemia with multiparameter flow cytometry.

    Science.gov (United States)

    Chen, Zhanguo; Li, Yan; Tong, Yongqing; Gao, Qingping; Mao, Xiaolu; Zhang, Wenjing; Xia, Zunen; Fu, Chaohong

    2016-03-01

    Diagnosis of acute promyelocytic leukemia (APL) has been accelerated by multiparameter flow cytometry (MFC). However, diagnostic interpretation of MFC readouts for APL depends on individual experience and knowledge, which inevitably increases the risk of arbitrariness. We appraised the feasibility of using stepwise discriminant function analysis (SDFA) based on MFC to optimize the minimal variables needed to distinguish APL from other acute myeloid leukemia (AML) without complicated data interpretation. Samples from 327 patients with APL (n = 51) and non-APL AML (n = 276) were randomly allocated into training (243 AML) and test sets (84 AML) for SDFA. The discriminant functions from SDFA were examined by correct classification, and the final variables were validated by differential expression. Finally, additional 20 samples from patients with atypical APL and AML confusable with APL were also identified by SDFA method and morphological analysis. The weighed discriminant function reveals seven differentially expressed variables (CD2/CD9/CD11b/CD13/CD34/HLA-DR/CD117), which predict a molecular result for APL characterization with an accuracy that approaches 99% (99.6 and 98.8% for AML samples in training and test sets, respectively). Furthermore, the SDFA outperformed either single variable analysis or the more limited 3-component analysis (CD34/CD117/HLA-DR) via separate SDFA, and was also superior to morphological analysis in terms of diagnostic efficacy. The established SDFA based on MFC with seven variables can precisely and rapidly differentiate APL and non-APL AML, which may contribute to the urgent initiation of all-trans-retinoic acid-based APL therapy.

  4. Implementation of the World Health Organization Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation

    Directory of Open Access Journals (Sweden)

    Jean-Bosco Ndihokubwayo

    2016-02-01

    Full Text Available Background: The increase in disease burden has continued to weigh upon health systems in Africa. The role of the laboratory has become increasingly critical in the improvement of health for diagnosis, management and treatment of diseases. In response, the World Health Organization Regional Office for Africa (WHO AFRO and its partners created the WHO AFRO Stepwise Laboratory (Quality Improvement Process Towards Accreditation (SLIPTA program.SLIPTA implementation process: WHO AFRO defined a governance structure with roles and responsibilities for six main stakeholders. Laboratories were evaluated by auditors trained and certified by the African Society for Laboratory Medicine. Laboratory performance was measured using the WHO AFRO SLIPTA scoring checklist and recognition certificates rated with 1–5 stars were issued.Preliminary results: By March 2015, 27 of the 47 (57% WHO AFRO member states had appointed a SLIPTA focal point and 14 Ministers of Health had endorsed SLIPTA as the desired programme for continuous quality improvement. Ninety-eight auditors from 17 African countries, competent in the Portuguese (3, French (12 and English (83 languages, were trained and certified. The mean score for the 159 laboratories audited between May 2013 and March 2015 was 69% (median 70%; SD 11.5; interquartile range 62–77. Of these audited laboratories, 70% achieved 55% compliance or higher (2 or more stars and 1% scored at least 95% (5 stars. The lowest scoring sections of the WHO AFRO SLIPTA checklist were sections 6 (Internal Audit and 10 (Corrective Action, which both had mean scores below 50%.Conclusion: The WHO AFRO SLIPTA is a process that countries with limited resources can adopt for effective implementation of quality management systems. Political commitment, ownership and investment in continuous quality improvement are integral components of the process.

  5. Implementation of the World Health Organization Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation

    Science.gov (United States)

    Maruta, Talkmore; Ndlovu, Nqobile; Moyo, Sikhulile; Yahaya, Ali Ahmed; Coulibaly, Sheick Oumar; Kasolo, Francis; Turgeon, David; Abrol, Angelii P.

    2016-01-01

    Background The increase in disease burden has continued to weigh upon health systems in Africa. The role of the laboratory has become increasingly critical in the improvement of health for diagnosis, management and treatment of diseases. In response, the World Health Organization Regional Office for Africa (WHO AFRO) and its partners created the WHO AFRO Stepwise Laboratory (Quality) Improvement Process Towards Accreditation (SLIPTA) program. SLIPTA implementation process WHO AFRO defined a governance structure with roles and responsibilities for six main stakeholders. Laboratories were evaluated by auditors trained and certified by the African Society for Laboratory Medicine. Laboratory performance was measured using the WHO AFRO SLIPTA scoring checklist and recognition certificates rated with 1–5 stars were issued. Preliminary results By March 2015, 27 of the 47 (57%) WHO AFRO member states had appointed a SLIPTA focal point and 14 Ministers of Health had endorsed SLIPTA as the desired programme for continuous quality improvement. Ninety-eight auditors from 17 African countries, competent in the Portuguese (3), French (12) and English (83) languages, were trained and certified. The mean score for the 159 laboratories audited between May 2013 and March 2015 was 69% (median 70%; SD 11.5; interquartile range 62–77). Of these audited laboratories, 70% achieved 55% compliance or higher (2 or more stars) and 1% scored at least 95% (5 stars). The lowest scoring sections of the WHO AFRO SLIPTA checklist were sections 6 (Internal Audit) and 10 (Corrective Action), which both had mean scores below 50%. Conclusion The WHO AFRO SLIPTA is a process that countries with limited resources can adopt for effective implementation of quality management systems. Political commitment, ownership and investment in continuous quality improvement are integral components of the process. PMID:28879103

  6. Successful implementation of the stepwise layer-by-layer growth of MOF thin films on confined surfaces: Mesoporous silica foam as a first case study

    KAUST Repository

    Shekhah, Osama

    2012-01-01

    Here we report the successful growth of highly crystalline homogeneous MOF thin films of HKUST-1 and ZIF-8 on mesoporous silica foam, by employing a layer-by-layer (LBL) method. The ability to control and direct the growth of MOF thin films on confined surfaces, using the stepwise LBL method, paves the way for new prospective applications of such hybrid systems. © 2012 The Royal Society of Chemistry.

  7. Zinc porphyrin-Re(I) bipyridyl-fullerene triad: synthesis, characterization, and kinetics of the stepwise electron-transfer processes initiated by visible excitation.

    Science.gov (United States)

    Cavigli, Paolo; Da Ros, Tatiana; Kahnt, Axel; Gamberoni, Marta; Indelli, Maria Teresa; Iengo, Elisabetta

    2015-01-05

    A new triad system featuring one zinc porphyrin and one fullerene moieties attached to a central redox-active Re(I) connector was obtained in remarkable yield by cleverly exploiting a facile two-step synthesis. Detailed description and discussion on the characterization of this multicomponent system and of its parent free-base analogue are presented, along with a kinetic study of the stepwise electron-transfer processes occurring upon visible excitation.

  8. Managing Colllinearity in Modeling the Effect of Age in the Prediction of Egg Components of Laying Hens Using Stepwise and Ridge Regression Analysis

    OpenAIRE

    TM Shafey; ES Hussein; AH Mahmoud; MA Abouheif; HA Al-Batshan

    2015-01-01

    ABSTRACT The relationships between egg measurements [egg weight (EGWT), egg width (EGWD), egg shape index (EGSI), egg volume (EGV) and egg density (EGD)], and egg components [eggshell (SWT), yolk (YWT) and albumen (AWT)] were investigated in laying hens with 32, 45, and 59 weeks of age with an objective of managing multicollinearity (MC), using stepwise regression (SR) and ridge regression (RR) analyses. There were significant correlations among egg traits that led to MC problems in all eggs....

  9. Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple FGIDs and Symptom Severity and Frequency.

    Science.gov (United States)

    Pinto-Sanchez, Maria Ines; Ford, Alexander C; Avila, Christian A; Verdu, Elena F; Collins, Stephen M; Morgan, David; Moayyedi, Paul; Bercik, Premysl

    2015-07-01

    Anxiety and depression occur frequently in patients with functional gastrointestinal disorders (FGIDs), but their precise prevalence is unknown. We addressed this issue in a large cohort of adult patients and determined the underlying factors. In total, 4,217 new outpatients attending 2 hospitals in Hamilton, Ontario, Canada completed questionnaires evaluating FGIDs and anxiety and depression (Hospital Anxiety and Depression scale). Chart review was performed in a random sample of 2,400 patients. Seventy-six percent of patients fulfilled Rome III criteria for FGIDs, but only 57% were diagnosed with FGIDs after excluding organic diseases, and the latter group was considered for the analysis. Compared with patients not meeting the criteria, prevalence of anxiety (odds ratio (OR) 2.66, 95% confidence interval (CI): 1.62-4.37) or depression (OR 2.04, 95% CI: 1.03-4.02) was increased in patients with FGIDs. The risk was comparable to patients with organic disease (anxiety: OR 2.12, 95% CI: 1.24-3.61; depression: OR 2.48, 95% CI: 1.21-5.09). The lowest prevalence was observed in asymptomatic patients (OR 1.37; 95% CI 0.58-3.23 and 0.51; 95% CI 0.10-2.48; for both conditions, respectively). The prevalence of anxiety and depression increased in a stepwise manner with the number of co-existing FGIDs and frequency and/or severity of gastrointestinal (GI) symptoms. Psychiatric comorbidity was more common in females with FGIDs compared with males (anxiety OR 1.73; 95% CI 1.35-2.28; depression OR 1.52; 95% CI 1.04-2.21). Anxiety and depression were formally diagnosed by the consulting physician in only 22% and 9% of patients, respectively. Psychiatric comorbidity is common in patients referred to a secondary care center but is often unrecognized. The prevalence of both anxiety and depression is influenced by gender, presence of organic diseases, and FGIDs, and it increases with the number of coexistent FGIDs and frequency and severity of GI symptoms.

  10. Evaluation of 41 candidate gene variants for obesity in the EPIC-Potsdam cohort by multi-locus stepwise regression.

    Science.gov (United States)

    Knüppel, Sven; Rohde, Klaus; Meidtner, Karina; Drogan, Dagmar; Holzhütter, Hermann-Georg; Boeing, Heiner; Fisher, Eva

    2013-01-01

    Obesity has become a leading preventable cause of morbidity and mortality in many parts of the world. It is thought to originate from multiple genetic and environmental determinants. The aim of the current study was to introduce haplotype-based multi-locus stepwise regression (MSR) as a method to investigate combinations of unlinked single nucleotide polymorphisms (SNPs) for obesity phenotypes. In 2,122 healthy randomly selected men and women of the EPIC-Potsdam cohort, the association between 41 SNPs from 18 obesity-candidate genes and either body mass index (BMI, mean=25.9 kg/m(2), SD=4.1) or waist circumference (WC, mean=85.2 cm, SD=12.6) was assessed. Single SNP analyses were done by using linear regression adjusted for age, sex, and other covariates. Subsequently, MSR was applied to search for the 'best' SNP combinations. Combinations were selected according to specific AICc and p-value criteria. Model uncertainty was accounted for by a permutation test. The strongest single SNP effects on BMI were found for TBC1D1 rs637797 (β = -0.33, SE=0.13), FTO rs9939609 (β=0.28, SE=0.13), MC4R rs17700144 (β=0.41, SE=0.15), and MC4R rs10871777 (β=0.34, SE=0.14). All these SNPs showed similar effects on waist circumference. The two 'best' six-SNP combinations for BMI (global p-value= 3.45⋅10(-6) and 6.82⋅10(-6)) showed effects ranging from -1.70 (SE=0.34) to 0.74 kg/m(2) (SE=0.21) per allele combination. We selected two six-SNP combinations on waist circumference (global p-value = 7.80⋅10(-6) and 9.76⋅10(-6)) with an allele combination effect of -2.96 cm (SE=0.76) at maximum. Additional adjustment for BMI revealed 15 three-SNP combinations (global p-values ranged from 3.09⋅10(-4) to 1.02⋅10(-2)). However, after carrying out the permutation test all SNP combinations lost significance indicating that the statistical associations might have occurred by chance. MSR provides a tool to search for risk-related SNP combinations of common traits or

  11. Structural and Logical Stepwise Design of Mechanism of Implementing the Socio-Economic Policy of the Region

    Directory of Open Access Journals (Sweden)

    Zadorozhneva Yuliya Vladimirovna

    2014-12-01

    Full Text Available The socio-economic policy of the region is characterized in two ways. On the one hand, it is an organizational form of interaction of the entities of regional socio-economic policy. This form defines the specifics of their relations, taking into account the existing conditions, resources and factors. On the other hand, it is a process of purposeful interaction between the entities and the impact on objects by the methods and tools. This process contributes to the spatio-temporal changes in the economic and social status of the regional economic system. Therefore, the structural and logical stepwise design of the mechanism of implementing the socio-economic policy of the region will allow to systematically present the content and the interconnections of its constituent entities. The author comes to the conclusion that the mechanism of implementing the socio-economic policy of the region, based on the subject-object and dynamic approaches, involves the allocation of: actors, objects, and the mechanism of actors interaction and the impact on objects within this policy. This mechanism includes the purpose, objectives, methods and tools for their achievement, as well as information and analytical system of monitoring and integrated evaluation, on the basis of which a decision is made on the effectiveness of socio-economic policy and the need for adjusting the initial goal and objectives, or choice of methods and tools for its implementation. This is reflected in the author’s structural and logical scheme of the considered mechanism, the practical significance of which lies in the ability to project in detail the main stages of implementation of socio-economic policy of the region on the basis of the principles of consistency, adequacy, resources integration, priority character, efficiency, responsibility. Each step of the suggested mechanism corresponds to the definite level of functional and structural organization – program

  12. Pig specific vascular anatomy allows acute infrarenal aortic occlusion without hind limb ischemia and stepwise occlusion without clinical signs.

    Science.gov (United States)

    Haacke, N; Unger, J K; Haidenhein, C; Russ, M; Hiebl, B; Niehues, S M

    2011-01-01

    In a porcine, aortic graft model we found 5 animals to develop and survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute occlusion but rather unspecific clinical symptoms. We investigated the pigs' vascular system to classify the anatomic capabilities to compensate for an acute abdominal aortic occlusion. Retrospective analysis of CT scans and clinical data to specify unexpected results in a case series of infrarenal occlusion in a porcine model. Collaborative study of experimental and clinical departments. Fifteen healthy female minipigs. All pigs underwent an infrarenal aortic graft intervention. Anesthesia and perioperative management of the animals were preformed along the standard operating procedures of the local Department of Experimental Medicine. All animals received perioperative antibiotics, ASS, and carprofen for postoperative analgesia. Arterial pressure, heart rate, body temperature, and diuresis were monitored during surgery and therapeutic interventions. Contrast media based computed tomography (CT) with total body scans were performed at 1, 4, 10, 12 weeks after surgery. Comparable scans of cardiovascular healthy subjects (humans and pigs) and patients with a Leriche's syndrome were analyzed. Neither acute (within the first 12 h after surgery) nor stepwise total aortic occlusion show unmistakable clinical signs. In pigs, the epigastric artery (EGA) - which is in connection with suprarenal lumbal arteries, subclavian and external iliac artery - is highly developed associated to the high number of mammary glands of about 7 on one side. In humans, the ratio of aortic to EGA-diameter is 1 : 0.15. In minipigs we found a ratio of 1 : 0.43 which changed during aortic occlusion resulting in a ratio of 1 : 0.58. Pigs with a slowly developing occlusion demonstrated an enlargement of the ureteric artery of about 210% completing a sufficient collateral system. While in the human Leriche's syndrome months are needed to enlarge the

  13. Clinical Trials

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    Full Text Available ... a laboratory (lab), where scientists first develop and test new ideas. If an approach seems promising, the ... Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study ...

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    Full Text Available ... review data from a clinical trial for safety problems or differences in results among different groups. The DSMB also reviews research results from other relevant studies. These results may ...

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    Full Text Available ... harm. In later phases of clinical trials, researchers learn more about the new approach's risks and benefits. ... Clinical Studies Web page. Children and Clinical Studies Learn more about Children and Clinical Studies Importance of ...

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    Full Text Available ... participants. Children and Clinical Studies Learn about the importance of children in clinical studies and get answers to common questions. NIH Clinical Research Trials and You Get additional guidance on participating ...

  17. Clinical Trials

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    Full Text Available ... get special protection as research subjects. Almost always, parents must give legal consent for their child to ... trial's potential risks are greater than minimal, both parents must give permission for their child to enroll. ...

  18. Clinical Trials

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    Full Text Available ... the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ... based on what is known to work in adults. To improve clinical care of children, more studies ...

  19. Clinical Trials

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    Full Text Available ... scale phase III trials begin, the FDA provides input on how these studies should be done. Patient ... of stakeholders and advisory groups, NHLBI has received input and has established a multi-pronged approach to ...

  20. Clinical Trials

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    Full Text Available ... or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that ...

  1. Clinical Trials

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    Full Text Available ... treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are ...

  2. Clinical Trials

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    Full Text Available ... long and careful research process. The process often begins in a laboratory (lab), where scientists first develop ... IRB reviews the trial's protocol before the study begins. An IRB will only approve research that deals ...

  3. Clinical Trials

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    Full Text Available ... always, parents must give legal consent for their child to take part in a clinical trial. When ... minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older ...

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    Full Text Available ... States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for new medicines ...

  7. Clinical Trials

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    Full Text Available ... Clinical trials are research studies that explore whether a medical strategy, treatment, or device is safe and ... drugs, and devices specific to children. Resources for a Wide Range of Audiences The Children and Clinical ...

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    Full Text Available ... care providers might be part of your treatment team. They will monitor your health closely. You may ... taking part in a clinical trial. Your treatment team also may ask you to do other tasks. ...

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    Full Text Available ... you to explore NIH Clinical Center for patient recruitment and clinical trial information. For more information, please email the NIH Clinical Center Office of Patient Recruitment at cc-prpl@cc.nih.gov or call ...

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    Full Text Available ... and devices specific to children. Resources for a Wide Range of Audiences The Children and Clinical Studies ... medical centers, and hospitals. ClinicalTrials.gov View a database of clinical studies (past and present) funded or ...

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    Full Text Available Skip to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ...

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    Full Text Available ... Masking, or "blinding," helps avoid bias. For this reason, researchers also may not be told which treatments ... from a study at any time, for any reason. Also, during the trial, you have the right ...

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    Full Text Available ... clinical trials are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees all research ...

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    Full Text Available ... you may get tests or treatments in a hospital, clinic, or doctor's office. In some ways, taking ... people will need to travel or stay in hospitals to take part in clinical trials. For example, ...

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    Full Text Available ... include factors such as a patient's age and gender, the type and stage of disease, and whether ... in a clinical trial, find out ahead of time about costs and coverage. You should learn about ...

  17. Stroke Trials Registry

    Science.gov (United States)

    ... News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions Sponsors ... a clinical trial near you Welcome to the Stroke Trials Registry Our registry of clinical trials in ...

  18. The role of multicollinearity in landslide susceptibility assessment by means of Binary Logistic Regression: comparison between VIF and AIC stepwise selection

    Science.gov (United States)

    Cama, Mariaelena; Cristi Nicu, Ionut; Conoscenti, Christian; Quénéhervé, Geraldine; Maerker, Michael

    2016-04-01

    Landslide susceptibility can be defined as the likelihood of a landslide occurring in a given area on the basis of local terrain conditions. In the last decades many research focused on its evaluation by means of stochastic approaches under the assumption that 'the past is the key to the future' which means that if a model is able to reproduce a known landslide spatial distribution, it will be able to predict the future locations of new (i.e. unknown) slope failures. Among the various stochastic approaches, Binary Logistic Regression (BLR) is one of the most used because it calculates the susceptibility in probabilistic terms and its results are easily interpretable from a geomorphological point of view. However, very often not much importance is given to multicollinearity assessment whose effect is that the coefficient estimates are unstable, with opposite sign and therefore difficult to interpret. Therefore, it should be evaluated every time in order to make a model whose results are geomorphologically correct. In this study the effects of multicollinearity in the predictive performance and robustness of landslide susceptibility models are analyzed. In particular, the multicollinearity is estimated by means of Variation Inflation Index (VIF) which is also used as selection criterion for the independent variables (VIF Stepwise Selection) and compared to the more commonly used AIC Stepwise Selection. The robustness of the results is evaluated through 100 replicates of the dataset. The study area selected to perform this analysis is the Moldavian Plateau where landslides are among the most frequent geomorphological processes. This area has an increasing trend of urbanization and a very high potential regarding the cultural heritage, being the place of discovery of the largest settlement belonging to the Cucuteni Culture from Eastern Europe (that led to the development of the great complex Cucuteni-Tripyllia). Therefore, identifying the areas susceptible to

  19. Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial.

    Science.gov (United States)

    Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

    2017-01-01

    The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). To describe the data management process and statistical analysis plan. The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. ClinicalTrials.gov number, NCT01374022.

  20. Isolation and Characterization of Chinese Standard Fulvic Acid Sub-fractions Separated from Forest Soil by Stepwise Elution with Pyrophosphate Buffer

    Science.gov (United States)

    Bai, Yingchen; Wu, Fengchang; Xing, Baoshan; Meng, Wei; Shi, Guolan; Ma, Yan; Giesy, John P.

    2015-01-01

    XAD-8 adsorption technique coupled with stepwise elution using pyrophosphate buffers with initial pH values of 3, 5, 7, 9, and 13 was developed to isolate Chinese standard fulvic acid (FA) and then separated the FA into five sub-fractions: FApH3, FApH5, FApH7, FApH9 and FApH13, respectively. Mass percentages of FApH3-FApH13 decreased from 42% to 2.5%, and the recovery ratios ranged from 99.0% to 99.5%. Earlier eluting sub-fractions contained greater proportions of carboxylic groups with greater polarity and molecular mass, and later eluting sub-fractions had greater phenolic and aliphatic content. Protein-like components, as well as amorphous and crystalline poly(methylene)-containing components were enriched using neutral and basic buffers. Three main mechanisms likely affect stepwise elution of humic components from XAD-8 resin with pyrophosphate buffers including: 1) the carboxylic-rich sub-fractions are deprotonated at lower pH values and eluted earlier, while phenolic-rich sub-fractions are deprotonated at greater pH values and eluted later. 2) protein or protein-like components can be desorbed and eluted by use of stepwise elution as progressively greater pH values exceed their isoelectric points. 3) size exclusion affects elution of FA sub-fractions. Successful isolation of FA sub-fractions will benefit exploration of the origin, structure, evolution and the investigation of interactions with environmental contaminants. PMID:25735451

  1. Paleozoic ages and excess 40Ar in garnets from the Bixiling eclogite in Dabieshan, China: New insights from 40Ar/ 39Ar dating by stepwise crushing

    Science.gov (United States)

    Qiu, Hua-Ning; Wijbrans, J. R.

    2006-05-01

    The 40Ar/ 39Ar stepwise crushing technique is applied for the first time to date garnet from ultra-high-pressure metamorphic (UHPM) eclogites. Three garnet samples from the Bixiling eclogites analyzed by 40Ar/ 39Ar stepwise crushing yield regular, predictable age spectra, and a clear separation between excess 40Ar and concordant plateau and isochron ages. All three age spectra begin with high apparent ages followed by step by step decreasing ages, and finally age plateaux with apparent ages in the range from 427 ± 20 to 444 ± 10 Ma. The data points constituting the age plateaux yield excellent isochrons with radiogenic intercept ages ranging from 448 ± 34 to 459 ± 58 Ma, corresponding to initial 40Ar/ 36Ar ratios from 292.1 ± 4.5 to 294.5 ± 6.7, statistically indistinguishable from the modern air. The high initial ages are interpreted to derive from secondary fluid inclusions containing excess 40Ar, whereas the plateau ages are attributed to gas from small primary fluid inclusions without significant excess 40Ar. The plateau ages are interpreted to approximate the time of garnet growth during initial UHPM metamorphism. Phengite analyzed by laser stepwise heating yielded a complicated two-saddle age spectrum with a scattered isochron corresponding to age of 463 ± 116 Ma and initial 40Ar/ 36Ar ratio of 1843 ± 1740 indicative of the presence of extraneous 40Ar within phengite. These concordant isochron ages measured on minerals diagnostic of eclogite grade metamorphism strongly suggest that Dabie UHPM eclogites were first formed in the early Paleozoic, during the same event that caused the Qinling-Northern Qaidam Basin-Altyn Tagh eclogites.

  2. Isolation and Characterization of Chinese Standard Fulvic Acid Sub-fractions Separated from Forest Soil by Stepwise Elution with Pyrophosphate Buffer

    Science.gov (United States)

    Bai, Yingchen; Wu, Fengchang; Xing, Baoshan; Meng, Wei; Shi, Guolan; Ma, Yan; Giesy, John P.

    2015-03-01

    XAD-8 adsorption technique coupled with stepwise elution using pyrophosphate buffers with initial pH values of 3, 5, 7, 9, and 13 was developed to isolate Chinese standard fulvic acid (FA) and then separated the FA into five sub-fractions: FApH3, FApH5, FApH7, FApH9 and FApH13, respectively. Mass percentages of FApH3-FApH13 decreased from 42% to 2.5%, and the recovery ratios ranged from 99.0% to 99.5%. Earlier eluting sub-fractions contained greater proportions of carboxylic groups with greater polarity and molecular mass, and later eluting sub-fractions had greater phenolic and aliphatic content. Protein-like components, as well as amorphous and crystalline poly(methylene)-containing components were enriched using neutral and basic buffers. Three main mechanisms likely affect stepwise elution of humic components from XAD-8 resin with pyrophosphate buffers including: 1) the carboxylic-rich sub-fractions are deprotonated at lower pH values and eluted earlier, while phenolic-rich sub-fractions are deprotonated at greater pH values and eluted later. 2) protein or protein-like components can be desorbed and eluted by use of stepwise elution as progressively greater pH values exceed their isoelectric points. 3) size exclusion affects elution of FA sub-fractions. Successful isolation of FA sub-fractions will benefit exploration of the origin, structure, evolution and the investigation of interactions with environmental contaminants.

  3. A stepwise retro-imino-ene as a key step in the mechanism of allene formation via the Crabbé acetylene homologation.

    Science.gov (United States)

    González, Marta; Rodríguez, Roi Álvarez; Cid, Maria Magdalena; López, Carlos Silva

    2012-05-15

    The mechanism of the acetylene homologation procedure accidentally discovered and further developed by Crabbé and coworkers is unknown. Kinetic isotope effect (KIE) experiments, however, suggest that an intramolecular hydrogen shift is the key step of the transformation. In this work, we present a computational study of this mechanism. We found that the reaction proceeds via an unexpected stepwise retro-imino-ene rearrangement. This mechanism justifies the role of Cu(I) as a reaction catalyst and is also compatible with the KIE experiments reported. Copyright © 2012 Wiley Periodicals, Inc.

  4. Real-time MRI-guided percutaneous sclerotherapy of low-flow head and neck lymphatic malformations in the pediatric population - a stepwise approach

    Energy Technology Data Exchange (ETDEWEB)

    Partovi, Sasan; Vidal, Lorenna; Lu, Ziang; Nakamoto, Dean A.; Buethe, Ji; Clampitt, Mark; Coffey, Michael; Patel, Indravadan J. [University Hospitals Cleveland Medical Center, Case Western Reserve University, Department of Radiology, Section of Vascular and Interventional Radiology, Cleveland, OH (United States)

    2017-05-15

    Real-time MRI-guided percutaneous sclerotherapy is a novel and evolving treatment for congenital lymphatic malformations in the head and neck. We elaborate on the specific steps necessary to perform an MRI-guided percutaneous sclerotherapy of lymphatic malformations including pre-procedure patient work-up and preparation, stepwise intraprocedural interventional techniques and post-procedure management. Based on our institutional experience, MRI-guided sclerotherapy with a doxycycline-gadolinium-based mixture as a sclerosant for lymphatic malformations of the head and neck region in children is well tolerated and effective. (orig.)

  5. Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques.

    Science.gov (United States)

    Roy, Kunal; Pratim Roy, Partha

    2009-07-01

    Twenty-eight structurally diverse cytochrome 3A4 (CYP3A4) inhibitors have been subjected to quantitative structure-activity relationship (QSAR) studies. The analyses were performed with electronic, spatial, topological, and thermodynamic descriptors calculated using Cerius 2 version 10 software. The statistical tools used were linear [multiple linear regression with factor analysis as preprocessing step (FA-MLR), stepwise MLR, partial least squares (PLS), genetic function algorithm (GFA), genetic PLS (G/PLS)] and non-linear methods [artificial neural network (ANN)]. All the five linear modeling methods indicate the importance of n-octanol/water partition coefficient (logP) along with different topological and electronic parameters. The best model obtained from the training set (stepwise regression) based on highest external predictive R(2) value and lowest RMSEP value also showed good internal predictive power. Other models like FA-MLR, PLS, GFA and G/PLS are also of statistically significant internal and external validation characteristics. The best model [according to r(m)(2) for the test set, as defined by P.P. Roy, K. Roy, QSAR Comb. Sci. 27 (2008) 302-313] obtained from ANN showed a good r(2) value (determination coefficient between observed and predicted values) for the test set compounds, which was superior to those of other statistical models except the stepwise regression derived model. However, based upon the r(m)(2) value (test set), which penalizes a model for large differences between observed and predicted values, the stepwise MLR model was found to be inferior to other methods except PLS. Considering r(m)(2) value for the whole set, the G/PLS derived model appears to be the best predictive model for this data set. For choosing the best predictive model from among comparable models, r(m)(2) for the whole set calculated based on leave-one-out predicted values of the training set and model-derived predicted values for the test set compounds is suggested

  6. A selective stepwise heme oxygenase model system: an iron(IV)-oxo porphyrin π-cation radical leads to a verdoheme-type compound via an isoporphyrin intermediate.

    Science.gov (United States)

    Garcia-Bosch, Isaac; Sharma, Savita K; Karlin, Kenneth D

    2013-11-06

    The selective oxidation of the α-position of two heme-Fe(III) tetraarylporphryinate complexes occurs when water(hydroxide) attacks their oxidized Cmpd I-type equivalents, high-valent Fe(IV)═O π-cation radical species ((P(+•))Fe(IV)═O). Stepwise intermediate formation occurs, as detected by UV-vis spectroscopic monitoring or mass spectrometric interrogation, being iron(III) isoporphyrins, iron(III) benzoyl-biliverdins, and the final verdoheme-like products. Heme oxygenase (HO) enzymes could proceed through heterolytic cleavage of an iron(III)-hydroperoxo intermediate to form a transient Cmpd I-type species.

  7. Efficient Synthesis of Ethanol from CH4 and Syngas on a Cu-Co/TiO2 Catalyst Using a Stepwise Reactor

    OpenAIRE

    Zhi-Jun Zuo; Fen Peng; Wei Huang

    2016-01-01

    Ethanol synthesis from CH4 and syngas on a Cu-Co/TiO2 catalyst is studied using experiments, density functional theory (DFT) and microkinetic modelling. The experimental results indicate that the active sites of ethanol synthesis from CH4 and syngas are Cu and CoO, over which the ethanol selectivity is approximately 98.30% in a continuous stepwise reactor. DFT and microkinetic modelling results show that *CH3 is the most abundant species and can be formed from *CH4 dehydrogenation or through ...

  8. Clinical Trials

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    Full Text Available ... This shows how the approach affects a living body and whether it's harmful. However, an approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed. For safety purposes, clinical trials start ...

  9. Clinical Trials

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    Full Text Available ... educational programs and materials, and offer advice on research-related issues. Data Safety Monitoring Board Every National Institutes of Health ( ... III clinical trial is required to have a Data and Safety Monitoring Board ... of a group of research and study topic experts. The NIH also requires ...

  10. Clinical Trials

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    Full Text Available ... examples of clinical trials that test principles or strategies include studies that explore whether surgery or other medical treatments ... board consists of a group of research and study topic experts. The NIH also ... alternative strategies for diagnosis or treatment. In addition, the NIH ...

  11. The Trial

    Science.gov (United States)

    Bryant, Jen

    2004-01-01

    Growing up in Flemington, New Jersey, put Jen Bryant in the heart of the lore behind the Lindbergh baby kidnapping. Family stories of the events of the day and extensive research led to "The Trial," a novel in verse. The first several parts of this novel are included here.

  12. Clinical Trials

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    Full Text Available ... taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don't directly ... risk procedures (such as gene therapy) or vulnerable patients (such as ... trial for safety problems or differences in results among different groups. ...

  13. Meet Clinical Trial Participants

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Clinical Trials Meet Clinical Trial Participants Past Issues / Fall 2016 Table ... Articles Clinical Trials, A Healthier Future for All / Meet Clinical Trial Participants / North Carolinians Volunteer for Knee ...

  14. Textbook of clinical trials

    National Research Council Canada - National Science Library

    Day, Simon; Machin, David; Green, Sylvan B

    2006-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 The Development of Clinical Trials Simon...

  15. Stepwise algorithm using computed tomography and magnetic resonance imaging for diagnosis of fat-poor angiomyolipoma in small renal masses: Development and external validation.

    Science.gov (United States)

    Tanaka, Hajime; Fujii, Yasuhisa; Tanaka, Hiroshi; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Uehara, Sho; Numao, Noboru; Yuasa, Takeshi; Yamamoto, Shinya; Masuda, Hitoshi; Yonese, Junji; Kihara, Kazunori

    2017-07-01

    To develop a stepwise diagnostic algorithm for fat-poor angiomyolipoma in small renal masses. Two cohorts of small renal masses magnetic resonance imaging and clinical findings were analyzed. Based on multivariate analysis, we developed two prediction models for fat-poor angiomyolipoma, the computed tomography model and the computed tomography + magnetic resonance imaging model, and a stepwise algorithm that proposes the sequential use of computed tomography and magnetic resonance imaging. The computed tomography model, which was composed of female aged magnetic resonance imaging model. The computed tomography + magnetic resonance imaging model, consisting of the first three factors of the computed tomography model, low signal intensity and absence of pseudocapsule on T2-weighted magnetic resonance imaging, re-stratified the tumors into low, intermediate and high angiomyolipoma-probability groups. The incidence of fat-poor angiomyolipoma in each group was 0%, 26% and 93%, respectively (area under the curve 0.981). External validation by two readers showed a high area under the curve (0.912 and 0.924) for each. The interobserver agreement was good (kappa score 0.77). The present algorithm differentiates fat-poor angiomyolipoma in small renal masses with high accuracy by adding magnetic resonance imaging to computed tomography in selected patients. © 2017 The Japanese Urological Association.

  16. Quantitative analysis of the thermal requirements for stepwise physical dormancy-break in seeds of the winter annual Geranium carolinianum (Geraniaceae).

    Science.gov (United States)

    Gama-Arachchige, N S; Baskin, J M; Geneve, R L; Baskin, C C

    2013-05-01

    Physical dormancy (PY)-break in some annual plant species is a two-step process controlled by two different temperature and/or moisture regimes. The thermal time model has been used to quantify PY-break in several species of Fabaceae, but not to describe stepwise PY-break. The primary aims of this study were to quantify the thermal requirement for sensitivity induction by developing a thermal time model and to propose a mechanism for stepwise PY-breaking in the winter annual Geranium carolinianum. Seeds of G. carolinianum were stored under dry conditions at different constant and alternating temperatures to induce sensitivity (step I). Sensitivity induction was analysed based on the thermal time approach using the Gompertz function. The effect of temperature on step II was studied by incubating sensitive seeds at low temperatures. Scanning electron microscopy, penetrometer techniques, and different humidity levels and temperatures were used to explain the mechanism of stepwise PY-break. The base temperature (Tb) for sensitivity induction was 17·2 °C and constant for all seed fractions of the population. Thermal time for sensitivity induction during step I in the PY-breaking process agreed with the three-parameter Gompertz model. Step II (PY-break) did not agree with the thermal time concept. Q10 values for the rate of sensitivity induction and PY-break were between 2·0 and 3·5 and between 0·02 and 0·1, respectively. The force required to separate the water gap palisade layer from the sub-palisade layer was significantly reduced after sensitivity induction. Step I and step II in PY-breaking of G. carolinianum are controlled by chemical and physical processes, respectively. This study indicates the feasibility of applying the developed thermal time model to predict or manipulate sensitivity induction in seeds with two-step PY-breaking processes. The model is the first and most detailed one yet developed for sensitivity induction in PY-break.

  17. Stepwise approach to curative surgery using percutaneous transhepatic cholangiodrainage and portal vein embolization for severe bile duct injury during laparoscopic cholecystectomy: a case report.

    Science.gov (United States)

    Honmyo, Naruhiko; Kuroda, Shintaro; Kobayashi, Tsuyoshi; Ishiyama, Kohei; Ide, Kentaro; Tahara, Hiroyuki; Ohira, Masahiro; Ohdan, Hideki

    2016-12-01

    Laparoscopic cholecystectomy (LC) has been recently adapted to acute cholecystitis. Major bile duct injury during LC, especially Strasberg-Bismuth classification type E, can be a critical problem sometimes requiring hepatectomy. Safety and definitive treatment without further morbidities, such as posthepatectomy liver failure, is required. Here, we report a case of severe bile duct injury treated with a stepwise approach using (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging to accurately estimate liver function.A 52-year-old woman diagnosed with acute cholecystitis underwent LC at another hospital and was transferred to our university hospital for persistent bile leakage on postoperative day 20. She had no jaundice or infection, although an intraperitoneal drainage tube discharged approximately 500 ml of bile per day. Recorded operation procedure showed removal of the gallbladder with a part of the common bile duct due to its misidentification, and each of the hepatic ducts and right hepatic artery was injured. Abdominal enhanced CT revealed obstructive jaundice of the left liver and arterial shunt through the hilar plate to the right liver. Magnetic resonance cholangiopancreatography revealed type E4 or more advanced bile duct injury according to the Bismuth-Strasberg classification. We planned a stepwise approach using percutaneous transhepatic cholangiodrainage (PTCD) and portal vein embolization (PVE) for secure right hemihepatectomy and biliary-jejunum reconstruction and employed (99m)Tc-GSA SPECT/CT fusion imaging to estimate future remnant liver function. The left liver function rate had changed from 26.2 % on admission to 26.3 % after PTCD and 54.5 % after PVE, while the left liver volume rate was 33.8, 33.3, and 49.6 %, respectively. The increase of liver function was higher than that of volume (28.3 vs. 15.8 %). On postoperative day 63, the curative operation, right

  18. Stepwise drying of Lake Turkana at the end of the African Humid Period: a forced regression modulated by solar activity variations?

    Science.gov (United States)

    Nutz, Alexis; Schuster, Mathieu

    2016-12-01

    Although the timing of the termination of the African Humid Period (AHP) is now relatively well established, the modes and controlling factors of this drying are still debated. Here, through a geomorphological approach, we characterize the regression of Lake Turkana at the end of the AHP. We show that lake level fall during this period was not continuous but rather stepwise and consisted of five episodes of rapid lake level fall separated by episodes marked by slower rates of lake level fall. Whereas the overall regressive trend reflects a decrease in regional precipitations linked to the gradual reduction in Northern Hemisphere summer insolation, itself controlled by orbital precession, we focus discussion on the origin of the five periods of accelerated lake level fall. We propose that these periods are due to temporary reductions in rainfall across the Lake Turkana area associated with repeated westward displacement of the Congo Air Boundary (CAB) during solar activity minima.

  19. Preparative isolation of osthol and xanthotoxol from Common Cnidium Fruit (Chinese traditional herb) using stepwise elution by high-speed counter-current chromatography.

    Science.gov (United States)

    Wei, Yun; Zhang, Tianyou; Ito, Yoichiro

    2004-04-16

    Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of osthol and xanthotoxol from Cnidium monnieri (L.) Cusson (Common Cnidium Fruit) using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v), and (5:5:6:4, v/v), which had been selected by analytical high-speed counter-current chromatography. Using a preparative unit of the HSCCC centrifuge, about a 308 mg amount of the crude extract was separated, yielding 88.3 mg of osthol and 19.4 mg of xanthotoxol at a high purity of over 98%.

  20. The autumn effect: timing of physical dormancy break in seeds of two winter annual species of Geraniaceae by a stepwise process.

    Science.gov (United States)

    Gama-Arachchige, N S; Baskin, J M; Geneve, R L; Baskin, C C

    2012-08-01

    The involvement of two steps in the physical dormancy (PY)-breaking process previously has been demonstrated in seeds of Fabaceae and Convolvulaceae. Even though there is a claim for a moisture-controlled stepwise PY-breaking in some species of Geraniaceae, no study has evaluated the role of temperature in the PY-breaking process in this family. The aim of this study was to determine whether a temperature-controlled stepwise PY-breaking process occurs in seeds of the winter annuals Geranium carolinianum and G. dissectum. Seeds of G. carolinianum and G. dissectum were stored under different temperature regimes to test the effect of storage temperature on PY-break. The role of temperature and moisture regimes in regulating PY-break was investigated by treatments simulating natural conditions. Greenhouse (non-heated) experiments on seed germination and burial experiments (outdoors) were carried out to determine the PY-breaking behaviour in the natural habitat. Irrespective of moisture conditions, sensitivity to the PY-breaking step in seeds of G. carolinianum was induced at temperatures ≥20 °C, and exposure to temperatures ≤20 °C made the sensitive seeds permeable. Sensitivity of seeds increased with time. In G. dissectum, PY-break occurred at temperatures ≥20 °C in a single step under constant wet or dry conditions and in two steps under alternate wet-dry conditions if seeds were initially kept wet. Timing of seed germination with the onset of autumn can be explained by PY-breaking processes involving (a) two temperature-dependent steps in G. carolinianum and (b) one or two moisture-dependent step(s) along with the inability to germinate under high temperatures in G. dissectum. Geraniaceae is the third of 18 families with PY in which a two-step PY-breaking process has been demonstrated.

  1. The autumn effect: timing of physical dormancy break in seeds of two winter annual species of Geraniaceae by a stepwise process

    Science.gov (United States)

    Gama-Arachchige, N. S.; Baskin, J. M.; Geneve, R. L.; Baskin, C. C.

    2012-01-01

    Background and Aims The involvement of two steps in the physical dormancy (PY)-breaking process previously has been demonstrated in seeds of Fabaceae and Convolvulaceae. Even though there is a claim for a moisture-controlled stepwise PY-breaking in some species of Geraniaceae, no study has evaluated the role of temperature in the PY-breaking process in this family. The aim of this study was to determine whether a temperature-controlled stepwise PY-breaking process occurs in seeds of the winter annuals Geranium carolinianum and G. dissectum. Methods Seeds of G. carolinianum and G. dissectum were stored under different temperature regimes to test the effect of storage temperature on PY-break. The role of temperature and moisture regimes in regulating PY-break was investigated by treatments simulating natural conditions. Greenhouse (non-heated) experiments on seed germination and burial experiments (outdoors) were carried out to determine the PY-breaking behaviour in the natural habitat. Key Results Irrespective of moisture conditions, sensitivity to the PY-breaking step in seeds of G. carolinianum was induced at temperatures ≥20 °C, and exposure to temperatures ≤20 °C made the sensitive seeds permeable. Sensitivity of seeds increased with time. In G. dissectum, PY-break occurred at temperatures ≥20 °C in a single step under constant wet or dry conditions and in two steps under alternate wet–dry conditions if seeds were initially kept wet. Conclusions Timing of seed germination with the onset of autumn can be explained by PY-breaking processes involving (a) two temperature-dependent steps in G. carolinianum and (b) one or two moisture-dependent step(s) along with the inability to germinate under high temperatures in G. dissectum. Geraniaceae is the third of 18 families with PY in which a two-step PY-breaking process has been demonstrated. PMID:22684684

  2. Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

    Science.gov (United States)

    Nakagami, Tomoko; Tominaga, Makoto; Nishimura, Rimei; Daimon, Makoto; Oizumi, Toshihide; Yoshiike, Nobuo; Tajima, Naoko

    2007-09-01

    Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.

  3. Theoretical investigation of hydrogen atom transfer in the cytosine-guanine base pair and its coupling with electronic rearrangement. Concerted vs stepwise mechanism.

    Science.gov (United States)

    Villani, Giovanni

    2010-07-29

    The transformation of the DNA base pairs from the Watson-Crick (WC) structures to its tautomers having imino-enol form can be achieved via two types of hydrogen atom transfer processes: (i) concerted, and/or (ii) stepwise (step by step). Here, we have studied and compared these two mechanisms in the cytosine-guanine (C-G) system. In the first mechanism there is the concerted movement of two hydrogen atoms along two of the three H-bridges that bond the bases, one from the cytosine to guanine and the other in the opposite direction. This movement must be coupled to an electronic reorganization, with some bond orders that pass from single to double and vice versa, in order to preserve the neutrality of these new structures. In the stepwise mechanism the movement of the hydrogen atoms and the electronic reorganization are not concerted, and it implicates the movement of a hydrogen atom at a time with the identification of two or more steps in this reaction. There are two possible neutral imino-enol structures in the C-G system, and both have been considered here. The principal result from this paper is that a different behavior is observed if the hydrogen transfer begins with a H of the guanine or of the cytosine and that a concerted (synchronic in the N-N and asynchronic in the N-O) double-hydrogen transfer can be activated only when the first H atom to move is that of the guanine, in particular. This is different from the A-T system(1) studied previously where the movement in a N-N bridge produces a zwitterionic structure and that in the N-O the concerted double-hydrogen transfer. In both cases a general conclusion can be given: the concerted double-hydrogen process begins with a hydrogen atom of a purinic base.

  4. Trial registration in pediatric surgery trials.

    Science.gov (United States)

    Rokhsefat, Sana; Morra, Deanna E; Offringa, Martin; Askie, Lisa M; Kelly, Lauren E

    2017-10-23

    Prospective clinical trial registration serves to increase transparency and to mitigate selective reporting bias. An assessment of adult surgical trials revealed poor trial registration practice with incomplete provision of information in registries and inconsistent information in the corresponding publication. The extent and completeness of pediatric surgical trial registration are unknown. We aimed to determine the proportion and adequacy of clinical trial registration in pediatric surgery trials published in 2014. Using sensitive search strategies in MEDLINE, abstracts and full-texts of prospective pediatric intervention studies published in 2014 were screened in duplicate. Pediatric surgical trials were included. Clinical trial registration numbers obtained from publications were searched in trial registries. Data were extracted based on WHO 20-item minimum data set to determine the completeness of registration data. The proportion of registered trials was recorded and registration data were compared to reported data in the corresponding publication. Our search and abstract screening identified 3375 articles for full text review. Following coding, a total of 54 pediatric surgical trials were included and analyzed; 28% (15/54) of which published a registration number. In trials which reported a registration number, 40% (6/15) were retrospectively registered and 40% (6/15) had made changes to their registered primary and/or secondary outcome measures. One included published trial reported an incorrect registration number. Analysis of pediatric surgery trials published in 2014 revealed a poor prospective trial registration rate and incomplete registration data. Our study supports future initiatives for improved registration behaviors in pediatric surgery trials to ensure high-quality, transparent, reproducible evidence is generated. Therapeutic (clinical trials), level II. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A fully automated effervescence assisted dispersive liquid–liquid microextraction based on a stepwise injection system. Determination of antipyrine in saliva samples

    Energy Technology Data Exchange (ETDEWEB)

    Medinskaia, Kseniia; Vakh, Christina; Aseeva, Darina [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation); Andruch, Vasil, E-mail: vasil.andruch@upjs.sk [Department of Analytical Chemistry, University of P.J. Šafárik, SK-04154 Košice (Slovakia); Moskvin, Leonid [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation); Bulatov, Andrey, E-mail: bulatov_andrey@mail.ru [Department of Analytical Chemistry, Institute of Chemistry, Saint Petersburg State University, RU-198504 Saint Petersburg (Russian Federation)

    2016-01-01

    A first attempt to automate the effervescence assisted dispersive liquid–liquid microextraction (EA-DLLME) has been reported. The method is based on the aspiration of a sample and all required aqueous reagents into the stepwise injection analysis (SWIA) manifold, followed by simultaneous counterflow injection of the extraction solvent (dichloromethane), the mixture of the effervescence agent (0.5 mol L{sup −1} Na{sub 2}CO{sub 3}) and the proton donor solution (1 mol L{sup −1} CH{sub 3}COOH). Formation of carbon dioxide microbubbles generated in situ leads to the dispersion of the extraction solvent in the whole aqueous sample and extraction of the analyte into organic phase. Unlike the conventional DLLME, in the case of EA-DLLME, the addition of dispersive solvent, as well as, time consuming centrifugation step for disruption of the cloudy state is avoided. The phase separation was achieved by gentle bubbling of nitrogen stream (2 mL min{sup −1} during 2 min). The performance of the suggested approach is demonstrated by determination of antipyrine in saliva samples. The procedure is based on the derivatization of antipyrine by nitrite-ion followed by EA-DLLME of 4-nitrosoantipyrine and subsequent UV–Vis detection using SWIA manifold. The absorbance of the yellow-colored extract at the wavelength of 345 nm obeys Beer's law in the range of 1.5–100 µmol L{sup −1} of antipyrine in saliva. The LOD, calculated from a blank test based on 3σ, was 0.5 µmol L{sup −1}. - Highlights: • First attempt to automate the effervescence assisted dispersive liquid–liquid microextraction. • Automation based on Stepwise injection analysis manifold in flow batch system. • Counterflow injection of extraction solvent and the effervescence agent. • Phase separation performed by gentle bubbling of nitrogen. • Application for the determination of antipyrine in saliva samples.

  6. Automated non-stepwise preparation of bioanalytical calibration standards and quality controls using an ultra-low volume digitizing liquid dispenser.

    Science.gov (United States)

    Liao, Debra; Chen, Susan; Paton, Martin; Qian, Mark G

    2014-06-15

    Stepwise preparation of calibration standards and quality controls (QCs) is one of the most routine and laborious steps in bioanalysis. An alternative non-contact dispenser using low picoliter digitized dispensing technology is evaluated for its application in non-stepwise preparation of calibration curve and QCs in bioanalysis. Fluorescein was initially used to assess the accuracy and precision of dispense volumes with fluorescent measurement. Various concentrations of MX-1, an in-house proprietary small molecule compound, in neat solution and in dog plasma were prepared manually with calibrated pipettors and digitally by the digital dispenser. The plasma samples were extracted by protein precipitation. The resultant extracted samples and neat solutions of MX-1 were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using an electrospray ionization (ESI) source in positive ion mode with selected reaction monitoring (SRM) of the mass transitions. In the three-day precision and accuracy assessment of dispensing volumes between 13 pL to 411.2 nL, the intra-day precision and accuracy ranged from 1.4% to 10.3% and -12.7% to 12.8%, respectively. The inter-day precision and accuracy ranged from 3.5% to 7.8% and -6.6% to 10.4%, respectively. For real analysis of in vivo study samples, all 49 samples analyzed showed a less than 5% difference between calibrations with digital and manual curve preparations. The resultant pharmacokinetic (PK) parameters were physiologically comparable as well. Using the digitized picoliter dispensing technology, high-speed automated precise and accurate dispense of a wide range of volumes can be achieved and tests for bioanalytical standards and QC preparations passed the stringent criteria set forth for regulated bioanalysis using LC/MS/MS-based technology. The digital dispenser has been found to be a useful tool in drug discovery for automatically preparing standards and QCs in seconds with low consumption of stock

  7. Stepwise sequential analysis of stable multiradicals formation in polyphenolic myricetin active OH groups throughout the antioxidant process to scavenge free radicals

    Science.gov (United States)

    Barzegar, Abolfazl; Rezaei-Sadabady, Rogaie

    2017-10-01

    Five galvinoxyl radicals (Grad) reduction by one polyphenolic myricetin (Myc, 3,3‧,4‧,5,5‧,7-Hexahydroxyflavone) molecule-using EPR method-demonstrated that each Myc should donate at least five H atoms resulted in multiradicals Myc5rad (5 Grad + 1Myc → 5 GH + 1 Myc5rad). The process that five H atoms donation occurs from different OH sites of Myc lead to appearing of five unpaired valence electrons of Myc5rad via two possible different mechanisms. First; concerted five H atoms donation from five different OH groups that directly results in Myc5rad radicals (Myc → Myc5rad). Second; the step-wise radical formation in five different OH groups of Myc (Myc → Mycrad → Myc2rad → Myc3rad → Myc4rad → Myc5rad). Computational DFT method was used to analyze all the six different OH groups of Myc which involved in free radical reactions for the purposes of clarification the stable multiradicals Myc5rad formation mechanism. The fast semi-empirical combined quantum method, AM1/DFT, as well as full DFT geometry optimization approaches of B3LYP functional DFT/DFT with different basis sets of 6-31G (d), 6-311 + G (d,p) and 6-311 + G (2d,2p) confirmed the stepwise H atom abstraction trend on the main three hydroxyl sites as 4‧-Orad → 4‧-Orad3-Orad → 4‧-Orad3-Orad-7Orad both in the gas and water phase. Spin delocalization over the entire Myc, adding the co-planarity, contributed to the stabilization of respective radical species. The excellent stability of Myc radicals should give an effective chain-breaking antioxidant activity for Myc in biological environment which is expected to have far fewer side effects. These findings may be useful to elucidate the radical scavenging mechanism of other flavonoids regarding to design novel antioxidants.

  8. Stepwise targeted drug delivery to liver cancer cells for enhanced therapeutic efficacy by galactose-grafted, ultra-pH-sensitive micelles.

    Science.gov (United States)

    Yan, Guoqing; Wang, Jun; Hu, Liefeng; Wang, Xin; Yang, Guanqing; Fu, Shengxiang; Cheng, Xu; Zhang, Panpan; Tang, Rupei

    2017-03-15

    To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7.4; (ii) responding to tumoral extracellular pH following gradually larger nanoparticles (NPs); (iii) conjugating receptors in the cell membrane of liver cancer through surface galactose-ligands of micelles; (iv) being sensitive to tumoral intracellular pH following further swelling for rapid drug release. In vitro cytotoxicity and cellular uptake measurement showed that POEAd-g-LA20-DOX micelle was more easily internalized and more toxic effect on tumor cells than free DOX. Moreover, in vivo biodistribution and tumor inhibition examinations demonstrated that POEAd-g-LA20-DOX formulation had more superior efficacy to significantly enhance drug accumulation in tumor, and then restrain tumor growth while decreasing drug concentration in heart. Chemotherapeutic efficacy is limited by poor tumor selectivity, which also causes severe toxicity in normal tissues and organs, although many targeted drug delivery systems have been developed by passive targeting strategies or active targeting strategies with specific targeting ligands in recent years. Herein, galactose-grafted, ultra-pH-sensitive, ortho ester-based drug carriers, which can respond to both extracellular and intracellular pH, and target to galactose-receptors in cell membrane, have been successfully constructed by facile method

  9. How Do Clinical Trials Work?

    Science.gov (United States)

    ... Back To Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical ... is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies that explore whether ...

  10. Preparative isolation and purification of lignans from Justicia procumbens using high-speed counter-current chromatography in stepwise elution mode.

    Science.gov (United States)

    Zhou, Peijuan; Luo, Qijun; Ding, Lijian; Fang, Fang; Yuan, Ye; Chen, Juanjuan; Zhang, Jinrong; Jin, Haixiao; He, Shan

    2015-04-20

    Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four lignans (justicidin B (1), justicidin A (2), 6'-hydroxyjusticidin C (3) and lignan J1 (4)) from J. procumbens using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1.3:1:1.3:1, v/v) and (2.5:1:2.5:1, v/v). The preparative HSCCC separation was performed on 300 mg of crude sample yielding compounds 1 (19.7 mg), 2 (9.86 mg), 3 (11.26 mg), and 4 (2.54 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, 1H-NMR and 13C-NMR. This is the first report on the application of HSCCC to the efficient separation of lignans from J. procumbens.

  11. Changes in the mobile phase composition on a stepwise counter-current chromatography elution for the isolation of flavonoids from Siparuna glycycarpa.

    Science.gov (United States)

    Costa, Fernanda das Neves; Garrard, Ian; da Silva, Antonio Jorge Ribeiro; Leitão, Gilda Guimarães

    2013-07-01

    This paper describes the isolation of flavonoids and other aromatic compounds from an ethyl acetate extract of leaves of Siparuna glycycarpa using stepwise elution counter-current chromatography (CCC). The elution profile yielded the following compounds: diglycosylated flavonoids, quercetin 3-O-rutinoside and quercetin 7-O-rutinoside, followed by monoglycosylated flavonoids, kaempferol-3-O-β-glucopyranoside, kaempferol-3-O-β-rhamnopiranoside, kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside, and quercetin-3-O-β-glucopyranoside, and then free phenolics, protocatechuic acid, and 2',6'-dihydroxy-4, 4'-dimethoxydihydrochalcone, which shows that this type of elution covers a broader range of polarity than the traditional isocratic mode. This makes it more suitable to perform separations of mixtures containing large differences in hydrophobicity. A GC analysis of a blank CCC run was performed to determine if changes in the mobile phase composition affect the chromatographic process. Results showed a gradual variation of the composition of the mobile phase emerging after the step gradient, favoring the selectivity of the solvent system. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. H-DROP: an SVM based helical domain linker predictor trained with features optimized by combining random forest and stepwise selection.

    Science.gov (United States)

    Ebina, Teppei; Suzuki, Ryosuke; Tsuji, Ryotaro; Kuroda, Yutaka

    2014-08-01

    Domain linker prediction is attracting much interest as it can help identifying novel domains suitable for high throughput proteomics analysis. Here, we report H-DROP, an SVM-based Helical Domain linker pRediction using OPtimal features. H-DROP is, to the best of our knowledge, the first predictor for specifically and effectively identifying helical linkers. This was made possible first because a large training dataset became available from IS-Dom, and second because we selected a small number of optimal features from a huge number of potential ones. The training helical linker dataset, which included 261 helical linkers, was constructed by detecting helical residues at the boundary regions of two independent structural domains listed in our previously reported IS-Dom dataset. 45 optimal feature candidates were selected from 3,000 features by random forest, which were further reduced to 26 optimal features by stepwise selection. The prediction sensitivity and precision of H-DROP were 35.2 and 38.8%, respectively. These values were over 10.7% higher than those of control methods including our previously developed DROP, which is a coil linker predictor, and PPRODO, which is trained with un-differentiated domain boundary sequences. Overall, these results indicated that helical linkers can be predicted from sequence information alone by using a strictly curated training data set for helical linkers and carefully selected set of optimal features. H-DROP is available at http://domserv.lab.tuat.ac.jp.

  13. Implementing Competency-Based Medical Education in a Postgraduate Family Medicine Residency Training Program: A Stepwise Approach, Facilitating Factors, and Processes or Steps That Would Have Been Helpful.

    Science.gov (United States)

    Schultz, Karen; Griffiths, Jane

    2016-05-01

    In 2009-2010, the postgraduate residency training program at the Department of Family Medicine, Queen's University, wrestled with the practicalities of competency-based medical education (CBME) implementation when its accrediting body, the College of Family Physicians of Canada, introduced the competency-based Triple C curriculum. The authors used a stepwise approach to implement CMBE; the steps were to (1) identify objectives, (2) identify competencies, (3) map objectives and competencies to learning experiences and assessment processes, (4) plan learning experiences, (5) develop an assessment system, (6) collect and interpret data, (7) adjust individual residents' training programs, and (8) distribute decisions to stakeholders. The authors also note overarching processes, costs, and facil itating factors and processes or steps that would have been helpful for CBME implementation. Early outcomes are encouraging. Residents are being directly observed more often with increased documented feedback about performance based on explicit competency standards (24,000 data points for 150 residents from 2013 to 2015). These multiple observations are being collated in a way that is allowing the identification of patterns of performance, red flags, and competency development trajectory. Outliers are being identified earlier, resulting in earlier individualized modification of their residency training program. The authors will continue to provide and refine faculty development, are developing an entrustable professional activity field note app for handheld devices, and are undertaking research to explore what facilitates learners' competency development, what increases assessors' confidence in making competence decisions, and whether residents are better trained as a result of CBME implementation.

  14. Managing Colllinearity in Modeling the Effect of Age in the Prediction of Egg Components of Laying Hens Using Stepwise and Ridge Regression Analysis

    Directory of Open Access Journals (Sweden)

    TM Shafey

    2015-12-01

    Full Text Available ABSTRACT The relationships between egg measurements [egg weight (EGWT, egg width (EGWD, egg shape index (EGSI, egg volume (EGV and egg density (EGD], and egg components [eggshell (SWT, yolk (YWT and albumen (AWT] were investigated in laying hens with 32, 45, and 59 weeks of age with an objective of managing multicollinearity (MC, using stepwise regression (SR and ridge regression (RR analyses. There were significant correlations among egg traits that led to MC problems in all eggs. Hen age influenced egg characteristics and the magnitude of the correlations among egg characteristics. Eggs produced at older age had significantly (p<0.01 higher EGWT, EGWD, EGV, YWT and AWT than those produced at younger age. The SR model alleviated MC problem in eggs produced at 32 weeks, with condition index greater than 30, and one predictor, EGWT had a model fit predicted egg components with R2 ranged from 60 to 99%. The SR model of eggs produced at 45 and 59 weeks indicated MC problem with variance inflation factors (VIF values greater than 10, and 4 predictors; EGWT, EGWD, EGV and EGD had a model fit that significantly predicted egg components with R2 % ranged from 76 to 99 %. The RR analysis provided lower VIF values than 10 and eliminated the MC problem for eggs produced at any age group. It is concluded that the RR analysis provided an ideal solution for managing the MC problem and successfully predicting egg components of laying hens from egg measurements.

  15. Quantitative laser-induced breakdown spectroscopy data using peak area step-wise regression analysis: an alternative method for interpretation of Mars science laboratory results

    Energy Technology Data Exchange (ETDEWEB)

    Clegg, Samuel M [Los Alamos National Laboratory; Barefield, James E [Los Alamos National Laboratory; Wiens, Roger C [Los Alamos National Laboratory; Dyar, Melinda D [MT HOLYOKE COLLEGE; Schafer, Martha W [LSU; Tucker, Jonathan M [MT HOLYOKE COLLEGE

    2008-01-01

    The ChemCam instrument on the Mars Science Laboratory (MSL) will include a laser-induced breakdown spectrometer (LIBS) to quantify major and minor elemental compositions. The traditional analytical chemistry approach to calibration curves for these data regresses a single diagnostic peak area against concentration for each element. This approach contrasts with a new multivariate method in which elemental concentrations are predicted by step-wise multiple regression analysis based on areas of a specific set of diagnostic peaks for each element. The method is tested on LIBS data from igneous and metamorphosed rocks. Between 4 and 13 partial regression coefficients are needed to describe each elemental abundance accurately (i.e., with a regression line of R{sup 2} > 0.9995 for the relationship between predicted and measured elemental concentration) for all major and minor elements studied. Validation plots suggest that the method is limited at present by the small data set, and will work best for prediction of concentration when a wide variety of compositions and rock types has been analyzed.

  16. Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Xi-song, E-mail: Xisong.Ke@gades.uib.no [The Gade Institute, University of Bergen, Bergen (Norway); Department of Microbiology, Haukeland, University Hospital, Bergen (Norway); Li, Wen-cheng [The Gade Institute, University of Bergen, Bergen (Norway); Urological Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hovland, Randi [Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen (Norway); Department of Molecular Biology, University of Bergen, Bergen (Norway); Qu, Yi [The Gade Institute, University of Bergen, Bergen (Norway); Liu, Run-hui [Modern Research Center for Traditional Chinese Medicine, Second Military Medical University, Shanghai (China); McCormack, Emmet [Department of Medicine, Haukeland University Hospital, Bergen (Norway); Thorsen, Frits [Department of Biomedicine, University of Bergen, Bergen (Norway); Olsen, Jan Roger [The Gade Institute, University of Bergen, Bergen (Norway); Molven, Anders [The Gade Institute, University of Bergen, Bergen (Norway); Department of Pathology, Haukeland University Hospital, Bergen (Norway); Kogan-Sakin, Ira; Rotter, Varda [Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot (Israel); Akslen, Lars A. [The Gade Institute, University of Bergen, Bergen (Norway); Department of Pathology, Haukeland University Hospital, Bergen (Norway); Oyan, Anne Margrete [The Gade Institute, University of Bergen, Bergen (Norway); Department of Microbiology, Haukeland, University Hospital, Bergen (Norway); Kalland, Karl-Henning, E-mail: Kalland@gades.uib.no [The Gade Institute, University of Bergen, Bergen (Norway); Department of Microbiology, Haukeland, University Hospital, Bergen (Norway)

    2011-01-15

    Epithelial to mesenchymal transition (EMT) is pivotal in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to cells with mesenchymal phenotype (EPT1) without malignant transformation. To promote prostate cell transformation, cells were maintained in saturation density cultures to select for cells overriding quiescence. Foci formed repeatedly following around 8 weeks in confluent EPT1 monolayers. Only later passage EPT1, but not EP156T cells of any passage, could form foci. Cells isolated from the foci were named EPT2 and formed robust colonies in soft agar, a malignant feature present neither in EP156T nor in EPT1 cells. EPT2 cells showed additional malignant traits in vitro, including higher ability to proliferate following confluence, higher resistance to apoptosis and lower dependence on exogenous growth factors than EP156T and EPT1 cells. Microarray profiling identified gene sets, many of which belong to cell junction modules, that changed expression from EP156T to EPT1 cells and continued to change from EPT1 to EPT2 cells. Our findings provide a novel stepwise cell culture model in which EMT emerges independently of transformation and is associated with subsequent accumulation of malignant features in prostate cells. Reprogramming of cell junction modules is involved in both steps.

  17. Crystallographic Characterization of Stepwise Changes in Ligand Conformations as Their Internal Topology Changes and Two Novel Cross-Bridged Tetraazamacrocyclic Copper(II) Complexes.

    Science.gov (United States)

    Hubin, Timothy J.; McCormick, James M.; Alcock, Nathaniel W.; Clase, Howard J.; Busch, Daryle H.

    1999-10-04

    The parallel syntheses of two new cross-bridged tetraazamacrocyclic complexes whose ligands are derived from 1,4,8,11-tetraazacyclotetradecane (cyclam = 14N4) and rac-1,4,8,11-tetraaza-5,5,7,12,12,14-hexamethylcyclotetradecane (tetB = 14N4Me(6)) have been characterized through the crystal structure determination of every stepwise intermediate ligand in the multistep ligand syntheses. These structures show that although the final ligand skeletons are nearly identical, the immediate precursors differ greatly because of the six additional methyl groups of the 14N4Me(6) macrocycle. The inversion from one diastereomer to another of the tetracycle derived from rac-14N4Me(6) has been chemically induced through the successive addition of methyl groups to the reactive tertiary nitrogens, and the novel heterocycles produced have been crystallographically characterized with one showing a conformation not previously known for these systems. The structures of the two copper(II) complexes have significant geometrical differences, and accordingly, their electrochemical and spectroscopic properties are compared. The complexes exhibit remarkable kinetic stability under harsh conditions.

  18. Organic Analysis of Catalytic Fischer-Tropsch Synthesis Products and Ordinary Chondrite Meteorites by Stepwise Pyrolysis-GCMS: Organics in the Early Solar Nebula

    Science.gov (United States)

    Locke, Darren R.; Yazzie, Cyriah A.; Burton, Aaron S.; Niles, Paul B.; Johnson, Natasha M.

    2014-01-01

    Abiotic generation of complex organic compounds, in the early solar nebula that formed our solar system, is hypothesized by some to occur via Fischer-Tropsch (FT) synthesis. In its simplest form, FT synthesis involves the low temperature (300degC) produces FT products that include lesser amounts of n-alkanes and greater alkene, alcohol, and polycyclic aromatic hydrocarbon (PAH) compounds. We have begun to experimentally investigate FT synthesis in the context of abiotic generation of organic compounds in the early solar nebula. It is generally thought that the early solar nebula included abundant hydrogen and carbon monoxide gases and nano-particulate matter such as iron and metal silicates that could have catalyzed the FT reaction. The effect of FT reaction temperature, catalyst type, and experiment duration on the resulting products is being investigated. These solid organic products are analyzed by thermal-stepwise pyrolysis-GCMS and yield the types and distribution of hydrocarbon compounds released as a function of temperature. We show how the FT products vary by reaction temperature, catalyst type, and experimental duration and compare these products to organic compounds found to be indigenous to ordinary chondrite meteorites. We hypothesize that the origin of organics in some chondritic meteorites, that represent an aggregation of materials from the early solar system, may at least in part be from FT synthesis that occurred in the early solar nebula.

  19. An optimal glucose feeding strategy integrated with step-wise regulation of the dissolved oxygen level improves N-acetylglucosamine production in recombinant Bacillus subtilis.

    Science.gov (United States)

    Zhu, Yanqiu; Liu, Yanfeng; Li, Jianghua; Shin, Hyun-dong; Du, Guocheng; Liu, Long; Chen, Jian

    2015-02-01

    In our previous work, a recombinant Bacillus subtilis strain for the microbial production of N-acetylglucosamine (GlcNAc) was constructed through modular pathway engineering. In this study, to enhance GlcNAc production, glucose feeding approaches and dissolved oxygen (DO) control methods in fed-batch culture were systematically investigated. We first studied the effects of different glucose feeding strategies, including exponential fed-batch culture, pulse fed-batch culture, constant rate fed-batch culture, and glucose control (5 g/L, 10 g/L, 15 g/L) fed-batch culture, on cell growth and GlcNAc synthesis. We found that GlcNAc production in glucose control (5 g/L) fed-batch culture reached 26.58 g/L, which was 3.10 times that in batch culture. Next, the effect of DO level (20%, 30%, 40%, and 50%) on GlcNAc production was investigated, and a step-wise DO control strategy (0-7 h, 30%; 7-15 h, 50%; 15-50 h, 40%; 50-72 h, 30%) was introduced. With the optimal glucose and DO control strategy, GlcNAc production reached 35.77 g/L, which was 4.17 times the production in batch culture without DO control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Preparative Separation of Sulfur-Containing Diketopiperazines from Marine Fungus Cladosporium sp. Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode

    Directory of Open Access Journals (Sweden)

    Binbin Gu

    2015-01-01

    Full Text Available High-speed counter-current chromatography (HSCCC was successively applied to the separation of three sulfur-containing diketopiperazines (DKPs (including two new compounds cladosporin A (1 and cladosporin B (3, and a known compound haematocin (2 from a marine fungus Cladosporium sp. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v and (2:1:2:1, v/v, in stepwise elution mode, was used for HSCCC. The preparative HSCCC separation was performed on 300 mg of crude sample yielding 26.7 mg of compound 3 at a purity of over 95%, 53.6 mg of a mixture of compounds 1 and 2, which was further separated by preparative-HPLC yielding 14.3 mg of compound 1 and 25.4 mg of compound 2 each at a purity of over 95%. Their structures were established by spectroscopic methods. The sulfur-containing DKPs suppressed the proliferation of hepatocellular carcinoma cell line HepG2. The present work represents the first application of HSCCC in the efficient preparation of marine fungal natural products.

  1. Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations

    DEFF Research Database (Denmark)

    Jensen, Rasmus Hare; Thyssen Astvad, Karen Marie; Vale Silva, Luis

    2015-01-01

    Objectives: The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance.  Methods: Nine clinical isolates (P-1 to P-9) were susceptibility tested...... by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC......-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel–Cox tests. Results: P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9...

  2. Preparative Isolation and Purification of Lignans from Justicia procumbens Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode

    Directory of Open Access Journals (Sweden)

    Peijuan Zhou

    2015-04-01

    Full Text Available Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC was successfully applied to the isolation and purification of four lignans (justicidin B (1, justicidin A (2, 6'-hydroxyjusticidin C (3 and lignan J1 (4 from J. procumbens using stepwise elution with a pair of two-phase solvent systems composed of n-hexane–ethyl acetate–methanol–water at (1.3:1:1.3:1, v/v and (2.5:1:2.5:1, v/v. The preparative HSCCC separation was performed on 300 mg of crude sample yielding compounds 1 (19.7 mg, 2 (9.86 mg, 3 (11.26 mg, and 4 (2.54 mg in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, 1H-NMR and 13C-NMR. This is the first report on the application of HSCCC to the efficient separation of lignans from J. procumbens.

  3. A stepwise increase in recombinant human growth hormone dosing during puberty achieves improved pubertal growth: a National Cooperative Growth Study report.

    Science.gov (United States)

    Riddick, Linda; Alter, Craig; Davis, D Aaron; Frane, James; Lippe, Barbara; Bakker, Bert

    2009-07-01

    The magnitude of the pubertal growth spurt contributes to adult height. Children treated with increased doses of recombinant human growth hormone (rhGH) during puberty have shown improved near adult height (NAH) outcomes that varied by treatment duration. Males, in a single clinic, treated with a prepubertal dose of rhGH (0.3 mg/kg/wk) received 0.1 mg/kg/wk dose increases with successive Tanner stages up to 0.6 mg/kg/wk. Changes in height and height SDS from pubertal onset to NAH were assessed in patients attaining NAH after > or =3 years (n = 23) and > or =4 years (n = 16). Using ANCOVA, outcomes were compared to closely matched patients (n = 758) from the National Cooperative Growth Study treated with a fixed dose (0.3 mg/kg/wk) throughout puberty. Compared to matched patients, a 3.6 cm greater increase in mean height gain and a 0.49 greater increase in mean height SDS (p or =3 years. Corresponding values were 3.9 cm and 0.54 (p or =4 years. Stepwise increases in rhGH improved pubertal height gain when compared to a fixed dose and may represent an alternate approach to managing the patient during puberty.

  4. Sound quality prediction based on systematic metric selection and shrinkage: Comparison of stepwise, lasso, and elastic-net algorithms and clustering preprocessing

    Science.gov (United States)

    Gauthier, Philippe-Aubert; Scullion, William; Berry, Alain

    2017-07-01

    Sound quality is the impression of quality that is transmitted by the sound of a device. Its importance in sound and acoustical design of consumer products no longer needs to be demonstrated. One of the challenges is the creation of a prediction model that is able to predict the results of a listening test while using metrics derived from the sound stimuli. Often, these models are either derived using linear regression on a limited set of experimenter-selected metrics, or using more complex algorithms such as neural networks. In the former case, the user-selected metrics can bias the model and reflect the engineer pre-conceived idea of sound quality while missing potential features. In the latter case, although prediction might be efficient, the model is often in the form of a black-box which is difficult to use as a sound design guideline for engineers. In this paper, preprocessing by participants clustering and three different algorithms are compared in order to construct a sound quality prediction model that does not suffer from these limitations. The lasso, elastic-net and stepwise algorithms are tested for listening tests of consumer product for which 91 metrics are used as potential predictors. Based on the reported results, it is shown that the most promising algorithm is the lasso which is able to (1) efficiently limit the number of metrics, (2) most accurately predict the results of listening tests, and (3) provide a meaningful model that can be used as understandable design guidelines.

  5. Factorial kriging and stepwise regression approach to identify environmental factors influencing spatial multi-scale variability of heavy metals in soils.

    Science.gov (United States)

    Lv, Jianshu; Liu, Yang; Zhang, Zulu; Dai, Jierui

    2013-10-15

    The knowledge about spatial variations of heavy metals in soils and their relationships with environmental factors is important for human impact assessment and soil management. Surface soils from Rizhao city, Eastern China with rapid urbanization and industrialization were analyzed for six key heavy metals and characterized by parent material and land use using GIS-based data. Factorial kriging analysis and stepwise multiple regression were applied to examine the scale-dependent relationships among heavy metals and to identify environmental factors affecting spatial variability at each spatial scale. Linear model of coregionalization fitting showed that spatial multi-scale variation of heavy metals in soils consisted of nugget effect, an exponential structure with the range of 12 km (short-range scale), as well as a spherical structure with the range of 36 km (long-range scale). The short-range variation of Cd, Pb and Zn were controlled by land use, with higher values in urban areas as well as cultivated land in mountain area, and were related to human influence; while parent material dominated the long structure variations of these elements. Spatial variations of Cr and Ni were associated with natural geochemical sources at short- and long-range scales. At both two scales, Hg dominated by land use, corresponded well to spatial distributions of urban areas, and was attributed to anthropic emissions and atmosphere deposition. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Stepwise evolution of resistance to toxic cardenolides via genetic substitutions in the Na+/K+ -ATPase of milkweed butterflies (lepidoptera: Danaini).

    Science.gov (United States)

    Petschenka, Georg; Fandrich, Steffi; Sander, Nils; Wagschal, Vera; Boppré, Michael; Dobler, Susanne

    2013-09-01

    Despite the monarch butterfly (Danaus plexippus) being famous for its adaptations to the defensive traits of its milkweed host plants, little is known about the macroevolution of these traits. Unlike most other animal species, monarchs are largely insensitive to cardenolides, because their target site, the sodium pump (Na(+)/K(+) -ATPase), has evolved amino acid substitutions that reduce cardenolide binding (so-called target site insensitivity, TSI). Because many, but not all, species of milkweed butterflies (Danaini) are associated with cardenolide-containing host plants, we analyzed 16 species, representing all phylogenetic lineages of milkweed butterflies, for the occurrence of TSI by sequence analyses of the Na(+)/K(+) -ATPase gene and by enzymatic assays with extracted Na(+)/K(+) -ATPase. Here we report that sensitivity to cardenolides was reduced in a stepwise manner during the macroevolution of milkweed butterflies. Strikingly, not all Danaini typically consuming cardenolides showed TSI, but rather TSI was more strongly associated with sequestration of toxic cardenolides. Thus, the interplay between bottom-up selection by plant compounds and top-down selection by natural enemies can explain the evolutionary sequence of adaptations to these toxins. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  7. Stepwise extinction of larger foraminifers at the Cenomanian-Turonian boundary: A shallow-water perspective on nutrient fluctuations during Oceanic Anoxic Event 2 (Bonarelli Event)

    Science.gov (United States)

    Parente, Mariano; Frijia, Gianluca; di Lucia, Matteo; Jenkyns, Hugh C.; Woodfine, Richard G.; Baroncini, Francesco

    2008-09-01

    A two-step pattern in the extinction of larger foraminifersis recorded in the upper Cenomanian shallow-water carbonatesof the southern Apennines (Italy). The first step eliminatedthe alveolinids, the most extreme oligotrophs, and reduced dramaticallythe diversity of larger foraminifers. The second step wipedout the few survivors, seemingly able to tolerate mesotrophicconditions, leaving a disaster fauna dominated by small heterotrophs.This pattern of extinction parallels the ecological successionof shallow-water benthic foraminiferal assemblages along a gradientof increasing nutrient availability. High-resolution carbonisotope stratigraphy shows that the extinction of alveolinidswas contemporaneous with the extinction of rotaliporid plankticforaminifers, the drowning of certain Tethyan carbonate platforms,and an episode of thermal instability recorded in sea-surfacetemperature in the open ocean. Ocean stratification, duringthe first phase of Oceanic Anoxic Event 2, would have promotedoligotrophic conditions in surface tropical waters and maximumdiversity of larger foraminifers. Following this, ocean overturningcaused by surface-water cooling is credited with deliveringto shallow-water environments the excess nutrient loads previouslystored at depth, triggering the environmental changes leadingto stepwise extinction of larger foraminifers.

  8. Efficient genetic transformation of Lotus corniculatus L. using a direct shoot regeneration protocol, stepwise hygromycin B selection, and a super-binary Agrobacterium tumefaciens vector

    Directory of Open Access Journals (Sweden)

    Nikolić Radomirka

    2007-01-01

    Full Text Available Cotyledons from 6-day-old Lotus corniculatus cv. Bokor seedlings, transversally cut into two halves, were capa­ble of regenerating buds without intervening callus formation. The explants were co-cultivated with the Agrobacterium tumefaciens LBA4404/pTOK233 superbinary vector carrying the uidA-intron gene and the genes hpt and nptII. They were cultured for 14 days on a regeneration medium, then subjected to a stepwise hygromycin B selection procedure consisting of gradually increasing antibiotic concentrations (5-15 mg L-1 over 21 weeks. Transformed shoots were obtained within 5 months after co-cultivation. Out of 124 initially co-cultivated explants, 52 (42% plants survived hygromycin B selection. The presence of transgenes in regenerated plants was verified by β-glucuronidase histochemical assays and PCR analysis for the presence of uidA gene sequences. Hygromycin B-resistant and PCR-positive T0 plants were cultured in the greenhouse to produce flowers and seeds. The obtained data demonstrate that the reported transformation protocol could be useful for introducing agriculturally important genes into the new L. corniculatus cultivar Bokor.

  9. A stepwise, 'test-all-positives' methodology to assess gluten-kernel contamination at the serving-size level in gluten-free (GF) oat production.

    Science.gov (United States)

    Chen, Yumin; Fritz, Ronald D; Kock, Lindsay; Garg, Dinesh; Davis, R Mark; Kasturi, Prabhakar

    2018-02-01

    A step-wise, 'test-all-positive-gluten' analytical methodology has been developed and verified to assess kernel-based gluten contamination (i.e., wheat, barley and rye kernels) during gluten-free (GF) oat production. It targets GF claim compliance at the serving-size level (of a pouch or approximately 40-50g). Oat groats are collected from GF oat production following a robust attribute-based sampling plan then split into 75-g subsamples, and ground. R-Biopharm R5 sandwich ELISA R7001 is used for analysis of all the first15-g portions of the ground sample. A >20-ppm result disqualifies the production lot, while a >5 to <20-ppm result triggers complete analysis of the remaining 60-g of ground sample, analyzed in 15-g portions. If all five 15-g test results are <20ppm, and their average is <10.67ppm (since a 20-ppm contaminant in 40g of oats would dilute to 10.67ppm in 75-g), the lot is passed. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Stepwise microhydration of aromatic amide cations: water solvation networks revealed by the infrared spectra of acetanilide(+)-(H2O)n clusters (n ≤ 3).

    Science.gov (United States)

    Klyne, Johanna; Schmies, Matthias; Miyazaki, Mitsuhiko; Fujii, Masaaki; Dopfer, Otto

    2017-09-15

    The structure and activity of peptides and proteins strongly rely on their charge state and the interaction with their hydration environment. Here, infrared photodissociation (IRPD) spectra of size-selected microhydrated clusters of cationic acetanilide (AA(+), N-phenylacetamide), AA(+)-(H2O)n with n ≤ 3, are analysed by dispersion-corrected density functional theory calculations at the ωB97X-D/aug-cc-pVTZ level to determine the stepwise microhydration process of this aromatic peptide model. The IRPD spectra are recorded in the informative X-H stretch (νOH, νNH, νCH, amide A, 2800-3800 cm(-1)) and fingerprint (amide I-II, 1000-1900 cm(-1)) ranges to probe the preferred hydration motifs and the cluster growth. In the most stable AA(+)-(H2O)n structures, the H2O ligands solvate the acidic NH proton of the amide by forming a hydrogen-bonded solvent network, which strongly benefits from cooperative effects arising from the excess positive charge. Comparison with neutral AA-H2O reveals the strong impact of ionization on the acidity of the NH proton and the topology of the interaction potential. Comparison with related hydrated formanilide clusters demonstrates the influence of methylation of the amide group (H → CH3) on the shape of the intermolecular potential and the structure of the hydration shell.

  11. Stepwise assembly of a semiconducting coordination polymer [Cd8S(SPh)14(DMF)(bpy)]n and its photodegradation of organic dyes.

    Science.gov (United States)

    Xu, Chao; Hedin, Niklas; Shi, Hua-Tian; Xin, ZhiFeng; Zhang, Qian-Feng

    2015-04-14

    Chalcogenolate clusters can be interlinked with organic linkers into semiconducting coordination polymers with photocatalytic properties. Here, discrete clusters of Cd8S(SPh)14(DMF)3 were interlinked with 4,4'-bipyridine into a one dimensional coordination polymer of [Cd8S(SPh)14(DMF)(bpy)]n with helical chains. A stepwise mechanism for the assembly of the coordination polymer in DMF was revealed by an ex situ dynamic light scattering study. The cluster was electrostatically neutral and showed a penta-supertetrahedral structure. During the assembly each cluster was interlinked with two 4,4'-bipyridine molecules, which replaced the two terminal DMF molecules of the clusters. In their solid-state forms, the cluster and the coordination polymer were semiconductors with wide band gaps of 3.08 and 2.80 ev. They photocatalytically degraded rhodamine B and methylene blue in aqueous solutions. The moderate conditions used for the synthesis could allow for further in situ studies of the reaction-assembly of related clusters and coordination polymers.

  12. Delineating chalk sand distribution of Ekofisk formation using probabilistic neural network (PNN) and stepwise regression (SWR): Case study Danish North Sea field

    Science.gov (United States)

    Haris, A.; Nafian, M.; Riyanto, A.

    2017-07-01

    Danish North Sea Fields consist of several formations (Ekofisk, Tor, and Cromer Knoll) that was started from the age of Paleocene to Miocene. In this study, the integration of seismic and well log data set is carried out to determine the chalk sand distribution in the Danish North Sea field. The integration of seismic and well log data set is performed by using the seismic inversion analysis and seismic multi-attribute. The seismic inversion algorithm, which is used to derive acoustic impedance (AI), is model-based technique. The derived AI is then used as external attributes for the input of multi-attribute analysis. Moreover, the multi-attribute analysis is used to generate the linear and non-linear transformation of among well log properties. In the case of the linear model, selected transformation is conducted by weighting step-wise linear regression (SWR), while for the non-linear model is performed by using probabilistic neural networks (PNN). The estimated porosity, which is resulted by PNN shows better suited to the well log data compared with the results of SWR. This result can be understood since PNN perform non-linear regression so that the relationship between the attribute data and predicted log data can be optimized. The distribution of chalk sand has been successfully identified and characterized by porosity value ranging from 23% up to 30%.

  13. Long-term survival and vitality outcomes of permanent teeth following deep caries treatment with step-wise and partial-caries-removal: A Systematic Review.

    Science.gov (United States)

    Hoefler, Vaughan; Nagaoka, Hiroko; Miller, Craig S

    2016-11-01

    A systematic review was performed to compare the long-term survival of deep dentine caries-affected permanent teeth treated with partial-caries-removal (PCR) versus similar teeth treated with stepwise-caries-removal techniques (SWT). Clinical studies investigating long-term PCR and SWT outcomes in unrestored permanent teeth with deep dentine caries were evaluated. Failures were defined as loss of pulp vitality or restorative failures following treatment. PubMed, Web of Science, Dentistry and Oral Sciences Source, and Central databases were systematically searched. From 136 potentially relevant articles, 9 publications utilizing data from 5 studies (2 RCTs, and 3 observational case-series) reporting outcomes for 426 permanent teeth over two to ten years were analyzed. Regarding restorative failures, >88% success at two years for both techniques was reported. For loss of pulp vitality, observational studies reported >96% vitality at two years for each technique, while one RCT reported significantly higher vitality (pdeep dentine caries. Partial-caries-removal may result in fewer pulpal complications over a three year period than SWT, although claims of a therapeutic advantage are based on very few, limited-quality studies. Partial-caries-removal and SWT are deep caries management techniques that reduce pulp exposure risk. Permanent teeth with deep dentine caries treated with either technique have a high likelihood for survival beyond two years. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Efficient Synthesis of Ethanol from CH4 and Syngas on a Cu-Co/TiO2 Catalyst Using a Stepwise Reactor

    Science.gov (United States)

    Zuo, Zhi-Jun; Peng, Fen; Huang, Wei

    2016-10-01

    Ethanol synthesis from CH4 and syngas on a Cu-Co/TiO2 catalyst is studied using experiments, density functional theory (DFT) and microkinetic modelling. The experimental results indicate that the active sites of ethanol synthesis from CH4 and syngas are Cu and CoO, over which the ethanol selectivity is approximately 98.30% in a continuous stepwise reactor. DFT and microkinetic modelling results show that *CH3 is the most abundant species and can be formed from *CH4 dehydrogenation or through the process of *CO hydrogenation. Next, the insertion of *CO into *CH3 forms *CH3CO. Finally, ethanol is formed through *CH3CO and *CH3COH hydrogenation. According to our results, small particles of metallic Cu and CoO as well as a strongly synergistic effect between metallic Cu and CoO are beneficial for ethanol synthesis from CH4 and syngas on a Cu-Co/TiO2 catalyst.

  15. Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions

    Directory of Open Access Journals (Sweden)

    Kosuke Kanke

    2014-06-01

    Full Text Available Pluripotent stem cells are a promising tool for mechanistic studies of tissue development, drug screening, and cell-based therapies. Here, we report an effective and mass-producing strategy for the stepwise differentiation of mouse embryonic stem cells (mESCs and mouse and human induced pluripotent stem cells (miPSCs and hiPSCs, respectively into osteoblasts using four small molecules (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], and a helioxanthin-derivative 4-(4-methoxyphenylpyrido[4′,3′:4,5]thieno[2,3-b]pyridine-2-carboxamide [TH] under serum-free and feeder-free conditions. The strategy, which consists of mesoderm induction, osteoblast induction, and osteoblast maturation phases, significantly induced expressions of osteoblast-related genes and proteins in mESCs, miPSCs, and hiPSCs. In addition, when mESCs defective in runt-related transcription factor 2 (Runx2, a master regulator of osteogenesis, were cultured by the strategy, they molecularly recapitulated osteoblast phenotypes of Runx2 null mice. The present strategy will be a platform for biological and pathological studies of osteoblast development, screening of bone-augmentation drugs, and skeletal regeneration.

  16. Selective synthesis of single- and multi-walled supramolecular nanotubes by using solvophobic/solvophilic controls: stepwise radial growth via "coil-on-tube" intermediates.

    Science.gov (United States)

    Prasanthkumar, Seelam; Zhang, Wei; Jin, Wusong; Fukushima, Takanori; Aida, Takuzo

    2015-09-14

    Novel hexa-peri-hexabenzocoronene (HBC) derivatives, (F) HBC and (F) HBC*, which carry perfluoroalkyl segments on one side of the HBC core and long alkyl tails on the other, were synthesized. Their perfluoroalkyl segments are highly solvated in C6 F6 (solvophilic effect) and do not assemble, whereas in CH2 Cl2 , they are excluded (solvophobic effect) and assemble together consequently. For example, the use of C6 F6 and CH2 Cl2 as assembling media for (F) HBC leads to the selective formation of single- and multi-walled nanotubes, respectively. When a higher monomer concentration is applied in CH2 Cl2 , multi-walled nanotubes with a larger number of walls result. (F) HBC in CH2 Cl2 self-assembles rather slowly, thereby allowing for the observation of coil-on-tube structures, which are possible intermediates for the stepwise radial growth of the nanotubular wall. Casting of the multi-walled nanotubes onto a quartz plate yields a superhydrophobic thin film with a water contact angle of 161±2°. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Purification of quinoline yellow components using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase.

    Science.gov (United States)

    Oka, Hisao; Harada, Ken-Ichi; Suzuki, Masanao; Fujii, Kiyonaga; Iwaya, Masato; Ito, Yuko; Goto, Tomomi; Matsumoto, Hiroshi; Ito, Yoichiro

    2003-03-14

    Quinoline yellow (Color Index No. 47005) consists of multiple components that show a large difference in their partition coefficients (K), ranging from 0.03 to 3.3 in the solvent system tert.-butyl methyl ether (MTBE)-1-butanol-acetonitrile-aqueous 0.1 M trifluoroacetic acid (TFA). Consequently, it requires an excessively long elution time for the simultaneous separation of all components by the standard high-speed counter-current chromatography technique, which uses a constant flow-rate of the mobile phase. In order to overcome this problem, we increased the flow-rate of the mobile phase stepwise from 0.1 to 2.0 mL/min. Using this new procedure, six components (0.2-6.1 mg) were successfully isolated from 25 mg of a commercial quinoline yellow preparation in a single run using a two-phase solvent system composed of MTBE-1-butanol-acetonitrile-aqueous 0.1 M TFA (1:3:1:5, v/v). The purified components were analyzed by high-performance liquid chromatography, electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy.

  18. Multiple Hypotheses Testing Procedures in Clinical Trials and Genomic Studies

    Directory of Open Access Journals (Sweden)

    Qing ePan

    2013-12-01

    Full Text Available We review and compare multiple hypothesis testing procedures used in clinical trials and those in genomic studies. Clinical trials often employ global tests, which draw an overall conclusion for all the hypotheses, such as SUM test, Two-Step test, Approximate Likelihood Ratio test (ALRT, Intersection Union Test (IUT and MAX test. The SUM and Two-Step tests are most powerful under homogeneous treatment effects, while the ALRT and MAX test are robust in cases with nonhomogeneous treatment effects. Furthermore, the ALRT is robust to unequal sample sizes across endpoints. In genomic studies, stepwise procedures are used to draw marker-specific conclusions and control family wise error rate (FWER or false discovery rate (FDR at the same time. FDR refers to the percent of false positives among all significant results and is preferred over FWER in screening high-dimensional genomic markers due to its interpretability. In cases where correlations between test statistics cannot be ignored, Westfall-Young resampling method can be employed to generate the joint distribution of P-values under the null and maintain their correlation structure. Finally, the GWAS from a clinical trial studying microvascular complications among Type 1 diabetes patients is used to illustrate various procedures.

  19. Stepwise morphological evolution of the active Yellow River (Huanghe) delta lobe (1976-2013): Dominant roles of riverine discharge and sediment grain size

    Science.gov (United States)

    Wu, Xiao; Bi, Naishuang; Xu, Jingping; Nittrouer, Jeffrey A.; Yang, Zuosheng; Saito, Yoshiki; Wang, Houjie

    2017-09-01

    The presently active Yellow River (Huanghe) delta lobe has been formed since 1976 when the river was artificially diverted. The process and driving forces of morphological evolution of the present delta lobe still remain unclear. Here we examined the stepwise morphological evolution of the active Yellow River delta lobe including both the subaerial and the subaqueous components, and illustrated the critical roles of riverine discharge and sediment grain size in dominating the deltaic evolution. The critical sediment loads for maintaining the delta stability were also calculated from water discharge and sediment load measured at station Lijin, the last gauging station approximately 100 km upstream from the river mouth. The results indicated that the development of active delta lobe including both subaerial and subaqueous components has experienced four sequential stages. During the first stage (1976-1981) after the channel migration, the unchannelized river flow enhanced deposition within the channel and floodplain between Lijin station and the river mouth. Therefore, the critical sediment supply calculated by the river inputs obtained from station Lijin was the highest. However, the actual sediment load at this stage (0.84 Gt/yr) was more than twice of the critical sediment load ( 0.35 Gt/yr) for sustaining the active subaerial area, which favored a rapid seaward progradation of the Yellow River subaerial delta. During the second stage (1981-1996), the engineering-facilitated channelized river flow and the increase in median grain size of suspended sediment delivered to the sea resulted in the critical sediment load for keeping the delta stability deceasing to 0.29 Gt/yr. The active delta lobe still gradually prograded seaward at an accretion rate of 11.9 km2/yr at this stage as the annual sediment load at Lijin station was 0.55 Gt/yr. From 1996 to 2002, the critical sediment load further decreased to 0.15 Gt/yr with the sediment grain size increased to 22.5

  20. A new class of cuprous bromide cluster-based hybrid materials: direct observation of the stepwise replacement of hydrogen bonds by coordination bonds.

    Science.gov (United States)

    Zhang, Xian-Ming; Hou, Juan-Juan; Guo, Cai-Hong; Li, Chun-Fang

    2015-01-20

    Although a variety of functional metal-organic frameworks (MOFs) have been synthesized, post-modified, and applied in various areas, there is little knowledge about how molecular cluster building units are stepwise evolved into MOFs via intermediates. Coordination bonds are generally stronger than hydrogen bonds, and thus equivalent replacement of X-H···Y hydrogen bonds by X-M-Y coordination bonds can transform hydrogen bond networks into MOFs. In this work, solvothermal in situ reduction reactions of CuBr2 and 1,4-diazoniabicyclo[2,2,2]octane (DABCO) generated a myriad of tunable photoluminescent cuprous body-centered cubic bromide cluster-based networks with the general formula [Cu4+xH4-xBr6(DABCO)4](HCO2)2·S (x = 0, 0.56, 0.81, 1.27, 1.39, 2.56, 2.78, and 4 for compounds 1-8, respectively). All of these compounds crystallize in the cubic space group with the largest volume difference being only 5.2%, but they belong to three remarkably different kinds of crystals. Complex 1 is a molecular crystal and consists of tetrahedral [Cu4Br6(HDABCO)4](2+) clusters with monodentate HDABCO groups that are supported via N-H···Br synthons in the hydrogen bond network. Compound 8 is a [Cu8Br6](2+) cube cluster-based MOF with bridged DABCO ligands. Complexes 2-7 are seemingly impossible Cu/H-substituted solid solutions of 1 and 8. The CuBr framework components in 1-8 are Cu4Br6, Cu4.56Br6, Cu4.81Br6, Cu5.27Br6, Cu5.39Br6, Cu6.56Br6, Cu6.78Br6, and Cu8Br6, respectively. Crystallization kinetics studies revealed that the [Cu4Br6(HDABCO)4](2+) cluster-based hydrogen bond network (1) was initially formed such that N-H···Br hydrogen bonds could be stepwise replaced by N-Cu-Br coordination bonds to form the [Cu8Br6](2+) cube cluster-based MOF (8) via solid solutions. These observations directly reveal the equivalence and transformation between the N-H···Br hydrogen bond and the N-Cu-Br coordination bond and the evolutionary mechanism of a molecular crystal to a MOF via

  1. Selective CO2 Sequestration with Monolithic Bimodal Micro/Macroporous Carbon Aerogels Derived from Stepwise Pyrolytic Decomposition of Polyamide-Polyimide-Polyurea Random Copolymers.

    Science.gov (United States)

    Saeed, Adnan M; Rewatkar, Parwani M; Majedi Far, Hojat; Taghvaee, Tahereh; Donthula, Suraj; Mandal, Chandana; Sotiriou-Leventis, Chariklia; Leventis, Nicholas

    2017-04-19

    Polymeric aerogels (PA-xx) were synthesized via room-temperature reaction of an aromatic triisocyanate (tris(4-isocyanatophenyl) methane) with pyromellitic acid. Using solid-state CPMAS (13)C and (15)N NMR, it was found that the skeletal framework of PA-xx was a statistical copolymer of polyamide, polyurea, polyimide, and of the primary condensation product of the two reactants, a carbamic-anhydride adduct. Stepwise pyrolytic decomposition of those components yielded carbon aerogels with both open and closed microporosity. The open micropore surface area increased from CO2 opened access to the closed pores and the micropore area increased by almost 4× to 1150 m(2) g(-1) (out of 1750 m(2) g(-1) of a total BET surface area). At 0 °C, etched carbon aerogels demonstrated a good balance of adsorption capacity for CO2 (up to 4.9 mmol g(-1)), and selectivity toward other gases (via Henry's law). The selectivity for CO2 versus H2 (up to 928:1) is suitable for precombustion fuel purification. Relevant to postcombustion CO2 capture and sequestration (CCS), the selectivity for CO2 versus N2 was in the 17:1 to 31:1 range. In addition to typical factors involved in gas sorption (kinetic diameters, quadrupole moments and polarizabilities of the adsorbates), it is also suggested that CO2 is preferentially engaged by surface pyridinic and pyridonic N on carbon (identified with XPS) in an energy-neutral surface reaction. Relatively high uptake of CH4 (2.16 mmol g(-1) at 0 °C/1 bar) was attributed to its low polarizability, and that finding paves the way for further studies on adsorption of higher (i.e., more polarizable) hydrocarbons. Overall, high CO2 selectivities, in combination with attractive CO2 adsorption capacities, low monomer cost, and the innate physicochemical stability of carbon render the materials of this study reasonable candidates for further practical consideration.

  2. Blood pressure gradients and cardiovascular risk factors in urban and rural populations in Abia State South Eastern Nigeria using the WHO STEPwise approach.

    Directory of Open Access Journals (Sweden)

    Ikechi Gareth Okpechi

    Full Text Available BACKGROUND: Developing countries of sub-Saharan Africa (SSA face a double burden of non-communicable diseases (NCDs and communicable diseases. As high blood pressure (BP is a common global cardiovascular (CV disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. METHODS: Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a population-based cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1; BP and anthropometric measurements (Step 2, and fasting blood cholesterol and glucose (Step 3. RESULTS: Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%, hypertension (31.4%, cigarette smoking (13.3%, use of smokeless tobacco (4.8%, physical inactivity (64.2% and being overweight or obese (33.7%. Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco and physical inactivity occurred more frequently in males than in females (p<0.05; while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p<0.05. The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. CONCLUSION: Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa.

  3. Stepwise flow diagram for the development of formulations of non spore-forming bacteria against foliar pathogens: The case of Lysobacter capsici AZ78.

    Science.gov (United States)

    Segarra, Guillem; Puopolo, Gerardo; Giovannini, Oscar; Pertot, Ilaria

    2015-12-20

    The formulation is a significant step in biopesticide development and is an efficient way to obtain consistency in terms of biological control under field conditions. Nonetheless, there is still a lack of information regarding the processes needed to achieve efficient formulation of non spore-forming bacterial biological control agents. In response to this, we propose a flow diagram made up of six steps including selection of growth parameters, checking of minimum shelf life, selection of protective additives, checking that the additives have no adverse effects, validation of the additive mix under field conditions and choosing whether to use additives as co-formulants or tank mix additives. This diagram is intended to provide guidance and decision-making criteria for the formulation of non spore-forming bacterial biological control agents against foliar pathogens. The diagram was then validated by designing an efficient formulation for a Gram-negative bacterium, Lysobacter capsici AZ78, to control grapevine downy mildew caused by Plasmopara viticola. A harvest of 10(10)L. capsici AZ78cellsml(-1) was obtained in a bench top fermenter. The viability of cells decreased by only one order of magnitude after one year of storage at 4°C. The use of a combination of corn steep liquor, lignosulfonate, and polyethyleneglycol in the formulation improved the survival of L. capsici AZ78 cells living on grapevine leaves under field conditions by one order of magnitude. Furthermore, the use of these additives also guaranteed a reduction of 71% in P. viticola attacks. In conclusion, this work presents a straightforward stepwise flow diagram to help researchers develop formulations for biological control agents that are easy to prepare, stable, not phytotoxic and able to protect the microorganims under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Effect of Stepwise Blanching and Calcium Chloride Solution on Texture and Structural Properties of Jalapeño Peppers in Brine

    Directory of Open Access Journals (Sweden)

    Dinora Judith Palma-Zavala

    2009-01-01

    Full Text Available Jalapeño peppers incur texture changes during thermal processing due to loss of turgor pressure, tissue softening, and pectin solubility in the cell wall, which affects their quality and acceptability as a processed product among consumers. The objective of this work is to evaluate the effect of stepwise blanching with calcium chloride solution on firmness, calcium absorption and microstructural changes of jalapeño peppers. Batches of 1 kg of pepper halves were blanched at 65 °C for 4 min at different concentrations of CaCl2 (0, 0.075, 0.15 and 0.3 mol/L. After blanching, the peppers were removed, placed in plastic bags and submerged in a water bath at 65 °C for different holding times (0, 15, 30 and 45 min. Then the peppers were blanched again in an acidified solution at 96 °C for 3 min to remove enzymatic activity. Afterwards, peppers were packed in glass containers with brine at 95 °C and pasteurized at 85 °C for 10 min. The product was stored for 10 days at room temperature, then analyzed for texture, calcium absorption, pH, acidity, and microstructural changes. Results showed that CaCl2 concentration and blanching improved firmness with a maximum value of 3.68 N, a 4.3-fold increase over control. Calcium absorption increased with CaCl2 concentration reaching a maximum of 0.68 g of Ca2+ per kg of samples. Microscopy showed reduced cell wall damage in the samples that were blanched in 0.3 mol/L of CaCl2 at 45 min of holding time. The optimum processing conditions determined in thisstudy can be used for improving the firmness of peppers.

  5. Structural mechanism of enoyl-CoA hydratase: three atoms from a single water are added in either an E1cb stepwise or concerted fashion.

    Science.gov (United States)

    Bahnson, Brian J; Anderson, Vernon E; Petsko, Gregory A

    2002-02-26

    We have determined the crystal structure of the enzyme enoyl-CoA hydratase (ECH) from rat liver with the bound substrate 4-(N,N-dimethylamino)cinnamoyl-CoA using X-ray diffraction data to a resolution of 2.3 A. In addition to the thiolester substrate, the catalytic water, which is added in the hydration reaction, has been modeled into well-defined electron density in each of the six active sites of the physiological hexamer within the crystallographic asymmetric unit. The catalytic water bridges Glu(144) and Glu(164) of the enzyme and has a lone pair of electrons poised to react with C(3) of the enzyme-bound alpha,beta-unsaturated thiolester. The water molecule, which bridges two glutamate residues, is reminiscent of the enolase active site. However, unlike enolase, which has a lysine available to donate a proton, there are no other sources of protons available from other active site residues in ECH. Furthermore, an analysis of the hydrogen-bonding network of the active site suggests that both Glu(144) and Glu(164) are ionized and carry a negative charge with no reasonable place to have a protonated carboxylate. This lack of hydrogen-bonding acceptors that could accommodate a source of a proton, other than from the water molecule, leads to a hypothesis that the three atoms from a single water molecule are added across the double bond to form the hydrated product. The structural results are discussed in connection with details of the mechanism, which have been elucidated from kinetics, site-directed mutagenesis, and spectroscopy of enzyme-substrate species, in presenting an atomic-resolution mechanism of the reaction. Contrary to the previous interpretation, the structure of the E-S complex together with previously determined kinetic isotope effects is consistent with either a concerted mechanism or an E1cb stepwise mechanism.

  6. Does migratory distance affect fuelling in a medium-distance passerine migrant?: results from direct and step-wise simulated magnetic displacements

    Directory of Open Access Journals (Sweden)

    Mihaela Ilieva

    2016-03-01

    Full Text Available In birds, fat accumulation before and during migration has been shown to be endogenously controlled and tuned by, among other factors, the Earth's magnetic field. However, our knowledge about the influence of the geomagnetic field on the fuelling in migrating birds is still limited to just a few nocturnally migrating passerine species. In order to study if variations of the magnetic field can also influence the fuelling of both day- and night-migrating passerines, we caught first-year dunnocks (Prunella modularis and subjected them to three magnetic field conditions simulated by a system of magnetic coils: (1 local geomagnetic field of southern Sweden, (2 magnetic field corresponding to the centre of the expected wintering area, and (3 magnetic field met at the northern limit of the species' breeding distribution. We did not find a difference in mass increase between the birds kept in a local magnetic field and a field resembling their wintering area, irrespectively of the mode of magnetic displacement, i.e. direct or step-wise. However, the dunnocks magnetically displaced north showed a lower rate of fuelling in comparison to the control group, probably due to elevated activity. Compared with previous studies, our results suggest that the fuelling response to magnetic displacements during the migration period is specific to the eco-physiological situation. Future studies need to address if there is an effect of magnetic field manipulation on the level of migratory activity in dunnocks and how widespread the influence of local geomagnetic field parameters is on fuelling decisions in different bird species, which have different migratory strategies, distances and migration history.

  7. A step-wise semi-distributed simulation approach to characterize a karst aquifer and to support dam construction in a data-scarce environment

    Science.gov (United States)

    Adinehvand, R.; Raeisi, E.; Hartmann, A.

    2017-11-01

    Karst systems provide significant volumes of drinking water for large parts of the world population. Due to chemical weathering, karst systems are characterized by strong heterogeneity resulting in a complex flow and storage behaviour. Presently available karst modelling strategies account for the karstic heterogeneity but often a lack of data limits their applicability in data-scarce regions. In this study, a step-wise simulation approach with a semi-distributed karst model is proposed to characterize a karst aquifer at a data-scarce region in Southwest Iran and to evaluate the leakage potential related to a future dam construction project at a river that cuts through the aquifer. Observed groundwater level time series were applied to calibrate and validate the model. In order to avoid over-parameterization, the karst aquifer was split into three sections down the hydraulic gradient. At each section, groundwater level observations were used to iteratively calibrate the model from the first to the last section. A spatial split-sample test and sensitivity analysis served to evaluate the prediction performance and the identifiability of the model parameters. Finally, simple scenarios of the river infiltration into the aquifer were applied to evaluate the leakage potential of the aquifer for future dam constructions. The spatial split-sample test showed that the semi-distributed model provided reliable predictions but prediction performance and parameter identifiability decreased from the first towards the last aquifer section, most probably due to increased aquifer complexity and propagation of uncertainty from the up-gradient model section. Using sensitivity analysis, we also show that parameter sensitivities increase significantly if parameter estimation was applied simultaneously to all three aquifer subsections. Using the model to assess the leakage potential indicated that, without further technical measures, the all river flow would be able infiltrate into the

  8. Homolog-focused profiling of ginsenosides based on the integration of step-wise formate anion-to-deprotonated ion transition screening and scheduled multiple reaction monitoring.

    Science.gov (United States)

    Song, Yuelin; Zhang, Na; Shi, Shepo; Li, Jun; Zhao, Yunfang; Zhang, Qian; Jiang, Yong; Tu, Pengfei

    2015-08-07

    Homolog-focused profiling is a favored option to bridge targeted metabolomics toward non-targeted metabolomics. In current study, an attempt was made for the large-scale ginsenoside-specific analysis in ginseng (G) and American ginseng (AG). When formic acid (0.1%, v/v) was introduced as the mobile phase additive, formate anion-to-deprotonated ion transitions ([M+HCOO](-)>[M-H](-)) with an optimal collision energy (-32eV) could result in satisfactory responses for ginsenosides. Therefore, a step-wise multiple reaction monitoring (MRM)-based method employing [M+HCOO](-)>[M-H](-) ion pairs was constructed to screen ginsenosides among 501-1250u (for Q1) with a step-size of 2u, and MRM also served as a survey experiment to trigger enhanced product ion scans for MS(2) spectrum acquisition on a hybrid triple quadrupole-linear ion trap mass spectrometer; then, the identification of those observed ginsenosides was achieved on the basis of the well-defined mass cracking patterns for ginsenosides; afterwards, scheduled MRM was introduced for large-scale relatively quantitative analysis of all detected ginsenosides. Finally, comparative metabolomics were performed to differentiate G, AG, and their processed products. Method validation was carried out using thirteen authentic compounds. A total of 221 ginsenosides, among which 185 ones were annotated, were observed and relatively quantitated. All crude materials were obviously classified into groups I-III. Above all, the MRM-based homolog-focused profiling of ginsenosides could be used as a reliable tool to gain an in-depth view for ginsenoside-enriched herbal products. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review.

    Science.gov (United States)

    Stuck, Anna K; Fuhrer, Evelyn; Limacher, Andreas; Méan, Marie; Aujesky, Drahomir

    2014-03-01

    Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Clinical trial methodology

    National Research Council Canada - National Science Library

    Peace, Karl E; Chen, Ding-Geng

    2011-01-01

    "Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide...

  11. Hepatitis C: Clinical Trials

    Science.gov (United States)

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  12. Informed Consent (Clinical Trials)

    Science.gov (United States)

    ... Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer Drugs ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer ...

  13. Research Areas - Clinical Trials

    Science.gov (United States)

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  14. Clinical trials of homoeopathy

    NARCIS (Netherlands)

    Kleijnen, J.; Knipschild, P.; ter Riet, G.

    1991-01-01

    OBJECTIVE: To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN: Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using

  15. Clinical Research and Clinical Trials

    Science.gov (United States)

    ... Contracts section of the NIH website. Find NICHD Clinical Trials NIH maintains the ClinicalTrials.gov website as the main database of publicly and privately funded clinical trials. Each trial has its own pre-defined research ...

  16. The COLOFOL trial

    DEFF Research Database (Denmark)

    Hansdotter Andersson, Pernilla; Wille-Jørgensen, Peer; Horváth-Puhó, Erzsébet

    2016-01-01

    INTRODUCTION: The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL...... trial, comparing demographic characteristics between randomized patients and eligible patients not included in the study. MATERIALS AND METHODS: COLOFOL was designed as a pragmatic trial with wide inclusion criteria and few exclusion criteria, in order to obtain a sample reflecting the general patient...... and localization. The analyses will be stratified by these variables. Taken together, we conclude that our trial results will be robust and possible to extrapolate to the target population....

  17. Understanding noninferiority trials

    Directory of Open Access Journals (Sweden)

    Seokyung Hahn

    2012-11-01

    Full Text Available Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

  18. A step-wise steerable source of illumination for low-noise "Violin-Mode" shadow sensors, intended for use in interferometric gravitational wave detectors

    Science.gov (United States)

    Lockerbie, N. A.; Tokmakov, K. V.

    2016-01-01

    A steerable low-noise source of illumination is described for shadow-sensors having a displacement sensitivity of ˜100 pm (rms)/√Hz, at 500 Hz, over a measuring span of at least ±0.5 mm. These sensors were designed to detect lateral "Violin-Mode" resonances in the highly tensioned fused-silica suspension fibres of the test-masses/mirrors for the Advanced Laser Interferometer Gravitational Wave Observatory gravitational wave detectors. The shadow sensors—one intended for each of the four fibres in a suspension—comprised a source of Near InfraRed (NIR) radiation (emitter) and a differential shadow-displacement sensor (detector), these bracketing the fibre under test. The suspension fibres themselves were approximately 600 mm long by 0.4 mm in diameter, and when illuminated from the side, they cast narrow, vertical, shadows onto their respective detectors—these being located at an effective distance of 50 fibre diameters behind the axes of the fibres themselves. The emitter described here was designed to compensate for a significant degree of mechanical drift or creep over time in the mean position of its suspension fibre. This was achieved by employing five adjacent columns of 8 × miniature NIR LEDs (Light Emitting Diodes, λ = 890 nm), with one column being activated at a time. When used in conjunction with a "reverse Galilean" telescope, the LED sources allowed the collimated beam from the emitter to be steered azimuthally in fine angular increments (0.65°), causing the fibre's shadow to move laterally, in a step-wise manner, across the plane of its facing detector. Each step in shadow position was approximately 0.23 mm in size, and this allowed the fibre's shadow to be re-centred, so as to bridge once again both elements of its photodiode detector—even if the fibre was off-centred by as much as ±0.5 mm. Re-centring allowed Violin-Mode vibrations of the fibre to be sensed once again as differential AC photocurrents, these flowing in anti-phase in the

  19. How are patients influenced when counseled for minimally invasive lumbar spine surgeries? A stepwise model assessing pivotal information for decision-making.

    Science.gov (United States)

    Hey, Hwee Weng Dennis; Kumar, Nishant; Teo, Alex Quok An; Tan, Kimberly-Anne; Kumar, Naresh; Liu, Ka-Po Gabriel; Wong, Hee-Kit

    2017-08-01

    Although minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF) has many evidence-based short-term benefits over open TLIF, both procedures have similar long-term outcomes. Patients' preference for MIS over open TLIF may be confounded by a lack of understanding of what each approach entails. The study aimed to identify the various factors influencing patients' choice between MIS and open TLIF. This is a cross-sectional study conducted at a tertiary health-care institution. Patients, for whom TLIF procedures were indicated, were recruited over a 3-month period from specialist outpatient clinics. The outcome measure was patients' choice of surgical approach (MIS or open). All patients were subjected to a stepwise interviewing process and were asked to select between open and MIS approaches at each step. Further subgroup analysis stratifying subjects based on stages of decision-making was performed to identify key predictors of selection changes. No sources of funding were required for this study and there are no conflicts of interests. Fifty-four patients with a mean age of 55.8 years participated in the study. Thirteen (24.1%) consistently selected a single approach, whereas 31 (57.4%) changed their selection more than once during the interviewing process. Overall, 12 patients (22.2%) had a final decision different from their initial choice, and 15 patients (27.8%) were unable to decide. A large proportion of patients (65.0%) initially favored the open approach's midline incision. This proportion dropped to 16.7% (p<.001) upon mention of the term MIS. The proportion of patients favoring MIS dropped significantly following discussion on the pros and cons (p=.002) of each approach, as well as conversion or revision surgery (p=.017). Radiation and cosmesis were identified as the two most important factors influencing patients' final decisions. The longer midline incision of the open approach is cosmetically more appealing to patients than the

  20. A Comparative Assessment of the Influences of Human Impacts on Soil Cd Concentrations Based on Stepwise Linear Regression, Classification and Regression Tree, and Random Forest Models.

    Science.gov (United States)

    Qiu, Lefeng; Wang, Kai; Long, Wenli; Wang, Ke; Hu, Wei; Amable, Gabriel S

    2016-01-01

    Soil cadmium (Cd) contamination has attracted a great deal of attention because of its detrimental effects on animals and humans. This study aimed to develop and compare the performances of stepwise linear regression (SLR), classification and regression tree (CART) and random forest (RF) models in the prediction and mapping of the spatial distribution of soil Cd and to identify likely sources of Cd accumulation in Fuyang County, eastern China. Soil Cd data from 276 topsoil (0-20 cm) samples were collected and randomly divided into calibration (222 samples) and validation datasets (54 samples). Auxiliary data, including detailed land use information, soil organic matter, soil pH, and topographic data, were incorporated into the models to simulate the soil Cd concentrations and further identify the main factors influencing soil Cd variation. The predictive models for soil Cd concentration exhibited acceptable overall accuracies (72.22% for SLR, 70.37% for CART, and 75.93% for RF). The SLR model exhibited the largest predicted deviation, with a mean error (ME) of 0.074 mg/kg, a mean absolute error (MAE) of 0.160 mg/kg, and a root mean squared error (RMSE) of 0.274 mg/kg, and the RF model produced the results closest to the observed values, with an ME of 0.002 mg/kg, an MAE of 0.132 mg/kg, and an RMSE of 0.198 mg/kg. The RF model also exhibited the greatest R2 value (0.772). The CART model predictions closely followed, with ME, MAE, RMSE, and R2 values of 0.013 mg/kg, 0.154 mg/kg, 0.230 mg/kg and 0.644, respectively. The three prediction maps generally exhibited similar and realistic spatial patterns of soil Cd contamination. The heavily Cd-affected areas were primarily located in the alluvial valley plain of the Fuchun River and its tributaries because of the dramatic industrialization and urbanization processes that have occurred there. The most important variable for explaining high levels of soil Cd accumulation was the presence of metal smelting industries. The

  1. Development of the scheme of stepwise combustion of coal in the inverter firebox of a power unit of 1000 MW power

    Science.gov (United States)

    Prokhorov, V. B.; Chernov, S. L.; Kirichkov, V. S.

    2017-09-01

    The desire to increase the efficiency of using the heat of burned solid fuel leads to the significant growth of the initial steam parameter at steam-turbine plants. At the maximum temperatures of fresh and secondary steam of 700-720°C, the price of connecting of steam pipelines between the boiler and turbine is up to 20% of the price of a power plant unit, which dictates the necessity to decrease their length. One of the methods to achieve this is the application of an inverter firebox. An M-shaped profile of boiler, allowing one to decrease the length of heat-resistant steam pipelines, was developed at NRU MPEI. A distinctive feature of the profile is two inclined connecting gas flues between the firebox and convective shaft, starting from the gas windows located in the lower third of the firebox height. The boiler was designed for the steam production of 2493 t/h with the parameters of fresh steam of 35 MPa and 710°C. Thermal and aerodynamic calculations made it possible to get the sizes of boiler and dimensions of heating surfaces, and they also allow one to get the values of temperatures in the characteristic points along the gas path. On the basis of the results of calculations, the coefficient of efficiency of the boiler was 93.07% and the fuel consumption was 91.13 kg/s. For this boiler, the technology of effective stepwise burning of coal in a direct-flow-vortex torch (DFVT) in a system of vertical and horizontal tangential torches in the mode of solid slag removal, previously successively used in boilers with a traditional profile and upgraded to an inverter firebox, is proposed. The layouts of the direct-flow burners and nozzles for even and odd vertical sections of the firebox and also in a horizontal section were proposed. Organization of staged air supply in the vertical direction with a high fraction of in-firebox recycle of hot gases leads to low concentration of nitrogen oxides.

  2. A Comparative Assessment of the Influences of Human Impacts on Soil Cd Concentrations Based on Stepwise Linear Regression, Classification and Regression Tree, and Random Forest Models.

    Directory of Open Access Journals (Sweden)

    Lefeng Qiu

    Full Text Available Soil cadmium (Cd contamination has attracted a great deal of attention because of its detrimental effects on animals and humans. This study aimed to develop and compare the performances of stepwise linear regression (SLR, classification and regression tree (CART and random forest (RF models in the prediction and mapping of the spatial distribution of soil Cd and to identify likely sources of Cd accumulation in Fuyang County, eastern China. Soil Cd data from 276 topsoil (0-20 cm samples were collected and randomly divided into calibration (222 samples and validation datasets (54 samples. Auxiliary data, including detailed land use information, soil organic matter, soil pH, and topographic data, were incorporated into the models to simulate the soil Cd concentrations and further identify the main factors influencing soil Cd variation. The predictive models for soil Cd concentration exhibited acceptable overall accuracies (72.22% for SLR, 70.37% for CART, and 75.93% for RF. The SLR model exhibited the largest predicted deviation, with a mean error (ME of 0.074 mg/kg, a mean absolute error (MAE of 0.160 mg/kg, and a root mean squared error (RMSE of 0.274 mg/kg, and the RF model produced the results closest to the observed values, with an ME of 0.002 mg/kg, an MAE of 0.132 mg/kg, and an RMSE of 0.198 mg/kg. The RF model also exhibited the greatest R2 value (0.772. The CART model predictions closely followed, with ME, MAE, RMSE, and R2 values of 0.013 mg/kg, 0.154 mg/kg, 0.230 mg/kg and 0.644, respectively. The three prediction maps generally exhibited similar and realistic spatial patterns of soil Cd contamination. The heavily Cd-affected areas were primarily located in the alluvial valley plain of the Fuchun River and its tributaries because of the dramatic industrialization and urbanization processes that have occurred there. The most important variable for explaining high levels of soil Cd accumulation was the presence of metal smelting industries

  3. Impact of renal function and demographic/anthropomorphic variables on peak thyrotropin after recombinant human thyrotropin stimulation: a stepwise forward multiple-regression analysis.

    Science.gov (United States)

    Hautzel, Hubertus; Pisar, Elisabeth; Lindner, David; Schott, Matthias; Grandt, Rüdiger; Müller, Hans-Wilhelm

    2013-06-01

    When applying the recommended standard doses of recombinant human thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with differentiated thyroid cancer (DTC), the resulting peak TSH levels vary extensively. Previous studies applying multivariate statistics identified patient-inherent variables influencing the rhTSH/peak TSH relation. However, those results were inconclusive and partly conflicting. Notably, no independent role of renal function was substantiated, despite the fact that the kidneys are known to play a prominent role in TSH clearance from blood. Therefore, the study's aim was to investigate the impact of renal function on the peak TSH concentration after the standard administration of rhTSH used in the management of thyroid cancer. The second objective was to calculate a ranking regarding the effect sizes of the selected variables on the peak TSH. There were 286 patients with DTC included in the study. Univariate and multivariate analyses were performed, testing the correlation of serum creatinine and glomerular filtration rate (GFR) as surrogate parameters of renal function, age, sex, weight, height, and body surface area (BSA) with the peak TSH level. In six additional patients, the subsequent TSH pharmacokinetics after the TSH peak were measured and qualitatively compared. By univariate analyses, TSH correlated negatively with BSA, GFR, weight, and height, and positively with age, female sex, and serum creatinine (panalysis, the stepwise forward multiple linear regression revealed BSA and renal function as the two most influential independent variables, followed by age, sex, and height. The pharmacokinetic datasets indicated that these identified parameters also influence the TSH decline over time. Identifying those patients with a favorable combination of parameters predicting a high-peak TSH is the first step toward an individualization of rhTSH dosing. Additionally, the subsequent TSH decrease over time needs to be taken

  4. A step-wise steerable source of illumination for low-noise “Violin-Mode” shadow sensors, intended for use in interferometric gravitational wave detectors

    Energy Technology Data Exchange (ETDEWEB)

    Lockerbie, N. A.; Tokmakov, K. V. [SUPA (Scottish Universities Physics Alliance), Department of Physics, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG (United Kingdom)

    2016-01-15

    A steerable low-noise source of illumination is described for shadow-sensors having a displacement sensitivity of ∼100 pm (rms)/√Hz, at 500 Hz, over a measuring span of at least ±0.5 mm. These sensors were designed to detect lateral “Violin-Mode” resonances in the highly tensioned fused-silica suspension fibres of the test-masses/mirrors for the Advanced Laser Interferometer Gravitational Wave Observatory gravitational wave detectors. The shadow sensors—one intended for each of the four fibres in a suspension—comprised a source of Near InfraRed (NIR) radiation (emitter) and a differential shadow-displacement sensor (detector), these bracketing the fibre under test. The suspension fibres themselves were approximately 600 mm long by 0.4 mm in diameter, and when illuminated from the side, they cast narrow, vertical, shadows onto their respective detectors—these being located at an effective distance of 50 fibre diameters behind the axes of the fibres themselves. The emitter described here was designed to compensate for a significant degree of mechanical drift or creep over time in the mean position of its suspension fibre. This was achieved by employing five adjacent columns of 8  × miniature NIR LEDs (Light Emitting Diodes, λ = 890 nm), with one column being activated at a time. When used in conjunction with a “reverse Galilean” telescope, the LED sources allowed the collimated beam from the emitter to be steered azimuthally in fine angular increments (0.65°), causing the fibre’s shadow to move laterally, in a step-wise manner, across the plane of its facing detector. Each step in shadow position was approximately 0.23 mm in size, and this allowed the fibre’s shadow to be re-centred, so as to bridge once again both elements of its photodiode detector—even if the fibre was off-centred by as much as ±0.5 mm. Re-centring allowed Violin-Mode vibrations of the fibre to be sensed once again as differential AC photocurrents, these flowing in

  5. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...

  6. Clinical trial structures

    OpenAIRE

    Evans, Scott R.

    2010-01-01

    Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed.

  7. The OA Trial Bank

    DEFF Research Database (Denmark)

    van Middelkoop, Marienke; Arden, N K; Atchia, I.

    2016-01-01

    Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA g...

  8. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Kraus, V B; Blanco, F J; Englund, M

    2015-01-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...... both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials...... and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety...

  9. Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin

    DEFF Research Database (Denmark)

    Friis, Stine; Madsen, Daniel H.; Bugge, Thomas H.

    2016-01-01

    and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular...

  10. Clinical trial registration in fertility trials - a case for improvement?

    Science.gov (United States)

    Farquhar, Cynthia M; Showell, Marian G; Showell, Emily A E; Beetham, Penny; Baak, Nora; Mourad, Selma; Jordan, Vanessa M B

    2017-09-01

    What is the prevalence and source of prospectively and retrospectively registered and unregistered trials in fertility treatments? Trial registration is low and does not appear to be changing over the 5 years studied. Trial registration is associated with lower risk of bias than in unregistered trials. The Cochrane Gynaecology and Fertility Group's specialised register was searched on 5 November 2015 for randomised controlled trials (RCTs) published from January 2010 to December 2014. Eligible trials included randomised women or men for fertility treatments, were published in full text, and written in English. Two reviewers independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. Of 693 eligible RCTS, only 44% were registered trials. Of 309 registered trials, 21.7% were prospectively registered, 15.8% were registered within 6 months of first patient enrolment and 62.5% were retrospectively registered trials. Prospective trial registration by country varied from 0% to 100%. The highest frequency of prospective trial registration amongst the top 10 publishing countries was 31% in the Netherlands. Only English language trials were included in this review. Prospective trial registration is still low. Journals, funders and ethics committees could have a greater role to increase trial registration. University of Auckland. No competing interests.

  11. Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART: Study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    2012-08-01

    Full Text Available Abstract Background Acute respiratory distress syndrome (ARDS is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART. Methods/Design ART is a pragmatic, multicenter, randomized (concealed, controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy. We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet. In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight and targeting plateau pressure ≤30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion If the ART strategy with maximum recruitment and PEEP titration improves

  12. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

    Science.gov (United States)

    Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

    2012-10-01

    To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

  13. Fundamentals of clinical trials

    CERN Document Server

    Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B

    2015-01-01

    This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise.  Most chapters have been revised considerably from the fourth edition.  A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded.  Many contemporary clinical trial examples have been added.  There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials.  This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...

  14. Concerted and stepwise proton-coupled electron transfers in aquo/hydroxo complex couples in water: oxidative electrochemistry of [Os(II)(bpy)(2)(py)(OH(2))](2+).

    Science.gov (United States)

    Costentin, Cyrille; Robert, Marc; Savéant, Jean-Michel; Teillout, Anne-Lucie

    2009-01-12

    Successive oxidation of transition metal(II) aqua complexes (M(II)OH(2) to M(III)OH) is a domain in which proton-coupled electron transfer reactions are extremely common. The mechanism of these PCET reactions-concerted or stepwise-is an important issue in the understanding and design of natural or artificial systems catalyzing the formation of dioxygen by four-electron oxidation of water. Concerted proton-coupled electron transfer from an aqua metal(II) to a hydroxo metal(III) complex requires the close proximity of a proton-accepting group with a pK value between those of the aqua complexes. Otherwise, stepwise electron-proton or proton-electron pathways involving high-energy intermediates are followed. Concerted proton-electron pathways involving water as proton-acceptor or proton-donor group are inefficient. Cyclic voltammetry of the title complex in buffered aqueous solution and re-examination of previous results for the same complex attached to an electrode surface are used to establish these conclusions, which provide a starting point on the route to higher degrees of oxidation, such as those involved in the catalysis of water oxidation.

  15. Evaluation of argon ages and integrity of fluid-inclusion compositions: Stepwise noble gas heating experiments on 1.87 Ga alunite from Tapajós Province, Brazil

    Science.gov (United States)

    Landis, G.P.; Snee, L.W.; Juliani, Caetano

    2005-01-01

    Quantitative analyses are reported for active (N2, CH4, CO, CO2, H2, O2, HF, HCl, H2S, SO2) and noble (He, Ar, Ne) gases released by crushing and step heating of magmatic-hydrothermal alunite from the Tapajós gold province in Brazil. This is the oldest known alunite (40Ar/39Ar age of 1.87 Ga), and because it has undergone minimal postdepositional thermal or tectonic strain, it is excellent material to test the retention of gas species in fluid inclusions and within the crystal structure over geological time. The gas compositions of a single sample, in combination with Ar age-spectrum data derived from stepwise heating of 10 related samples, have been used to constrain the limits of modification of primary gas compositions in fluid inclusions and the possible extent of the loss of radiogenic Ar. The observed variations in the isotopic compositions of He, Ne, and Ar released by stepwise heating have been used to identify the residence sites and determine the diffusion coefficients of the gases in the mineral. The data suggest that the only modification to primary gas compositions after entrapment in fluid inclusions and formation of the mineral is due to radiogenic and nucleogenic processes which affect the noble gas isotopic compositions.

  16. UPLC-QTOFMS based metabolomics followed by stepwise partial least square-discriminant analysis (PLS-DA) explore the possible relation between the variations in secondary metabolites and the phylogenetic divergences of the genus Panax.

    Science.gov (United States)

    Nguyen, Huy Truong; Lee, Dong-Kyu; Lee, Won Jun; Lee, GwangJin; Yoon, Sang Jun; Shin, Byong-Kyu; Nguyen, Minh Duc; Park, Jeong Hill; Lee, Jeongmi; Kwon, Sung Won

    2016-02-15

    Phylogenetic and metabolomic approaches have long been employed to study evolutionary relationships among plants. Nonetheless, few studies have examined the difference in metabolites within a clade and between clades of the phylogenetic tree. We attempted to relate phylogenetic studies to metabolomics using stepwise partial least squares-discriminant analysis (PLS-DA) for the genus Panax. Samples were analyzed by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOFMS) to obtain metabolite profiles. Initially, conventional principal component analysis was subsequently applied to the metabolomic data to show the limitations in relating the expression of metabolites to divisions in the phylogenetic tree. Thereafter, we introduced stepwise PLS-DA with optimized scaling methods, which were properly applied according to the branches of the phylogenetic tree of the four species. Our approach highlighted metabolites of interest by elucidating the directions and degrees of metabolic alterations in each clade of the phylogenetic tree. The results revealed the relationship between metabolic changes in the genus Panax and its species' evolutionary adaptations to different climates. We believe our method will be useful to help understand the metabolite-evolution relationship. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Optimization of elution salt concentration in stepwise elution of protein chromatography using linear gradient elution data. Reducing residual protein A by cation-exchange chromatography in monoclonal antibody purification.

    Science.gov (United States)

    Ishihara, Takashi; Kadoya, Toshihiko; Endo, Naomi; Yamamoto, Shuichi

    2006-05-05

    Our simple method for optimization of the elution salt concentration in stepwise elution was applied to the actual protein separation system, which involves several difficulties such as detection of the target. As a model separation system, reducing residual protein A by cation-exchange chromatography in human monoclonal antibody (hMab) purification was chosen. We carried out linear gradient elution experiments and obtained the data for the peak salt concentration of hMab and residual protein A, respectively. An enzyme-linked immunosorbent assay was applied to the measurement of the residual protein A. From these data, we calculated the distribution coefficient of the hMab and the residual protein A as a function of salt concentration. The optimal salt concentration of stepwise elution to reduce the residual protein A from the hMab was determined based on the relationship between the distribution coefficient and the salt concentration. Using the optimized condition, we successfully performed the separation, resulting in high recovery of hMab and the elimination of residual protein A.

  18. Comparability of prostate trials

    DEFF Research Database (Denmark)

    Suciu, S; Sylvester, R; Iversen, P

    1993-01-01

    The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type...... of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity....... In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials...

  19. Clinical Trials - Multiple Languages

    Science.gov (United States)

    ... clínicos: Tema de salud de MedlinePlus - español (Spanish) National Library of Medicine Clinical Trials - English ... PDF American Cancer Society Characters not displaying correctly on this page? See language ...

  20. Anchor Trial Launch

    Science.gov (United States)

    NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

  1. ClinicalTrials.gov

    Data.gov (United States)

    U.S. Department of Health & Human Services — Provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases...

  2. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Katz, J N; Losina, E; Lohmander, L S

    2015-01-01

    To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For each...... relating to obsolescence, fidelity of intervention delivery, and adherence and crossover. Assessment and analysis raise questions regarding blinding and clustering of observations. This paper describes methodological problems in the design and conduct of surgical randomized trials and proposes strategies...

  3. Amiodarone: clinical trials.

    Science.gov (United States)

    Naccarelli, G V; Wolbrette, D L; Patel, H M; Luck, J C

    2000-01-01

    Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This article reviews the results and clinical implications of primary and secondary prevention trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction primary prevention trials include the European Myocardial Infarct Amiodarone Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In congestive heart failure patients, amiodarone was studied as a primary prevention strategy in two pivotal trials: Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiac en Argentina (GESICA) and Amiodarone in Patients With Congestive Heart Failure and Asymptomatic Ventricular Arrhythmia (CHF-STAT). Amiodarone was associated with a neutral overall survival and a trend toward improved survival in nonischemic cardiomyopathy patients in CHF/STAT and improved survival in GESICA. In post-myocardial infarction patients with nonsustained ventricular tachycardia and a depressed ejection fraction, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated that implantable cardioverter-defibrillators (ICD) statistically improved survival compared to the antiarrhythmic drug arm, most of whose patients were taking amiodarone. In patients with histories of sustained ventricular tachycardia or ventricular fibrillation, the Cardiac Arrest Study in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared to other drugs guided by serial Holter or electrophysiologic studies. However, arrhythmic death rates were high in both treatment arms of the study. Several secondary prevention trials, including the Antiarrhythmics Versus Implantable Defibrillators Study (AVID), the Canadian Implantable Defibrillator Study

  4. Fundamentals of clinical trial design

    OpenAIRE

    Evans, Scott R.

    2010-01-01

    Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. Issues in trial conduct and analyses should be anticipated during trial design and thoughtfully addressed. Fundamental clinical trial design issues are discussed.

  5. How to Capitalize on the Retest Effect in Future Trials on Huntington’s Disease

    Science.gov (United States)

    Schramm, Catherine; Katsahian, Sandrine; Youssov, Katia; Démonet, Jean-François; Krystkowiak, Pierre; Supiot, Frédéric; Verny, Christophe; Cleret de Langavant, Laurent; Bachoud-Lévi, Anne-Catherine

    2015-01-01

    The retest effect—improvement of performance on second exposure to a task—may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington’s disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington’s Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington’s Disease (RIL-HD). All were assessed with the Unified Huntington’s Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required. PMID:26714284

  6. How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Catherine Schramm

    Full Text Available The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington's disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington's Disease (MIG-HD trial and 39 in the placebo arm of the Riluzole trial in Huntington's Disease (RIL-HD. All were assessed with the Unified Huntington's Disease Rating Scale (UHDRS plus additional cognitive tasks at baseline (A1, shortly after baseline (A2 and one year later (A3. We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required.

  7. How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease.

    Science.gov (United States)

    Schramm, Catherine; Katsahian, Sandrine; Youssov, Katia; Démonet, Jean-François; Krystkowiak, Pierre; Supiot, Frédéric; Verny, Christophe; Cleret de Langavant, Laurent; Bachoud-Lévi, Anne-Catherine

    2015-01-01

    The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington's disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington's Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington's Disease (RIL-HD). All were assessed with the Unified Huntington's Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required.

  8. Controlled release of volatile secondary and tertiary alcohols by neighboring group participation: stepwise cyclization and re-opening of 2,2'-bis(carbamoyl)dibenzoates at neutral pH.

    Science.gov (United States)

    Trachsel, Alain; Govoni, Alexandra; de Saint Laumer, Jean-Yves; Frérot, Eric; Herrmann, Andreas

    2008-12-01

    Bioactive, volatile, secondary and tertiary fragrance alcohols are efficiently released by intramolecular neighboring-group-assisted hydrolysis of 2,2'-bis(carbamoyl)dibenzoates at neutral pH. The stepwise cyclization of 2,2'-[(methylimino)bis(propane-3,1-diylcarbamoyl)]dibenzoates is followed by the re-opening of the intermediately formed diphthalimide and proceeds in an overall four-step consecutive reaction sequence. Kinetic rate constants for all four reaction steps could be determined pairwise by reversed-phase HPLC. At neutral pH, secondary alcohols were released by one order of magnitude faster than the tertiary alcohols, and the rate constants for the re-opening of the diphthalimides were found to be in the same order of magnitude as the release of the tertiary alcohols. Dynamic headspace analysis on a dry cotton surface finally confirmed the efficient release of tertiary alcohols under mild reaction conditions generally encountered for applications in functional perfumery.

  9. Comparison of QSAR models based on combinations of genetic algorithm, stepwise multiple linear regression, and artificial neural network methods to predict Kd of some derivatives of aromatic sulfonamides as carbonic anhydrase II inhibitors.

    Science.gov (United States)

    Maleki, Afshin; Daraei, Hiua; Alaei, Loghman; Faraji, Aram

    2014-01-01

    Four stepwise multiple linear regressions (SMLR) and a genetic algorithm (GA) based multiple linear regressions (MLR), together with artificial neural network (ANN) models, were applied for quantitative structure-activity relationship (QSAR) modeling of dissociation constants (Kd) of 62 arylsulfonamide (ArSA) derivatives as human carbonic anhydrase II (HCA II) inhibitors. The best subsets of molecular descriptors were selected by SMLR and GA-MLR methods. These selected variables were used to generate MLR and ANN models. The predictability power of models was examined by an external test set and cross validation. In addition, some tests were done to examine other aspects of the models. The results show that for certain purposes GA-MLR is better than SMLR and for others, ANN overcomes MLR models.

  10. [Controlled randomized clinical trials].

    Science.gov (United States)

    Jaillon, Patrice

    2007-01-01

    It is generally agreed that the first comparative clinical trial in history was done by James Lind in 1747, in the treatment of scurvy. The general bases of modern experimental medicine were published by Claude Bernard in 1865. However, it is the development of new drugs and the evolution of methodological concepts that led to the first randomized controlled clinical trial, in 1948, which showed that the effects of streptomycin on pulmonary tuberculosis were significantly different from those of a placebo. Today, "evidence-based" medicine aims to rationalize the medical decision-making process by taking into account, first and foremost, the results of controlled randomized clinical trials, which provide the highest level of evidence. In the second half of the 20th century it became clear that different kinds of clinical trials might not provide the same level of evidence. Practitioners' intimate convictions must be challenged by the results of controlled clinical trials. Take the CAST trial for example, which, in 1989, tested antiarrhythmic drugs versus placebo in patients with myocardial infarction. It was well known that ventricular arrhythmias were a factor of poor prognosis in coronary heart disease, and it was therefore considered self-evident that drug suppression of these ventricular arrhythmias would reduce the mortality rate. In the event, the CAST trial showed the exact opposite, with an almost 3-fold increase in total mortality among patients with coronary heart disease who were treated with antiarrhythmic drugs. These results had a profound impact on the use of antiarrythmic drugs, which became contraindicated after myocardial infarction. A clinical trial has to fulfill certain methodological standards to be accepted as evidence-based medicine. First, a working hypothesis has to be formulated, and then the primary outcome measure must be chosen before beginning the study. An appropriate major endpoint for efficacy must be selected, in keeping with the

  11. Multi-scale analysis of the relationship between landscape patterns and a water quality index (WQI) based on a stepwise linear regression (SLR) and geographically weighted regression (GWR) in the Ebinur Lake oasis.

    Science.gov (United States)

    Wang, Xiaoping; Zhang, Fei

    2017-12-22

    Water quality is highly dependent on landscape characteristics. This study explored the relationships between landscape patterns and water quality in the Ebinur Lake oasis in China. The water quality index (WQI) has been used to identify threats to water quality and contribute to better water resource management. This study established the WQI and analyzed the influence of landscapes on the WQI based on a stepwise linear regression (SLR) model and geographically weighted regression (GWR) models. The results showed that the WQI was between 56.61 and 2886.51. The map of the WQI showed poor water quality. Both positive and negative relationships between certain land use and land cover (LULC) types and the WQI were observed for different buffers. This relationship is most significant for the 400-m buffer. There is a significant relationship between the water quality index and landscape index (i.e., PLAND, DIVISION, aggregation index (AI), COHESION, landscape shape index (LSI), and largest patch index (LPI)), demonstrated by using stepwise multiple linear regressions under the 400-m scale, which resulted in an adjusted R 2 between 0.63 and 0.88. The local R 2 between the LPI and LSI for forest grasslands and the WQI are high in the Akeqisu River and the Kuitun rivers and low in the Bortala River, with an R 2 ranging from 0.57 to 1.86. The local R 2 between the LSI for croplands and the WQI is 0.44. The local R 2 values between the LPI for saline lands and the WQI are high in the Jing River and low in the Bo River, Akeqisu River, and Kuitun rivers, ranging from 0.57 to 1.86.

  12. DFT and ONIOM(DFT:MM) studies on Co-C bond cleavage and hydrogen transfer in B12-dependent methylmalonyl-CoA mutase. Stepwise or concerted mechanism?

    Science.gov (United States)

    Li, Xin; Chung, Lung Wa; Paneth, Piotr; Morokuma, Keiji

    2009-04-15

    The considerable protein effect on the homolytic Co-C bond cleavage to form the 5'-deoxyadenosyl (Ado) radical and cob(II)alamin and the subsequent hydrogen transfer from the methylmalonyl-CoA substrate to the Ado radical in the methylmalonyl-CoA mutase (MMCM) have been extensively studied by DFT and ONIOM(DFT/MM) methods. Several quantum models have been used to systematically study the protein effect. The calculations have shown that the Co-C bond dissociation energy is very much reduced in the protein, compared to that in the gas phase. The large protein effect can be decomposed into the cage effect, the effect of coenzyme geometrical distortion, and the protein MM effect. The largest contributor is the MM effect, which mainly consists of the interaction of the QM part of the coenzyme with the MM part of the coenzyme and the surrounding residues. In particular, Glu370 plays an important role in the Co-C bond cleavage process. These effects tremendously enhance the stability of the Co-C bond cleavage state in the protein. The initial Co-C bond cleavage and the subsequent hydrogen transfer were found to occur in a stepwise manner in the protein, although the concerted pathway for the Co-C bond cleavage coupled with the hydrogen transfer is more favored in the gas phase. The assumed concerted transition state in the protein has more deformation of the coenzyme and the substrate and has less interaction with the protein than the stepwise route. Key factors and residues in promoting the enzymatic reaction rate have been discussed in detail.

  13. Fluxional sigma-bonds of 2,5,8-tri-tert-butyl-1,3-diazaphenalenyl dimers: stepwise [3,3], [5,5] and [7,7] sigmatropic rearrangements via pi-dimer intermediates.

    Science.gov (United States)

    Tian, Yong-Hui; Huang, Jingsong; Kertesz, Miklos

    2010-05-21

    Inspired by experimental evidence of the thermally accessible pi-dimer of the title compound, DAzPh (7), we propose that the sigma-dimer (8) can undergo a variety of sigma-bond shifts representing very unusual multi-faceted fluxional bonding between two neutral pi-radicals. In this paper, we present a theoretical study of the sigmatropic rearrangement of the DAzPh sigma-dimers. Out of the six sigma-bonded tautomers three are competitive: a degenerate pair resulting from a [5,5] sigmatropic rearrangement and a non-degenerate product of a [3,3] sigmatropic rearrangement with barriers of 10.21 kcal mol(-1) and 10.00 kcal mol(-1), respectively. Both of these rearrangements occur stepwise through a pi-dimer intermediate (9), which is 1.33 kcal mol(-1) higher in energy than the sigma-dimer (8). These data are consistent with optical and paramagnetic susceptibility experiments and offer a natural interpretation for the unusual C-C contact distance of 2.153 A obtained by X-ray diffraction by Morita et al. Another new sigma-dimer (15) with a different dipole-dipole stacking pattern is predicted, the energy of which is very close to that of 8, and is likely to be isolable under suitable conditions. The new sigma-dimer (15) is expected to undergo stepwise [7,7] sigmatropic rearrangement. Thus we observed a complete spectrum of sigmatropic rearrangement reactions in these DAzPh dimers. The pi-dimers 4, 9 and 17 show decreasing order of SOMO-SOMO splittings consistent with the UV-vis absorbance. The calculated paramagnetism is in good agreement with experiments providing further evidence for the presented interpretation of fluxional bonding in the DAzPh sigma-dimers.

  14. The CYTONOX trial

    DEFF Research Database (Denmark)

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed

    2016-01-01

    INTRODUCTION: In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact...... of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E......1 and CYP1A2 substrates in obese versus non-obese children. METHODS: The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which...

  15. The CYTONOX trial

    DEFF Research Database (Denmark)

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed

    2016-01-01

    of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E...... will be defined by using well-tested probes; midazolam, chlorzoxazone and caffeine. Each of the probes will be administered as a single dose. Subsequently, blood and urine samples will be collected at pre-specified times. CONCLUSION: The aim of the CYTONOX trial is to investigate the in vivo activity of CYP3A4...

  16. Medio-lateral knee fluency in anterior cruciate ligament-injured athletes during dynamic movement trials.

    Science.gov (United States)

    Panos, Joseph A; Hoffman, Joshua T; Wordeman, Samuel C; Hewett, Timothy E

    2016-03-01

    Correction of neuromuscular impairments after anterior cruciate ligament injury is vital to successful return to sport. Frontal plane knee control during landing is a common measure of lower-extremity neuromuscular control and asymmetries in neuromuscular control of the knee can predispose injured athletes to additional injury and associated morbidities. Therefore, this study investigated the effects of anterior cruciate ligament injury on knee biomechanics during landing. Two-dimensional frontal plane video of single leg drop, cross over drop, and drop vertical jump dynamic movement trials was analyzed for twenty injured and reconstructed athletes. The position of the knee joint center was tracked in ImageJ software for 500 milliseconds after landing to calculate medio-lateral knee motion velocities and determine normal fluency, the number of times per second knee velocity changed direction. The inverse of this calculation, analytical fluency, was used to associate larger numerical values with fluent movement. Analytical fluency was decreased in involved limbs for single leg drop trials (P=0.0018). Importantly, analytical fluency for single leg drop differed compared to cross over drop trials for involved (Pfluency values exhibited a stepwise trend in relative magnitudes. Decreased analytical fluency in involved limbs is consistent with previous studies. Fluency asymmetries observed during single leg drop tasks may be indicative of abhorrent landing strategies in the involved limb. Analytical fluency differences in unilateral tasks for injured limbs may represent neuromuscular impairment as a result of injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The ONTARGET trial programme

    DEFF Research Database (Denmark)

    Unger, Thomas; Kintscher, Ulrich; Kappert, Kai

    2009-01-01

    The ONTARGET trial programme tested the effects of the angiotensin AT1 receptor blocker (ARB), telmisartan, alone or in combination with the angiotensin converting enzyme (ACE) inhibitor, ramipril, in more than 25.000 patients at high cardiovascular risk including diabetes on a combined endpoint...

  18. Statistically Valid Planting Trials

    Science.gov (United States)

    C. B. Briscoe

    1961-01-01

    More than 100 million tree seedlings are planted each year in Latin America, and at least ten time'that many should be planted Rational control and development of a program of such magnitude require establishing and interpreting carefully planned trial plantings which will yield statistically valid answers to real and important questions. Unfortunately, many...

  19. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Emery, C. A.; Roos, Ewa M.; Verhagen, E.

    2015-01-01

    The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...

  20. Registration of randomized clinical trials

    DEFF Research Database (Denmark)

    Østervig, R M; Sonne, A; Rasmussen, L S

    2015-01-01

    starting enrolment before 2010 to 63.2% after 2010 (24/38, P clinical trials were registered at clinicaltrials.gov. CONCLUSION: Many published randomized controlled trials from Acta Anaesthesiologica Scandinavica were not adequately registered but the requirement of trial registration has...... the proportion of correctly registered randomized controlled trials (RCTs) published in Acta from 2009 to 2014. METHODS: We manually searched all Acta issues from 2009 to 2014 for RCTs. Information about timing of data collection and registration in trial registries was extracted. We classified RCTs as correctly...... registered when it could be verified that patient enrolment was started after registration in a trial registry. RESULTS: We identified 200 RCTs. Dates for patient enrolment were not specified in 51 (25.5%). The proportion of correctly registered trials increased significantly from 17.1% (19/111) for trials...

  1. Trial in absentia

    Directory of Open Access Journals (Sweden)

    Knežević Saša

    2014-01-01

    Full Text Available The active participation of parties and other procedural subjects in trial proceedings is essential for the exercise of the principle of immediacy. The presence of parties and other subjects in the presentation of evidence is essential in the process of fact-finding and deciding on the admissibility of evidence, either by hearing testimonies or examining the presented material evidence. The international instruments on human rights' protection promote the right of the defendant to participate in the proceedings involving charges raised against him/her. Although the defendant's testimony is primarily used as a tool for the effective operation of the defense, legislations do not refute this highly important source of evidence. The defendant's presence in trial is highly important for the exercise of the immediacy principle and other basic procedural principles. The process of determining the factual grounds is further aggravated if the parties are not present in court proceedings. Consequently, legislations provide a wide range of measures to ensure the defendant's presence in criminal proceedings. The Serbian Criminal Procedure Act provides the instruments for securing the presence of parties in criminal proceedings. It is particularly important to ensure the presence of the defendant in the central stage of the criminal proceedings. Yet, there are sometimes significant criminal and political reasons for the defendant to be tried in absentia, which implies a divergence from some important procedural principles. The presentation of evidence and fact-finding may ensue even without the defendant's physical presence in the proceedings in case of the defendant's default (failure to appear] in summary proceedings and in case where the defendant is a fugitive from justice or unavailable to public authorities (either in summary or in regular trial proceedings]. Trial in absentia is not allowed in trials involving minors.

  2. Street Law Mock Trial Manual.

    Science.gov (United States)

    McGuire, Patricia, Ed.; O'Brien, Edward L.; Arbetman, Lee; Mills, Vivian H.; Pannell, Andrew

    Designed to facilitate the expanded use of mock trials, this manual is divided into two principle sections--a teacher's guide and a student's guide. The teacher's guide contains specific advice to teachers on all aspects of preparing for a mock trial and seven specific lesson plans for a 2- to 3-week mock trial unit. Each lesson contains…

  3. The Trial of Katherine Harrison.

    Science.gov (United States)

    Woodward, Walter W.

    2003-01-01

    Presents a lesson plan in which the teacher and students participate in a mock trial of Katherine Harrison, who was accused of witchcraft in the seventeenth century. Provides background information about the trial, as well as primary sources of the testimonies given by witnesses during the trial. (CMK)

  4. The Feedback Intervention Trial (FIT) — Improving Hand-Hygiene Compliance in UK Healthcare Workers: A Stepped Wedge Cluster Randomised Controlled Trial

    Science.gov (United States)

    Fuller, Christopher; Michie, Susan; Savage, Joanne; McAteer, John; Besser, Sarah; Charlett, Andre; Hayward, Andrew; Cookson, Barry D.; Cooper, Ben S.; Duckworth, Georgia; Jeanes, Annette; Roberts, Jenny; Teare, Louise; Stone, Sheldon

    2012-01-01

    Introduction Achieving a sustained improvement in hand-hygiene compliance is the WHO’s first global patient safety challenge. There is no RCT evidence showing how to do this. Systematic reviews suggest feedback is most effective and call for long term well designed RCTs, applying behavioural theory to intervention design to optimise effectiveness. Methods Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals (16 Intensive Therapy Units [ITU]; 44 Acute Care of the Elderly [ACE] wards) routinely implementing a national cleanyourhands campaign). Intervention-based on Goal & Control theories. Repeating 4 week cycle (20 mins/week) of observation, feedback and personalised action planning, recorded on forms. Computer-generated stepwise entry of all hospitals to intervention. Hospitals aware only of own allocation. Primary outcome: direct blinded hand hygiene compliance (%). Results All 16 trusts (60 wards) randomised, 33 wards implemented intervention (11 ITU, 22 ACE). Mixed effects regression analysis (all wards) accounting for confounders, temporal trends, ward type and fidelity to intervention (forms/month used). Intention to Treat Analysis Estimated odds ratio (OR) for hand hygiene compliance rose post randomisation (1.44; 95% CI 1.18, 1.76;phand-hygiene compliance, in wards implementing a national hand-hygiene campaign. Further implementation studies are needed to maximise the intervention’s effect in different settings. Trial Registration Controlled-Trials.com ISRCTN65246961 PMID:23110040

  5. Funding oncology clinical trials: are cooperative group trials sustainable?

    Science.gov (United States)

    Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew

    2012-05-01

    Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.

  6. The FOCUS trial

    DEFF Research Database (Denmark)

    Glenthøj, Louise B; Fagerlund, Birgitte; Randers, Lasse

    2015-01-01

    of the cognitive training to their everyday lives. Follow-up assessments will be conducted at 6 and 12 months after randomisation. The primary outcome is the composite score on the Brief Assessment of Cognition in Schizophrenia at cessation of treatment after 6 months. Secondary outcomes are social and daily...... versus standard treatment. The cognitive remediation consists of 24 weekly group-based and manualised sessions targeting neurocognition and social cognition. In addition to the group sessions, the patients will be offered 12 individual sessions aiming at maximising the transfer of the effects......: This is the first trial to evaluate the effects of neurocognitive and social cognitive remediation in UHR patients. The FOCUS trial results will provide evidence on the effect of targeted and comprehensive cognitive rehabilitation on cognition, daily living, and symptomatology as well as long-term outcome...

  7. Levomepromazine versus chlorpromazine in treatment-resistant schizophrenia: a double-blind randomized trial

    Science.gov (United States)

    Lal, Samarthji; Thavundayil, Joseph X.; Nair, N.P. Vasavan; Annable, Lawrence; Ng Ying Kin, Ng M.K.; Gabriel, Antoine; Schwartz, George

    2006-01-01

    Objective We compared the effect of levomepromazine (LMP) with chlorpromazine (CPZ) in treatment-resistant schizophrenia (TRS). Methods We carried out a double-blind, parallel group study (n = 19/arm) with balanced randomization in blocks of 4 and stratification by sex. Subjects entered a 30-week trial, of which phases I–III were open: phase I (wk 0–6) baseline; phase II (wk 7–9) stepwise transition to haloperidol (HAL), 30 mg/d, plus benztropine (BT), 4 mg/d; phase III (wk 10–15) HAL, 40–60 mg/d, plus BT, 4–6 mg/d; phase IV (wk 16–20) stepwise transition to LMP or CPZ (500 mg/d) following randomization; phase V (wk 21–28) stepwise increase of LMP or CPZ (600–1000 mg/d, dose reduction permitted) to establish optimum dose; and phase VI (wk 29–30) optimized dose maintained. Criteria for TRS were based on those established by Kane et al in 1988. The criterion for a response to treatment was a reduction of 25% or more in total Brief Psychiatric Rating Scale score. Results Both LMP (p = 0.007) and CPZ (p = 0.030) improved TRS relative to baseline. Although there was no significant difference between the 2 groups in treatment response at study end point, hierarchical linear modelling of longitudinal outcome revealed a significant (p = 0.006) advantage of LMP over CPZ for the BPRS total score. Ten of 19 participants on LMP and 8 of 19 on CPZ met the criterion for treatment response, and 9 of the 18 responders did so on 200–700 mg/d phenothiazine. The mean dose of responders was 710 (standard deviation [SD] 265) mg/d (LMP) and 722 (SD 272) mg/d (CPZ). Akathisia was associated with a nonresponse to phenothiazines (p = 0.010). BPRS scores increased significantly on HAL (p = 0.006). Two of 19 participants on LMP and 5 of 19 on CPZ withdrew early from the study. Conclusion LMP and CPZ may be useful in the management of TRS. A modest advantage of LMP compared with CPZ was seen in longitudinal analysis. High doses of neuroleptics may contribute to TRS

  8. Retrieval of Chlorophyll-a and Total Suspended Solids Using Iterative Stepwise Elimination Partial Least Squares (ISE-PLS Regression Based on Field Hyperspectral Measurements in Irrigation Ponds in Higashihiroshima, Japan

    Directory of Open Access Journals (Sweden)

    Zuomin Wang

    2017-03-01

    Full Text Available Concentrations of chlorophyll-a (Chl-a and total suspended solids (TSS are significant parameters used to assess water quality. The objective of this study is to establish a quantitative model for estimating the Chl-a and the TSS concentrations in irrigation ponds in Higashihiroshima, Japan, using field hyperspectral measurements and statistical analysis. Field experiments were conducted in six ponds and spectral readings for Chl-a and TSS were obtained from six field observations in 2014. For statistical approaches, we used two spectral indices, the ratio spectral index (RSI and the normalized difference spectral index (NDSI, and a partial least squares (PLS regression. The predictive abilities were compared using the coefficient of determination (R2, the root mean squared error of cross validation (RMSECV and the residual predictive deviation (RPD. Overall, iterative stepwise elimination based on PLS (ISE–PLS, using the first derivative reflectance (FDR, showed the best predictive accuracy, for both Chl-a (R2 = 0.98, RMSECV = 6.15, RPD = 7.44 and TSS (R2 = 0.97, RMSECV = 1.91, RPD = 6.64. The important wavebands for estimating Chl-a (16.97% of all wavebands and TSS (8.38% of all wavebands were selected by ISE–PLS from all 501 wavebands over the 400–900 nm range. These findings suggest that ISE–PLS based on field hyperspectral measurements can be used to estimate water Chl-a and TSS concentrations in irrigation ponds.

  9. Preparative isolation and purification of bergapten and imperatorin from the medicinal plant Cnidium monnieri using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase.

    Science.gov (United States)

    Lia, Hua-Bin; Chen, Feng

    2004-12-17

    A high-speed counter-current chromatography (HSCCC) method was developed for the preparative separation and purification of bergapten and imperatorin from the Chinese medicinal plant Cnidium monnieri (L.) Cusson. The crude extract was obtained by extraction with ethanol from the dried fruits of Cnidium monnieri (L.) Cusson under sonication. Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (5:5:5:5, v/v/v/v) was successfully performed by increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml min(-1) after 180 min. The components purified and collected were analyzed by high-performance liquid chromatography. The method yielded 45.8 mg of bergapten at 96.5% purity and 118.3 mg of imperatorin at 98.2% purity from 500 mg of the crude extract in a single run. The recoveries of bergapten and imperatorin were 92.1 and 93.7%, respectively.

  10. Clinical trials in dentistry in India: Analysis from trial registry

    Directory of Open Access Journals (Sweden)

    S Gowri

    2017-01-01

    Conclusion: The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

  11. Randomized clinical trials in HEPATOLOGY

    DEFF Research Database (Denmark)

    Kjaergard, L L; Nikolova, D; Gluud, C

    1999-01-01

    Evidence shows that the quality of randomized clinical trials (RCTs) affects estimates of intervention efficacy, which is significantly exaggerated in low-quality trials. The present study examines the quality of all 235 RCTs published in HEPATOLOGY from the initiation in 1981 through August 1998......-blinding. The median quality score of all trials was 3 points (range, 1-5 points). Multiple logistic regression analysis explored the association between quality and therapeutic areas, number of centers, external funding, year of publication, and country of origin. High-quality trials were most likely to investigate......, single-center trials, and trials with no external funding. Quality did not improve with time and was not associated with country of origin. The main conclusions are that the quality of RCTs in HEPATOLOGY needs improvement and that the probability of high quality increased with the number of centers...

  12. Fibrolase: Trials and Tribulations

    Science.gov (United States)

    Markland, Francis S.; Swenson, Steve

    2010-01-01

    Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (α2Μ). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(α)-chain of fibrinogen and the B(β)-chain at a slower rate; it has no activity on the γ-chain. The enzyme exhibits the same specificity with fibrin, cleaving the α-chain more rapidly than the β-chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino-terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial

  13. The CHANGE trial

    DEFF Research Database (Denmark)

    Speyer, Helene; Norgaard, Hans Christian Brix; Birk, Merete

    2016-01-01

    Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel-group, superiority...... cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal...

  14. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    McAlindon, T. E.; Driban, J. B.; Henrotin, Y.

    2015-01-01

    the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population......The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct...

  15. Clinical trials in dentistry in India: Analysis from trial registry.

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

    Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

  16. Switchable sensitizers stepwise lighting up lanthanide emissions

    Science.gov (United States)

    Zhang, Yan; Jiao, Peng-Chong; Xu, Hai-Bing; Tang, Ming-Jing; Yang, Xiao-Ping; Huang, Shaoming; Deng, Jian-Guo

    2015-01-01

    Analagous to a long-ranged rocket equipped with multi-stage engines, a luminescent compound with consistent emission signals across a large range of concentrations from two stages of sensitizers can be designed. In this approach, ACQ, aggregation-caused quenching effect of sensitizers, would stimulate lanthanide emission below 10−4 M, and then at concentrations higher than 10−3 M, the “aggregation-induced emission” (AIE) effect of luminophores would be activated with the next set of sensitizers for lanthanide emission. Simultaneously, the concentration of the molecules could be monitored digitally by the maximal excitation wavelengths, due to the good linear relationship between the maximal excitation wavelengths and the concentrations {lg(M)}. This model, wherein molecules are assembled with two stages (both AIE and ACQ effect) of sensitizers, may provide a practicable strategy for design and construction of smart lanthanide bioprobes, which are suitable in complicated bioassay systems in which concentration is variable. PMID:25791467

  17. Stepwise Approach to Accessible MOOC Development.

    Science.gov (United States)

    Draffan, E A; Wald, Mike; Dickens, Kate; Zimmermann, Gottfried; Kelle, Sebastian; Miesenberger, Klaus; Petz, Andrea

    2015-01-01

    Developing resources for online learning in its many guises and more recently for MOOCs has been discussed across the educational sector, usually by individuals working for one institution or organisation. Rarely are there discussions that highlight the issues of collaborative working on content that is delivered over a period of weeks for a wide range of abilities and skills. In particular there is a reluctance to face the issues presented by barriers to access for those with disabilities and even the issues that could arise should an academic be unable to access the development platform to present content. This paper aims to approach these issues by providing guidance in a series of practical steps that highlight an inclusive design approach.

  18. Stepwise Grouping Algorithm for Statistical Learning Framework

    Energy Technology Data Exchange (ETDEWEB)

    An, Sang Ha; Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Heo, Gyun Young [Kyung Hee University, Yongin (Korea, Republic of); Seo, Ho Joon; Kim, Su Young [BNF Technology Inc., Daejeon (Korea, Republic of)

    2009-10-15

    In general, condition-based maintenance means the maintenance program which introduces additional sensors like vibration, acoustic, ultrasonic and infrared sensor to monitor equipment condition. The methodology which uses only process variables already installed in the system to detect anomalies, efficiency degradation or malfunction of sensors also have been studied. Among them, commercialization potential of process/sensor anomalies detection system using empirical model is considered high because it does not have additional system requirements for complex systems. However, some problems have been pointed out while these solutions having been introduced. For example, (1) missing important signals in variable selection and (2) variable duplicity problem for empirical model have been pointed out. This paper proposes complementary framework and detailed methodologies, and performs experimental validation by using a heat conduction experimental device which is available for flexible fault injections.

  19. Redesigning TRACER trial after TRITON.

    Science.gov (United States)

    Serebruany, Victor L

    2015-10-15

    Designing of smart clinical trials is critical for regulatory approval and future drug utilization. Importantly, trial design should be reconsidered if the interim analyses suggest unexpected harm, or conflicting results were yielded from the other trials within the same therapeutic area. With regard to antiplatelet agents, the perfect example is redesigning of the ongoing PRoFESS trial by eliminating aspirin from clopidogrel arm after the earlier MATCH trial results became available. The goal was to aseess the unchanged TRACER trial design in light of the evidence yielded from the earlier completed TRITON trial. TRACER was designed as a triple versus dual antiplatelet trial in NSTEMI patients with no previous long-term outcome data supporting such aggressive strategy. TRITON data represented dual versus dual antiplatelet therapy, and became available before TRACER enrollment starts revealing prasugrel front-loaded early vascular benefit predominantly in STEMI patients with the growing over time bleeding and cancer risks. Moreover, large prasugrel NSTEMI TRITON cohort exhibited trend towards excess mortality in experimental arm warning against aggressive TRACER design. The long-term TRITON results in general, and especially in the NSTEMI patients challenge unchanged TRACER trial design. Applying dual, rather than triple antiplatelet therapy protocol modification should be considered in TRACER to minimize bleeding, cancer, and non-cardiovascular death risks. Copyright © 2015. Published by Elsevier Ireland Ltd.

  20. Practical trials in medical education

    DEFF Research Database (Denmark)

    Tolsgaard, Martin G; Kulasegaram, Kulamakan M; Ringsted, Charlotte

    2017-01-01

    administration, quality of care, patient outcomes and cost. CONCLUSIONS: Practical trials in medical education may contribute to bridge the gap between education theory and practice and aid decision makers in making evidence-based choices and priorities. Conducting practical trials is not without challenges...... controlled settings generalise to the real-life education context. One way of bridging this gap is applying the concept of practical trials in medical education. In this paper we elaborate on characteristics of practical trials and based on examples from medical education we discuss the challenges...

  1. The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients

    Science.gov (United States)

    Echouffo-Tcheugui, Justin B; Simmons, Rebecca K; Williams, Kate M; Barling, Roslyn S; Prevost, A Toby; Kinmonth, Ann Louise; Wareham, Nicholas J; Griffin, Simon J

    2009-01-01

    Background The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, the benefits of such a strategy remain uncertain. Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i) a stepwise screening strategy for type 2 diabetes; and (ii) intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control), screening followed by intensive treatment (IT) and screening plus routine care (RC) in an unbalanced (1:3:3) randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals. Discussion ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary

  2. The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients

    Directory of Open Access Journals (Sweden)

    Kinmonth Ann

    2009-05-01

    Full Text Available Abstract Background The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, the benefits of such a strategy remain uncertain. Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i a stepwise screening strategy for type 2 diabetes; and (ii intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control, screening followed by intensive treatment (IT and screening plus routine care (RC in an unbalanced (1:3:3 randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals. Discussion ADDITION-Cambridge is conducted in a defined high-risk group

  3. Efficient folding/assembly in Chinese hamster ovary cells is critical for high quality (low aggregate content) of secreted trastuzumab as well as for high production: stepwise multivariate regression analyses.

    Science.gov (United States)

    Ishii, Yoichi; Murakami, Junko; Sasaki, Kazue; Tsukahara, Masayoshi; Wakamatsu, Kaori

    2014-08-01

    When developing cell culture processes for therapeutic antibodies, the low content of aggregated proteins is the most critical because administering aggregated antibody molecules might result in adverse effects such as immunogenicity. To characterize cells with high productivity and quality, we determined factors that are closely related to antibody titer, which is a productivity indicator, and the area percentage of high molecular weight species in cultivated media, which is equivalent to aggregate content and is used as a quality indicator. We examined the factors influencing antibody titer and aggregate content using various data from 28 cell lines throughout their culture periods from growth to death phases. Our study using correlation analysis revealed that statistically significant correlations between factors and indicators changes with sampling points, hence we thought that various factors would influence each indicator simultaneously. To understand the relationship between these factors and titer/aggregates contents, we performed stepwise multiple linear regression analyses and deduced a multiple linear model for each indicator. The titer was found to positively associate with specific growth rate and specific production rate and negatively with intracellular heavy chain content. The aggregate content was found to positively associate with protein disulfide isomerase mRNA level and negatively with light chain secreted into culture media, specific production rate, intracellular light chain content, and specific growth rate. Our observations suggest that correct and efficient assembling and/or folding of an antibody molecule in an endoplasmic reticulum are important for high titer and low aggregates contents. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic Excursion (TAPSE) - A Novel Parameter for Stepwise Echocardiographic Risk Stratification in Normotensive Patients With Acute Pulmonary Embolism.

    Science.gov (United States)

    Ciurzyński, Michał; Kurnicka, Katarzyna; Lichodziejewska, Barbara; Kozłowska, Marta; Pływaczewska, Magdalena; Sobieraj, Piotr; Dzikowska-Diduch, Olga; Goliszek, Sylwia; Bienias, Piotr; Kostrubiec, Maciej; Pruszczyk, Piotr

    2018-01-26

    Patients with intermediate-risk acute pulmonary embolism (APE) are a heterogeneous group with an early mortality rate of 2-15%. The tricuspid annulus plane systolic excursion (TAPSE) and tricuspid regurgitation peak gradient (TRPG) can be used for risk stratification, so we analyzed the prognostic value of a new echo parameter (TRPG/TAPSE) for prediction of APE-related 30-day death or need for rescue thrombolysis in initially normotensive APE patients.Methods and Results:The study group consists of 400 non-high-risk APE patients (191 men, age: 63.1±18.9 years) who had undergone echocardiography within the first 24 h of admission. The TRPG/TAPSE parameter was calculated. The clinical endpoint (CE) was a combination of 30-day APE-related death and/or rescue thrombolysis. The CE occurred in 8 (2%) patients. All patients with TAPSE ≥20 mm (n=193, 48.2%) had a good prognosis. Among 206 patients with TAPSE 4.5 were 0.2 and 0.98, respectively. The CE was significantly more frequent in 19 (9.2%) patients with TRPG/TAPSE >4.5 than in 188 (90.8%) with TRPG/TAPSE ≤4.5 (4 (21.1%) vs. 4 (2.1%), P=0.0005). Among normotensive APE patients with TAPSE 4.5 was associated with 21.1% risk of APE-related death or rescue thrombolysis. TRPG/TAPSE, a novel echocardiographic parameter, may be useful for stepwise echocardiographic risk stratification in normotensive patients with APE, and it identifies patients with a poor prognosis.

  5. Topics in clinical trial management

    NARCIS (Netherlands)

    B.A. Kirwan (Bridget Anne)

    2004-01-01

    textabstractThe aim of this thesis is to show how clinical trial conduct can be managed while respecting the underlying scientific principles. Chapter 2 describes the main results of PICO (PImobendan in COngestive heart failure), a trial which investigated a positive inotropic agent in patients

  6. Defendants' Rights in Criminal Trials.

    Science.gov (United States)

    Martin, Ralph C., II; Keeley, Elizabeth

    1997-01-01

    Reviews the protections afforded by the Constitution for defendants in criminal trials. These include the right to a jury trial (in cases of possible incarceration), an impartial jury, and the requirement of a unanimous verdict. Defends the use of plea bargaining as essential to an efficient criminal justice system. (MJP)

  7. LTDNA Evidence on Trial.

    Science.gov (United States)

    Roberts, Paul

    2016-01-01

    Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially

  8. Do Current Clinical Trials Meet Society's Needs?

    National Research Council Canada - National Science Library

    Stuart J Pocock; Bernard J Gersh

    2014-01-01

    .... Topics covered include the inadequacy of trial research on medical devices, problems with industry-sponsored trials, the lack of head-to-head trials of new effective treatments, the need for wiser...

  9. Using simulation to aid trial design: Ring-vaccination trials.

    Directory of Open Access Journals (Sweden)

    Matt David Thomas Hitchings

    2017-03-01

    Full Text Available The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination.We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design.Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the

  10. Planning an Academic Clinical Trial.

    Science.gov (United States)

    Champion, Kim M; Jones, Gemma R

    2015-01-01

    Clinical trials are performed to discover or verify the efficacy and safety of one or more investigational medicinal product (IMP). Biological medicinal products, including gene therapies, offer groundbreaking new opportunities for the treatment of disease and injury, but they are also highly regulated and trials with these products can be logistically challenging to set up and execute. To ensure a compliant and successful trial, it is important to know and understand the regulatory framework, and to be aware of available guidance documents published to advise the different stakeholders on how to develop, manufacture, handle, administer, or destroy these products safely and legally. This chapter summarizes the standard requirements and considerations applicable for clinical trials with IMPs and also describes additional requirements for trials with gene therapies or genetically modified microorganisms (GMM).This chapter has been written from the perspective of a UK noncommercial (academic) sponsor. As such, the discussion and guidance has its basis in gene therapy research as governed by UK law. Nevertheless, European legislation and guidance documents are also referenced; most of the following recommendations will be applicable to clinical trials with a gene therapy medicinal product in any European Member State, and the overriding principles would be applicable to any trial.

  11. Medio-lateral Knee Fluency in Anterior Cruciate Ligament-Injured Athletes During Dynamic Movement Trials

    Science.gov (United States)

    Panos, Joseph A.; Hoffman, Joshua T.; Wordeman, Samuel C.; Hewett, Timothy E.

    2016-01-01

    Background Correction of neuromuscular impairments after anterior cruciate ligament injury is vital to successful return to sport. Frontal plane knee control during landing is a common measure of lower-extremity neuromuscular control and asymmetries in neuromuscular control of the knee can predispose injured athletes to additional injury and associated morbidities. Therefore, this study investigated the effects of anterior cruciate ligament injury on knee biomechanics during landing. Methods Two-dimensional frontal plane video of single leg drop, cross over drop, and drop vertical jump dynamic movement trials was analyzed for twenty injured and reconstructed athletes. The position of the knee joint center was tracked in ImageJ software for 500 milliseconds after landing to calculate medio-lateral knee motion velocities and determine normal fluency, the number of times per second knee velocity changed direction. The inverse of this calculation, analytical fluency, was used to associate larger numerical values with fluent movement. Findings Analytical fluency was decreased in involved limbs for single leg drop trials (P=0.0018). Importantly, analytical fluency for single leg drop differed compared to cross over drop trials for involved (P<0.001), but not uninvolved limbs (P=0.5029). For involved limbs, analytical fluency values exhibited a stepwise trend in relative magnitudes. Interpretation Decreased analytical fluency in involved limbs is consistent with previous studies. Fluency asymmetries observed during single leg drop tasks may be indicative of abhorrent landing strategies in the involved limb. Analytical fluency differences in unilateral tasks for injured limbs may represent neuromuscular impairment as a result of injury. PMID:26895446

  12. Frailty Intervention Trial (FIT

    Directory of Open Access Journals (Sweden)

    Lockwood Keri

    2008-10-01

    Full Text Available Abstract Background Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity. Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty. We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people. Methods and Design A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period. Discussion This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a

  13. Designing clinical trials for amblyopia.

    Science.gov (United States)

    Holmes, Jonathan M

    2015-09-01

    Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Modelling Trial-by-Trial Changes in the Mismatch Negativity

    Science.gov (United States)

    Lieder, Falk; Daunizeau, Jean; Garrido, Marta I.; Friston, Karl J.; Stephan, Klaas E.

    2013-01-01

    The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors. PMID:23436989

  15. GAUSS Project Trials Results

    Science.gov (United States)

    Di Fazio, Antonella; Vernucci, Antonio; Rossini, Eugenio

    2003-07-01

    the Consortium Partners. The former ones constitute the ground and space segments, the latter ones include the advanced user terminal and the applications. The assembled system was used as test-bed during the trail campaign, to validate and prove the provided services and developed applications.The GAUSS Demonstrator includes the following components:ß The Mobile User Terminal installed on a car (van) or on a boat. An innovative multi-mode user equipment was developed, consisting of the following main components:- An integrated NAV / COM digital receive front-end (DFRE), able to de-multiplex the NAV signals (the current GNSS1 band and the simulated Galileo bands), and the COM signal in the S-UMTS band;- For COM: a transmit front-end, and a baseband & control section operating in CDMA and supporting the upper protocol layers (UMTS packet transmission standard based - for short packet); a RF subsystem, including the L→S bands conversion;- For NAV: a GNSS (GPS, EGNOS) navigation receiver, the GNSS1 System (MTB - Mediterranean Test bed, ESTB / EGNOS System Test Bed) for navigation;* The Communication capacity on the INMARSAT 3F5 Satellite* The Gateway, located in LARIO Telespazio premises* The Lario07 Station* The Service Centre* The Service Provider.The GAUSS Demonstrator reflects all the main elements of a complete user platform for service provisioning: mobility assistance, safety and transport efficient management are the core of the developed applications. Applications were developed, specifically to provide reliable and effective services to the citizens: road info-mobility and fleet management, inland waterways vessel traffic management and information, port/terminals appointment monitoring & control, dangerous goods transhipment supervision, emergency assistance.A trial campaign, run into real environments, was performed in Summer 2002. GAUSS Demonstrator performances and benefits were validated with the direct involvement of an inter-modal transport user

  16. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution.

    Science.gov (United States)

    Khokhlova, Olga E; Hung, Wei-Chun; Wan, Tsai-Wen; Iwao, Yasuhisa; Takano, Tomomi; Higuchi, Wataru; Yachenko, Svetlana V; Teplyakova, Olga V; Kamshilova, Vera V; Kotlovsky, Yuri V; Nishiyama, Akihito; Reva, Ivan V; Sidorenko, Sergey V; Peryanova, Olga V; Reva, Galina V; Teng, Lee-Jene; Salmina, Alla B; Yamamoto, Tatsuo

    2015-01-01

    239Kras, a new (Siberian Russian) clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR.

  17. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution

    Science.gov (United States)

    Khokhlova, Olga E.; Hung, Wei-Chun; Wan, Tsai-Wen; Iwao, Yasuhisa; Takano, Tomomi; Higuchi, Wataru; Yachenko, Svetlana V.; Teplyakova, Olga V.; Kamshilova, Vera V.; Kotlovsky, Yuri V.; Nishiyama, Akihito; Reva, Ivan V.; Sidorenko, Sergey V.; Peryanova, Olga V.; Reva, Galina V.; Teng, Lee-Jene; Salmina, Alla B.; Yamamoto, Tatsuo

    2015-01-01

    239Kras, a new (Siberian Russian) clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR. PMID:26047024

  18. Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution.

    Directory of Open Access Journals (Sweden)

    Olga E Khokhlova

    239Kras, a new (Siberian Russian clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR.

  19. Clinical Trials in Vision Research

    Science.gov (United States)

    ... Clinical Trials in Vision Research Booklet for Nook, iPad and iPhone (EPUB - 1.6MB) Download the Clinical ... NEI Office of Science Communications, Public Liaison, and Education. Technical questions about this website can be addressed ...

  20. Clinical Trials: Information and Options for People with Mood Disorders

    Science.gov (United States)

    ... Clinical Trials: Information and Options for People with Mood Disorders What are clinical trials? Clinical trials are research ... during a clinical trial? Clinical trials that test mood disorder treatments are usually conducted on an outpatient basis, ...

  1. 5 CFR 316.304 - Trial period.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Trial period. 316.304 Section 316.304... Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial... completion of the required trial period in the same manner as prescribed by § 315.802 of this chapter. (b...

  2. 32 CFR 935.105 - Trial.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  3. Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

    Science.gov (United States)

    Pagidipati, Neha J; Navar, Ann Marie; Pieper, Karen S; Green, Jennifer B; Bethel, M Angelyn; Armstrong, Paul W; Josse, Robert G; McGuire, Darren K; Lokhnygina, Yuliya; Cornel, Jan H; Halvorsen, Sigrun; Strandberg, Timo E; Delibasi, Tuncay; Holman, Rury R; Peterson, Eric D

    2017-09-26

    Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205. © 2017 American Heart Association, Inc.

  4. Successful recruitment to trials: findings from the SCIMITAR+ Trial.

    Science.gov (United States)

    Peckham, Emily; Arundel, Catherine; Bailey, Della; Callen, Tracy; Cusack, Christina; Crosland, Suzanne; Foster, Penny; Herlihy, Hannah; Hope, James; Ker, Suzy; McCloud, Tayla; Romain-Hooper, Crystal-Bella; Stribling, Alison; Phiri, Peter; Tait, Ellen; Gilbody, Simon

    2018-01-19

    Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

  5. Frailty Intervention Trial (FIT).

    Science.gov (United States)

    Fairhall, Nicola; Aggar, Christina; Kurrle, Susan E; Sherrington, Catherine; Lord, Stephen; Lockwood, Keri; Monaghan, Noeline; Cameron, Ian D

    2008-10-13

    Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity). Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty.We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people. A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period. This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further

  6. a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    MS Yıldırım

    2016-02-01

    Full Text Available The aim of this study was to compare the effects of static stretching, proprioceptive neuromuscular facilitation (PNF stretching and Mulligan technique on hip flexion range of motion (ROM in subjects with bilateral hamstring tightness. A total of 40 students (mean age: 21.5±1.3 years, mean body height: 172.8±8.2 cm, mean body mass index: 21.9±3.0 kg • m-2 with bilateral hamstring tightness were enrolled in this randomized trial, of whom 26 completed the study. Subjects were divided into 4 groups performing (I typical static stretching, (II PNF stretching, (III Mulligan traction straight leg raise (TSLR technique, (IV no intervention. Hip flexion ROM was measured using a digital goniometer with the passive straight leg raise test before and after 4 weeks by two physiotherapists blinded to the groups. 52 extremities of 26 subjects were analyzed. Hip flexion ROM increased in all three intervention groups (p<0.05 but not in the no-intervention group after 4 weeks. A statistically significant change in initial–final assessment differences of hip flexion ROM was found between groups (p<0.001 in favour of PNF stretching and Mulligan TSLR technique in comparison to typical static stretching (p=0.016 and p=0.02, respectively. No significant difference was found between Mulligan TSLR technique and PNF stretching (p=0.920. The initial–final assessment difference of hip flexion ROM was similar in typical static stretching and no intervention (p=0.491. A 4-week stretching intervention is beneficial for increasing hip flexion ROM in bilateral hamstring tightness. However, PNF stretching and Mulligan TSLR technique are superior to typical static stretching. These two interventions can be alternatively used for stretching in hamstring tightness.

  7. LTDNA Evidence on Trial

    Directory of Open Access Journals (Sweden)

    Paul Roberts

    2016-10-01

    factfinders in criminal trials.

  8. The implementation of the serial trial intervention for pain and challenging behaviour in advanced dementia patients (STA OP!: a clustered randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Francke Anneke L

    2011-03-01

    Full Text Available Abstract Background Pain (physical discomfort and challenging behaviour are highly prevalent in nursing home residents with dementia: at any given time 45-80% of nursing home residents are in pain and up to 80% have challenging behaviour. In the USA Christine Kovach developed the serial trial intervention (STI and established that this protocol leads to less discomfort and fewer behavioural symptoms in moderate to severe dementia patients. The present study will provide insight into the effects of implementation of the Dutch version of the STI-protocol (STA OP! in comparison with a control intervention, not only on behavioural symptoms, but also on pain, depression, and quality of life. This article outlines the study protocol. Methods/Design The study is a cluster randomized controlled trial in 168 older people (aged >65 years with mild or moderate dementia living in nursing homes. The clusters, Dutch nursing homes, are randomly assigned to either the intervention condition (training and implementation of the STA OP!-protocol or the control condition (general training focusing on challenging behaviour and pain, but without the step-wise approach. Measurements take place at baseline, after 3 months (end of the STA OP! training period and after 6 months. Primary outcome measures are symptoms of challenging behaviour (measured with the Cohen-Mansfield Agitation Inventory (CMAI and the Neuropsychiatric Inventory-Nursing Home version (NPI-NH, and pain (measure with the Dutch version of the Pain Assessment Checklist for Seniors (PACSLAC-D and the Minimum Data Set of the Resident Assessment Instrument (MDS-RAI pain scale. Secondary outcome measures include symptoms of depression (Cornell and MDS-RAI depression scale, Quality of Live (Qualidem, changes in prescriptions of analgesics and psychotropic drugs, and the use of non-pharmacological comfort interventions (e.g. snoezelen, reminiscence therapy. Discussion The transfer from the American design to

  9. Use of clustering analysis in randomized controlled trials in orthopaedic surgery.

    Science.gov (United States)

    Oltean, Hanna; Gagnier, Joel J

    2015-03-08

    The effects of clustering in randomized controlled trials (RCTs) and the resulting potential violation of assumptions of independence are now well recognized. When patients in a single study are treated by several therapists, there is good reason to suspect that the variation in outcome will be smaller for patients treated in the same group than for patients treated in different groups. This potential correlation of outcomes results in a loss of independence of observations. The purpose of this study is to examine the current use of clustering analysis in RCTs published in the top five journals of orthopaedic surgery. RCTs published from 2006 to 2010 in the top five journals of orthopaedic surgery, as determined by 5-year impact factor, that included multiple therapists and/or centers were included. Identified articles were assessed for accounting for the effects of clustering of therapists and/or centers in randomization or analysis. Logistic regression used both univariate and multivariate models, with use of clustering analysis as the outcome. Multivariate models were constructed using stepwise deletion. An alpha level of 0.10 was considered significant. A total of 271 articles classified as RCTs were identified from the five journals included in the study. Thirty-two articles were excluded due to inclusion of nonhuman subjects. Of the remaining 239 articles, 186 were found to include multiple centers and/or therapists. The prevalence of use of clustering analysis was 21.5%. Fewer than half of the studies reported inclusion of a statistician, epidemiologist or clinical trials methodologist on the team. In multivariate modeling, adjusting for clustering was associated with a 6.7 times higher odds of inclusion of any type of specialist on the team (P = 0.08). Likewise, trials that accounted for clustering had 3.3 times the odds of including an epidemiologist/clinical trials methodologist than those that did not account for clustering (P = 0.04). Including

  10. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial.

    Science.gov (United States)

    Husebo, Bettina S; Ballard, Clive; Sandvik, Reidun; Nilsen, Odd Bjarte; Aarsland, Dag

    2011-07-15

    To determine whether a systematic approach to the treatment of pain can reduce agitation in people with moderate to severe dementia living in nursing homes. Cluster randomised controlled trial. 60 clusters (single independent nursing home units) in 18 nursing homes within five municipalities of western Norway. 352 residents with moderate to severe dementia and clinically significant behavioural disturbances randomised to a stepwise protocol for the treatment of pain for eight weeks with additional follow-up four weeks after the end of treatment (33 clusters; n = 175) or to usual treatment (control, 27 clusters; n = 177). Participants in the intervention group received individual daily treatment of pain for eight weeks according to the stepwise protocol, with paracetamol (acetaminophen), morphine, buprenorphine transdermal patch, or pregabaline. The control group received usual treatment and care. Primary outcome measure was agitation (scores on Cohen-Mansfield agitation inventory). Secondary outcome measures were aggression (scores on neuropsychiatric inventory-nursing home version), pain (scores on mobilisation-observation-behaviour-intensity-dementia-2), activities of daily living, and cognition (mini-mental state examination). Agitation was significantly reduced in the intervention group compared with control group after eight weeks (repeated measures analysis of covariance adjusting for baseline score, P scores for agitation was 17% (treatment effect estimate -7.0, 95% confidence interval -3.7 to -10.3). Treatment of pain was also significantly beneficial for the overall severity of neuropsychiatric symptoms (-9.0, -5.5 to -12.6) and pain (-1.3, -0.8 to -1.7), but the groups did not differ significantly for activities of daily living or cognition. A systematic approach to the management of pain significantly reduced agitation in residents of nursing homes with moderate to severe dementia. Effective management of pain can play an important part in the treatment

  11. Factors that influence the efficacy of acarbose and metformin as initial therapy in Chinese patients with newly diagnosed type 2 diabetes: a subanalysis of the MARCH trial.

    Science.gov (United States)

    Zhang, Jinping; Wang, Na; Xing, Xiaoyan; Yang, Zhaojun; Wang, Xin; Yang, Wenying

    2016-01-01

    To conduct a subanalysis of the randomized MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment) trial to investigate whether specific characteristics are associated with the efficacy of either acarbose or metformin as initial therapy. A total of 657 type 2 diabetes patients who were randomly assigned to 48 weeks of therapy with either acarbose or metformin in the MARCH trial were divided into two groups based upon their hemoglobin A1c (HbA1c) levels at the end of follow-up: HbA1c influenced by HbA1c, fasting blood glucose (FBG), and 2 hour postprandial venous blood glucose (2hPPG) levels, as well as by changes in body mass index (BMI) (p ≤ 0.006). Multivariate analysis and stepwise linear regression analyses indicated that lower baseline 2hPPG values and greater changes in BMI were factors that positively influenced efficacy in both treatment groups (p ≤ 0.05). Stepwise regression model analysis also revealed that a lower baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR) and higher serum insulin area under the curve (AUC) were factors positively influencing HbA1c normalization in all patients (p ≤ 0.032). Newly diagnosed type 2 diabetes patients with lower baseline 2hPPG and HOMA-IR values are more likely to achieve glucose control with acarbose or metformin treatment. Furthermore, the change in BMI after acarbose or metformin treatment is also a factor influencing HbA1c normalization. A prospective study with a larger sample size is necessary to confirm our results as well as measure β cell function and examine the influence of the patients' dietary habits.

  12. Exercise motivation and adherence in cancer survivors after participation in a randomized controlled trial: an attribution theory perspective.

    Science.gov (United States)

    Courneya, Kerry S; Friedenreich, Christine M; Sela, Rami A; Quinney, H Arthur; Rhodes, Ryan E; Jones, Lee W

    2004-01-01

    The purpose of this study was to examine postprogram exercise motivation and adherence in cancer survivors who participated in the Group Psychotherapy and Home-Based Physical Exercise (GROUP-HOPE; Courneya, Friedenreich, Sela, Quinney, & Rhodes, 2002) trial. At the completion of the GROUP-HOPE trial, 46 of 51 (90%) participants in the exercise group completed measures of attribution theory constructs. A 5-week follow-up self-report of exercise was then completed by 30 (65%) participants. Correlational analyses indicated that program exercise, perceived success, expected success, and affective reactions were strong predictors of postprogram exercise. In multivariate stepwise regression analyses, program exercise and perceived success were the strongest predictors of postprogram exercise. Additionally, perceived success was more important than objective success in understanding the attribution process, and it interacted with personal control to influence expected success and negative affect. Finally, postprogram quality of life and changes in physical fitness were correlates of perceived success. We concluded that attribution theory may have utility for understanding postprogram exercise motivation and adherence in cancer survivors.

  13. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010

    NARCIS (Netherlands)

    Califf, R.M.; Zarin, D.A.; Kramer, J.M.; Sherman, R.E.; Aberle, L.H.; Tasneem, A.

    2012-01-01

    CONTEXT: Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials

  14. Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements

    NARCIS (Netherlands)

    Nieuwenhuis, Joost B.; Irving, Elaine; Oude Rengerink, Katrien; Lloyd, Emily; Goetz, Iris; Grobbee, Diederick E.; Stolk, Pieter; Groenwold, Rolf H H; Zuidgeest, Mira G P

    2016-01-01

    OBJECTIVE: To illustrate how pragmatic trial design elements, or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision and operational feasibility. STUDY DESIGN AND SETTING: From illustrative examples identified through the IMI Get Real Consortium, we

  15. Clinical trials. A pending subject.

    Science.gov (United States)

    Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D

    2017-07-31

    Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  16. Increased Risk for Falling Associated with Subtle Cognitive Impairment: Secondary Analysis of a Randomized Clinical Trial

    Science.gov (United States)

    Gleason, Carey E.; Gangnon, Ronald E.; Fischer, Barbara L.; Mahoney, Jane E.

    2009-01-01

    Background/Aims Having dementia increases patients’ risk for accidental falls. However, it is unknown if having mild cognitive deficits also elevates a person's risk for falls. This study sought to clarify the relationship between subtle cognitive impairment, measured with a widely-used, clinic-based assessment, the Mini Mental State Exam (MMSE), and risk for falls. Methods In a secondary analysis of the Kenosha County Falls Prevention Study, a randomized controlled trial targeting older adults at risk for falls, we examined the association between baseline MMSE and prospective rate of falls over 12 months in 172 subjects randomized to control group. Results Using univariate analysis, the rate of falls increased with each unit decrease in MMSE score down to at least 22 (rate ratio 1.25, 95% confidence interval (CI) 1.09–1.45, p = 0.0026). Using stepwise multivariate regression, controlling for ability to perform activities of daily living, use of assistive device, current exercise, and arthritis, the association between MMSE score and falls rate persisted (rate ratio 1.20, 95% CI 1.03–1.40, p = 0.021). Conclusion Minimal decrements on the MMSE were associated with elevations in rate of falls, suggesting that subtle cognitive deficits reflected in MMSE scores above a cut-off consistent with a diagnosis of dementia, can influence risk for falls. PMID:19602883

  17. [Pharmacy standards for clinical trials].

    Science.gov (United States)

    Terkola, Robert

    2008-01-01

    The procurement, transport, storage, manufacturing or compounding, the application, disposal, documentation, and the quality assurance of investigational medicinal products (IMPs) have to be done according to the pharmaceutical sciences. Medicines related to clinical trials in the European Union are regulated in volume 10 of the EudraLex. The rules for commercially manufactured medicines for human use are not valid for medicines which are individually compounded for a certain patient in the pharmacy. They are also not valid for medicines dedicated for experiments in research and development. The present article describes standards concerning the participation of the pharmacy in clinical trials, the pathway of the drug including the role of the study personnel, and its qualification and training. The issue of stability and compatibility of IMPs is an important topic which may influence the outcome of clinical trials. To avoid quality shifts Standard Operating Procedures (SOPs) have to be established. Copyright 2008 S. Karger AG, Basel.

  18. Adaptive designs in clinical trials

    Directory of Open Access Journals (Sweden)

    Suresh Bowalekar

    2011-01-01

    Full Text Available In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  19. Adaptive designs in clinical trials.

    Science.gov (United States)

    Bowalekar, Suresh

    2011-01-01

    In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  20. Clinical trial insurance in Serbia

    Directory of Open Access Journals (Sweden)

    Žagar Zlatko A.

    2015-01-01

    Full Text Available Prior the commencement of the clinical trial in Serbia the Sponsor is obliged to provide the insurance policy covering the patient's bodily injury and damaged health caused by the clinical trial. According to provisions of Serbian Insurance law insurance polices have to be issued by the insurance companies established in Serbia. Every insurance policy not issued by the insurance company established in Serbia shall be deemed as null and void. The only expectance, is when the foreign clinical trial liability policy is stipulated that the insurance contract acknowledges the jurisdiction of Serbian domestic courts and other Serbian authorities to decide on damage claims (that never happened in Serbian practice. The Sponsor will fulfill this obligation stipulated in Serbian law when provides the Clinical Trial Liability policy issued by the Serbian insurance company. Nowadays, few of Serbian insurance companies are issuing such polices. Under the clinical trial liability insurance cover the insured's are: Sponsor, Medical Centers in Serbia performing or controlling the clinical trial, Principal Investigators and their assistant staff performing or controlling the clinical trial. The beneficiaries of the insurance cover are patients and/or members of their families - inheritresses. The insurance company will indemnify the beneficiary mentioned in the policy when the insured event occurred i.e. when occurred bodily injury, psychic disease and alienation, psychic damages, illnesses and deaths caused by the clinical trial. The amount of indemnity by the insurance company to the beneficiaries is limited by the amount of sum insured per occurrence and/or by the total amount of the sum insured for the total period of the insurance cover. According to case-law in Serbia the total sum insured between EUR 500.000 and EUR 1.000.000 is considered as sufficient so far to indemnify the patients in case of the insured event. If an insurance event occurs the