WorldWideScience

Sample records for relating adverse biological

  1. Identifying Adverse Drug Events by Relational Learning.

    Science.gov (United States)

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2012-07-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task , related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events.

  2. Non-hemorrhage-related adverse effects of rivaroxaban

    OpenAIRE

    Christopoulou, Eliza C.; Filippatos, Theodosios D.; Elisaf, Moses S.

    2017-01-01

    The direct oral anticoagulant rivaroxaban is useful in various indications that include venous deep vein thrombosis prophylaxis/treatment after knee/hip replacement surgery and prevention of stroke in patients with non-valvular atrial fibrillation. Its mechanism of action has been mostly associated with hemorrhage-related adverse effects; thus a number of non-hemorrhage-related adverse effects of the drug have received less attention or go unrecognized. These adverse effects mainly include li...

  3. Admissions and Readmissions Related to Adverse Events, 2007-2014

    Science.gov (United States)

    2015-12-01

    DRG is a classification system primarily used for billing purposes. It uses the principle and secondary diagnoses to assign clinical conditions to...This study assessed adverse events as they relate to readmissions in the Military Health System (MHS). Among 142,579 admissions with an adverse event...The following study retrospectively assessed admissions and readmissions for adverse events in the Military Health System (MHS) by quantifying

  4. Informatics approaches in the Biological Characterization of Adverse Outcome Pathways

    Science.gov (United States)

    Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational ...

  5. Magnitude of income-related disparities in adverse perinatal outcomes

    OpenAIRE

    Shankardass, Ketan; O’Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, KS; Morinis, Julia; Allen, Victoria M

    2014-01-01

    Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 11...

  6. Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain : a six-year cohort study

    NARCIS (Netherlands)

    Generaal, E.; Vogelzangs, N.; Macfarlane, G.J.; Geenen, R.; de Geus, E.; Smit, J.H.; Penninx, B.W.; Dekker, J.

    2015-01-01

    Background Dysregulated biological stress systems and adverse life events, both independently and in interaction, have been hypothesized to initiate chronic pain. Objectives We examine whether (i) function of biological stress systems, (ii) adverse life events, and (iii) their combination predict

  7. Adverse effects of biologics: a network meta-analysis and Cochrane overview

    DEFF Research Database (Denmark)

    Singh, J. A.; Wells, G. A.; Christensen, Robin Daniel Kjersgaard

    2011-01-01

    Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious...

  8. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    DEFF Research Database (Denmark)

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse...

  9. Genetics in Relation to Biology.

    Science.gov (United States)

    Stewart, J. Bird

    1987-01-01

    Claims that most instruction dealing with genetics is limited to sex education and personal hygiene. Suggests that the biology curriculum should begin to deal with other issues related to genetics, including genetic normality, prenatal diagnoses, race, and intelligence. Predicts these topics will begin to appear in British examination programs.…

  10. The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Liefbroer, Aart C.

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  11. The longitudinal relation between accumulation of adverse life events and body mass index from early adolescence to young adulthood

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Liefbroer, Aart C.

    2017-01-01

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  12. The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood

    NARCIS (Netherlands)

    Elsenburg, L.; Smidt, N.; Liefbroer, A.C.

    2017-01-01

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  13. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

    Science.gov (United States)

    Carrascosa, J M; Del-Alcazar, E

    2018-04-01

    Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

  14. Serious Adverse Events Associated With Using Biological Agents To Treat Rheumatic Diseases

    DEFF Research Database (Denmark)

    Tarp, Simon; Tarp, Ulrik; Andersen, Lis S

    Background/Purpose: Clinical guidelines are needed to help clinicians provide optimal medical treatment and advise patients about the potential hazards associated with certain drugs. Our objective was to compare the number of serious adverse events (SAEs) for the biologics available for inflammat...

  15. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    Science.gov (United States)

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  16. THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK: A FRAMEWORK FOR ORGANIZING BIOLOGICAL KNOWLEDGE LEADING TO HEALTH RISKS.

    Science.gov (United States)

    An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecul...

  17. Magnitude of income-related disparities in adverse perinatal outcomes.

    Science.gov (United States)

    Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M

    2014-03-04

    To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.

  18. Interaction of Adverse Disease Related Pathways in Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Rowin, Ethan J; Maron, Martin S; Chan, Raymond H; Hausvater, Anais; Wang, Wendy; Rastegar, Hassan; Maron, Barry J

    2017-12-15

    Hypertrophic cardiomyopathy (HC) has been characterized as a generally progressive genetic heart disease, creating an ominous perspective for patients and managing cardiologists. We explored the HC disease burden and interaction of adverse clinical pathways to clarify patient expectations over long time periods in the contemporary therapeutic era. We studied 1,000 consecutive HC patients (52 ± 17 years) at Tufts Medical Center, followed 9.3 ± 8 years from diagnosis, employing a novel disease pathway model: 46% experienced a benign course free of adverse pathways, but 42% of patients progressed along 1 major pathway, most commonly refractory heart failure to New York Heart Association class III or IV requiring surgical myectomy (or alcohol ablation) or heart transplant; repetitive or permanent atrial fibrillation; and least commonly arrhythmic sudden death events. Eleven percent experienced 2 of these therapeutic end points at different times in their clinical course, most frequently the combination of advanced heart failure and atrial fibrillation, whereas only 1% incurred all 3 pathways. Freedom of progression from 1 to 2 disease pathways, or from 2 to 3 was 80% and 93% at 5 years, respectively. Annual HC-related mortality did not differ according to the number of pathways: 1 (0.8%), 2 (0.8%), or 3 (2.4%) (p = 0.56), and 93% of patients were in New York Heart Association classes I or II at follow-up. In conclusion, it is uncommon for HC patients to experience multiple adverse (but treatable) disease pathways, underscoring the principle that HC is not a uniformly progressive disease. These observations provide a measure of clarity and/or reassurance to patients regarding the true long-term disease burden of HC. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Ameliorating the biological impacts of childhood adversity: A review of intervention programs.

    Science.gov (United States)

    Purewal Boparai, Sukhdip K; Au, Vanessa; Koita, Kadiatou; Oh, Debora Lee; Briner, Susan; Burke Harris, Nadine; Bucci, Monica

    2018-05-01

    Childhood adversity negatively impacts the biological development of children and has been linked to poor health outcomes across the life course. The purpose of this literature review is to explore and evaluate the effectiveness of interventions that have addressed an array of biological markers and physical health outcomes in children and adolescents affected by adversity. PubMed, CINAHL, PsychInfo, Sociological Abstracts databases and additional sources (Cochrane, WHO, NIH trial registries) were searched for English language studies published between January 2007 and September 2017. Articles with a childhood adversity exposure, biological health outcome, and evaluation of intervention using a randomized controlled trial study design were selected. The resulting 40 intervention studies addressed cortisol outcomes (n = 20) and a range of neurological, epigenetic, immune, and other outcomes (n = 22). Across institutional, foster care, and community settings, intervention programs demonstrated success overall for improving or normalizing morning and diurnal cortisol levels, and ameliorating the impacts of adversity on brain development, epigenetic regulation, and additional outcomes in children. Factors such as earlier timing of intervention, high quality and nurturant parenting traits, and greater intervention engagement played a role in intervention success. This study underlines progress and promise in addressing the health impacts of adversity in children. Ongoing research efforts should collect baseline data, improve retention, replicate studies in additional samples and settings, and evaluate additional variables, resilience factors, mediators, and long-term implications of results. Clinicians should integrate lessons from the intervention sciences for preventing and treating the health effects of adversity in children and adolescents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior.

    Science.gov (United States)

    Mackey, Scott; Chaarani, Bader; Kan, Kees-Jan; Spechler, Philip A; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Paillère Martinot, Marie-Laure; Artiges, Eric; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Poustka, Luise; Smolka, Michael N; Jurk, Sarah; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Althoff, Robert R; Garavan, Hugh

    2017-08-15

    Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use). Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Mechanisms and assessment of statin-related muscular adverse effects

    Science.gov (United States)

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  2. Home visiting and the biology of toxic stress: opportunities to address early childhood adversity.

    Science.gov (United States)

    Garner, Andrew S

    2013-11-01

    Home visiting is an important mechanism for minimizing the lifelong effects of early childhood adversity. To do so, it must be informed by the biology of early brain and child development. Advances in neuroscience, epigenetics, and the physiology of stress are revealing the biological mechanisms underlying well-established associations between early childhood adversity and suboptimal life-course trajectories. Left unchecked, mediators of physiologic stress become toxic, alter both genome and brain, and lead to a vicious cycle of chronic stress. This so-called "toxic stress" results a wide array of behavioral attempts to blunt the stress response, a process known as "behavioral allostasis." Although behaviors like smoking, overeating, promiscuity, and substance abuse decrease stress transiently, over time they become maladaptive and result in the unhealthy lifestyles and noncommunicable diseases that are the leading causes of morbidity and mortality. The biology of toxic stress and the concept of behavioral allostasis shed new light on the developmental origins of lifelong disease and highlight opportunities for early intervention and prevention. Future efforts to minimize the effects of childhood adversity should focus on expanding the capacity of caregivers and communities to promote (1) the safe, stable, and nurturing relationships that buffer toxic stress, and (2) the rudimentary but foundational social-emotional, language, and cognitive skills needed to develop healthy, adaptive coping skills. Building these critical caregiver and community capacities will require a public health approach with unprecedented levels of collaboration and coordination between the healthcare, childcare, early education, early intervention, and home visiting sectors.

  3. Practical management of adverse events related to apomorphine therapy

    DEFF Research Database (Denmark)

    Bhidayasiri, Roongroj; Garcia Ruiz, Pedro J; Henriksen, Tove

    2016-01-01

    The potential for adverse events is often cited as a barrier to the use of subcutaneous apomorphine therapy (intermittent injections and continuous infusion) in the management of Parkinson's disease. However, with proactive management most adverse effects are manageable if reported and tackled...... titration, initiation and long-term treatment, and discuss practical management strategies....

  4. The relativity of biological function.

    Science.gov (United States)

    Laubichler, Manfred D; Stadler, Peter F; Prohaska, Sonja J; Nowick, Katja

    2015-12-01

    Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.

  5. Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database.

    Science.gov (United States)

    Perlman, Amichai; Hirsh Raccah, Bruria; Matok, Ilan; Muszkat, Mordechai

    2018-05-07

    Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia. We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System from July 2015 to March 2017. Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries. During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan. Based on the broad definition, sacubitril-valsartan was associated with cognition- and dementia-related adverse events in 459 reports (5.1%), but this was lower than the proportion of these reports among other medications (6.6%, reporting odds ratio [ROR] 0.72, 95% confidence interval [CI] 0.65-0.79). Restricting the comparison to cases with age >60 years and with the use of a comparator group with heart failure resulted in no association between sacubitril-valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions (ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively). Sacubitril-valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports. Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

    Science.gov (United States)

    Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

    2017-01-01

    Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior

    NARCIS (Netherlands)

    Mackey, Scott; Chaarani, Bader; Kan, Kees Jan; Spechler, Philip A.; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L.W.; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Paillère Martinot, Marie Laure; Artiges, Eric; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Poustka, Luise; Smolka, Michael N.; Jurk, Sarah; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Althoff, Robert R.; Garavan, Hugh

    2017-01-01

    Background Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Methods Impulsivity was estimated

  8. Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

    Science.gov (United States)

    O'Callaghan, J; Griffin, B T; Morris, J M; Bermingham, Margaret

    2018-06-01

    In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines. The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire. There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs. This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

  9. Detection and Management of Adverse Drug Reactions Related to ...

    African Journals Online (AJOL)

    The objective of this study was to establish the detection, prevalence and management of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care Centre (CCC) of Kiambu District Hospital. The study was a cross sectional survey where the patients included ...

  10. Why Does Military Combat Experience Adversely Affect Marital Relations?

    Science.gov (United States)

    Gimbel, Cynthia; Booth, Alan

    1994-01-01

    Describes investigation of ways in which combat decreases marital quality and stability. Results support three models: (1) factors propelling men into combat also make them poor marriage material; (2) combat causes problems that increase marital adversity; and (3) combat intensifies premilitary stress and antisocial behavior which then negatively…

  11. Sex and age related differences in postmyelographic adverse reactions

    International Nuclear Information System (INIS)

    Maly, P.

    1989-01-01

    Differences in frequency of postmyelographic adverse reactions were analyzed with respect to sex and age in a prospective study including 1026 patients injected with metrizamide and 739 injected with iohexol. Regardless of the type of contrast medium or myelography, all types of adverse reactions were 1.4-3.8 times as frequent in women as in men. Most of the differences were statistically significant. Headache was more frequent, while vomiting and dizziness were less frequent in both women and men aged 26-50 years compared with those over 50 years of age. Dizziness and increased low back pain were consistently reported spontaneously by the patients less frequently than emerged via formal interview. The large differences between the sexes suggest that further research on contrast media toxicity would be best performed with separation of the data by gender. (orig.)

  12. Modeling biology using relational databases.

    Science.gov (United States)

    Peitzsch, Robert M

    2003-02-01

    There are several different methodologies that can be used for designing a database schema; no one is the best for all occasions. This unit demonstrates two different techniques for designing relational tables and discusses when each should be used. These two techniques presented are (1) traditional Entity-Relationship (E-R) modeling and (2) a hybrid method that combines aspects of data warehousing and E-R modeling. The method of choice depends on (1) how well the information and all its inherent relationships are understood, (2) what types of questions will be asked, (3) how many different types of data will be included, and (4) how much data exists.

  13. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    Science.gov (United States)

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-05

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Intangible life functorial connections in relational biology

    CERN Document Server

    Louie, A H

    2017-01-01

    This rare publication continues an exploratory journey in relational biology, a study of biology in terms of the organization of networked connections in living systems. It builds on the author’s two earlier monographs which looked at the epistemology of life and the ontogeny of life. Here the emphasis is on the intangibility of life, that the real nature of living systems is conveyed not by their tangible material basis but by their intangible inherent processes.    Relational biology is the approach that hails ‘function dictates structure’; it is mathematics decoded into biological realizations. Therefore, the work begins with a concise introduction to category theory, equiping the reader with the mathematical metalanguage of relation biology. The book is organized around three parts:   Part I is a comprehensive study of the most important functor in relational biology, the power set functor.  The author lays the set-theoretic foundations of the functorial connections in relational biology, explor...

  15. Severity and workload related to adverse events in the ICU.

    Science.gov (United States)

    Serafim, Clarita Terra Rodrigues; Dell'Acqua, Magda Cristina Queiroz; Castro, Meire Cristina Novelli E; Spiri, Wilza Carla; Nunes, Hélio Rubens de Carvalho

    2017-01-01

    To analyze whether an increase in patient severity and nursing workload are correlated to a greater incidence of adverse events (AEs) in critical patients. A prospective single cohort study was performed on a sample of 138 patients hospitalized in an intensive care unit (ICU). A total of 166 AEs, occurred, affecting 50.7% of the patients. Increased patient severity presented a direct relationship to the probability of AEs occurring. However, nursing workload did not present a statistically significant relationship with the occurrence of AEs. The results cast light on the importance of using evaluation tools by the nursing personnel in order to optimize their daily activities and focus on patient safety. Analisar se o aumento da gravidade do paciente e a carga de trabalho de enfermagem está relacionado à maior incidência de Eventos Adversos (EAs) em pacientes críticos. Estudo de coorte única, prospectivo, com amostra de 138 pacientes internados em uma Unidade de Terapia Intensiva (UTI). Ao todo, foram evidenciados 166 EAs, que acometeram 50,7% dos pacientes. O aumento da gravidade do paciente apresentou relação direta com a chance de ocorrência de EAs. Entretanto, a carga de trabalho de enfermagem não apresentou relação estatisticamente significativa, na ocorrência de EAs. Os resultados permitem refletir acerca da importância da equipe de enfermagem, em utilizar instrumentos de avaliação, com o objetivo de melhorar e planejar suas ações diárias, com foco na segurança do paciente.

  16. Biomarkers in natural fish populations indicate adverse biological effects of offshore oil production.

    Directory of Open Access Journals (Sweden)

    Lennart Balk

    Full Text Available Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills.Samples from natural populations of haddock (Melanogrammus aeglefinus and Atlantic cod (Gadus morhua in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea.It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production.

  17. Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

    Science.gov (United States)

    Bey, K; Lennertz, L; Riesel, A; Klawohn, J; Kaufmann, C; Heinzel, S; Grützmann, R; Kathmann, N; Wagner, M

    2017-04-01

    The etiology of obsessive-compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD. A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first-degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire. Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive-compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls. Our results provide further evidence for a diathesis-stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Relations between Intuitive Biological Thinking and Biological Misconceptions in Biology Majors and Nonmajors

    Science.gov (United States)

    Coley, John D.; Tanner, Kimberly

    2015-01-01

    Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed misconceptions, among biology students across biological domains. In parallel, cognitive and developmental psychologists have described intuitive conceptual systems—teleological, essentialist, and anthropocentric thinking—that humans use to reason about biology. We hypothesize that seemingly unrelated biological misconceptions may have common origins in these intuitive ways of knowing, termed cognitive construals. We presented 137 undergraduate biology majors and nonmajors with six biological misconceptions. They indicated their agreement with each statement, and explained their rationale for their response. Results indicate frequent agreement with misconceptions, and frequent use of construal-based reasoning among both biology majors and nonmajors in their written explanations. Moreover, results also show associations between specific construals and the misconceptions hypothesized to arise from those construals. Strikingly, such associations were stronger among biology majors than nonmajors. These results demonstrate important linkages between intuitive ways of thinking and misconceptions in discipline-based reasoning, and raise questions about the origins, persistence, and generality of relations between intuitive reasoning and biological misconceptions. PMID:25713093

  19. The relative biological effectiveness of antiprotons

    DEFF Research Database (Denmark)

    Holzscheiter, Michael H.; Alsner, Jan; Bassler, Niels

    2016-01-01

    Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the re......Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase...... of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight. Materials and methods: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target...

  20. Relations between intuitive biological thinking and biological misconceptions in biology majors and nonmajors.

    Science.gov (United States)

    Coley, John D; Tanner, Kimberly

    2015-03-02

    Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed misconceptions, among biology students across biological domains. In parallel, cognitive and developmental psychologists have described intuitive conceptual systems--teleological, essentialist, and anthropocentric thinking--that humans use to reason about biology. We hypothesize that seemingly unrelated biological misconceptions may have common origins in these intuitive ways of knowing, termed cognitive construals. We presented 137 undergraduate biology majors and nonmajors with six biological misconceptions. They indicated their agreement with each statement, and explained their rationale for their response. Results indicate frequent agreement with misconceptions, and frequent use of construal-based reasoning among both biology majors and nonmajors in their written explanations. Moreover, results also show associations between specific construals and the misconceptions hypothesized to arise from those construals. Strikingly, such associations were stronger among biology majors than nonmajors. These results demonstrate important linkages between intuitive ways of thinking and misconceptions in discipline-based reasoning, and raise questions about the origins, persistence, and generality of relations between intuitive reasoning and biological misconceptions. © 2015 J. D. Coley and K. Tanner. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    Science.gov (United States)

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

  2. Severe adverse events related to tattooing: An retrospective analysis of 11 years

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2012-01-01

    Full Text Available Background: The incidence of tattoos has been increased markedly during the last 20 years. Aims: To analyze the patient files for severe adverse medical reactions related to tattooing. Settings: Academic Teaching Hospital in South-East Germany. Materials and Methods: Retrospective investigation from March 2001 to May 2012. Results: The incidence of severe adverse medical reactions has been estimated as 0.02%. Infectious and non-infectious severe reactions have been observed. The consequences were medical drug therapies and surgery. Conclusions: Tattooing may be associated with severe adverse medical reactions with significant morbidity. Regulations, education and at least hygienic controls are tools to increase consumer safety.

  3. Life adverse experiences in relation with obesity and binge eating disorder: A systematic review

    Science.gov (United States)

    Palmisano, Giovanni Luca; Innamorati, Marco; Vanderlinden, Johan

    2016-01-01

    Background and aims Several studies report a positive association between adverse life experiences and adult obesity. Despite the high comorbidity between binge eating disorder (BED) and obesity, few authors have studied the link between trauma and BED. In this review the association between exposure to adverse life experiences and a risk for the development of obesity and BED in adulthood is explored. Methods Based on a scientific literature review in Medline, PubMed and PsycInfo databases, the results of 70 studies (N = 306,583 participants) were evaluated including 53 studies on relationship between adverse life experiences and obesity, 7 studies on post-traumatic stress disorder (PTSD) symptoms in relation to obesity, and 10 studies on the association between adverse life experiences and BED. In addition, mediating factors between the association of adverse life experiences, obesity and BED were examined. Results The majority of studies (87%) report that adverse life experiences are a risk factor for developing obesity and BED. More precisely a positive association between traumatic experiences and obesity and PTSD and obesity were found, respectively, in 85% and 86% of studies. Finally, the great majority of studies (90%) between trauma and the development of BED in adulthood strongly support this association. Meanwhile, different factors mediating between the trauma and obesity link were identified. Discussion and conclusions Although research data show a strong association between life adverse experiences and the development of obesity and BED, more research is needed to explain this association. PMID:28092189

  4. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  5. Biological stress systems, adverse life events and the onset of chronic multi-site musculoskeletal pain: a six-year cohort study

    NARCIS (Netherlands)

    Generaal, E.; Vogelzangs, N.; MacFarlane, G.J.; Geenen, R.|info:eu-repo/dai/nl/087017571; Smit, J.H.; de Geus, E.J.C.N.; Penninx, B.W.J.H.; Dekker, J.

    2016-01-01

    Objectives Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic

  6. Gender differences in the effects of childhood adversity on alcohol, drug, and polysubstance-related disorders.

    Science.gov (United States)

    Evans, Elizabeth A; Grella, Christine E; Upchurch, Dawn M

    2017-07-01

    To examine gender differences in the associations between childhood adversity and different types of substance use disorders and whether gender moderates these relationships. We analyzed data from 19,209 women and 13,898 men as provided by Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender moderates the associations between childhood adversity and DSM-IV defined lifetime occurrence of alcohol, drug, and polysubstance-related disorders. We used multinomial logistic regression, weighted to be representative of the US adult civilian, noninstitutionalized population, and we calculated predicted probabilities by gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pair-wise comparisons corrected for multiple comparisons using Bonferroni's method. For each type of substance use disorder, risk was increased by more exposure to childhood adversity, and women had a lower risk than men. However, moderation effects revealed that with more experiences of childhood adversity, the gender gap in predicted probability for a disorder narrowed in relation to alcohol, it converged in relation to drugs such that risk among women surpassed that among men, and it widened in relation to polysubstances. Knowledge regarding substance-specific gender differences associated with childhood adversity exposure can inform evidence-based treatments. It may also be useful for shaping other types of gender-sensitive public health initiatives to ameliorate or prevent different types of substance use disorders.

  7. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    Science.gov (United States)

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

  8. Diffusion processes and related topics in biology

    CERN Document Server

    Ricciardi, Luigi M

    1977-01-01

    These notes are based on a one-quarter course given at the Department of Biophysics and Theoretical Biology of the University of Chicago in 1916. The course was directed to graduate students in the Division of Biological Sciences with interests in population biology and neurobiology. Only a slight acquaintance with probability and differential equations is required of the reader. Exercises are interwoven with the text to encourage the reader to play a more active role and thus facilitate his digestion of the material. One aim of these notes is to provide a heuristic approach, using as little mathematics as possible, to certain aspects of the theory of stochastic processes that are being increasingly employed in some of the population biol­ ogy and neurobiology literature. While the subject may be classical, the nov­ elty here lies in the approach and point of view, particularly in the applica­ tions such as the approach to the neuronal firing problem and its related dif­ fusion approximations. It is a ple...

  9. Pathways to Disease: The Biological Consequences of Social Adversity on Asthma in Minority Youth

    Science.gov (United States)

    2017-10-01

    the maximal change. 1adjusted for sex , age, maternal education, recruitment center, in utero smoke exposure, daycare attendance, baseline lung...levels were noted among kids with asthma by adversity exposure. Similarly, we found that CHI3L1 (YKL-40), a cytokine elevated in asthma, was

  10. Bacillus: A Biological Tool for Crop Improvement through Bio-Molecular Changes in Adverse Environments

    Directory of Open Access Journals (Sweden)

    Ramalingam Radhakrishnan

    2017-09-01

    Full Text Available Crop productivity is affected by environmental and genetic factors. Microbes that are beneficial to plants are used to enhance the crop yield and are alternatives to chemical fertilizers and pesticides. Pseudomonas and Bacillus species are the predominant plant growth-promoting bacteria. The spore-forming ability of Bacillus is distinguished from that of Pseudomonas. Members of this genus also survive for a long time under unfavorable environmental conditions. Bacillus spp. secrete several metabolites that trigger plant growth and prevent pathogen infection. Limited studies have been conducted to understand the physiological changes that occur in crops in response to Bacillus spp. to provide protection against adverse environmental conditions. This review describes the current understanding of Bacillus-induced physiological changes in plants as an adaptation to abiotic and biotic stresses. During water scarcity, salinity and heavy metal accumulate in soil, Bacillus spp. produce exopolysaccharides and siderophores, which prevent the movement of toxic ions and adjust the ionic balance and water transport in plant tissues while controlling the pathogenic microbial population. In addition, the synthesis of indole-3-acetic acid, gibberellic acid and1-aminocyclopropane-1-carboxylate (ACC deaminase by Bacillus regulates the intracellular phytohormone metabolism and increases plant stress tolerance. Cell-wall-degrading substances, such as chitosanase, protease, cellulase, glucanase, lipopeptides and hydrogen cyanide from Bacillus spp. damage the pathogenic bacteria, fungi, nematodes, viruses and pests to control their populations in plants and agricultural lands. The normal plant metabolism is affected by unfavorable environmental stimuli, which suppress crop growth and yield. Abiotic and biotic stress factors that have detrimental effects on crops are mitigated by Bacillus-induced physiological changes, including the regulation of water transport

  11. Bacillus: A Biological Tool for Crop Improvement through Bio-Molecular Changes in Adverse Environments

    Science.gov (United States)

    Radhakrishnan, Ramalingam; Hashem, Abeer; Abd_Allah, Elsayed F.

    2017-01-01

    Crop productivity is affected by environmental and genetic factors. Microbes that are beneficial to plants are used to enhance the crop yield and are alternatives to chemical fertilizers and pesticides. Pseudomonas and Bacillus species are the predominant plant growth-promoting bacteria. The spore-forming ability of Bacillus is distinguished from that of Pseudomonas. Members of this genus also survive for a long time under unfavorable environmental conditions. Bacillus spp. secrete several metabolites that trigger plant growth and prevent pathogen infection. Limited studies have been conducted to understand the physiological changes that occur in crops in response to Bacillus spp. to provide protection against adverse environmental conditions. This review describes the current understanding of Bacillus-induced physiological changes in plants as an adaptation to abiotic and biotic stresses. During water scarcity, salinity and heavy metal accumulate in soil, Bacillus spp. produce exopolysaccharides and siderophores, which prevent the movement of toxic ions and adjust the ionic balance and water transport in plant tissues while controlling the pathogenic microbial population. In addition, the synthesis of indole-3-acetic acid, gibberellic acid and1-aminocyclopropane-1-carboxylate (ACC) deaminase by Bacillus regulates the intracellular phytohormone metabolism and increases plant stress tolerance. Cell-wall-degrading substances, such as chitosanase, protease, cellulase, glucanase, lipopeptides and hydrogen cyanide from Bacillus spp. damage the pathogenic bacteria, fungi, nematodes, viruses and pests to control their populations in plants and agricultural lands. The normal plant metabolism is affected by unfavorable environmental stimuli, which suppress crop growth and yield. Abiotic and biotic stress factors that have detrimental effects on crops are mitigated by Bacillus-induced physiological changes, including the regulation of water transport, nutrient up-take and

  12. Evaluating legacy contaminants and emerging chemicals in marine environments using adverse outcome pathways and biological effects-directed analysis

    International Nuclear Information System (INIS)

    Hutchinson, Thomas H.; Lyons, Brett P.; Thain, John E.; Law, Robin J.

    2013-01-01

    Natural and synthetic chemicals are essential to our daily lives, food supplies, health care, industries and safe sanitation. At the same time protecting marine ecosystems and seafood resources from the adverse effects of chemical contaminants remains an important issue. Since the 1970s, monitoring of persistent, bioaccumulative and toxic (PBT) chemicals using analytical chemistry has provided important spatial and temporal trend data in three important contexts; relating to human health protection from seafood contamination, addressing threats to marine top predators and finally providing essential evidence to better protect the biodiversity of commercial and non-commercial marine species. A number of regional conventions have led to controls on certain PBT chemicals over several years (termed ‘legacy contaminants’; e.g. cadmium, lindane, polycyclic aromatic hydrocarbons [PAHs] and polychlorinated biphenyls [PCBs]). Analytical chemistry plays a key role in evaluating to what extent such regulatory steps have been effective in leading to reduced emissions of these legacy contaminants into marine environments. In parallel, the application of biomarkers (e.g. DNA adducts, CYP1A-EROD, vitellogenin) and bioassays integrated with analytical chemistry has strengthened the evidence base to support an ecosystem approach to manage marine pollution problems. In recent years, however, the increased sensitivity of analytical chemistry, toxicity alerts and wider environmental awareness has led to a focus on emerging chemical contaminants (defined as chemicals that have been detected in the environment, but which are currently not included in regulatory monitoring programmes and whose fate and biological impacts are poorly understood). It is also known that natural chemicals (e.g. algal biotoxins) may also pose a threat to marine species and seafood quality. Hence complex mixtures of legacy contaminants, emerging chemicals and natural biotoxins in marine ecosystems represent

  13. Evaluating legacy contaminants and emerging chemicals in marine environments using adverse outcome pathways and biological effects-directed analysis.

    Science.gov (United States)

    Hutchinson, Thomas H; Lyons, Brett P; Thain, John E; Law, Robin J

    2013-09-30

    Natural and synthetic chemicals are essential to our daily lives, food supplies, health care, industries and safe sanitation. At the same time protecting marine ecosystems and seafood resources from the adverse effects of chemical contaminants remains an important issue. Since the 1970s, monitoring of persistent, bioaccumulative and toxic (PBT) chemicals using analytical chemistry has provided important spatial and temporal trend data in three important contexts; relating to human health protection from seafood contamination, addressing threats to marine top predators and finally providing essential evidence to better protect the biodiversity of commercial and non-commercial marine species. A number of regional conventions have led to controls on certain PBT chemicals over several years (termed 'legacy contaminants'; e.g. cadmium, lindane, polycyclic aromatic hydrocarbons [PAHs] and polychlorinated biphenyls [PCBs]). Analytical chemistry plays a key role in evaluating to what extent such regulatory steps have been effective in leading to reduced emissions of these legacy contaminants into marine environments. In parallel, the application of biomarkers (e.g. DNA adducts, CYP1A-EROD, vitellogenin) and bioassays integrated with analytical chemistry has strengthened the evidence base to support an ecosystem approach to manage marine pollution problems. In recent years, however,the increased sensitivity of analytical chemistry, toxicity alerts and wider environmental awareness has led to a focus on emerging chemical contaminants (defined as chemicals that have been detected in the environment, but which are currently not included in regulatory monitoring programmes and whose fate and biological impacts are poorly understood). It is also known that natural chemicals (e.g. algal biotoxins) may also pose a threat to marine species and seafood quality. Hence complex mixtures of legacy contaminants, emerging chemicals and natural biotoxins in marine ecosystems represent

  14. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

    International Nuclear Information System (INIS)

    Chen Yuhchyau; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

    2006-01-01

    Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods

  15. Biological Sensitivity to the Effects of Childhood Family Adversity on Psychological Well-Being in Young Adulthood.

    Science.gov (United States)

    Somers, Jennifer A; Ibrahim, Mariam Hanna; Luecken, Linda J

    2017-08-01

    The theory of biological sensitivity to context may inform our understanding of why some children exposed to family adversity develop mental health problems in emerging adulthood whereas others demonstrate resilience. This study investigated the interactive effects of heart rate (HR) reactivity and childhood family adversity (maltreatment and changes in family structure) on depressive symptoms and positive affect among 150 undergraduate students (18-28 years old; 77% White, non-Hispanic; 61% female). Participants reported on childhood parental divorce or death, and child maltreatment, and current depressive symptoms and positive affect. HR reactivity was assessed in response to a laboratory interpersonal stressor. HR reactivity moderated the effects of child maltreatment on depressive symptoms and positive affect; higher maltreatment was associated with more depressive symptoms and less positive affect, but only among those with average and higher levels of HR reactivity. Results suggest that higher physiological reactivity may confer greater susceptibility to environmental contexts.

  16. Gender-related dimensions of childhood adversities in the general population.

    Science.gov (United States)

    Coêlho, Bruno M; Santana, Geilson L; Viana, Maria C; Andrade, Laura H; Wang, Yuan-Pang

    2018-06-11

    Childhood adversities (CAs) comprise a group of negative experiences individuals may suffer in their lifetimes. The goal of the present study was to investigate the cluster discrimination of CAs through psychometric determination of the common attributes of such experiences for men and women. Parental mental illness, substance misuse, criminality, death, divorce, other parental loss, family violence, physical abuse, sexual abuse, neglect, physical illness, and economic adversity were assessed in a general-population sample (n=5,037). Exploratory and confirmatory factor analysis determined gender-related dimensions of CA. The contribution of each individual adversity was explored through Rasch analysis. Adversities were reported by 53.6% of the sample. A three-factor model of CA dimensions fit the data better for men, and a two-factor model for women. For both genders, the dimension of family maladjustment - encompassing physical abuse, neglect, parental mental disorders, and family violence - was the core cluster of CAs. Women endorsed more CAs than men. Rasch analysis found that sexual abuse, physical illness, parental criminal behavior, parental divorce, and economic adversity were difficult to report in face-to-face interviews. CAs embrace sensitive personal information, clustering of which differed by gender. Acknowledging CAs may have an impact on medical and psychiatric outcomes in adulthood.

  17. Gender-related dimensions of childhood adversities in the general population

    Directory of Open Access Journals (Sweden)

    Bruno M. Coêlho

    2018-06-01

    Full Text Available Objective: Childhood adversities (CAs comprise a group of negative experiences individuals may suffer in their lifetimes. The goal of the present study was to investigate the cluster discrimination of CAs through psychometric determination of the common attributes of such experiences for men and women. Methods: Parental mental illness, substance misuse, criminality, death, divorce, other parental loss, family violence, physical abuse, sexual abuse, neglect, physical illness, and economic adversity were assessed in a general-population sample (n=5,037. Exploratory and confirmatory factor analysis determined gender-related dimensions of CA. The contribution of each individual adversity was explored through Rasch analysis. Results: Adversities were reported by 53.6% of the sample. A three-factor model of CA dimensions fit the data better for men, and a two-factor model for women. For both genders, the dimension of family maladjustment – encompassing physical abuse, neglect, parental mental disorders, and family violence – was the core cluster of CAs. Women endorsed more CAs than men. Rasch analysis found that sexual abuse, physical illness, parental criminal behavior, parental divorce, and economic adversity were difficult to report in face-to-face interviews. Conclusion: CAs embrace sensitive personal information, clustering of which differed by gender. Acknowledging CAs may have an impact on medical and psychiatric outcomes in adulthood.

  18. Ventilator-Related Adverse Events: A Taxonomy and Findings From 3 Incident Reporting Systems.

    Science.gov (United States)

    Pham, Julius Cuong; Williams, Tamara L; Sparnon, Erin M; Cillie, Tam K; Scharen, Hilda F; Marella, William M

    2016-05-01

    In 2009, researchers from Johns Hopkins University's Armstrong Institute for Patient Safety and Quality; public agencies, including the FDA; and private partners, including the Emergency Care Research Institute and the University HealthSystem Consortium (UHC) Safety Intelligence Patient Safety Organization, sought to form a public-private partnership for the promotion of patient safety (P5S) to advance patient safety through voluntary partnerships. The study objective was to test the concept of the P5S to advance our understanding of safety issues related to ventilator events, to develop a common classification system for categorizing adverse events related to mechanical ventilators, and to perform a comparison of adverse events across different adverse event reporting systems. We performed a cross-sectional analysis of ventilator-related adverse events reported in 2012 from the following incident reporting systems: the Pennsylvania Patient Safety Authority's Patient Safety Reporting System, UHC's Safety Intelligence Patient Safety Organization database, and the FDA's Manufacturer and User Facility Device Experience database. Once each organization had its dataset of ventilator-related adverse events, reviewers read the narrative descriptions of each event and classified it according to the developed common taxonomy. A Pennsylvania Patient Safety Authority, FDA, and UHC search provided 252, 274, and 700 relevant reports, respectively. The 3 event types most commonly reported to the UHC and the Pennsylvania Patient Safety Authority's Patient Safety Reporting System databases were airway/breathing circuit issue, human factor issues, and ventilator malfunction events. The top 3 event types reported to the FDA were ventilator malfunction, power source issue, and alarm failure. Overall, we found that (1) through the development of a common taxonomy, adverse events from 3 reporting systems can be evaluated, (2) the types of events reported in each database were related

  19. Ventilator-Related Adverse Events: A Taxonomy and Findings From 3 Incident Reporting Systems

    Science.gov (United States)

    Pham, Julius Cuong; Williams, Tamara L; Sparnon, Erin M; Cillie, Tam K; Scharen, Hilda F; Marella, William M

    2016-01-01

    BACKGROUND: In 2009, researchers from Johns Hopkins University's Armstrong Institute for Patient Safety and Quality; public agencies, including the FDA; and private partners, including the Emergency Care Research Institute and the University HealthSystem Consortium (UHC) Safety Intelligence Patient Safety Organization, sought to form a public-private partnership for the promotion of patient safety (P5S) to advance patient safety through voluntary partnerships. The study objective was to test the concept of the P5S to advance our understanding of safety issues related to ventilator events, to develop a common classification system for categorizing adverse events related to mechanical ventilators, and to perform a comparison of adverse events across different adverse event reporting systems. METHODS: We performed a cross-sectional analysis of ventilator-related adverse events reported in 2012 from the following incident reporting systems: the Pennsylvania Patient Safety Authority's Patient Safety Reporting System, UHC's Safety Intelligence Patient Safety Organization database, and the FDA's Manufacturer and User Facility Device Experience database. Once each organization had its dataset of ventilator-related adverse events, reviewers read the narrative descriptions of each event and classified it according to the developed common taxonomy. RESULTS: A Pennsylvania Patient Safety Authority, FDA, and UHC search provided 252, 274, and 700 relevant reports, respectively. The 3 event types most commonly reported to the UHC and the Pennsylvania Patient Safety Authority's Patient Safety Reporting System databases were airway/breathing circuit issue, human factor issues, and ventilator malfunction events. The top 3 event types reported to the FDA were ventilator malfunction, power source issue, and alarm failure. CONCLUSIONS: Overall, we found that (1) through the development of a common taxonomy, adverse events from 3 reporting systems can be evaluated, (2) the types of

  20. Statin-associated muscle-related adverse effects: a case series of 354 patients.

    Science.gov (United States)

    Cham, Stephanie; Evans, Marcella A; Denenberg, Julie O; Golomb, Beatrice A

    2010-06-01

    To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. University-affiliated health care system. Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy. Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, pstatins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (pstatin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose-dependent relationship between MAE risk and recurrence suggest

  1. Linking MedDRA®-coded Clinical Phenotypes to Biological Mechanisms by The Ontology of Adverse Events: A pilot study on Tyrosine Kinase Inhibitors (TKIs)

    Science.gov (United States)

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G.; Zaman, Shadia; Burkhart, Keith K.; Omenn, Gilbert S.; He, Yongqun; Athey, Brian D.; Abernethy, Darrell R.

    2016-01-01

    Introduction A translational bioinformatics challenge lies in connecting population and individual’s clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA®) is the default dictionary for Adverse Event (AE) reporting in the FDA Adverse Event Reporting System (FAERS). The Ontology of Adverse Events (OAE) represents AEs as pathological processes occurring after drug exposures. Objectives The aim is to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA® in FAERS data analysis. We investigated the AEs associated with Tyrosine Kinase Inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The selected 5 TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Results Statistical analysis of FAERS data identified 1,053 distinct MedDRA® terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA®. The data integration to provide insights into molecular mechanisms for drug-associated AEs is performed by including linkages in OAE for all related AE terms to MedDRA® and existing ontologies including Human Phenotype Ontology (HP), Uber Anatomy Ontology (UBERON), and Gene Ontology (GO). Sixteen AEs are shared by all 5 TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed ‘cardiac failure’ using the relations established in OAE with other ontologies, and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. Conclusion By expanding existing OAE ontological design, our TKI use case demonstrates that the combination of OAE and Med

  2. Linking MedDRA(®)-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G; Zaman, Shadia; Burkhart, Keith K; Omenn, Gilbert S; He, Yongqun; Athey, Brian D; Abernethy, Darrell R

    2016-07-01

    A translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA(®)) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures. The aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA(®) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Statistical analysis of FAERS data identified 1053 distinct MedDRA(®) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA(®). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA(®) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination

  3. Relational aggression and adverse psychosocial and physical health symptoms among urban adolescents.

    Science.gov (United States)

    Williams, Jessica Roberts; Fredland, Nina; Han, Hae-Ra; Campbell, Jacquelyn C; Kub, Joan E

    2009-01-01

    The purpose of this study was to examine relational aggression and its relationship with adverse psychosocial and physical health symptoms among urban, African American youth. Quantitative, cross-sectional survey design. The sample consisted of 185 predominantly African American (95.1%) seventh-grade students (mean age: 13.0; female: 58%) attending 4 urban middle schools. The Children's Social Behavior Scale and Social Experience Questionnaire were used to measure relational aggression and relational victimization. The Pediatric Symptom Checklist was used to assess psychosocial difficulties, including internalizing behaviors, externalizing behaviors, and attention problems. Physical health symptoms were measured with questions about colds/flu, headaches, and stomach aches. 2-way multivariate analysis of variance revealed significant differences in externalizing behavior, with perpetrators reporting higher levels than nonperpetrators. Victims reported more internalizing behavior than nonvictims; however, this was only significant for males. For females, significant negative effects on health outcomes were found, resulting from the interaction of perpetration and victimization. Findings suggest that relational aggression is a common occurrence among urban, minority adolescents and may result in adverse health outcomes. These results provide several avenues for future research and implications for healthcare practice. Intervention strategies are needed to prevent relational aggression and continual or subsequent adverse health symptoms.

  4. Biological stress systems, adverse life events and the improvement of chronic multi-site musculoskeletal pain across a 6-year follow-up

    NARCIS (Netherlands)

    Generaal, E.; Vogelzangs, N.; Macfarlane, G.J.; Geenen, R.; Smit, J.H.; de Geus, E.J.C.N.; Dekker, J.; Penninx, B.W.J.H.

    Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1)

  5. Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up

    NARCIS (Netherlands)

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

    Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1)

  6. The epigenetic impacts of social stress: how does social adversity become biologically embedded?

    Science.gov (United States)

    Cunliffe, Vincent T

    2016-01-01

    Epigenetic mechanisms are implicated in the processes through which social stressors erode health in humans and other animals. Here I review progress in elucidating the biological pathways underlying the social gradient in health, with particular emphasis on how behavioral stresses influence epigenomic variation linked to health. The evidence that epigenetic changes are involved in embedding of social status-linked chronic stress is reviewed in the context of current knowledge about behavior within animal dominance hierarchies and the impacts of social position on behaviors that affect health. The roles of epigenetic mechanisms in responses to trauma and the evidence for their involvement in intergenerational transmission of the biological impacts of traumatic stress are also considered. Taken together, the emerging insights have important implications for development of strategies to improve societal health and well-being. PMID:27869483

  7. Transfusion-related adverse reactions: From institutional hemovigilance effort to National Hemovigilance program

    Directory of Open Access Journals (Sweden)

    Rahul Vasudev

    2016-01-01

    Full Text Available Aims: In this study we have evaluated the various adverse reactions related to transfusion occurring in our institution as a pilot institutional effort toward a hemovigilance program. This study will also help in understanding the problems faced by blood banks/Transfusion Medicine departments in implementing an effective hemovigilance program. Materials and Methods: All the adverse reactions related to transfusion of whole blood and its components in various clinical specialties were studied for a period of 1 year. Any transfusion-related adverse event was worked up in accordance with guidelines laid down by the Directorate General of Health Services (DGHS and departmental standard operating procedures. Results: During the study period from November 1, 2011 to October 31, 2012, 45812 components were issued [30939 WB/PRBC; 12704 fresh frozen plasma (FFP; 2169 platelets]. Risk estimation per 1000 units of red cells (WB/PRBC transfused was estimated to be: 0.8 for febrile nonhemolytic transfusion reaction (FNHTR, 0.7 for allergic reaction, 0.19 for acute hemolytic transfusion reaction (AcHTR, 0.002 for anaphylactoid reactions, 0.1 for bacterial sepsis, and 0.06 for hypervolemia and hypocalcemia. 0.09 is the risk for delayed transfusion reaction and 0.03 is the risk for transfusion-related acute lung injury (TRALI. Risk estimate per 1,000 units of platelets transfused was estimated to be 1.38 for FNHTR, 1.18 for allergic reaction, and 1 in case of bacterial sepsis. Risk estimation per 1,000 units of FFP was estimated to be 0.15 for FNHTR and 0.2 for allergic reactions. Conclusions: Factors such as clerical checks at various levels, improvement in blood storage conditions outside blood banks, leukodepletion, better inventory management, careful donor screening, bedside monitoring of transfusion, and documentation of adverse events may decrease transfusion-related adverse events. Better coordination between transfusion specialists and various clinical

  8. Suicidality and profiles of childhood adversities, conflict related trauma and psychopathology in the Northern Ireland population.

    Science.gov (United States)

    McLafferty, Margaret; Armour, Cherie; O'Neill, Siobhan; Murphy, Sam; Ferry, Finola; Bunting, Brendan

    2016-08-01

    Over 30 years of conflict in Northern Ireland (NI) has impacted on the population's mental health. However, childhood adversities may add to the psychological impact of conflict. The aims of the study were to assess co-occurrence across childhood adversities, conflict related traumas, and psychological health, then explore demographic variations between identified classes, and examine the impact of class membership on suicidal ideation and behaviour. Data was obtained from the Northern Ireland Study of Health and Stress, a representative epidemiological study which used the CIDI to assess psychopathology and related risk factors in the NI population (N=4340, part 2 n=1986; response rate 64%). Latent Class Analysis uncovered 4 discrete profiles; a conflict class (n=191; 9.6%), a multi-risk class endorsing elevated levels of childhood adversities, conflict related traumas and psychopathology (n=85; 4.3%), a psychopathology class (n=290; 14.6%), and a low risk class (n=1420; 71.5%). Multinomial logistic regression analysis revealed that individuals who grew up during the worst years of the Troubles were more likely to have experienced multiple traumas and psychopathology. Individuals in the multi-risk class were more than fifteen times more likely to endorse suicidal ideation and behaviour. The main limitations are that the study may not be fully representative of the NI population due to the exclusion criteria applied and also the possible misclassification of conflict related events. The findings indicate that treatment providers should be cognisant that those with wide ranging adversity profiles are those also likely to be reporting psychological distress and suicidality. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Immune-related adverse effects of cancer immunotherapy- Implications for rheumatology

    OpenAIRE

    Cappelli, Laura C.; Shah, Ami A.; Bingham, Clifton O.

    2016-01-01

    Immune checkpoint inhibitors (ICIs) are being increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAE). Some IRAE including inflammatory arthritis, sicca syndrome, myositis and vasculitis are of special interest to rheumatologists. As use of ICIs increases, recogniti...

  10. Adverse biological effects of Milan urban PM looking for suitable molecular markers of exposure

    Directory of Open Access Journals (Sweden)

    Mantecca Paride

    2012-01-01

    Full Text Available The results presented summarise the ones obtained in the coordinated research project Tosca, which extensively analysed the impact of Milan urban PM on human health. The molecular markers of exposure and effects of seasonally and size-fractionated PMs (summer and winter PM10, PM2.5 were investigated in in vitro (human lung cell lines and in vivo (mice systems. The results obtained by the analyses of cytotoxic, pro-inflammatory and genotoxic parameters demonstrate that the biological responses are strongly dependent upon the PM samples seasonal and dimensional variability, that ultimately reflect their chemical composition and source. In fact summer PM10, enriched in crustal elements and endotoxins, was the most cytotoxic and pro-inflammatory fraction, while fine winter PMs induced genotoxic effects and xenobiotic metabolizing enzymes (like CYP1B1 production, likely as a consequence of the higher content in combustion derived particles reach in PAHs and heavy toxic metals. These outcomes outline the need of a detailed knowledge of the PMs physico-chemical composition on a local scale, coupled with the biological hazard directly associated to PM exposure. Apparently this is the only way allowing scientists and police-makers to establish the proper relationships between the respirable PM quantity/quality and the health outcomes described by clinicians and epidemiologists.

  11. Relations between Intuitive Biological Thinking and Biological Misconceptions in Biology Majors and Nonmajors

    Science.gov (United States)

    Coley, John D.; Tanner, Kimberly

    2015-01-01

    Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed "misconceptions," among biology students across biological domains. In parallel, cognitive and developmental psychologists…

  12. Relation between dose of bendrofluazide, antihypertensive effect, and adverse biochemical effects

    DEFF Research Database (Denmark)

    Carlsen, J E; Køber, L; Torp-Pedersen, C

    1990-01-01

    OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or place...... of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses....... relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses...

  13. Act to keep patients safe: device-related adverse event reporting.

    Science.gov (United States)

    Schoem, Scott R; Shah, Udayan K

    2010-05-01

    Primum non nocere- "Above all do no harm." Since the first year of medical school, we have all heard and spoken this dictum countless times. Translating this dictum into action may present challenges in our daily practice. Every day, clinicians must distinguish between scientific evidence, clinical experience, and marketing claims by industry vendors of improved efficacy and safety regarding medical devices. Adverse event reporting and device failure notification are generally laid out well in hospital practice settings. Reporting beyond the local level takes on a new dimension for most surgeons. Perceived stigma from peers and corporations, lack of confidentiality, and cynicism regarding protective actions for patients should not limit one from "raising the alarm" when concerns arise about device safety or performance. This commentary aims to explain the process for reporting device-related adverse events. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

  14. Does Employment-Related Resilience Affect the Relationship between Childhood Adversity, Community Violence, and Depression?

    Science.gov (United States)

    Welles, Seth L; Patel, Falguni; Chilton, Mariana

    2017-04-01

    Depression is a barrier to employment among low-income caregivers receiving Temporary Assistance for Needy Families (TANF), and adverse childhood experiences (ACEs) and exposure to community violence (ECV) are often associated with depression. Using baseline data of 103 TANF caregivers of young children of the Building Wealth and Health Network Randomized Controlled Trial Pilot, this study investigated associations of two forms of employment-related resilience-self-efficacy and employment hope-with exposure to adversity/violence and depression, measured by the Center for Epidemiologic Studies Depression (CES-D) short form. Using contingency table analysis and regression analysis, we identified associations between ACEs and depression [OR = 1.70 (1.25-2.32), p = 0.0008] and having high levels of ECV with a 6.9-fold increased risk for depression when compared with those without ECV [OR = 6.86 (1.43-33.01), p = 0.02]. While self-efficacy and employment hope were significantly associated with depression, neither resilience factor impacted the association of ACE level and depression, whereas self-efficacy and employment hope modestly reduced the associations between ECV and depression, 13 and 16%, respectively. Results suggest that self-efficacy and employment hope may not have an impact on the strong associations between adversity, violence, and depression.

  15. Preventing drug-related adverse events following hospital discharge: the role of the pharmacist

    Directory of Open Access Journals (Sweden)

    Nicholls J

    2017-02-01

    Full Text Available Justine Nicholls,1 Craig MacKenzie,1 Rhiannon Braund2 1Dunedin Hospital Pharmacy, 2School of Pharmacy, University of Otago, Dunedin, New Zealand Abstract: Transition of care (ToC points, and in particular hospital admission and discharge, can be associated with an increased risk of adverse drug events (ADEs and other drug-related problems (DRPs. The growing recognition of the pharmacist as an expert in medication management, patient education and communication makes them well placed to intervene. There is evidence to indicate that the inclusion of pharmacists in the health care team at ToC points reduces ADEs and DRPs and improves patient outcomes. The objectives of this paper are to outline the following using current literature: 1 the increased risk of medication-related problems at ToC points; 2 to highlight some strategies that have been successful in reducing these problems; and 3 to illustrate how the role of the pharmacist across all facets of care can contribute to the reduction of ADEs, particularly for patients at ToC points. Keywords: pharmacist, adverse drug events, drug-related problems, transitions of care, hospital discharge

  16. Adverse Events of Massage Therapy in Pain-Related Conditions: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ping Yin

    2014-01-01

    Full Text Available Pain-related massage, important in traditional Eastern medicine, is increasingly used in the Western world. So the widening acceptance demands continual safety assessment. This review is an evaluation of the frequency and severity of adverse events (AEs reported mainly for pain-related massage between 2003 and 2013. Relevant all-languages reports in 6 databases were identified and assessed by two coauthors. During the 11-year period, 40 reports of 138 AEs were associated with massage. Author, year of publication, country of occurrence, participant related (age, sex or number of patients affected, the details of manual therapy, and clinician type were extracted. Disc herniation, soft tissue trauma, neurologic compromise, spinal cord injury, dissection of the vertebral arteries, and others were the main complications of massage. Spinal manipulation in massage has repeatedly been associated with serious AEs especially. Clearly, massage therapies are not totally devoid of risks. But the incidence of such events is low.

  17. Students’ Relational Understanding in Quadrilateral Problem Solving Based on Adversity Quotient

    Science.gov (United States)

    Safitri, A. N.; Juniati, D.; Masriyah

    2018-01-01

    The type of research is qualitative approach which aims to describe how students’ relational understanding of solving mathematic problem that was seen from Adversity Quotient aspect. Research subjects were three 7th grade students of Junior High School. They were taken by category of Adversity Quotient (AQ) such quitter, camper, and climber. Data collected based on problem solving and interview. The research result showed that (1) at the stage of understanding the problem, the subjects were able to state and write down what is known and asked, and able to mention the concepts associated with the quadrilateral problem. (2) The three subjects devise a plan by linking concepts relating to quadrilateral problems. (3) The three subjects were able to solve the problem. (4) The three subjects were able to look back the answers. The three subjects were able to understand the problem, devise a plan, carry out the plan and look back. However, the quitter and camper subjects have not been able to give a reason for the steps they have taken.

  18. Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database.

    Science.gov (United States)

    Naganuma, Misa; Motooka, Yumi; Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Fukuda, Akiho; Nakao, Satoshi; Shimada, Kazuyo; Hirade, Koseki; Mori, Takayuki; Yoshimura, Tomoaki; Kato, Takeshi; Nakamura, Mitsuhiro

    2018-01-01

    Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5-3.0), 0.6 (0.5-0.7), 0.8 (0.7-1.0), and 1.3 (0.8-2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower-upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0-8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient's background prior to treatment.

  19. CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

    Directory of Open Access Journals (Sweden)

    St Sauver JL

    2017-07-01

    Full Text Available Jennifer L St Sauver,1,2 Janet E Olson,1,3 Veronique L Roger,1,2,4 Wayne T Nicholson,5 John L Black III,3,6 Paul Y Takahashi,7 Pedro J Caraballo,7 Elizabeth J Bell,2 Debra J Jacobson,1,2 Nicholas B Larson,1 Suzette J Bielinski,1,3 1Department of Health Sciences Research, 2Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, 3Center for Individualized Medicine, 4Department of Cardiovascular Diseases, 5Department of Anesthesiology and Perioperative Medicine, 6Department of Laboratory Medicine and Pathology, 7Department of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN, USA Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients.Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression.Results: Overall, 257 (25% of RIGHT Protocol participants patients received at least one opioid prescription; of these, 40 (15% were poor metabolizers, 146 (57% were intermediate to extensive metabolizers, and 71 (28% were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38. After adjusting for age and sex, patients with a poor or ultrarapid

  20. [Description of contributing factors in adverse events related to patient safety and their preventability].

    Science.gov (United States)

    Guerra-García, María Mercedes; Campos-Rivas, Beatriz; Sanmarful-Schwarz, Alexandra; Vírseda-Sacristán, Alicia; Dorrego-López, M Aránzazu; Charle-Crespo, Ángeles

    2017-11-25

    To assess the extent of healthcare related adverse events (AEs), their effect on patients, and their seriousness. To analyse the factors leading to the development of AEs, their relationship with the damage caused, and their degree of preventability. Retrospective descriptive study. Porriño, Pontevedra, Spain, Primary Care Service, from January-2014 to April-2016. Reported AEs were entered into the Patient Safety Reporting and Learning System (SiNASP). The variables measured were: Near Incident (NI) an occurrence with no effect or harm on the patient; Adverse Event (AE) an occurrence that affects or harms a patient. The level of harm is classified as minimal, minor, moderate, critical, and catastrophic. Preventability was classified as little evidence of being preventable, 50% preventable, and sound evidence of being preventable. percentages and Chi-squared test for qualitative variables; P<.05 with SPSS.15. SiNASP. Ethical considerations: approved by the Research Ethics Committee (2016/344). There were 166 recorded AEs (50.6% in males, and 46.4% in women. The mean age was 60.80years). Almost two-thirds 62.7% of AEs affected the patient, with 45.8% causing minimal damage, while 2.4% caused critical damages. Healthcare professionals were a contributing factor in 71.7% of the AEs, with the trend showing that poor communication and lack of protocols were related to the damage caused. Degree of preventability: 96.4%. Most AEs affected the patient, and were related to medication, diagnostic tests, and laboratory errors. The level of harm was related to communication problems, lack of, or deficient, protocols and a poor safety culture. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure

    Science.gov (United States)

    Meeker, John D.; Benedict, Merle D.

    2013-01-01

    A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated. PMID:23888128

  2. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects.

    Science.gov (United States)

    Cormie, Prue; Zopf, Eva M; Zhang, Xiaochen; Schmitz, Kathryn H

    2017-01-01

    The combination of an increasing number of new cancer cases and improving survival rates has led to a large and rapidly growing population with unique health-care requirements. Exercise has been proposed as a strategy to help address the issues faced by cancer patients. Supported by a growing body of research, major health organizations commonly identify the importance of incorporating exercise in cancer care and advise patients to be physically active. This systematic review comprehensively summarizes the available epidemiologic and randomized controlled trial evidence investigating the role of exercise in the management of cancer. Literature searches focused on determining the potential impact of exercise on 1) cancer mortality and recurrence and 2) adverse effects of cancer and its treatment. A total of 100 studies were reviewed involving thousands of individual patients whose exercise behavior was assessed following the diagnosis of any type of cancer. Compared with patients who performed no/less exercise, patients who exercised following a diagnosis of cancer were observed to have a lower relative risk of cancer mortality and recurrence and experienced fewer/less severe adverse effects. The findings of this review support the view that exercise is an important adjunct therapy in the management of cancer. Implications on cancer care policy and practice are discussed. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

    Science.gov (United States)

    Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

    2016-01-01

    Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

  4. Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

    Science.gov (United States)

    Gupta, Arpana; Labus, Jennifer; Kilpatrick, Lisa A; Bonyadi, Mariam; Ashe-McNalley, Cody; Heendeniya, Nuwanthi; Bradesi, Sylvie; Chang, Lin; Mayer, Emeran A

    2016-04-01

    Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit.

  5. The biology of perch and related fish

    National Research Council Canada - National Science Library

    Craig, John F; Craig, John

    1987-01-01

    This book presents a definitive volume on perch and related fish. In the introduction an outline is given on the characteristics of the order Perciformes, the suborder Percoidea and the family Percidae...

  6. Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

    Science.gov (United States)

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

    2017-02-01

    Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which

  7. Adverse Biological Effect of TiO2 and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement

    Directory of Open Access Journals (Sweden)

    Jiangxue Wang

    2016-05-01

    Full Text Available The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO2 nanoparticles (NPs to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris–mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants.

  8. What doesn't kill me…: Adversity-related experiences are vital in the development of superior Olympic performance.

    Science.gov (United States)

    Sarkar, Mustafa; Fletcher, David; Brown, Daniel J

    2015-07-01

    Recent research suggests that experiencing some adversity can have beneficial outcomes for human growth and development. The purpose of this paper was to explore the adversities that the world's best athletes encounter and the perceived role that these experiences play in their psychological and performance development. A qualitative design was employed because detailed information of rich quality was required to better understand adversity-related experiences in the world's best athletes. Semi-structured interviews were conducted with 10 Olympic gold medalists from a variety of sports. Inductive thematic analysis was used to analyze the data. The findings indicate that the participants encountered a range of sport- and non-sport adversities that they considered were essential for winning their gold medals, including repeated non-selection, significant sporting failure, serious injury, political unrest, and the death of a family member. The participants described the role that these experiences played in their psychological and performance development, specifically focusing on their resultant trauma, motivation, and learning. Adversity-related experiences were deemed to be vital in the psychological and performance development of Olympic champions. In the future, researchers should conduct more in-depth comparative studies of Olympic athletes' adversity- and growth-related experiences, and draw on existing and alternative theoretical explanations of the growth-performance relationship. For professional practitioners, adversity-related experiences offer potential developmental opportunities if they are carefully and purposely harnessed. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  9. Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

    Directory of Open Access Journals (Sweden)

    Keisuke Imafuku

    2017-04-01

    Full Text Available Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms.

  10. Marine Biology Activities. Ocean Related Curriculum Activities.

    Science.gov (United States)

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  11. L'identification des relations de discours implicites : le cas de l'adversation

    Directory of Open Access Journals (Sweden)

    Corminboeuf Gilles

    2014-07-01

    (2\tJohn is tall but he’s no good at basketball. (ibid. il est montré que les « Denials of expectation » peuvent être scindés en deux groupes, (i des enchaînements contre-argumentatifs indirects et (ii des enchaînements contre-argumentatifs directs. Les constructions à valeur adversative « non marquées » par des connecteurs explicites sont des enchaînements comme (1’ et (2’ : (1’\tJohn est grand, Bill est petit. (2’\tJohn est grand et il n’est pas bon au basketball. Les connecteurs « pourtant » ou « mais » (« but » dans 1 et 2 marqueraient l’opposition de manière explicite, alors que « et »(dans 2’ n’est a priori pas spécialisé pour connecter des prédications contradictoires. On présente les propriétés oppositives de chacune de ces trois organisations discursives où la valeur adversative est à reconstruire par inférence. L’étude se conclut sur un plaidoyer pour une étude des relations de discours implicites, ce qui revient notamment à dissocier l’analyse des « marqueurs de discours » de celle des relations de discours.

  12. A theory of biological relativity: no privileged level of causation.

    Science.gov (United States)

    Noble, Denis

    2012-02-06

    Must higher level biological processes always be derivable from lower level data and mechanisms, as assumed by the idea that an organism is completely defined by its genome? Or are higher level properties necessarily also causes of lower level behaviour, involving actions and interactions both ways? This article uses modelling of the heart, and its experimental basis, to show that downward causation is necessary and that this form of causation can be represented as the influences of initial and boundary conditions on the solutions of the differential equations used to represent the lower level processes. These insights are then generalized. A priori, there is no privileged level of causation. The relations between this form of 'biological relativity' and forms of relativity in physics are discussed. Biological relativity can be seen as an extension of the relativity principle by avoiding the assumption that there is a privileged scale at which biological functions are determined.

  13. Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.

    Science.gov (United States)

    Seo, Seung Hee; Kim, Sung-Eun; Kang, Yoon-Koo; Ryoo, Baek-Yeol; Ryu, Min-Hee; Jeong, Jae Ho; Kang, Shin Sook; Yang, Mihi; Lee, Jung Eun; Sung, Mi-Kyung

    2016-11-18

    Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (cancer patients.

  14. Antibiotic-Related Adverse Drug Reactions at a Tertiary Care Hospital in South Korea

    Directory of Open Access Journals (Sweden)

    In Young Jung

    2017-01-01

    Full Text Available Background. Adverse drug reactions (ADRs are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea. Methods. This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated. Results. 1,277 (62.8% patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%. Totally, 44 (3.4% patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%, followed by third-generation cephalosporins (14.9%. The most frequently experienced side effects were skin manifestations (45.1% followed by gastrointestinal disorders (32.6%. Conclusion. Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.

  15. Children’s Autonomic Nervous System Reactivity Moderates the Relations between Family Adversity and Sleep Problems in Latino 5-Year Olds in the CHAMACOS Study

    Directory of Open Access Journals (Sweden)

    Abbey Alkon

    2017-06-01

    Full Text Available Sleep problems are common for young children especially if they live in adverse home environments. Some studies investigate if young children may also be at a higher risk of sleep problems if they have a specific biological sensitivity to adversity. This paper addresses the research question, does the relations between children’s exposure to family adversities and their sleep problems differ depending on their autonomic nervous system’s sensitivity to challenges? As part of a larger cohort study of Latino, low-income families, we assessed the cross-sectional relations among family demographics (education, marital status, adversities [routines, major life events (MLE], and biological sensitivity as measured by autonomic nervous system (ANS reactivity associated with parent-rated sleep problems when the children were 5 years old. Mothers were interviewed in English or Spanish and completed demographic, family, and child measures. The children completed a 15-min standardized protocol while continuous cardiac measures of the ANS [respiratory sinus arrhythmia (RSA, preejection period (PEP] were collected during resting and four challenge conditions. Reactivity was defined as the mean of the responses to the four challenge conditions minus the first resting condition. Four ANS profiles, co-activation, co-inhibition, reciprocal low RSA and PEP reactivity, and reciprocal high RSA and PEP reactivity, were created by dichotomizing the reactivity scores as high or low reactivity. Logistic regression models showed there were significant main effects for children living in families with fewer daily routines having more sleep problems than for children living in families with daily routines. There were significant interactions for children with low PEP reactivity and for children with the reciprocal, low reactivity profiles who experienced major family life events in predicting children’s sleep problems. Children who had a reciprocal, low reactivity

  16. Exercise during pregnancy and gestational diabetes-related adverse effects: a randomised controlled trial.

    Science.gov (United States)

    Barakat, Ruben; Pelaez, Mireia; Lopez, Carmina; Lucia, Alejandro; Ruiz, Jonatan R

    2013-07-01

    To examine the effect of regular moderate-intensity exercise (three training sessions/week) on the incidence of gestational diabetes mellitus (GDM, primary outcome). We also examined if the exercise intervention modifies the association between GDM and birth weight and risk of macrosomia, gestational age, risk of caesarean delivery and maternal weight gain (secondary outcomes). We randomly assigned 510 healthy gravida to either an exercise intervention or a usual care (control) group (n=255 each). The exercise programme focused on moderate-intensity resistance and aerobic exercises (three times/week, 50-55 min/session). GDM diabetes was diagnosed according to the WHO criteria and the International Association for Diabetes in Pregnancy Study Group (IADPSG). The intervention did not reduce the risk of developing GDM (OR 0.84, 95% CI 0.50 to 1.40) when using the WHO criteria. We observed that the intervention reduced by 58% the GDM-related risk (WHO criteria) of having a newborn with macrosomia (OR 1.76, 95% CI 0.04 to 78.90 vs 4.22, 95% CI 1.35 to 13.19) in exercise and control groups, respectively), and by 34% the GDM-related risk of having acute and elective caesarean delivery (OR 1.30, 95% CI 0.44 to 3.84 vs 1.99, 95% CI 0.98 to 4.06 in exercise and control groups, respectively). Gestational age was similar across the treatment groups (control, exercise) and GDM category (GDM or non-GDM), and maternal weight gain was ∼12% lower in the exercise group independent of whether women developed GDM. The results were similar when the IADPSG criteria were used instead. Regular moderate-intensity exercise performed over the second-third trimesters of pregnancy can be used to attenuate important GDM-related adverse outcomes.

  17. Making sense of root cause analysis investigations of surgery-related adverse events.

    Science.gov (United States)

    Cassin, Bryce R; Barach, Paul R

    2012-02-01

    This article discusses the limitations of root cause analysis (RCA) for surgical adverse events. Making sense of adverse events involves an appreciation of the unique features in a problematic situation, which resist generalization to other contexts. The top priority of adverse event investigations must be to inform the design of systems that help clinicians to adapt and respond effectively in real time to undesirable combinations of design, performance, and circumstance. RCAs can create opportunities in the clinical workplace for clinicians to reflect on local barriers and identify enablers of safe and reliable outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Clinical review: kinase inhibitors: adverse effects related to the endocrine system.

    Science.gov (United States)

    Lodish, Maya B

    2013-04-01

    The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

  19. Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

    Science.gov (United States)

    Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

    2013-01-01

    One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery.

  20. Causal Factors and Adverse Events of Aviation Accidents and Incidents Related to Integrated Vehicle Health Management

    Science.gov (United States)

    Reveley, Mary S.; Briggs, Jeffrey L.; Evans, Joni K.; Jones, Sharon M.; Kurtoglu, Tolga; Leone, Karen M.; Sandifer, Carl E.

    2011-01-01

    Causal factors in aviation accidents and incidents related to system/component failure/malfunction (SCFM) were examined for Federal Aviation Regulation Parts 121 and 135 operations to establish future requirements for the NASA Aviation Safety Program s Integrated Vehicle Health Management (IVHM) Project. Data analyzed includes National Transportation Safety Board (NSTB) accident data (1988 to 2003), Federal Aviation Administration (FAA) incident data (1988 to 2003), and Aviation Safety Reporting System (ASRS) incident data (1993 to 2008). Failure modes and effects analyses were examined to identify possible modes of SCFM. A table of potential adverse conditions was developed to help evaluate IVHM research technologies. Tables present details of specific SCFM for the incidents and accidents. Of the 370 NTSB accidents affected by SCFM, 48 percent involved the engine or fuel system, and 31 percent involved landing gear or hydraulic failure and malfunctions. A total of 35 percent of all SCFM accidents were caused by improper maintenance. Of the 7732 FAA database incidents affected by SCFM, 33 percent involved landing gear or hydraulics, and 33 percent involved the engine and fuel system. The most frequent SCFM found in ASRS were turbine engine, pressurization system, hydraulic main system, flight management system/flight management computer, and engine. Because the IVHM Project does not address maintenance issues, and landing gear and hydraulic systems accidents are usually not fatal, the focus of research should be those SCFMs that occur in the engine/fuel and flight control/structures systems as well as power systems.

  1. Molecular confirmation of Bacillus Calmette Guerin vaccine related adverse events among Saudi Arabian children.

    Directory of Open Access Journals (Sweden)

    Sahal Al-Hajoj

    Full Text Available Bacillus Calmette Guerin (BCG is the only available vaccine for tuberculosis (TB. Low grade complications in healthy recipients and disseminated vaccine associated complications among immuno-suppressed individuals were noticed globally after administration. Recently a series of clinically suspected BCG associated suppurative and non-suppurative lymphadenitis cases were reported from different regions of Saudi Arabia. However a molecular confirmative analysis was lacking to prove these claims.During 2009-2010, 42 Mycobacterium bovis BCG suspected clinical isolates from children diagnosed with suppurative lymphadenitis from different provinces of the country were collected and subjected to 24 loci based MIRU-VNTR typing, spoligotyping and first line anti-TB drugs susceptibility testing.Of the total 42 cases, 41 (97.6% were Saudi nationals and particularly male (64.3%. Majority of the cases were aged below 6 months (83.3% with a median of age 4 months. All the enrolled subjects showed left axillary mass which suppurated in a median of 4 months after vaccination. Among the study subjects, 1 (2.4% case was reactive to HIV antigen and 2 (4.8% case had severe combined immunodeficiency. Genotyping results showed that, 41 (97.6% isolates were identical to the vaccine strain Danish 1331 and one to Tokyo 172-1. Phylogenetic analysis revealed all the Danish 1331 isolates in a single cluster.Elevated proportion of suppurative lymphadenitis caused by M. bovis BCG reported in the country recently is majorly related to the vaccine strain Danish 1331. However lack of nationwide data on real magnitude of BCG related adverse events warrants population centric, long term future studies.

  2. Victimization and adversity among children experiencing war-related parental absence or deployment in a nationally representative US sample.

    Science.gov (United States)

    Turner, Heather A; Finkelhor, David; Hamby, Sherry; Henly, Megan

    2017-05-01

    This study compares children and youth who have experienced lifetime war-related parental absence or deployment with those having no such history on a variety of victimization types, non-victimization adversity, trauma symptoms, and delinquency; and assesses whether cumulative adversity and victimization help to explain elevated emotional and behavioral problems among children of parents who have experienced war-related absence or deployment. The National Surveys of Children's Exposure to Violence (NatSCEV) are comprised of three cross-sectional telephone surveys conducted in 2008, 2011, and 2014. Data were collected on the experiences of children aged one month to seventeen years. In each survey, interviews were conducted with youth 10-17 years old and with caregivers of children 0-9 years old. The analyses use pooled data from all three U.S. nationally-representative samples (total sample size of 13,052). Lifetime parental war-related absence or deployment was a marker for elevated childhood exposure to a wide array of victimization and adversity types. Cumulative past year exposure to multiple forms of victimization and adversity fully explained elevated trauma symptoms and delinquency in this population of children. Given the breadth of victimization and adversity risk, children with histories of parental war-related absence or deployment, as well as their families, represent important target groups for broad-based prevention and interventions to reduce exposure and ameliorate consequences when it does occur. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Is Prenatal Alcohol Exposure Related to Inattention and Hyperactivity Symptoms in Children? Disentangling the Effects of Social Adversity

    Science.gov (United States)

    Rodriguez, A.; Olsen, J.; Kotimaa, A. J.; Kaakinen, M.; Moilanen, I.; Henriksen, T. B.; Linnet, K. M.; Miettunen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Jarvelin, M. R.

    2009-01-01

    Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting…

  4. Leukocytes and transfusion related adverse events: the effects of leuko-reduction process in the prevention of adverse reactions resulted from the transfusion of blood components: review article

    Directory of Open Access Journals (Sweden)

    Ehteramolsadat Hosseini

    2017-05-01

    Full Text Available Blood transfusion is commonly implemented to manage life and health-threatening conditions on a rapid and short-term basis. Over the years, ongoing technical advances have dramatically improved transfusion medicine to provide more safety and effectiveness. However, transfusion is still complicated with different adverse events that mainly induced by the presence of allogeneic leukocytes in the blood products. Several lines of evidence have shown that leukocytes in blood components are involved in the induction of febrile nonhemolytic transfusion reactions (FNHTRs, HLA alloimmunization and platelet refractoriness as well as the increased risk of the infectious diseases transmitted by leukotropic viruses including cytomegalovirus (CMV, human T-lymphotropic virus (HTLV-I/II and Epstein-Barr virus (EBV. During current decades, introducing various leuko-reduction techniques have shown to be associated with less transfusion related adverse events and improved clinical outcomes. The lower incidence and severity of febrile transfusion reactions; reduced risk of transfusion related transmission of CMV or other leukocyte-associated infections, lowered incidence of alloimmune platelet refractoriness in addition to reducing risk of mortality and morbidity in patients are considered as clinical benefits of leuko-reduced products. Currently, by the use of 3rd and 4th generation of filters, the highest levels of leukoreduction in blood components have been achieved. Filtration techniques have also the advantages of being performed shortly after preparation of components (pre-storage or post-storage even at the patient’s bedside. However, it seems that pre-storage depletion of leukocytes provides better protection than post-storage techniques due to the elimination of leukocyte-derived cytokines effects which are increasingly released during storage. Particularly in platelet products, the earlier depletion of leukocyte also favors less platelet

  5. Inter-level relations in computer science, biology, and psychology

    NARCIS (Netherlands)

    Boogerd, F.; Bruggeman, F.; Jonker, C.M.; Looren de Jong, H.; Tamminga, A.; Treur, J.; Westerhoff, H.V.; Wijngaards, W.C.A.

    2002-01-01

    Investigations into inter-level relations in computer science, biology and psychology call for an empirical turn in the philosophy of mind. Rather than concentrate on a priori discussions of inter-level relations between 'completed' sciences, a case is made for the actual study of the way

  6. Inter-level relations in computer science, biology and psychology

    NARCIS (Netherlands)

    Boogerd, F.C.; Bruggeman, F.J.; Jonker, C.M.; Looren De Jong, H.; Tamminga, A.M.; Treur, J.; Westerhoff, H.V.; Wijngaards, W.C.A.

    2002-01-01

    Investigations into inter-level relations in computer science, biology and psychology call for an empirical turn in the philosophy of mind. Rather than concentrate on a priori discussions of inter-level relations between "completed" sciences, a case is made for the actual study of the way

  7. Inter-level relations in computer science, biology, and psychology

    NARCIS (Netherlands)

    Boogerd, Fred; Bruggeman, Frank; Jonker, Catholijn; Looren de Jong, Huib; Tamminga, Allard; Treur, Jan; Westerhoff, Hans; Wijngaards, Wouter

    2002-01-01

    Investigations into inter-level relations in computer science, biology and psychology call for an *empirical* turn in the philosophy of mind. Rather than concentrate on *a priori* discussions of inter-level relations between “completed” sciences, a case is made for the actual study of the way

  8. Transfusion-related adverse events at the tertiary care center in North India: An institutional hemovigilance effort

    Directory of Open Access Journals (Sweden)

    Bhattacharya Prasun

    2011-01-01

    Full Text Available Aim: This study was designed to analyze the incidence and spectrum of adverse effects of blood transfusion so as to initiate measures to minimize risks and improve overall transfusion safety in the institute. Materials and Methods: During the period from July 2002 to July 2003 all the adverse events related to transfusion of blood and blood components in various clinical specialties were recorded. They were analyzed and classified on the basis of their clinical features and laboratory tests. Attempt was also made to study the predisposing risk factors. Results: During the study period 56,503 blood and blood components were issued to 29,720 patients. A total of 105 adverse reactions due to transfusion were observed during the study period. A majority of the adverse reactions was observed in hemato-oncology patients 43% (n = 45 and in presensitized patient groups 63% (n = 66. FNHTR 41% (n = 43 and allergic reactions 34% (n = 36 were the most common of all types of adverse transfusion reactions, followed by AcHTR 8.56% (n = 9. Majority of these AcHTR were due to unmonitored storage of blood in the refrigerator of wards resulting in hemolysis due to thermal injury. Less frequently observed reactions were anaphylactoid reactions (n = 4, bacterial sepsis (n = 4, hypervolemia (n = 2, hypocalcemia (n = 2, TRALI (n = 1, DHTR (n = 1, and TAGvHD (n = 1. Conclusion: Analysis of transfusion-related adverse outcomes is essential for improving safety. Factors such as improvement of blood storage conditions outside the blood bank, improvement in cross-matching techniques, careful donor screening, adherence to good manufacturing practices while component preparation, bedside monitoring of transfusion, and documentation of adverse events will help in reducing transfusion-related morbidity and mortality.

  9. Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile.

    Science.gov (United States)

    Mauro, Francesca R; Molica, Stefano; Laurenti, Luca; Cortelezzi, Agostino; Carella, Angelo M; Zaja, Francesco; Chiarenza, Annalisa; Angrilli, Francesco; Nobile, Francesco; Marasca, Roberto; Musolino, Caterina; Brugiatelli, Maura; Piciocchi, Alfonso; Vignetti, Marco; Fazi, Paola; Gentile, Giuseppe; De Propris, Maria S; Della Starza, Irene; Marinelli, Marilisa; Chiaretti, Sabina; Del Giudice, Ilaria; Nanni, Mauro; Albano, Francesco; Cuneo, Antonio; Guarini, Anna; Foà, Robin

    2014-02-01

    In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

    Science.gov (United States)

    Krejci, Charlene B; Bissada, Nabil F

    2012-01-01

    To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

  11. Report of adverse events related to treatments to Institute de Veille sanitaire

    International Nuclear Information System (INIS)

    Maingon, P.; Simmon-Tellier, S.

    2007-01-01

    The 'code de sante publique' imposes to all health professionals an obligation to declare serious and undesirable events following cares applied during treatment investigations or prevention actions. An experimentation has been installed under the responsibility of the Institut de Veille sanitaire further to the 9 August 2004 bill. It aims to define how to declare undesirable adverse events to test its feasibility, its efficiency and to identify the necessary conditions to widespread its modalities. The field of these experimentations concerns all health professionals, working in public hospital or in private practice. The definition of undesirable adverse events should be clarified. Different ways to declare these events will be discussed with S.F.R.O. (Societe francaise de radiotherapie oncologique) to improve the current management of incidents and adverse events. (authors)

  12. The Adverse Drug Event Collaborative: a joint venture to measure medication-related patient harm.

    Science.gov (United States)

    Seddon, Mary E; Jackson, Aaron; Cameron, Chris; Young, Mary L; Escott, Linda; Maharaj, Ashika; Miller, Nigel

    2012-01-25

    To measure the extent of patient harm caused by medications (rate of Adverse Drug Events) in three DHBs, using a standardised trigger tool method. Counties Manukau, Capital and Coast and Canterbury DHBs decided to work collaboratively to implement the ADE Trigger Tool (TT). Definitions of ADE were agreed on and triggers refined. A random sample of closed charts (from March 2010 to February 2011) was obtained excluding patients who were admitted for <48 hours, children under the age of 18 and psychiatric admissions. In each DHB trained reviewers scanned these in a structured way to identify any of the 19 triggers. If triggers were identified, a more detailed, though time-limited review of the chart was done to determine whether an ADE had occurred. The severity of patient harm was categorised using the National Coordinating Council for Medication Error Reporting and Prevention Index. No attempt was made to determine preventability of harm and ADEs from acts of omission were excluded. The ADE TT was applied to 1210 charts and 353 ADE were identified, with an average rate of 28.9/100 admissions and 38/1,000 bed days. 94.5% of the ADE identified were in the lower severity scales with temporary harm, however in 5 patients it was considered that the ADE contributed to their death, 9 required an intervention to sustain life and 4 suffered permanent harm. The most commonly implicated drugs were morphine and other opioids, anticoagulants, antibiotics, Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and diuretics. Patients who suffered an ADE were more likely to be female, older with more complex medical illnesses, and have a longer length of stay. The rate of medication-related harm identified by the ADE TT is considerably higher than that identified through traditional voluntary reporting mechanisms. The ADE TT provides a standardised measure of harm over time that can be used to determine trends and the effect of medication safety improvement programmes. This study not

  13. A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients.

    Directory of Open Access Journals (Sweden)

    Rosliana Rosli

    Full Text Available Spontaneous reporting on adverse drug reactions (ADR has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups.Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification, category of ADR (according to system organ class as well as the severity of the ADR.In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%. The most common ADRs reported were from the following system organ classes: application site disorders (32.2%, skin and appendages disorders (20.6%, body as a whole general disorders (12.8% and central and peripheral nervous system disorders (11.2%. Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0% were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%. Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities.ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of

  14. Computerized surveillance of opioid-related adverse drug events in perioperative care: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Gattis Katherine G

    2009-08-01

    Full Text Available Abstract Background Given the complexity of surgical care, perioperative patients are at high risk of opioid-related adverse drug events. Existing methods of detection, such as trigger tools and manual chart review, are time-intensive which makes sustainability challenging. Using strategic rule design, computerized surveillance may be an efficient, pharmacist-driven model for event detection that leverages existing staff resources. Methods Computerized adverse drug event surveillance uses a logic-based rules engine to identify potential adverse drug events or evolving unsafe clinical conditions. We extended an inpatient rule (administration of naloxone to detect opioid-related oversedation and respiratory depression to perioperative care at a large academic medical center. Our primary endpoint was the adverse drug event rate. For all patients with a naloxone alert, manual chart review was performed by a perioperative clinical pharmacist to assess patient harm. In patients with confirmed oversedation, other patient safety event databases were queried to determine if they could detect duplicate, prior, or subsequent opioid-related events. Results We identified 419 cases of perioperative naloxone administration. Of these, 101 were given postoperatively and 69 were confirmed as adverse drug events after chart review yielding a rate of 1.89 adverse drug events/1000 surgical encounters across both the inpatient and ambulatory settings. Our ability to detect inpatient opioid adverse drug events increased 22.7% by expanding surveillance into perioperative care. Analysis of historical surveillance data as well as a voluntary reporting database revealed that 11 of our perioperative patients had prior or subsequent harmful oversedation. Nine of these cases received intraoperative naloxone, and 2 had received naloxone in the post-anesthesia care unit. Pharmacist effort was approximately 3 hours per week to evaluate naloxone alerts and confirm adverse drug

  15. Assessing planetary and regional nitrogen boundaries related to food security and adverse environmental impacts

    NARCIS (Netherlands)

    Vries, de W.; Kros, J.; Kroeze, C.; Seitzinger, S.P.

    2013-01-01

    This paper first describes the concept of, governance interest in, and criticism on planetary boundaries, specifically with respect to the nitrogen (N) cycle. These criticisms are then systematically evaluated. We argue that planetary N boundaries should include both the benefits and adverse impacts

  16. Population attributable risk for adverse pregnancy outcomes related to smoking in adolescents and adults

    NARCIS (Netherlands)

    Delpisheh, A.; Kelly, Y.; Rizwan, S.; Attia, E.; Drammond, S.; Brabin, B. J.

    2007-01-01

    BACKGROUND: Little is known about how population-attributable risks (PAR) for adverse birth outcomes due to smoking differ in adolescent and adult pregnancies. METHODS: An analysis of community and hospital-based cross-sectional studies in Liverpool was undertaken to estimate the PAR values of low

  17. (Un)Healthy in the city : Adverse health effects of traffic-related noise and air pollution

    NARCIS (Netherlands)

    Zijlema, Wilma

    2016-01-01

    We investigated the adverse health effects of urbanity, traffic-related noise and air pollution. We used harmonized data from multiple European cohort studies: LifeLines, HUNT, FINRISK, EPIC-Oxford and KORA. Based on our studies, we concluded that the living environment may be associated with

  18. Biologic relativity: Who is the observer and what is observed?

    Science.gov (United States)

    Torday, John S; Miller, William B

    2016-05-01

    When quantum physics and biological phenomena are analogously explored, it emerges that biologic causation must also be understood independently of its overt appearance. This is similar to the manner in which Bohm characterized the explicate versus the implicate order as overlapping frames of ambiguity. Placed in this context, the variables affecting epigenetic inheritance can be properly assessed as a key mechanistic principle of evolution that significantly alters our understanding of homeostasis, pleiotropy, and heterochrony, and the purposes of sexual reproduction. Each of these become differing manifestations of a new biological relativity in which biologic space-time becomes its own frame. In such relativistic cellular contexts, it is proper to question exactly who has observer status, and who and what are being observed. Consideration within this frame reduces biology to cellular information sharing through cell-cell communication to resolve ambiguities at every scope and scale. In consequence, it becomes implicit that eukaryotic evolution derives from the unicellular state, remaining consistently adherent to it in a continuous evolutionary arc based upon elemental, non-stochastic physiologic first principles. Furthermore, the entire cell including its cytoskeletal apparatus and membranes that participate in the resolution of biological uncertainties must be considered as having equivalent primacy with genomes in evolutionary terms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

    Science.gov (United States)

    Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

    2015-01-01

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

  20. Bragg peak and relative biological efficiency of different ions

    Czech Academy of Sciences Publication Activity Database

    Lokajíček st., Miloš; Judas, Libor; Kundrát, Pavel

    2002-01-01

    Roč. 64, Suppl. 1 (2002), S309-S309 ISSN 0167-8140 R&D Projects: GA AV ČR(CZ) KSK4055109 Keywords : Bragg peak * relative biological efficisncy * radiological mechanism Subject RIV: CC - Organic Chemistry Impact factor: 2.838, year: 2002

  1. 9 CFR 101.3 - Biological products and related terms.

    Science.gov (United States)

    2010-01-01

    ... as required by the regulations. (e) Released product. A finished product released for marketing after... total quantity of completed product which has been thoroughly mixed in a single container and identified... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products and related terms...

  2. Biological Sensitivity to Context: The Interactive Effects of Stress Reactivity and Family Adversity on Socioemotional Behavior and School Readiness

    Science.gov (United States)

    Obradovic, Jelena; Bush, Nicole R.; Stamperdahl, Juliet; Adler, Nancy E.; Boyce, W. Thomas

    2010-01-01

    This study examined the direct and interactive effects of stress reactivity and family adversity on socioemotional and cognitive development in three hundred and thirty-eight 5- to 6-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and…

  3. Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

    2014-11-14

    The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

  4. Sex and age related differences in postmyelographic adverse reactions. A prospective study of 1765 myelographies

    Energy Technology Data Exchange (ETDEWEB)

    Maly, P

    1989-09-01

    Differences in frequency of postmyelographic adverse reactions were analyzed with respect to sex and age in a prospective study including 1026 patients injected with metrizamide and 739 injected with iohexol. Regardless of the type of contrast medium or myelography, all types of adverse reactions were 1.4-3.8 times as frequent in women as in men. Most of the differences were statistically significant. Headache was more frequent, while vomiting and dizziness were less frequent in both women and men aged 26-50 years compared with those over 50 years of age. Dizziness and increased low back pain were consistently reported spontaneously by the patients less frequently than emerged via formal interview. The large differences between the sexes suggest that further research on contrast media toxicity would be best performed with separation of the data by gender. (orig.).

  5. Causal Factors and Adverse Conditions of Aviation Accidents and Incidents Related to Integrated Resilient Aircraft Control

    Science.gov (United States)

    Reveley, Mary S.; Briggs, Jeffrey L.; Evans, Joni K.; Sandifer, Carl E.; Jones, Sharon Monica

    2010-01-01

    The causal factors of accidents from the National Transportation Safety Board (NTSB) database and incidents from the Federal Aviation Administration (FAA) database associated with loss of control (LOC) were examined for four types of operations (i.e., Federal Aviation Regulation Part 121, Part 135 Scheduled, Part 135 Nonscheduled, and Part 91) for the years 1988 to 2004. In-flight LOC is a serious aviation problem. Well over half of the LOC accidents included at least one fatality (80 percent in Part 121), and roughly half of all aviation fatalities in the studied time period occurred in conjunction with LOC. An adverse events table was updated to provide focus to the technology validation strategy of the Integrated Resilient Aircraft Control (IRAC) Project. The table contains three types of adverse conditions: failure, damage, and upset. Thirteen different adverse condition subtypes were gleaned from the Aviation Safety Reporting System (ASRS), the FAA Accident and Incident database, and the NTSB database. The severity and frequency of the damage conditions, initial test conditions, and milestones references are also provided.

  6. Air pollution in India and related adverse respiratory health effects: past, present, and future directions.

    Science.gov (United States)

    Khilnani, Gopi C; Tiwari, Pawan

    2018-03-01

    The review describes current status of air pollution in India, summarizes recent research on adverse health effects of ambient and household air pollution, and outlines the ongoing efforts and future actions required to improve air quality and reduce morbidity and mortality because of air pollution in India. Global burden of disease data analysis reveals more than one million premature deaths attributable to ambient air pollution in 2015 in India. More than one million additional deaths can be attributed to household air pollution. Particulate matter with diameter 2.5 μm or less has been causatively linked with most premature deaths. Acute respiratory tract infections, asthma, chronic obstructive pulmonary disease, exacerbations of preexisting obstructive airway disease and lung cancer are proven adverse respiratory effects of air pollution. Targeting air quality standards laid by WHO can significantly reduce morbidity and mortality because of air pollution in India. India is currently exposed to high levels of ambient and household air pollutants. Respiratory adverse effects of air pollution are significant contributors to morbidity and premature mortality in India. Substantial efforts are being made at legislative, administrative, and community levels to improve air quality. However, much more needs to be done to change the 'status quo' and attain the target air quality standards. VIDEO ABSTRACT: http://links.lww.com/COPM/A24.

  7. The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients.

    Science.gov (United States)

    Tachi, Tomoya; Teramachi, Hitomi; Tanaka, Kazuhide; Asano, Shoko; Osawa, Tomohiro; Kawashima, Azusa; Yasuda, Masahiro; Mizui, Takashi; Nakada, Takumi; Noguchi, Yoshihiro; Tsuchiya, Teruo; Goto, Chitoshi

    2015-01-01

    The objective of our study was to clarify the impact of adverse events associated with the initial course of outpatient chemotherapy on the quality of life of breast cancer patients. We conducted a survey to assess the quality of life in 48 breast cancer patients before and after receiving their first course of outpatient chemotherapy at Gifu Municipal Hospital. Patients completed the European Quality of Life 5 Dimensions and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs before and after 1 course of outpatient chemotherapy. European Quality of Life 5 Dimensions utility value and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score decreased significantly after chemotherapy (pQuality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs decreased significantly after chemotherapy (p = 0.003, pquality of life according to individual adverse events, the decrease in quality of life after chemotherapy in terms of the European Quality of Life 5 Dimensions utility value and the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score was greater in anorexic patients than in non-anorexic patients (p = 0.009 and pquality of life. Our findings reveal that anticancer drug-related adverse events, particularly anorexia, reduce overall quality of life following the first course of outpatient chemotherapy in current breast cancer patients. These findings are extremely useful and important in understanding the impact of anticancer drug-related adverse events on quality of life.

  8. Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

    Science.gov (United States)

    Lee, Chunsoo; Lee, Kyungsang; Yu, Hyewon; Ryu, Seung-Ho; Moon, Seok Woo; Han, Changsu; Lee, Jun-Young; Lee, Young Min; Kim, Shin-Gyeom; Kim, Ki Woong; Lee, Dong Woo; Kim, Seong Yoon; Lee, Sang-Yeol; Bae, Jae Nam; Jung, Young-Eun; Kim, Jeong Lan; Kim, Byung-Soo; Shin, Il-Seon; Kim, Young Hoon; Kim, Bong Jo; Kang, Hyo Shin; Myung, Woojae; Carroll, Bernard J; Kim, Doh Kwan

    2017-08-01

    Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

  9. Total petroleum hydrocarbons and heavy metals in the surface sediments of Bohai Bay, China: long-term variations in pollution status and adverse biological risk.

    Science.gov (United States)

    Zhou, Ran; Qin, Xuebo; Peng, Shitao; Deng, Shihuai

    2014-06-15

    Surface sediments collected from 2001 to 2011 were analyzed for total petroleum hydrocarbons (TPH) and five heavy metals. The sediment concentration ranges of TPH, Zn, Cu, Pb, Cd and Hg were 6.3-535 μg/g, 58-332 μg/g, 7.2-63 μg/g, 4.3-138 μg/g, 0-0.98μg/g, and 0.10-0.68 μg/g, respectively. These results met the highest marine sediment quality standards in China, indicating that the sediment was fairly clean. However, based on the effects range-median (ERM) quotient method, the calculated values for all of the sampling sites were higher than 0.10, suggesting that there was a potential adverse biological risk in Bohai Bay. According to the calculated results, the biological risk decreased from 2001 to 2007 and increased afterwards. High-risk sites were mainly distributed along the coast. This study suggests that anthropogenic influences might be responsible for the potential risk of adverse biological effects from TPH and heavy metals in Bohai Bay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system

    Directory of Open Access Journals (Sweden)

    Rashid N

    2016-10-01

    Full Text Available Nazia Rashid,1 Han A Koh,2 Hilda C Baca,3 Kathy J Lin,1 Susan E Malecha,4 Anthony Masaquel5 1Drug Information Services, Kaiser Permanente, Downey, 2Southern California Permanente Medical Group, Kaiser Permanente, Bellflower, 3Pharmacy Analytical Services, Kaiser Permanente, Downey, 4US Medical Affairs, Genetech Inc., San Francisco, 5Health Economics and Outcomes, Genentech Inc., San Francisco, CA, USA Background: Breast cancer is treated with many different modalities, including chemotherapy that can be given as a single agent or in combination. Patients often experience adverse events from chemotherapy during the cycles of treatment which can lead to economic burden.Objective: The objective of this study was to evaluate costs related to chemotherapy-related adverse events in patients with metastatic breast cancer (mBC in an integrated health care delivery system.Methods: Patients with mBC newly initiated on chemotherapy were identified and the first infusion was defined as the index date. Patients were ≥18 years old at time of index date, had at least 6 months of health plan membership and drug eligibility prior to their index date. The chemotherapy adverse events were identified after the index date and during first line of chemotherapy. Episodes of care (EOC were created using healthcare visits. Chart review was conducted to establish whether the adverse events were related to chemotherapy. Costs were calculated for each visit, including medications related to the adverse events, and aggregated to calculate the total EOC cost.Results: A total of 1,682 patients with mBC were identified after applying study criteria; 54% of these patients had one or more adverse events related to chemotherapy. After applying the EOC method, there were a total of 5,475 episodes (4,185 single episodes [76.4%] and 1,290 multiple episodes [23.6%] related to chemotherapy-related adverse events. Within single episodes, hematological (1,387 EOC, 33

  11. The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem.

    Science.gov (United States)

    Yen, Cheng-Fang; Yang, Pinchen; Wu, Yu-Yu; Cheng, Chung-Ping

    2013-11-01

    This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.

  12. Adverse childhood experiences and health-related quality of life in adulthood: revelations from a community needs assessment

    OpenAIRE

    Salinas-Miranda, Abraham A.; Salemi, Jason L.; King, Lindsey M.; Baldwin, Julie A.; Berry, Estrellita ?Lo?; Austin, Deborah A.; Scarborough, Kenneth; Spooner, Kiara K.; Zoorob, Roger J.; Salihu, Hamisu M.

    2015-01-01

    Background Adverse childhood experiences (ACE) have been previously linked to quality of life, health conditions, and life expectancy in adulthood. Less is known about the potential mechanisms which mediate these associations. This study examined how ACE influences adult health-related quality of life (HRQoL) in a low-income community in Florida. Methods A community-based participatory needs assessment was conducted from November 2013 to March 2014 with 201 residents of Tampa, Florida, USA. H...

  13. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    DEFF Research Database (Denmark)

    Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated t......Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator......-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months...... 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not...

  14. The relative biological effectiveness of out-of-field dose

    International Nuclear Information System (INIS)

    Balderson, Michael; Koger, Brandon; Kirkby, Charles

    2016-01-01

    Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions. (paper)

  15. Boarding is associated with higher rates of medication delays and adverse events but fewer laboratory-related delays.

    Science.gov (United States)

    Sri-On, Jiraporn; Chang, Yuchiao; Curley, David P; Camargo, Carlos A; Weissman, Joel S; Singer, Sara J; Liu, Shan W

    2014-09-01

    Hospital crowding and emergency department (ED) boarding are large and growing problems. To date, there has been a paucity of information regarding the quality of care received by patients boarding in the ED compared with the care received by patients on an inpatient unit. We compared the rate of delays and adverse events at the event level that occur while boarding in the ED vs while on an inpatient unit. This study was a secondary analysis of data from medical record review and administrative databases at 2 urban academic teaching hospitals from August 1, 2004, through January 31, 2005. We measured delayed repeat cardiac enzymes, delayed partial thromboplastin time level checks, delayed antibiotic administration, delayed administration of home medications, and adverse events. We compared the incidence of events during ED boarding vs while on an inpatient unit. Among 1431 patient medical records, we identified 1016 events. Emergency department boarding was associated with an increased risk of home medication delays (risk ratio [RR], 1.54; 95% confidence interval [CI], 1.26-1.88), delayed antibiotic administration (RR, 2.49; 95% CI, 1.72-3.52), and adverse events (RR, 2.36; 95% CI, 1.15-4.72). On the contrary, ED boarding was associated with fewer delays in repeat cardiac enzymes (RR, 0.17; 95% CI, 0.09-0.27) and delayed partial thromboplastin time checks (RR, 0.54; 95% CI, 0.27-0.96). Compared with inpatient units, ED boarding was associated with more medication-related delays and adverse events but fewer laboratory-related delays. Until we can eliminate ED boarding, it is critical to identify areas for improvement. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

    Science.gov (United States)

    Eichstadt, L R; Moore, G E; Childress, M O

    2017-12-01

    Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer. © 2016 John Wiley & Sons Ltd.

  17. Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

    Science.gov (United States)

    Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

    2012-01-01

    Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

  18. Important sources and chemical species of ambient fine particles related to adverse health effects

    Science.gov (United States)

    Heo, J.

    2017-12-01

    contributor to PM2.5, leading to adverse human health effects.

  19. Risk of Fall-Related Injury due to Adverse Weather Events, Philadelphia, Pennsylvania, 2006-2011.

    Science.gov (United States)

    Gevitz, Kathryn; Madera, Robbie; Newbern, Claire; Lojo, José; Johnson, Caroline C

    Following a surge in fall-related visits to local hospital emergency departments (EDs) after a severe ice storm, the Philadelphia Department of Public Health examined the association between inclement winter weather events and fall-related ED visits during a 5-year period. Using a standardized set of keywords, we identified fall-related injuries in ED chief complaint logs submitted as part of Philadelphia Department of Public Health's syndromic surveillance from December 2006 through March 2011. We compared days when falls exceeded the winter fall threshold (ie, "high-fall days") with control days within the same winter season. We then conducted matched case-control analysis to identify weather and patient characteristics related to increased fall-related ED visits. Fifteen high-fall days occurred during winter months in the 5-year period. In multivariable analysis, 18- to 64-year-olds were twice as likely to receive ED care for fall-related injuries on high-fall days than on control days. The crude odds of ED visits occurring from 7:00 am to 10:59 am were 70% higher on high-fall days vs control days. Snow was a predictor of a high-fall day: the adjusted odds of snow before a high-fall day as compared with snow before a control day was 13.4. The association between the number of fall-related ED visits and weather-related fall injuries, age, and timing suggests that many events occurred en route to work in the morning. Promoting work closures or delaying openings after severe winter weather would allow time for better snow or ice removal, and including "fall risk" in winter weather advisories might effectively warn morning commuters. Both strategies could help reduce the number of weather-related fall injuries.

  20. Review of studies validating the protective efficacy of a new technology designed to compensate adverse biological effects caused by vdu and GSM cell phone radiation

    International Nuclear Information System (INIS)

    Youbicier-Simo, B.J.; Messagier, R.; Fillion-Robin, M

    2001-01-01

    A total of 13 studies were initiated and coordinated by Technolab Research Center in 6 laboratories from 3 countries (France, UK, Japan). These studies were aimed at: 1) investigating potential adverse biological effects associated with exposure to non ionizing radiation emitted by two types of communication devices, video display units and cell phones; 2) assessing the efficacy of a compensation magnetic oscillating technology designed to protect from non ionizing radiation. Five types of biological systems including chicken embryos, young chickens, healthy mice, mice suffering from cancer and humans were used. A set of 10 biological parameters were assessed, including embryonic mortality, hormones, antibodies, haematological parameters, stress, mood, ocular damage, neurogenesis, micronuclei formation and intracellular calcium. Overall endpoints were affected by irradiation, in terms of increased embryonic mortality, immune depression, depletion of hormones crucial for the regulation of the immune system, changes in haematological parameters, increased stress, mood alteration, induction of ophthalmologic disorders, inhibition of the neurogenesis in brain areas associated with memory processes, induction of symptoms of cell dysfunction, apoptosis or cancer, and disruption of trans-membrane fluxes of calcium. On the other hand, the compensation magnetic oscillation technology tested allowed significant correction of altered physiological parameters, as well as improvement or disappearance of observed pathological symptoms (author)

  1. Financial compensation for radiotherapy-related adverse events in a judicial system where proof of medical negligence is not required

    International Nuclear Information System (INIS)

    Nyandoto, Paul; Muhonen, Timo; Hakala, Tapani; Dombrowski, Mitchell P.; Joensuu, Heikki

    2001-01-01

    Purpose: To examine the frequency of adverse events related to radiation therapy that lead to financial compensation in a judicial system that is not based on litigation in court but on statutory insurance where proof of medical negligence is not required for obtaining compensation. Methods and Materials: In Finland, an injured patient does not sue through the courts, but submits an insurance claim to the Patient Insurance Association. Proof of medical negligence is not required for obtaining compensation. We reviewed all filed claims associated with radiotherapy presented to the Patient Insurance Association from May 1987 to January 1999. During this time period, 1,732,000 patient visits to radiation therapy units were made, and the estimated number of radiotherapy treatments was 86,600. The data collected included descriptions of the adverse events, examination of the radiation therapy procedures followed, assessment of the causal relation of the event to radiotherapy by the therapists involved and by independent reviewers, and the sums used for compensation. Results: Only 102 patients (about 0.1%) had filed a claim for financial compensation, and in 18 (0.02%) cases the claim led to compensation. The mean national annual expenditure used for compensation was $35,200, and the sums paid in single cases ranged from $310 to $287,430 (median, $1,970). The expenditure used for compensating adverse radiation events was about $4 per treated patient, which is about 0.3% of all radiation therapy costs. Conclusions: The frequency of radiation therapy injuries that are financially compensated can remain low in an insurance-based judicial system where no litigation or attorneys are involved

  2. Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems

    Science.gov (United States)

    2011-01-01

    Background We review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively. Results We describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equation f = f (f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing. Conclusions We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete. PMID:21689427

  3. The relative biological effectiveness of radiations of different quality

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    This paper is a review of the literature relevant to the selection of relative biological effectiveness (RBE) values for use in arriving at values of the quality factor (Q). Emphasis is placed on response to small ( M . In a wide variety of systems, the RBE M for fast (fission) neutrons, with low doses and dose rates, appears to be of the order of 20 or more compared to moderately filtered 250 kVp x rays and 40 or more compared to higher energy gamma rays. These values, which are much larger than those observed with large doses delivered at high dose rates, are due mainly, but not entirely, to a decrease in the slope of the curve for the ow-LET reference radiation at low dose

  4. Relative biological effectiveness of protons and heavy particles

    International Nuclear Information System (INIS)

    Vyglenov, A.; Fedorenko, B.; Kabachenko, A.

    1986-01-01

    The genetic effectiveness was studied of protons (9 GeB/nuclon, 0,72 Gy/min), α-particles (4 GeB/nuclon, 0,9 Gy/min) and carbon ions (4 GeB/nuclon 0,36 Gy/min). The translocation yield in mouse spermatogonia was used as indicator of radiation-induced genetic injury. Reciprocal translocation were registered six months after the irradiation on spermatocytes in diakinesmetaphase I. Comparison was made with gamma-irradiated animals from 60 Co source with dose rate 1,44 Gy/min. The relative biological effectiveness (RBE) was determined by comparing the regression coefficients from the linear dose translocation yield dependency. The values of the RBE coefficients were 0.8, 0.9 and 1.2, accordingly for protons, α-particles and carbon ions

  5. Review of the inhibition of biological activities of food-related selected toxins by natural compounds.

    Science.gov (United States)

    Friedman, Mendel; Rasooly, Reuven

    2013-04-23

    There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term 'chemical genetics' has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet.

  6. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    Science.gov (United States)

    Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

  7. Safety in the operating room during orthopedic trauma surgery-incidence of adverse events related to technical equipment and logistics

    NARCIS (Netherlands)

    van Delft, E. A. K.; Schepers, T.; Bonjer, H. J.; Kerkhoffs, G. M. M. J.; Goslings, J. C.; Schep, N. W. L.

    2017-01-01

    Safety in the operating room is widely debated. Adverse events during surgery are potentially dangerous for the patient and staff. The incidence of adverse events during orthopedic trauma surgery is unknown. Therefore, we performed a study to quantify the incidence of these adverse events. Primary

  8. Glaucoma-related adverse events in the first five years after unilateral cataract removal in the Infant Aphakia Treatment Study

    Science.gov (United States)

    Freedman, Sharon F.; Lynn, Michael J.; Beck, Allen D.; Bothun, Erick D.; Orge, Faruk H.; Lambert, Scott R.

    2015-01-01

    Importance Glaucoma-related adverse events constitute major sight-threatening complications of cataract removal in infancy, yet their relationship to aphakia versus primary intraocular lens (IOL) implantation remains unsettled. Objective To identify and characterize cases of glaucoma and glaucoma-related adverse events (glaucoma+glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of five years. Design, Setting, and Participants A multicenter randomized controlled trial of 114 infants with unilateral congenital cataract who were between age 1–6 months at surgery. Interventions Participants were randomized at cataract surgery to either primary IOL, or no IOL implantation (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcome Measures Development of glaucoma and glaucoma+glaucoma suspect in operated eyes up to age five years, plus intraocular pressure, visual acuity, and axial length at age five years. Results Product limit estimates of the risk of glaucoma and glaucoma+glaucoma suspect at 4.8 years after surgery were 17% (95%CI=11%–25%) and 31% (95%CI=24%–41%), respectively. The CL and IOL groups were not significantly different for either outcome: glaucoma (hazard ratio(HR)=0.8[95%CI=0.3–2.0],p=0.62); glaucoma+glaucoma suspect: (HR=1.3[95%CI=0.6–2.5],p=0.58). Younger (versus older) age at surgery conferred increased risk of glaucoma (26% versus 9%, respectively at 4.8 years after surgery (HR=3.2[95%CI=1.2–8.3]), and smaller (versus larger) corneal diameter showed increased risk for glaucoma+glaucoma suspect (HR=2.5[95%CI=1.3–5.0]). Age and corneal diameter were significantly positively correlated. Glaucoma was predominantly open angle (19/20 cases, 95%), most eyes received medication (19/20, 95%), and 8/20 (40%) eyes had surgery. Conclusions and Relevance These results suggest that glaucoma-related adverse events

  9. Peripheral Venous Catheter-Related Adverse Events: Evaluation from a Multicentre Epidemiological Study in France (the CATHEVAL Project.

    Directory of Open Access Journals (Sweden)

    Katiuska Miliani

    Full Text Available Peripheral venous catheters (PVC are medical devices most frequently used during hospital care. Although the frequency of specific PVC-related adverse events (PVCAEs has been reported, the global risk related to the insertion of this device is poorly estimated. The aim of this study is to determine the incidence of PVCAEs during the indwell time, after catheter removal, and to identify practice-mirroring risk factors.A prospective observational study was conducted as a part of a research project, called CATHEVAL, in one surgery ward and four medicine wards from three public general tertiary care hospitals in Northern France that were invited to participate between June-2013 and June-2014. Each participating ward included during a two-month study period all patients older than 15 years carrying a PVC. All inserted PVCs were monitored from insertion of PVC to up to 48 hours after removal. Monitored data included several practice-mirroring items, as well as the occurrence of at least one PVCAE. A multivariate Cox proportional hazard model, based on a marginal risk approach, was used to identify factors associated with the occurrence of at least one PVCAE.Data were analysed for 815 PVCs (1964 PVC-days in 573 patients. The incidence of PVCAE was 52.3/100 PVCs (21.9/100 PVC-days. PVCAEs were mainly clinical: phlebitis (20.1/100 PVCs, haematoma (17.7/100 PVCs and liquid/blood escape (13.1/100 PVCs. Infections accounted for only 0.4/100 PVCs. The most frequent mechanical PVCAEs, was obstruction/occlusion of PVC (12.4/100 PVCs. The incidence of post-removal PVCAEs was 21.7/100 PVCs. Unstable PVC and unclean dressing were the two main risk factors.Limitation of breaches in healthcare quality including post-removal monitoring should be reinforced to prevent PVC-related adverse events in hospital settings.

  10. The relative biological effectiveness of I-125 and Pd-103

    International Nuclear Information System (INIS)

    Ling, C. Clifton; Li, William X.; Anderson, Lowell L.

    1995-01-01

    Purpose: To determine the relative biological effectiveness (RBE) of I-125 and Pd-103 relative to Co-60. Methods and Materials: A cell line REC:ras, derived from rat embryo cells, was used. Cells in exponential or plateau phase were irradiated at dose rates of about 0.07 Gy/h and 0.14 Gy/h. To circumvent the interface effect, cells were grown and irradiated on membranes made of cellulose acetate, which has an effective Z of 7.5. I-125 and Pd-103 seeds were placed in a custom designed template that yielded a homogeneous dose distribution in the plane of the cell culture. The dose rates of irradiation were measured by calibrated thermoluminescence dosimetry (TLD) chips. Results and Conclusions: Our measurements yielded an RBE of about 1.4 for I-125 at dose rates of about 0.07 Gy/h, and an RBE of about 1.9 for Pd-103 at dose rates of about 0.07 Gy/h and 0.14 Gy/h. The RBE of I-125 is similar to those measured by other investigators, the RBE for Pd-103 is being reported for the first time

  11. Evolution and Personal Religious Belief: Christian University Biology-Related Majors' Search for Reconciliation

    Science.gov (United States)

    Winslow, Mark W.; Staver, John R.; Scharmann, Lawrence C.

    2011-01-01

    The goal of this study was to explore Christian biology-related majors' perceptions of conflicts between evolution and their religious beliefs. This naturalistic study utilized a case study design of 15 undergraduate biology-related majors at or recent biology-related graduates from a mid-western Christian university. The broad sources of data…

  12. Relative biological effectiveness if alpha radiation for human lung exposure

    International Nuclear Information System (INIS)

    Yarmoshenko, I.; Kirdin, I.; Zhukovsky, M.

    2006-01-01

    Full text of publication follows: The concept of RBE, which introduced by ICRP and ICRU about 50 years ago to compare biological effects of ionizing radiation of different types, still continues to be the essential element of current and projected radiation protection systems in terms of deriving quantities (quality factor and radiation weighting factor). For example, RBE for the stochastic effects induction has to be considered for appropriate radiation weighting of the absorbed dose while estimating equivalent dose. Simulation of lung cancer radiation risk for the cases of inhalation of radon progeny and incorporation of plutonium in lung in comparison with external reference radiation allows assessment of RBE for alpha-radiation. Specific radiation risk models were developed by results of the direct epidemiological studies and used for such simulation. Simulation included published risk models for nuclear workers of the Mayak facilities in the former Soviet Union exposed to incorporated plutonium (Kreisheimer et al., 2003; Gilbert et al., 2004) and underground miners exposed to radon progenies (BEIR VI, 1999). Additionally lung cancer risk model was developed for a case of population indoor radon exposure. Lung cancer risk related to external exposure is estimated using the risk model develop ed using data of Life Span Study of Japanese atomic bomb survivors. By results of lifetime lung cancer risk simulation using Monte Carlo approach estimated median value of RBE in case of indoor radon exposure is 1.5 (with 90% range 0.4 to 7). In case of the two models developed by BEIR VI for lung cancer risk due to radon exposure in underground miners the median values of RBE are 2.1 and 4.4 (with 90% ranges 0.3 to 17 and 0.7 to 45) respectively.Two different models for lung cancer risk related to plutonium exposure resulted in close estimates of RBE: median value of 12 and 13 (with 90% range 4 to 104 and 4 to 136) respectively. Considerable discrepancy between RBE

  13. Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction

    DEFF Research Database (Denmark)

    Cannon, Jane A.; Shen, Li; Jhund, Pardeep S.

    2017-01-01

    Aims: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril....... As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context...... of other recently conducted HFrEF trials. Methods and results: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory...

  14. Adverse childhood experiences and health-related quality of life in adulthood: revelations from a community needs assessment.

    Science.gov (United States)

    Salinas-Miranda, Abraham A; Salemi, Jason L; King, Lindsey M; Baldwin, Julie A; Berry, Estrellita Lo; Austin, Deborah A; Scarborough, Kenneth; Spooner, Kiara K; Zoorob, Roger J; Salihu, Hamisu M

    2015-08-11

    Adverse childhood experiences (ACE) have been previously linked to quality of life, health conditions, and life expectancy in adulthood. Less is known about the potential mechanisms which mediate these associations. This study examined how ACE influences adult health-related quality of life (HRQoL) in a low-income community in Florida. A community-based participatory needs assessment was conducted from November 2013 to March 2014 with 201 residents of Tampa, Florida, USA. HRQoL was measured by an excessive number of unhealthy days experienced during the previous 30-day window. Mediation analyses for dichotomous outcomes were conducted with logistic regression. Bootstrapped confidence intervals were generated for both total and specific indirect effects. Most participants reported 'good to excellent health' (76%) and about a fourth reported 'fair to poor health' (24%). The mean of total unhealthy days was 9 days per month (SD ± 10.5). Controlling for demographic and neighborhood covariates, excessive unhealthy days was associated with ACE (AOR = 1.23; 95% CI: 1.06, 1.43), perceived stress (AOR = 1.07; 95% CI: 1.03, 1.10), and sleep disturbance (AOR = 8.86; 3.61, 21.77). Mediated effects were significant for stress (β = 0.08) and sleep disturbances (β = 0.11) as they related to the relationship between ACE and excessive unhealthy days. ACE is linked to adult HRQoL. Stress and sleep disturbances may represent later consequences of childhood adversity that modulate adult quality of life.

  15. Relative Biological Effectiveness and Peripheral Damage of Antiproton Annihilation

    CERN Multimedia

    Kavanagh, J N; Kaiser, F; Tegami, S; Schettino, G; Kovacevic, S; Hajdukovic, D; Knudsen, H; Currell, F J; Toelli, H T; Doser, M; Holzscheiter, M; Herrmann, R; Timson, D J; Alsner, J; Landua, R; Comor, J; Moller, S P; Beyer, G

    2002-01-01

    The use of ions to deliver radiation to a body for therapeutic purposes has the potential to be significant improvement over the use of low linear energy transfer (LET) radiation because of the improved energy deposition profile and the enhanced biological effects of ions relative to photons. Proton therapy centers exist and are being used to treat patients. In addition, the initial use of heavy ions such as carbon is promising to the point that new treatment facilities are planned. Just as with protons or heavy ions, antiprotons can be used to deliver radiation to the body in a controlled way; however antiprotons will exhibit additional energy deposition due to annihilation of the antiprotons within the body. The slowing down of antiprotons in matter is similar to that of protons except at the very end of the range beyond the Bragg peak. Gray and Kalogeropoulos estimated the additional energy deposited by heavy nuclear fragments within a few millimeters of the annihilation vertex to be approximately 30 MeV (...

  16. Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

    Science.gov (United States)

    Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

    2017-05-01

    Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Adverse effects of automobiles related PB/sup 2+/ pollution on photosynthetic attributes and water relations of roadside vegetation

    International Nuclear Information System (INIS)

    Ahmad, I.; Hussain, M.; Hameed, M.; Ahmad, R.

    2018-01-01

    This research was designed for the phyto-monitoring of Pb2+ pollution emitted from automobiles running along Motorway (M-2) and G.T. road and its effects on photosynthetic attributes and water relations of selected plant species growing along these roads. The data were collected from specified sites at different time intervals during all four seasons of the year. The results revealed significantly (p<0.05) higher Pb2+ content plant leaves growing in the vicinity of roadside (0 m distance) as compared to plant leaves collected from 50 m distance (Control) along both roads (M-2 and G.T. road). The leaves of Nerium oleander (2.45 mg kg-1 dry wt.) collected from M-2 trapped the higher amount of Pb2+ (p<0.001) at Kalar Kahar in Summer and Calotropis procera (2.78 mg kg-1 dry wt.) had the highest (p<0.05) Pb2+ deposition at Bahyria Town during summer. Photosynthetic rate, transpiration rate and stomatal conductance decreased significantly (p<0.01) in plants along roadsides; whereas, inconsistent results in water use efficiency were perceived in plants at 0 m distance as compared to those collected from 50 m distance. These outcomes are important to identify the existence of roadside vehicular pollutants on plants and to its ecological hazards. (author)

  18. Relative biological effectiveness (RBE) of proton beams in radiotherapy

    International Nuclear Information System (INIS)

    Calugaru, V.

    2011-01-01

    Treatment planning in proton therapy uses a generic value for the Relative Biological Efficiency (RBE) of 1.1 relative to 60 Co gamma-rays throughout the Spread Out Bragg Peak (SOBP). We have studied the variation of the RBE at three positions in the SOBP of the 76 and 201 MeV proton beams used for cancer treatment at the Institut Curie Proton Therapy in Orsay (ICPO) in two human tumor cell lines using clonogenic cell death and the incidence of DNA double-strand breaks (DSB) as measured by pulse-field gel electrophoresis without and with endonuclease treatment to reveal clustered lesions as endpoints.The RBE for induced cell killing by the 76 MeV beam increased with depth in the SOBP. However for the 201 MeV protons it was close to that for 137 Cs gamma-rays and did not vary significantly. The incidence of DSBs and clustered lesions was higher for protons than for 137 Cs g-rays, but did not depend on the proton energy or the position in the SOBP. In the second part of our work, we have shown using cell clones made deficient for known repair genes by stable or transient shRNA transfection, that the D-NHEJ pathway determine the response to protons. The response of DNA damages created in the distal part of the 76 MeV SOBP suggests that those damages belong to the class of DNA 'complex lesions' (LMDS). It also appears that the particle fluence is a major determinant of the outcome of treatment in the distal part of the SOBP. (author)

  19. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  20. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  1. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-02

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Immunoregulation, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics...

  2. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. The...

  3. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-04-05

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends to...

  4. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-22

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research...

  5. Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression.

    Science.gov (United States)

    Chung, Steve; Williams, Betsy; Dobrinsky, Cindy; Patten, Anna; Yang, Haichen; Laurenza, Antonio

    2017-10-01

    In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Adverse events related to gastrointestinal endoscopic procedures in pediatric patients under anesthesia care and a predictive risk model (AEGEP Study).

    Science.gov (United States)

    Ariza, F; Montilla-Coral, D; Franco, O; González, L F; Lozano, L C; Torres, A M; Jordán, J; Blanco, L F; Suárez, L; Cruz, G; Cepeda, M

    2014-01-01

    Multiple studies have analyzed perioperative factors related to adverse events (AEs) in children who require gastrointestinal endoscopic procedures (GEP) in settings where deep sedation is the preferred anesthetic technique over general anesthesia (GA) but not for the opposite case. We reviewed our anesthesia institutional database, seeking children less than 12 years who underwent GEP over a 5-year period. A logistic regression was used to determine significant associations between preoperative conditions, characteristics of the procedure, airway management, anesthetic approaches and the presence of serious and non-serious AEs. GA was preferred over deep sedation [77.8% vs. 22.2% in 2178 GEP under anesthesia care (n=1742)]. We found 96 AEs reported in 77 patients, including hypoxemia (1.82%), bronchospasm (1.14%) and laryngospasm (0.91%) as the most frequent. There were 2 cases of severe bradycardia related to laryngospasm/hypoxemia and a case of aspiration resulting in unplanned hospitalization, but there were no cases of intra- or postoperative deaths. Final predictive model for perioperative AEs included age risk factors and ventilation by facial mask as a protector against these events (prisk factors for AEs in these patients. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  7. Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials.

    Science.gov (United States)

    Cao, Meihui; Li, Feifei; Wang, Yue; Zhang, Jingdong

    2017-12-01

    Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm). Data on SAEs and FAEs were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% confidence intervals (CIs). A total of four phase 3 RCTs involving 1736 cancer patients met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with regorafenib were 0.23 (95%CI, 0.05-0.40) and 0.02 (95%CI, 0.01-0.03), respectively. Compared with control, the summary RR of developing a regorafenib-related SAE was 1.60 (95%CI, 0.95-2.68, P=0.07), the summary RR of developing a regorafenib-related FAE was 1.71 (95%CI, 0.69-4.24, P=0.25). No evidence was found for the association between regorafenib and higher risk of SAEs and FAEs. This association varied significantly with cancer types (P=0.02) for SAEs but no evidence of heterogeneity was found for FAEs. This meta-analysis demonstrates no evidence for the association between regorafenib and higher risk of SAEs and FAEs. This analysis will be important when considering the trade-off of regorafenib treatment during clinical decision-making.

  8. Anticipating demand for emergency health services due to medication-related adverse events after rapid mass prophylaxis campaigns.

    Science.gov (United States)

    Hupert, Nathaniel; Wattson, Daniel; Cuomo, Jason; Benson, Samuel

    2007-03-01

    Mass prophylaxis against infectious disease outbreaks carries the risk of medication-related adverse events (MRAEs). The authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable MRAEs. The authors created a spreadsheet-based computer model that calculates scenario-specific predicted daily MRAE rates from user inputs by applying a probability distribution to the reported timing of MRAEs. A hypothetical two- to ten-day prophylaxis campaign for one million people using recent data from both smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled. The length of a mass prophylaxis campaign plays an important role in determining the subsequent intensity in emergency services utilization due to real or suspected adverse events. A two-day smallpox vaccination scenario would produce an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at 5,246 health care encounters six days after the start of the campaign; in contrast, a ten-day campaign would lead to 41% lower peak surge, with a maximum of 3,106 encounters on the busiest day, ten days after initiation of the campaign. MRAEs with longer lead times, such as those associated with anthrax chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124 out of an estimated 1,400 hospitalizations on day 20 after a two-day campaign versus 103 on day 24 after a ten-day campaign). The duration of a mass prophylaxis campaign may have a substantial impact on the timing and peak number of clinically significant MRAEs, with very short campaigns overwhelming existing emergency department (ED) capacity to treat real or suspected medication-related injuries. While better reporting of both incidence and timing of MRAEs in future prophylaxis campaigns should improve the application of this model to community-based emergency preparedness planning, these results highlight the need

  9. Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.

    Science.gov (United States)

    Hernández, M Victoria; Sanmartí, Raimon; Cañete, Juan D; Descalzo, Miguel A; Alsina, Mercè; Carmona, Loreto; Gomez-Reino, Juan J

    2013-12-01

    To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases. Copyright © 2013 by the American College of Rheumatology.

  10. Current Diagnosis and Management of Immune Related Adverse Events (irAEs Induced by Immune Checkpoint Inhibitor Therapy

    Directory of Open Access Journals (Sweden)

    Vivek Kumar

    2017-02-01

    Full Text Available The indications of immune checkpoint inhibitors (ICIs are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs. The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4 and programmed cell death protein 1 (PD-1/PD-L1 antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.

  11. Systems Biology for Mapping Genotype-Phenotype Relations in Yeast

    KAUST Repository

    Nielsen, Jens

    2016-01-01

    . Besides its wide industrial use, S. cerevisiae serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. Among these genome-scale metabolic models have shown to be most successful as they easy

  12. MILK KEFIR: COMPOSITION, MICROBIAL CULTURES, BIOLOGICAL ACTIVITIES AND RELATED PRODUCTS

    Directory of Open Access Journals (Sweden)

    Maria Rosa Prado

    2015-10-01

    Full Text Available In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

  13. Milk kefir: composition, microbial cultures, biological activities, and related products.

    Science.gov (United States)

    Prado, Maria R; Blandón, Lina Marcela; Vandenberghe, Luciana P S; Rodrigues, Cristine; Castro, Guillermo R; Thomaz-Soccol, Vanete; Soccol, Carlos R

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir's exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir's microflora and the importance of kefiran as a beneficial health substance.

  14. Cell Biology of Chromerids: Autotrophic Relatives to Apicomplexan Parasites

    Czech Academy of Sciences Publication Activity Database

    Oborník, Miroslav; Lukeš, Julius

    2013-01-01

    Roč. 306, č. 2013 (2013), s. 333-369 ISSN 1937-6448 R&D Projects: GA ČR GBP505/12/G112 Institutional support: RVO:60077344 Keywords : long-branch attraction * Plasmodium falciparum * Toxoplasma gondii * phylogenetic analysis * extrachromosomal DNA * sterol composition * ribosomal RNA * life cycle * phtotosynthetic alveolata Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.522, year: 2013

  15. Systems Biology for Mapping Genotype-Phenotype Relations in Yeast

    KAUST Repository

    Nielsen, Jens

    2016-01-25

    The yeast Saccharomyces cerevisiae is widely used for production of fuels, chemicals, pharmaceuticals and materials. Through metabolic engineering of this yeast a number of novel new industrial processes have been developed over the last 10 years. Besides its wide industrial use, S. cerevisiae serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. Among these genome-scale metabolic models have shown to be most successful as they easy integrate with omics data and at the same time have been shown to have excellent predictive power. Despite our extensive knowledge of yeast metabolism and its regulation we are still facing challenges when we want to engineer complex traits, such as improved tolerance to toxic metabolites like butanol and elevated temperatures or when we want to engineer the highly complex protein secretory pathway. In this presentation it will be demonstrated how we can combine directed evolution with systems biology analysis to identify novel targets for rational design-build-test of yeast strains that have improved phenotypic properties. In this lecture an overview of systems biology of yeast will be presented together with examples of how genome-scale metabolic modeling can be used for prediction of cellular growth at different conditions. Examples will also be given on how adaptive laboratory evolution can be used for identifying targets for improving tolerance towards butanol, increased temperature and low pH and for improving secretion of heterologous proteins.

  16. Cytogenetic measurements of the relative biological effectiveness of tritium

    International Nuclear Information System (INIS)

    Chopra, C.; Heddle, J.A.

    1988-10-01

    Chromosome aberrations in peripheral blood lymphocytes, which are used to estimate radiation dose biologically, were induced by tritium 1.14 times as effectively as X-rays (95% confidence limits: 0.8 - 1.5). Chromosome translocations in spermatogonia, which are one component of genetic risk, were induced by tritium 1.21 times as effectively as X-rays (95% confidence limits: 0.8 -1.9). All experimental measurements were made in CBA/H mice injected with tritiated water or exposed to X-rays at a comparable dose rate

  17. Adverse effects and complications related to the use of barium sulphate contrast media for radiological examinations of the gastrointestinal tract - a literature review

    International Nuclear Information System (INIS)

    Periard, M.A.

    2003-01-01

    Barium sulphate is considered a safe and efficacious contrast medium that is routinely used for radiologic examinations of the gastrointestinal tract. Although the examinations rarely result in complications, the technique is moderately invasive and not entirely innocuous. Complications resulting from the procedures, and adverse reactions from the barium itself, have ranged from mild to severe and in rare instances have led to patient death. This paper reviews the clinical application, biological requirements and clinical properties of barium sulphate contrast media used in diagnostic x-ray imaging. It also outlines the risk factors and associated adverse reactions and complications involved with the use of barium sulphate, and presents documented cases where iatrogenic injuries have resulted. (author)

  18. Latino children’s autonomic nervous system reactivity moderates the relations between cumulative socioeconomic adversity in the first five years and externalizing behavior problems at seven years

    Directory of Open Access Journals (Sweden)

    Abbey Alkon

    2016-05-01

    Full Text Available Background: Thirty-seven percent of Hispanic and Latino children under 5 years of age are living in poverty in the United States. Children growing up under conditions of cumulative adversity are at much greater risk for compromised psychosocial adjustment with long-lasting ramifications for mental and physical health. This study assessed whether the relations between adversity early in life and later externalizing behaviors was moderated by children’s autonomic nervous system (ANS reactivity for immigrant, poor, MexicanAmerican children. Methods: A cumulative socioeconomic adversity index of children’s exposure to poverty, father’s absence, household crowding, mothers speaking Spanish, and poor housing condition at 6 months and 1, 3.5, and 5 years of age was calculated. At 5 years, ANS profiles during resting and social- and emotion-evoking challenges were calculated as combined parasympathetic and sympathetic difference scores. At 7 years, parents assessed children’s externalizing behavior problems. Results: Multiple regression models (n=220 showed that the relations between cumulative socioeconomic adversity and externalizing behaviors were moderated by children’s ANS profiles of coactivation during a social, not emotion-evoking, challenge, controlling for relevant covariates. Conclusions: Children living in adverse conditions early in life with specific psychobiologic responses to social challenges may be at risk for developing externalizing behavior problems later in life.

  19. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-07-18

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... consideration of the appropriateness of cell lines derived from human tumors for vaccine manufacture. FDA...

  20. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-28

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... vaccines for a post-exposure prophylaxis indication using the animal rule. On November 17, 2010, the...

  1. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide...) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On November 15, 2012, the committee will meet...

  2. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-03-14

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Polysaccharides, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review...

  3. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-19

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2010 - 2011 influenza season. FDA intends to make background material available to...

  4. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-09-07

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Laboratory of Method Development, Division of Viral Products, Office of Vaccines Research and Review, Center...

  5. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-01-20

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... the influenza virus vaccine for the 2011-2012 influenza season. The committee will also hear an update...

  6. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2013- 2014 influenza season. FDA intends to make background material available to...

  7. Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome

    DEFF Research Database (Denmark)

    Sandset, Else C; Murray, Gordon D; Bath, Philip M W

    2012-01-01

    The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome....

  8. Speciation needs in relation with environmental and biological purposes

    International Nuclear Information System (INIS)

    Moulin, V.; Ansoborlo, E.; Bion, L.; Doizi, D.; Moulin, C.; Cote, G.; Madic, C.; Van Der Lee, J.

    2004-01-01

    Radionuclides can occur in the environment either through chronic releases of nuclear facilities, or due to incidents or accidents. In order to study their behaviour in the environment (migration, retention, transfer, and in human organisms (metabolism, retention, excretion), it is of prime importance to know their solution chemistry, and more particularly thermodynamic constants, which will allow to determine their speciation. In fact, speciation governs the migration, the bioavailability and the toxicity of elements. Moreover, this knowledge is also of great interest for decorporation or decontamination purposes. In this framework, a CEA working group on speciation has been created in order to share data both on thermodynamic constants and on speciation analytical methods, interesting chemists, environmentalists and biologists. It has been focused, in a first time, on actinides, namely Th, U, Pu, Am, Np, taking into account their most important oxidation states occurring in environmental or biological environments: Th(IV), U(IV, VI), Pu(III, IV, VI), Am(III), Np(IV, V). A particular attention was devoted to the choice of ligands (inorganic and organic) for being the most representative of environmental and biological media. The thermodynamic database used is BASSIST for Base Applied to Speciation in Solution and at Interfaces and Solubility (developed by CEA), in interaction with the code JCHESS. Different examples will be then presented on the selection of data (thermodynamic constants, ligands of interest) through benchmark exercises (case of U(VI), Am(III), Pu(IV)) which will show the lacks or weakness of knowledge. Speciation diagrams will support these discussions. Moreover, analytical methods to determine thermodynamic constants or direct speciation will also be presented and discussed. (author)

  9. Prevalence of Topical Corticosteroids Related Adverse Drug Events and Associated Factors in Selected Community Pharmacies and Cosmetic Shops of Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Mahlet Tsegaye

    2018-03-01

    Conclusion: Majority of the topical corticosteroids were obtained without prescription for the purpose of beautification rather than treatment. A higher proportion of cosmetic users reported to have experienced at least one adverse event. There needs to consider safety concerns related to topical corticosteroids use in the city.

  10. Relative biological efficiency of 592 MeV protons. Analysis of the biological effect of secondary radiation

    International Nuclear Information System (INIS)

    Legeay, G.; Baarli, J.

    1968-01-01

    The relative biological efficiency (RBE) of high energy protons is of importance because of their effects in the field of radioprotection around large accelerators and during space-flights. The nature of the interactions between 592 MeV protons and biological tissues makes it necessary to take into consideration the contribution of secondary radiation to the biological effect. Since it is not possible to obtain from a synchrotron a beam having a sufficiently large cross-section to irradiate large animals, one has to resort to certain devices concerning the mode of exposure when small laboratory animals are used. By irradiating rats individually and in groups, and by using the lethal test as a function of time, the authors show that the value of the RBE is different for animals of the same species having the same biological parameters. Thus there appears an increase in the biological effect due to secondary radiation produced in nuclear cascades which develop in a large volume, for example that of a human being. (author) [fr

  11. Social network size relates to developmental neural sensitivity to biological motion

    Directory of Open Access Journals (Sweden)

    L.A. Kirby

    2018-04-01

    Full Text Available The ability to perceive others’ actions and goals from human motion (i.e., biological motion perception is a critical component of social perception and may be linked to the development of real-world social relationships. Adult research demonstrates two key nodes of the brain’s biological motion perception system—amygdala and posterior superior temporal sulcus (pSTS—are linked to variability in social network properties. The relation between social perception and social network properties, however, has not yet been investigated in middle childhood—a time when individual differences in social experiences and social perception are growing. The aims of this study were to (1 replicate past work showing amygdala and pSTS sensitivity to biological motion in middle childhood; (2 examine age-related changes in the neural sensitivity for biological motion, and (3 determine whether neural sensitivity for biological motion relates to social network characteristics in children. Consistent with past work, we demonstrate a significant relation between social network size and neural sensitivity for biological motion in left pSTS, but do not find age-related change in biological motion perception. This finding offers evidence for the interplay between real-world social experiences and functional brain development and has important implications for understanding disorders of atypical social experience. Keywords: Biological motion, Social networks, Middle childhood, Neural specialization, Brain-behavior relations, pSTS

  12. The reflection of life functional entailment and imminence in relational biology

    CERN Document Server

    Louie, A H

    2013-01-01

    A. H. Louie’s The Reflection of Life: Functional Entailment and Imminence in Relational Biology is a continuation of the exploratory journey in relational biology which began with his 2009 monograph More Than Life Itself: A Synthetic Continuation in Relational Biology. The theme of his first book was ‘What is life?’; the theme of this sequel is “How do two life forms interact?” Biology is a subject concerned with organization of relations. Relational biology is the approach that advocates ‘function dictates structure”, rather than ‘structure implies function’. It is mathematics decoded into biological realizations. The book demonstrates some of the powers of the approach of relational biology, and illustrates how pertinent problems in biology can be better addressed this way. In the first volume the theory was developed by using partially ordered sets, lattices, simulations, models, Aristotle’s four causes, graphs, categories, simple and complex systems, anticipatory systems, and metabolis...

  13. RANKING RELATIONS USING ANALOGIES IN BIOLOGICAL AND INFORMATION NETWORKS1

    Science.gov (United States)

    Silva, Ricardo; Heller, Katherine; Ghahramani, Zoubin; Airoldi, Edoardo M.

    2013-01-01

    Analogical reasoning depends fundamentally on the ability to learn and generalize about relations between objects. We develop an approach to relational learning which, given a set of pairs of objects S = {A(1) : B(1), A(2) : B(2), …, A(N) : B(N)}, measures how well other pairs A : B fit in with the set S. Our work addresses the following question: is the relation between objects A and B analogous to those relations found in S? Such questions are particularly relevant in information retrieval, where an investigator might want to search for analogous pairs of objects that match the query set of interest. There are many ways in which objects can be related, making the task of measuring analogies very challenging. Our approach combines a similarity measure on function spaces with Bayesian analysis to produce a ranking. It requires data containing features of the objects of interest and a link matrix specifying which relationships exist; no further attributes of such relationships are necessary. We illustrate the potential of our method on text analysis and information networks. An application on discovering functional interactions between pairs of proteins is discussed in detail, where we show that our approach can work in practice even if a small set of protein pairs is provided. PMID:24587838

  14. Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

    Science.gov (United States)

    Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

    2017-01-01

    The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

  15. Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior.

    Science.gov (United States)

    Tielbeek, Jorim J; Karlsson Linnér, Richard; Beers, Koko; Posthuma, Danielle; Popma, Arne; Polderman, Tinca J C

    2016-07-01

    Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Rooting depths of plants relative to biological and environmental factors

    International Nuclear Information System (INIS)

    Foxx, T.S.; Tierney, G.D.; Williams, J.M.

    1984-11-01

    In 1981 to 1982 an extensive bibliographic study was completed to document rooting depths of native plants in the United States. The data base presently contains 1034 citations with approximately 12,000 data elements. In this paper the data were analyzed for rooting depths as related to life form, soil type, geographical region, root type, family, root depth to shoot height ratios, and root depth to root lateral ratios. Average rooting depth and rooting frequencies were determined and related to present low-level waste site maintenance

  17. Relative biological effectiveness of 160 MeV protons. II. Biological data and their interpretation in terms of microdosimetry

    International Nuclear Information System (INIS)

    Hall, E.J.; Kellerer, A.M.; Rossi, H.H.; Lam, Y.M.P.

    1978-01-01

    The radiobiological effectiveness of 160 MeV protons was measured relative to 60 Co γ rays using Chinese hamster cells cultured in vitro. Separate experiments were performed with cells irradiated in suspension, or attached to plastic tissue culture flasks. Proton irradiations were performed in the incident plateau of the depth dose profile and with the Bragg peak spread out to cover 10 cm. In all cases the relative biological effectiveness (RBE) for protons relative to gamma rays was 1.2 for doses in excess of about 200 rad. The attached cell experiments indicate an increasing RBE at low doses, which is consistent with the microdosimetric measurements

  18. Event-related potentials, cognition, and behavior: a biological approach.

    Science.gov (United States)

    Kotchoubey, Boris

    2006-01-01

    The prevailing cognitive-psychological accounts of event-related brain potentials (ERPs) assume that ERP components manifest information processing operations leading from stimulus to response. Since this view encounters numerous difficulties already analyzed in previous studies, an alternative view is presented here that regards cortical control of behavior as a repetitive sensorimotor cycle consisting of two phases: (i) feedforward anticipation and (ii) feedback cortical performance. This view allows us to interpret in an integrative manner numerous data obtained from very different domains of ERP studies: from biophysics of ERP waves to their relationship to the processing of language, in which verbal behavior is viewed as likewise controlled by the same two basic control processes: feedforward (hypothesis building) and feedback (hypothesis checking). The proposed approach is intentionally simplified, explaining numerous effects on the basis of few assumptions and relating several levels of analysis: neurophysiology, macroelectrical processes (i.e. ERPs), cognition and behavior. It can, therefore, be regarded as a first approximation to a general theory of ERPs.

  19. Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

  20. Work-related asthma, financial barriers to asthma care, and adverse asthma outcomes: asthma call-back survey, 37 states and District of Columbia, 2006 to 2008.

    Science.gov (United States)

    Knoeller, Gretchen E; Mazurek, Jacek M; Moorman, Jeanne E

    2011-12-01

    Proper asthma management and control depend on patients having affordable access to healthcare yet financial barriers to asthma care are common. To examine associations of work-related asthma (WRA) with financial barriers to asthma care and adverse asthma outcomes. Cross-sectional, random-digit-dial survey conducted in 37 states and District of Columbia. A total of 27,927 ever-employed adults aged ≥18 years with current asthma. Prevalence ratios (PR) for the associations of WRA with financial barriers to asthma care and of WRA with adverse asthma outcomes stratified by financial barriers. Persons with WRA were significantly more likely than those with non-WRA to have at least 1 financial barrier to asthma care [PR, 1.66; 95% confidence interval (CI), 1.43-1.92]. Individuals with WRA were more likely to experience adverse asthma outcomes such as asthma attack (PR, 1.31; 95% CI, 1.22-1.40), urgent treatment for worsening asthma (PR, 1.57; 95% CI, 1.39-1.78), asthma-related emergency room visit (PR, 1.69; 95% CI, 1.41-2.03), and very poorly controlled asthma (PR, 1.54; 95% CI: 1.36-1.75). After stratifying for financial barriers to asthma care, the associations did not change. Financial barriers to asthma care should be considered in asthma management, and individuals with WRA are more likely to experience financial barriers. However, individuals with WRA are more likely to experience adverse asthma outcomes than individuals with non-WRA, regardless of financial barriers. Additional studies are needed to identify medical, behavioral, occupational, or environmental factors associated with adverse asthma outcomes among individuals with WRA.

  1. Energy drink exposures reported to Texas poison centers: Analysis of adverse incidents in relation to total sales, 2010-2014.

    Science.gov (United States)

    Borron, Stephen W; Watts, Susan H; Herrera, Jessica; Larson, Joshua; Baeza, Salvador; Kingston, Richard L

    2018-05-21

    The ill-defined term "energy drink" includes a disparate group of products (beverages, shots, concentrates, and workout powders) having large differences in caffeine content and concentration and intended use. Hence, inaccurate conclusions may be drawn when describing adverse events associated with "energy drinks". The FDA is considering new regulation of these products but product specificity is needed to evaluate safety. To help address this, we queried Texas Poison Center Network data for single substance exposures to "energy drinks" from 2010 to 2014, then analyzed adverse events by product type. We specifically compared energy beverage exposures with sales data for the same time period to evaluate the safety profile of this category of energy drinks. Among 855 documented "energy drink" exposures, poison center-determined outcome severity revealed 291 with no/minimal effects, 417 judged nontoxic or minor/not followed, 64 moderate and 4 major effects, and no deaths. Serious complications included 2 seizures and 1 episode of ventricular tachycardia. Outcome severity by category for beverages: 11 moderate/1 major effects (none in children energy drinks". Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Differences in Work-Related Adverse Events by Sex and Industry in Cases Involving Compensation for Mental Disorders and Suicide in Japan From 2010 to 2014.

    Science.gov (United States)

    Yamauchi, Takashi; Sasaki, Takeshi; Yoshikawa, Toru; Matsumoto, Shun; Takahashi, Masaya; Suka, Machi; Yanagisawa, Hiroyuki

    2018-04-01

    This study aimed to clarify whether work-related adverse events in cases involving compensation for mental disorders and suicide differ by sex and industry using a database containing all relevant cases reported from 2010 to 2014 in Japan. A total of 1362 eligible cases involving compensation for mental disorders (422 females and 940 males) were analyzed. Among males, 55.7% of cases were attributed to "long working hours." In both sexes, the frequencies of cases attributed to "long working hours" and other events differed significantly by industry. Among cases involving compensation for suicide, 71.4% were attributed to "long working hours." The frequency distribution of work-related adverse events differed significantly by sex and industry. These differences should be taken into consideration in the development of industry-specific preventive measures for occupational mental disorders.

  3. Drinking motives moderate the impact of pre-drinking on heavy drinking on a given evening and related adverse consequences-an event-level study

    OpenAIRE

    Kuntsche Emmanuel; Labhart Florian

    2013-01-01

    Aims: To test whether (i) drinking motives predict the frequency of pre drinking (i.e. alcohol consumption before going out); (ii) drinking motives predict HDGE (heavy drinking on a given evening: 4+ for women 5+ for men) and related adverse consequences (hangover injuries blackouts etc.) even when pre drinking is accounted for and (iii) drinking motives moderate the impact of pre drinking on HDGE and consequences. Design: Using the internet based cellphone optimized assessment technique (ICA...

  4. The role of general cognitive ability in moderating the relation of adverse life events to emotional and behavioural problems.

    Science.gov (United States)

    Flouri, Eirini; Mavroveli, Stella; Panourgia, Constantina

    2013-02-01

    Previous studies have established the role of various measures of cognitive functioning in dampening the association between adverse life events ('life stress') and adolescents' emotional and behavioural problems. However, it is not yet clear if general cognitive ability ('intelligence') is a protective factor. In this study of 1,175 10- to 19-year-olds in five secondary schools in England, we explored this issue. We found that even after controlling for sex, age, family poverty, and special educational needs, the association of life stress with emotional, hyperactivity, and conduct problems was significant. General cognitive ability moderated the association between life stress and conduct problems; among adolescents with higher than average general cognitive ability, the association between life stress and conduct problems was non-significant. © 2012 The British Psychological Society.

  5. [Adverse effects of oxcarbazepine].

    Science.gov (United States)

    Fang, Shu; Gong, Zhi-Cheng

    2015-04-01

    Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

  6. Immigration, transition into adult life and social adversity in relation to psychological distress and suicide attempts among young adults.

    Directory of Open Access Journals (Sweden)

    Kyriaki Kosidou

    Full Text Available BACKGROUND: The increasing incidence of mental health problems among young people is a major concern in many Western countries. The causal mechanisms underlying these trends are not well established, but factors influenced by current societal changes ought to be implicated. Such factors include immigration and social adversity as well as the timing of taking on adult social roles (e.g. gainful employment, parenthood and own housing tenure. We therefore examined relationships between these factors and the risks of psychological distress as well as suicide attempts in young adults, with a focus on gender differences. METHODS: We conducted a population-based study including 10,081 individuals aged 18-29, recruited in 2002 and 2006 in Stockholm, Sweden. Data were collected by record linkage and questionnaires. RESULTS: Non-European immigrants had an increased risk of distress, and female non-European immigrants had a markedly higher risk of suicide attempts. Both early parenthood (≤ 24 years and not being a parent, being a student and the lack of own housing tenure were associated with distress, but only in women. In both sexes, financial strain was associated with the increased risk of distress and suicide attempts, while unemployment was only associated with distress. CONCLUSIONS: Immigration from outside Europe and social adversity are associated with mental health problems in young adults, especially females. Postponed transition into adulthood is associated with poor mental health in young women. These factors are influenced by current societal changes, and may have contributed to the increasing incidence of mental health problems among young people in Western countries.

  7. Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

    Science.gov (United States)

    Hall, Victoria; Johnson, Douglas; Torresi, Joseph

    2018-01-01

    Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

  8. Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks

    Science.gov (United States)

    2018-01-01

    Signaling pathways represent parts of the global biological molecular network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce analytical “reduced Google matrix” method for the analysis of biological network structure. The method allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes. We investigate how the structure of hidden causal relations can be reprogrammed as a result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks in a computationally efficient way. PMID:29370181

  9. The relation between an adverse psychological and social environment in childhood and the development of adult obesity: a systematic literature review

    DEFF Research Database (Denmark)

    Vámosi, M; Heitmann, B L; Kyvik, K O

    2010-01-01

    The prevalence of obesity is on a global-wide increase, but still the aetiology of adult obesity is poorly understood. It has been shown that overweight children suffer from adverse psychological events, but less is known about the potential effects of adverse psychological factors among normal...... weight children for later development of obesity. The purpose of this study was to systematically review current literature on associations between psychological factors in childhood and development of obesity in adulthood. A systematic search was conducted in three electronic databases MEDLINE...... (silverplatter 1977-2008), PsycINFO (1972-2008) and PsycINFO Weekly (week 1 January 2007-week 3 July 2008) to identify studies of interest. Six prospective and two retrospective studies were identified. Psychosocial factors related to adult obesity were lack of childhood care, abuse and childhood anxiety...

  10. Quantifying risk: the role of absolute and relative measures in interpreting risk of adverse reactions from product labels of antipsychotic medications.

    Science.gov (United States)

    Citrome, Leslie

    2009-09-01

    Pharmaceutical product labeling as approved by regulatory agencies include statements of adverse event risk. Product labels include descriptive statements such as whether events are uncommon or rare, as well as percentage occurrence for more common events. In addition tables are provided with the frequencies of the latter events for both product and placebo as observed in clinical trials. Competing products are not mentioned in a specific drug's product labeling but indirect comparisons can be made using the corresponding label information for the alternate product. Two types of tools are easily used for this purpose: absolute measures such as number needed to harm (NNH), and relative measures such as relative risk increase (RRI). The calculations for both of these types of quantitative measures are presented using as examples the oral first-line second-generation antipsychotic medications. Among three sample outcomes selected a priori, akathisia, weight gain, and discontinuation from a clinical trial because of an adverse reaction, there appears to be differences among the different antipsychotics versus placebo. Aripiprazole was associated with the highest risk for akathisia, particularly when used as adjunctive treatment of major depressive disorder (NNH 5, 95% CI 4-7; RRI 525%, 95% CI 267%-964%). Although insufficient information was available in product labeling to calculate the CI, olanzapine was associated with the highest risk for weight gain of at least 7% from baseline (NNH 6, RRI 640% for adults; NNH 4, RRI 314% for adolescents), and quetiapine for the indication of bipolar depression was associated with the highest risk of discontinuation from a clinical trial because of an adverse reaction (NNH 8, RRI 265% for 600 mg/d; NNH 15, RRI 137% for 300 mg/d). In conclusion, with certain limitations, it is possible for the clinician to extract information from medication product labeling regarding the frequency with which certain adverse reactions can be

  11. Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study.

    Science.gov (United States)

    Courjon, J; Pulcini, C; Cua, E; Risso, K; Guillouet, F; Bernard, E; Roger, P-M

    2013-12-01

    Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P antibiotic when several options are possible.

  12. Indoor Exposure and Adverse Birth Outcomes Related to Fetal Growth, Miscarriage and Prematurity—A Systematic Review

    Directory of Open Access Journals (Sweden)

    Evridiki Patelarou

    2014-06-01

    Full Text Available The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in “westernized” countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed.

  13. The Adverse Health Effects of Shift Work in Relation to Risk of Illness/Disease: A Review

    Directory of Open Access Journals (Sweden)

    Shariat A.

    2015-05-01

    Full Text Available Biological rhythm of sleeping is a natural disparity in an organism corresponding to and in reply to cyclic environmental changes, such as daylight hours and hours of darkness or elevated and low down flow. There is some evidence, based upon epidemiological studies as well as studies upon smaller groups of subjects, that individuals who work during the night and sleep during the daytime show cognitive impairment at work, have poorer and fragmented daytime sleep, and have increased risks of developing a wide range of social, psychological, physiological and medical impairments and disorders. Circadian rhythms are one of the most important effective factors on the physiological and physical performances of humans and disturbing this normal rhythm leads to different groups of diseases. The majority of investigations in biological rhythm demeanor vary noticeably in regards to the exact type of disease, population and protocols of sampling over the other outcomes or issues. We conducted a systematic review of [Science Direct, Pubmed, Scopus] to identify influence of different kinds of diseases among shift workers in response to abnormal rhythm of sleeping. The results of this review indicate that abnormal patterns of sleeping can lead to immunological issues, hypertension, metabolic syndrome, insomnia, cardiovascular disease, obesity and depression. It is vital for subsequent investigations to find a way to reduce negative effects (such as decreased amount of works’ time and altered diet without side effects to help them.

  14. Mineralogical characteristics of the silica polymorphs in relation to their biological activities

    Energy Technology Data Exchange (ETDEWEB)

    Guthrie, G.D. Jr. [Los Alamos National Lab., NM (United States); Heaney, P.J. [Princeton Univ., NJ (United States). Dept. of Geological and Geophysical Sciences

    1993-10-01

    Numerous aspects of minerals (including the silica polymorphs) can effect their biological activities. These include periodic structures, compositional variations, dissolution characteristics, surface properties, and particle size/shape. In order to understand mineral-induced pathogenesis in a mechanistic way, the links between these properties and biochemical processes must be elucidated. This paper presents some of the basic properties of the silica polymorphs that may relate to pathogenicity and mineralogical strategies for designing biological assays to evaluate these properties.

  15. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    Science.gov (United States)

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  16. I'm so tired: biological and genetic mechanisms of cancer-related fatigue

    NARCIS (Netherlands)

    Barsevick, Andrea; Frost, Marlene; Zwinderman, Aeilko; Hall, Per; Halyard, Michele; Abertnethy, Amy P.; Baas, Frank; Barsevick, Andrea M.; Bartels, Meike; Boomsma, Dorret I.; Chauhan, Cynthia; Cleeland, Charles S.; Dueck, Amylou C.; Frost, Marlene H.; Halyard, Michele Y.; Klepstad, Pål; Martin, Nicholas G.; Miaskowski, Christine; Mosing, Miriam; Movsas, Benjamin; van Noorden, Cornelis J. F.; Patrick, Donald L.; Pedersen, Nancy L.; Ropka, Mary E.; Shi, Quiling; Shinozaki, Gen; Singh, Jasvinder A.; Sloan, Jeff A.; Sprangers, Mirjam A. G.; Veenhoven, Ruut; Yang, Ping

    2010-01-01

    Objective The goal of this paper is to discuss cancer-related fatigue (CRF) and address issues related to the investigation into potential biological and genetic causal mechanisms. The objectives are to: (1) describe CRF as a component of quality of life (QOL); (2) address measurement issues that

  17. The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

    Science.gov (United States)

    Hirai, Masahiro; Hiraki, Kazuo

    2006-01-01

    We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

  18. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    International Nuclear Information System (INIS)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation

  19. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    Energy Technology Data Exchange (ETDEWEB)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

  20. Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period.

    Science.gov (United States)

    Shimada, Yutaka; Fujimoto, Makoto; Nogami, Tatsuya; Watari, Hidetoshi; Kitahara, Hideyuki; Misawa, Hiroki; Kimbara, Yoshiyuki

    2017-12-21

    Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety. We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events. Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was

  1. Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

    NARCIS (Netherlands)

    Hazelbag, Christijan M; Klungel, Olaf H; van Staa, Tjeerd P; de Boer, Anthonius; Groenwold, Rolf H H

    PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

  2. Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events

    NARCIS (Netherlands)

    Hazelbag, Christijan M.; Klungel, Olaf H.; van Staa, Tjeerd P.; de Boer, Anthonius; Groenwold, Rolf H H

    2015-01-01

    PURPOSE: To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. METHODS: A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative

  3. Effect of threatening life experiences and adverse family relations in ulcerative colitis: analysis using structural equation modeling and comparison with Crohn's disease.

    Science.gov (United States)

    Slonim-Nevo, Vered; Sarid, Orly; Friger, Michael; Schwartz, Doron; Sergienko, Ruslan; Pereg, Avihu; Vardi, Hillel; Singer, Terri; Chernin, Elena; Greenberg, Dan; Odes, Shmuel

    2017-05-01

    We published that threatening life experiences and adverse family relations impact Crohn's disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC). Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE). Analysis included multiple linear and quantile regressions and structural equation modeling, comparing CD. UC patients (N=148, age 47.55±16.04 years, 50.6% women) had scores [median (interquartile range)] as follows: SCAAI, 2 (0.3-4.8); FAD, 1.8 (1.3-2.2); LTE, 1.0 (0-2.0); SF-36 Physical Health, 49.4 (36.8-55.1); SF-36 Mental Health, 45 (33.6-54.5); Brief Symptom Inventory-Global Severity Index (GSI), 0.5 (0.2-1.0). SIBDQ was 49.76±14.91. There were significant positive associations for LTE and SCAAI (25, 50, 75% quantiles), FAD and SF-36 Mental Health, FAD and LTE with GSI (50, 75, 90% quantiles), and ES with SF-36 and SIBDQ. The negative associations were as follows: LTE with SF-36 Physical/Mental Health, SIBDQ with FAD and LTE, ES with GSI (all quantiles), and P-SCCAI (75, 90% quantiles). In structural equation modeling analysis, LTE impacted ES negatively and ES impacted GSI negatively; LTE impacted GSI positively and GSI impacted P-SCCAI positively. In a split model, ES had a greater effect on GSI in UC than CD, whereas other path magnitudes were similar. Threatening life experiences, adverse family relations, and poor ES make UC patients less healthy both physically and mentally. The impact of ES is worse in UC than CD.

  4. Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in Older Inpatients: A Study Proposal.

    Science.gov (United States)

    Le Pogam, Marie-Annick; Quantin, Catherine; Reich, Oliver; Tuppin, Philippe; Fagot-Campagna, Anne; Paccaud, Fred; Peytremann-Bridevaux, Isabelle; Burnand, Bernard

    2017-05-11

    Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients. This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients. GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients' conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data

  5. Visual event-related potentials to biological motion stimuli in autism spectrum disorders

    Science.gov (United States)

    Bletsch, Anke; Krick, Christoph; Siniatchkin, Michael; Jarczok, Tomasz A.; Freitag, Christine M.; Bender, Stephan

    2014-01-01

    Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD. PMID:23887808

  6. Relational Databases: A Transparent Framework for Encouraging Biology Students to Think Informatically

    Science.gov (United States)

    Rice, Michael; Gladstone, William; Weir, Michael

    2004-01-01

    We discuss how relational databases constitute an ideal framework for representing and analyzing large-scale genomic data sets in biology. As a case study, we describe a Drosophila splice-site database that we recently developed at Wesleyan University for use in research and teaching. The database stores data about splice sites computed by a…

  7. Correlation of microdosimetric measurements with relative biological effectiveness from clinical experience for two neutron therapy beams

    International Nuclear Information System (INIS)

    Stinchcomb, T.G.; Kuchnir, F.T.; Myrianthopoulos, L.C.; Horton, J.L. Jr.; Roberts, W.K.

    1986-01-01

    Microdosimetric measurements were made for the neutron therapy beams at the University of Chicago and at the Cleveland Clinic with the same geometry and phantom material using the same tissue-equivalent spherical proportional counter and standard techniques. The energy deposition spectra (dose distributions in lineal energy) are compared for these beams and for their scattered components (direct beam blocked). The model of dual radiation action (DRA) of Kellerer and Rossi is employed to interpret these data in terms of biological effectiveness over this limited range of radiation qualities. The site-diameter parameter of the DRA theory is determined for the Cleveland beam by setting the biological effectiveness (relative to 60 Co gamma radiation) equal to the relative biological effectiveness value deduced from radiobiology experiments and clinical experience. The resulting value of this site-diameter parameter is then used to predict the biological effectiveness of the Chicago beam. The prediction agrees with the value deduced from radiobiology and clinical experience. The biological effectiveness of the scattered components of both beams is also estimated using the model

  8. The impact of traffic-related pollution and temperature on adverse birth outcomes in Madrid. An analysis of time series

    Directory of Open Access Journals (Sweden)

    Julio Díaz

    2016-12-01

    Full Text Available Preterm birth (< 37 weeks, low birth weight (< 2500 g and fetal mortality are perinatal morbi-mortality causes impacting public health, society and the economy. Their etiology is multifaceted. There is scientific evidence pointing to environmental variables being risk factors. The purpose of this study was to analyze and quantify the impact on a daily and a weekly basis of PM2.5, NO2 and O3 (μg/m3, noise levels (Leq, and temperature (°C on variables detrimental to health in Madrid from 2001 till 2009. Poisson regression models were prepared from an ecological study of time series, and the results were expressed in terms of the Relative Risk (RR. The environmental variables were included in previously identified explanatory delays. 298,705 births were analyzed: the average weekly prematurity was 7.5, the average low weight 6.9, and the average fetal mortality 3.7. In the case of preterm births, a relation with PM2.5 during the 2nd quarter of pregnancy [RR: 1.026 (1.018-1.034] and with Leq in the week prior to childbirth [RR: 1.020 (1.012-1.028] was detected. This impact was also noticeable in the daily results. In addition, heat waves also affect prematurity. With regard to low birth weight, noise levels had an impact throughout the pregnancy and the effect of NO2 during the 2nd quarter thereof. As for fetal mortality, the most significant effects were those of the three analyzed pollutants during the 2nd and 3rd quarters. The gestating population is a group that is particularly vulnerable to the analyzed environmental factors, so it should be taken into account in the existing prevention plans.

  9. Germline glutathione S-transferase variants in breast cancer: Relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy

    International Nuclear Information System (INIS)

    Edvardsen, Hege; Kristensen, Vessela N.; Grenaker Alnaes, Grethe Irene B.Sc.; Bohn, Mona; Erikstein, Bjorn; Helland, Aslaug; Borresen-Dale, Anne-Lise; Fossa, Sophie Dorothea

    2007-01-01

    Purpose: To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation-induced adverse effects after two fractionation patterns of adjuvant radiotherapy. Methods and Materials: The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy-induced side effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period). Results: None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation-induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant. Conclusion: The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy

  10. Antiretroviral therapy related adverse effects: Can sub-Saharan Africa cope with the new "test and treat" policy of the World Health Organization?

    Science.gov (United States)

    Nansseu, Jobert Richie N; Bigna, Jean Joel R

    2017-02-15

    Recent studies have shown that early antiretroviral therapy (ART) initiation results in significant HIV transmission reduction. This is the rationale behind the "test and treat" policy of the World Health Organization (WHO). Implementation of this policy will lead to an increased incidence of ART-related adverse effects, especially in sub-Saharan Africa (SSA). Is the region yet ready to cope with such a challenging issue? The introduction and widespread use of ART have drastically changed the natural history of HIV/AIDS, but exposure to ART leads to serious medication-related adverse effects mainly explained by mitochondrial toxicities, and the situation will get worse in the near future. Indeed, ART is associated with an increased risk of developing cardiovascular disease, lipodystrophy, prediabetes and overt diabetes, insulin resistance and hyperlactatemia/lactic acidosis. The prevalence of these disorders is already high in SSA, and the situation will be exacerbated by the implementation of the new WHO recommendations. Most SSA countries are characterized by (extreme) poverty, very weak health systems, inadequate and low quality of health services, inaccessibility to existing health facilities, lack of (qualified) health personnel, lack of adequate equipment, inaccessibility and unaffordability of medicines, and heavy workload in a context of a double burden of disease. Additionally, there is dearth of data on the incidence and predictive factors of ART-related adverse effects in SSA, to anticipate on strategies that should be put in place to prevent the occurrence of these conditions or properly estimate the upcoming burden and prepare an adequate response plan. These are required if we are to anticipate and effectively prevent this upcoming burden. While SSA would be the first region to experience the huge benefits of implementing the "test and treat" policy of the WHO, the region is not yet prepared to manage the consequential increased burden of ART-related

  11. Biological Maturity Status Strongly Intensifies the Relative Age Effect in Alpine Ski Racing.

    Directory of Open Access Journals (Sweden)

    Lisa Müller

    Full Text Available The relative age effect (RAE is a well-documented phenomenon in youth sports. This effect exists when the relative age quarter distribution of selected athletes shows a biased distribution with an over-representation of relatively older athletes. In alpine ski racing, it exists in all age categories (national youth levels up to World Cup. Studies so far could demonstrate that selected ski racers are relatively older, taller and heavier. It could be hypothesized that relatively younger athletes nearly only have a chance for selection if they are early maturing. However, surprisingly this influence of the biological maturity status on the RAE could not be proven, yet. Therefore, the aim of the present study was to investigate the influence of the biological maturity status on the RAE in dependence of the level of competition. The study investigated 372 elite youth ski racers: 234 provincial ski racers (P-SR; high level of competition and 137 national ski racers (N-SR; very high level of competition. Anthropometric characteristics were measured to calculate the age at peak height velocity (APHV as an indicator of the biological maturity status. A significant RAE was present among both P-SR and N-SR, with a larger effect size among the latter group. The N-SR significantly differed in APHV from the P-SR. The distribution of normal, early and late maturing athletes significantly differed from the expected normal distribution among the N-SR, not among the P-SR. Hardly any late maturing N-SR were present; 41.7% of the male and 34% of the female N-SR of the last relative age quarter were early maturing. These findings clearly demonstrate the significant influence of the biological maturity status on the selection process of youth alpine ski racing in dependence of the level of competition. Relatively younger athletes seem to have a chance of selection only if they are early maturing.

  12. Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?

    Science.gov (United States)

    Kanner, Andres M; Barry, John J; Gilliam, Frank; Hermann, Bruce; Meador, Kimford J

    2012-06-01

    To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)-related adverse events (AEs) in persons with epilepsy (PWE). The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory-II (BDI-II) scores >12 or the Centers of Epidemiologic Studies-Depression (CES-D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED-related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. Depressive and anxiety disorders worsen AED-related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  13. German National Proficiency Scales in Biology: Internal Structure, Relations to General Cognitive Abilities and Verbal Skills

    Science.gov (United States)

    KÖLLER, OLAF

    2016-01-01

    ABSTRACT National and international large‐scale assessments (LSA) have a major impact on educational systems, which raises fundamental questions about the validity of the measures regarding their internal structure and their relations to relevant covariates. Given its importance, research on the validity of instruments specifically developed for LSA is still sparse, especially in science and its subdomains biology, chemistry, and physics. However, policy decisions for the improvement of educational quality based on LSA can only be helpful if valid information on students’ achievement levels is provided. In the present study, the nature of the measurement instruments based on the German Educational Standards in Biology is examined. On the basis of data from 3,165 students in Grade 10, we present dimensional analyses and report the relationship between different subdimensions of biology literacy and cognitive covariates such as general cognitive abilities and verbal skills. A theory‐driven two‐dimensional model fitted the data best. Content knowledge and scientific inquiry, two subdimensions of biology literacy, are highly correlated and show differential correlational patterns to the covariates. We argue that the underlying structure of biology should be incorporated into curricula, teacher training and future assessments. PMID:27818532

  14. Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears.

    Science.gov (United States)

    Knott, Katrina K; Schenk, Patricia; Beyerlein, Susan; Boyd, Daryle; Ylitalo, Gina M; O'Hara, Todd M

    2011-11-01

    We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione peroxidase activity) and thyroid status (concentrations and ratios of thyroxine, T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among cohorts, and relationships to circulating concentrations of contaminants. Concentrations of total mercury (Hg) in whole blood were similar among cohorts (prime aged males and females, older animals, ages≥16 years, and young animals, ages 1-5 years; 48.44±35. 81; p=0.253). Concentrations of sum of seven polychlorinated biphenyls (∑PCB7) in whole blood were greater in females (with and without cubs, 26.44±25.82 ng/g ww) and young (26.81±10.67 ng/g ww) compared to males (8.88±5.76 ng/g ww, p0.08). Thyroid hormones were greater in females (solitary females and females with cubs) compared to males (ppolar bears (ppolar bears were more susceptible to changes in blood-based biomarkers of selenium and thyroid status than males. Further classifications of the physiologic states of polar bears and repeated measures of individuals over time are needed to accurately assess the biological impact of combined toxicant exposures. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Relational Analysis of High School Students' Cognitive Self-Regulated Learning Strategies and Conceptions of Learning Biology

    Science.gov (United States)

    Sadi, Özlem

    2017-01-01

    The purpose of this study was to analyze the relation between students' cognitive learning strategies and conceptions of learning biology. The two scales, "Cognitive Learning Strategies" and "Conceptions of Learning Biology", were revised and adapted to biology in order to measure the students' learning strategies and…

  16. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.

    Science.gov (United States)

    Brahmer, Julie R; Lacchetti, Christina; Schneider, Bryan J; Atkins, Michael B; Brassil, Kelly J; Caterino, Jeffrey M; Chau, Ian; Ernstoff, Marc S; Gardner, Jennifer M; Ginex, Pamela; Hallmeyer, Sigrun; Holter Chakrabarty, Jennifer; Leighl, Natasha B; Mammen, Jennifer S; McDermott, David F; Naing, Aung; Nastoupil, Loretta J; Phillips, Tanyanika; Porter, Laura D; Puzanov, Igor; Reichner, Cristina A; Santomasso, Bianca D; Seigel, Carole; Spira, Alexander; Suarez-Almazor, Maria E; Wang, Yinghong; Weber, Jeffrey S; Wolchok, Jedd D; Thompson, John A

    2018-02-14

    Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is

  17. Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence.

    Science.gov (United States)

    Matthews, Edwin J; Frid, Anna A

    2010-04-01

    This is the first of two reports that describes the compilation of a database of drug-related cardiac adverse effects (AEs) that was used to construct quantitative structure-activity relationship (QSAR) models to predict these AEs, to identify properties of pharmaceuticals correlated with the AEs, and to identify plausible mechanisms of action (MOAs) causing the AEs. This database of 396,985 cardiac AE reports was linked to 1632 approved drugs and their chemical structures, 1851 clinical indications (CIs), 997 therapeutic targets (TTs), 432 pharmacological MOAs, and 21,180 affinity coefficients (ACs) for the MOA receptors. AEs were obtained from the Food and Drug Administration's (FDA's) Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) and publicly available medical literature. Drug TTs were obtained from Integrity; drug MOAs and ACs were predicted by BioEpisteme. Significant cardiac AEs and patient exposures were estimated based on the proportional reporting ratios (PRRs) for each drug and each AE endpoint as a percentage of the total AEs. Cardiac AE endpoints were bundled based on toxicological mechanism and concordance of drug-related findings. Results revealed that significant cardiac AEs formed 9 clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes), and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). Based on the observation that each drug had one TT and up to 9 off-target MOAs, cardiac AEs were highly correlated with drugs affecting cardiovascular and cardioneurological functions and certain MOAs (e.g., alpha- and beta-adeno, dopamine, and hydroxytryptomine receptors). Copyright 2010. Published by Elsevier Inc.

  18. Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution

    International Nuclear Information System (INIS)

    Paganetti, H.

    2005-01-01

    Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological 'track structure' model and the more mechanistic 'lethal lesion/potentially lethal lesion' (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values

  19. Plant ecdysteroids: plant sterols with intriguing distributions, biological effects and relations to plant hormones.

    Science.gov (United States)

    Tarkowská, Danuše; Strnad, Miroslav

    2016-09-01

    The present review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones. Plant ecdysteroids (phytoecdysteroids) are natural polyhydroxylated compounds that have a four-ringed skeleton, usually composed of either 27 carbon atoms or 28-29 carbon atoms (biosynthetically derived from cholesterol or other plant sterols, respectively). Their physiological roles in plants have not yet been confirmed and their occurrence is not universal. Nevertheless, they are present at high concentrations in various plant species, including commonly consumed vegetables, and have a broad spectrum of pharmacological and medicinal properties in mammals, including hepatoprotective and hypoglycaemic effects, and anabolic effects on skeletal muscle, without androgenic side-effects. Furthermore, phytoecdysteroids can enhance stress resistance by promoting vitality and enhancing physical performance; thus, they are considered adaptogens. This review summarises current knowledge of phytoecdysteroids' biosynthesis, distribution within plants, biological importance and relations to plant hormones.

  20. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles

    International Nuclear Information System (INIS)

    Polf, Jerimy C.; Gillin, Michael; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata

    2011-01-01

    The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%-20% for those cells containing internalized gold nanoparticles.

  1. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles

    Science.gov (United States)

    Polf, Jerimy C.; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata; Gillin, Michael

    2011-01-01

    The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%–20% for those cells containing internalized gold nanoparticles. PMID:21915155

  2. Adverse mood symptoms with oral contraceptives.

    Science.gov (United States)

    Poromaa, Inger Sundström; Segebladh, Birgitta

    2012-04-01

    In spite of combined oral contraceptives (COCs) having been available for more than 50 years, surprisingly little is known about the prevalence of truly COC-related adverse mood symptoms and about the underlying biological mechanisms of proposed changes in mood and affect. Precise estimates of COC-related adverse mood symptoms are not available due to the lack of placebo-controlled trials. In prospective trials the frequency of women who report deteriorated mood or deteriorated emotional well-being varies between 4 and 10%, but it can be assumed that the causal relation in these prevalence rates is overestimated. Adverse mood symptoms and somatic symptoms are most pronounced during the pill-free interval of the treatment cycles, but whether extended COC regimens would be more favorable in this respect is not known. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms than progestagens with a more androgenic profile. Available data suggest that lower doses of ethinylestradiol could be beneficial. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Postoperative pain and patient-controlled epidural analgesia-related adverse effects in young and elderly patients: a retrospective analysis of 2,435 patients

    Directory of Open Access Journals (Sweden)

    Koh JC

    2017-04-01

    Full Text Available Jae Chul Koh, Young Song, So Yeon Kim, Sooyeun Park, Seo Hee Ko, Dong Woo Han Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, South Korea Abstract: In this retrospective study, data of 2,435 patients who received fentanyl and ropivacaine-based patient-controlled epidural analgesia (PCEA for pain relief after elective surgery under general or spinal anesthesia were reviewed. Differences in postoperative pain, incidence of patient-controlled analgesia (PCA-related adverse effects, and risk factors for the need for rescue analgesics for 48 hours postsurgery in young (age 20–39 years and elderly (age ≥70 years patients were evaluated. Although there were no significant differences in postoperative pain intensity between the two groups until 6 hours postsurgery, younger patients experienced greater postoperative pain intensity compared with older patients 6–48 hours postsurgery. While younger patients exhibited greater incidence of numbness, motor weakness, and discontinuation of PCA postsurgery, elderly patients exhibited greater incidence of hypotension, nausea/vomiting, rescue analgesia, and antiemetic administration. Upon multivariate analysis, low fentanyl dosage and history of smoking were found to be associated with an increased need for rescue analgesia among younger patients, while physical status classification III/IV and thoracic surgery were associated with a decreased need for rescue analgesia among the elderly. Discontinuation of PCA was more frequent among younger patients than the elderly (18.5% vs 13.5%, P=0.001. Reasons for discontinuation of PCA among young and elderly patients, respectively, were nausea and vomiting (6.8% vs 26.6%, numbness or motor weakness (67.8% vs 11.5%, urinary retention (7.4% vs 8.7%, dizziness (2.2% vs 5.2%, and hypotension (3.1% vs 20.3%. In conclusion, PCEA was more frequently associated with numbness, motor

  4. Identifying biological concepts from a protein-related corpus with a probabilistic topic model

    Directory of Open Access Journals (Sweden)

    Lu Xinghua

    2006-02-01

    Full Text Available Abstract Background Biomedical literature, e.g., MEDLINE, contains a wealth of knowledge regarding functions of proteins. Major recurring biological concepts within such text corpora represent the domains of this body of knowledge. The goal of this research is to identify the major biological topics/concepts from a corpus of protein-related MEDLINE© titles and abstracts by applying a probabilistic topic model. Results The latent Dirichlet allocation (LDA model was applied to the corpus. Based on the Bayesian model selection, 300 major topics were extracted from the corpus. The majority of identified topics/concepts was found to be semantically coherent and most represented biological objects or concepts. The identified topics/concepts were further mapped to the controlled vocabulary of the Gene Ontology (GO terms based on mutual information. Conclusion The major and recurring biological concepts within a collection of MEDLINE documents can be extracted by the LDA model. The identified topics/concepts provide parsimonious and semantically-enriched representation of the texts in a semantic space with reduced dimensionality and can be used to index text.

  5. Asthma and respiratory symptoms in hospital workers related to dampness and biological contaminants.

    Science.gov (United States)

    Cox-Ganser, J M; Rao, C Y; Park, J-H; Schumpert, J C; Kreiss, K

    2009-08-01

    The National Institute for Occupational Safety and Health investigated respiratory symptoms and asthma in relation to damp indoor environments in employees of two hospitals. A cluster of six work-related asthma cases from one hospital department, whose symptoms arose during a time of significant water incursions, led us to conduct a survey of respiratory health in 1171/1834 employees working in the sentinel cases hospital and a nearby hospital without known indoor environmental concerns. We carried out observational assessment of dampness, air, chair, and floor dust sampling for biological contaminants, and investigation of exposure-response associations for about 500 participants. Many participants with post-hire onset asthma reported diagnosis dates in a period of water incursions and renovations. Post-hire asthma and work-related lower respiratory symptoms were positively associated with the dampness score. Work-related lower respiratory symptoms showed monotonically increasing odds ratios with ergosterol, a marker of fungal biomass. Other fungal and bacterial indices, particle counts, cat allergen and latex allergen were associated with respiratory symptoms. Our data imply new-onset of asthma in relation to water damage, and indicate that work-related respiratory symptoms in hospital workers may be associated with diverse biological contaminants. In healthcare facilities with indoor dampness and microbial contamination, possible associations between such conditions and respiratory health effects should be considered. Good building maintenance and housekeeping procedures should lead to improvements in employee respiratory health.

  6. An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...

  7. Systematic review of pediatric health outcomes associated with childhood adversity.

    Science.gov (United States)

    Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

    2018-02-23

    Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better

  8. Synthetic biology as it relates to CAM photosynthesis: challenges and opportunities.

    Science.gov (United States)

    DePaoli, Henrique C; Borland, Anne M; Tuskan, Gerald A; Cushman, John C; Yang, Xiaohan

    2014-07-01

    To meet future food and energy security needs, which are amplified by increasing population growth and reduced natural resource availability, metabolic engineering efforts have moved from manipulating single genes/proteins to introducing multiple genes and novel pathways to improve photosynthetic efficiency in a more comprehensive manner. Biochemical carbon-concentrating mechanisms such as crassulacean acid metabolism (CAM), which improves photosynthetic, water-use, and possibly nutrient-use efficiency, represent a strategic target for synthetic biology to engineer more productive C3 crops for a warmer and drier world. One key challenge for introducing multigene traits like CAM onto a background of C3 photosynthesis is to gain a better understanding of the dynamic spatial and temporal regulatory events that underpin photosynthetic metabolism. With the aid of systems and computational biology, vast amounts of experimental data encompassing transcriptomics, proteomics, and metabolomics can be related in a network to create dynamic models. Such models can undergo simulations to discover key regulatory elements in metabolism and suggest strategic substitution or augmentation by synthetic components to improve photosynthetic performance and water-use efficiency in C3 crops. Another key challenge in the application of synthetic biology to photosynthesis research is to develop efficient systems for multigene assembly and stacking. Here, we review recent progress in computational modelling as applied to plant photosynthesis, with attention to the requirements for CAM, and recent advances in synthetic biology tool development. Lastly, we discuss possible options for multigene pathway construction in plants with an emphasis on CAM-into-C3 engineering. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. ["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

    Science.gov (United States)

    Wu, Shu-Xin; Sun, Hong-Feng; Yang, Xiao-Hui; Long, Hong-Zhu; Ye, Zu-Guang; Ji, Shao-Liang; Zhang, Li

    2014-08-01

    We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in

  10. METHODS OF ASSESSMENT OF THE RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS IN NEUTRON THERAPY

    Directory of Open Access Journals (Sweden)

    V. A. Lisin

    2017-01-01

    Full Text Available The relative biological effectiveness (RBE of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

  11. Human development I: Twenty Fundamental Problems of Biology, Medicine, and Neuro-Psychology Related to Biological Information

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2006-01-01

    Full Text Available In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: “metamorphous top down” evolution and “adult human metamorphosis”. The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai’s model for the modulated structure of the human cerebral cortex and Jerne’s theory of the immunological regulatory anti-idiotypic network.

  12. The relative importance of physical and biological energy in landscape evolution

    Science.gov (United States)

    Turowski, J. M.; Schwanghart, W.

    2017-12-01

    Landscapes are formed by the interplay of uplift and geomorphic processes, including interacting and competing physical and biological processes. For example, roots re-inforce soil and thereby stabilize hillslopes and the canopy cover of the forest may mediate the impact of precipitation. Furthermore, plants and animals act as geomorphic agents, directly altering landscape response and dynamics by their actions: tree roots may crack rocks, thus changing subsurface water flows and exposing fresh material for denudation; fungi excrete acids that accelerate rates of chemical weathering, and burrowing animals displace soil and rocks while digging holes for shelter or in search of food. Energetically, landscapes can be viewed as open systems in which topography stores potential energy above a base level. Tectonic processes add energy to the system by uplift and mechanically altering rock properties. Especially in unvegetated regions, erosion and transport by wind can be an important geomorphic process. Advection of atmospheric moisture in high altitudes provides potential energy that is converted by water fluxes through catchments. At the same time, the conversion of solar energy through atmospheric and biological processes drives primary production of living organisms. If we accept that biota influence geomorphic processes, then what is their energetic contribution to landscape evolution relative to physical processes? Using two case studies, we demonstrate that all components of energy input are negligible apart from biological production, quantified by net primary productivity (NPP) and potential energy conversion by water that is placed high up in the landscape as rainfall and leaves it as runoff. Assuming that the former is representative for biological energy and the latter for physical energy, we propose that the ratio of these two values can be used as a proxy for the relative importance of biological and physical processes in landscape evolution. All necessary

  13. Correlation of liquid chromatographic and biological assay for potency assessment of filgrastim and related impurities.

    Science.gov (United States)

    Skrlin, Ana; Kosor Krnic, Ela; Gosak, Darko; Prester, Berislav; Mrsa, Vladimir; Vuletic, Marko; Runac, Domagoj

    2010-11-02

    In vivo and in vitro potency assays have always been a critical tool for confirmation of protein activity. However, due to their complexity and time consuming procedures, it remains a challenge to find an alternative analytical approach that would enable their replacement with no impact on the quality of provided information. The goal of this research was to determine if a correlation between liquid chromatography assays and in vitro biological assay could be established for filgrastim (recombinant human granulocyte-colony stimulating factor, rhG-CSF) samples containing various amounts of related impurities. For that purpose, relevant filgrastim related impurities were purified to homogeneity and characterized by liquid chromatography and mass spectrometry. A significant correlation (R(2)>0.90) between the two types of assays was revealed. Potency of oxidized filgrastim was determined to be approximately 25% of filgrastim stated potency (1 x 10(8)IU/mg of protein). Formyl-methionine filgrastim had potency of 89% of the filgrastim stated potency, while filgrastim dimer had 67% of filgrastim stated potency. A mathematical model for the estimation of biological activity of filgrastim samples from chromatography data was established and a significant correlation between experimental potency values and potency values estimated by the mathematical model was obtained (R(2)=0.92). Based on these results a conclusion was made that reversed phase high performance liquid chromatography could be used as an alternative for the in vitro biological assay for potency assessment of filgrastim samples. Such an alternative model would enable substitution of a complex and time consuming biological assay with a robust and precise instrumental method in many practical cases. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  14. A graphical method for reducing and relating models in systems biology.

    Science.gov (United States)

    Gay, Steven; Soliman, Sylvain; Fages, François

    2010-09-15

    In Systems Biology, an increasing collection of models of various biological processes is currently developed and made available in publicly accessible repositories, such as biomodels.net for instance, through common exchange formats such as SBML. To date, however, there is no general method to relate different models to each other by abstraction or reduction relationships, and this task is left to the modeler for re-using and coupling models. In mathematical biology, model reduction techniques have been studied for a long time, mainly in the case where a model exhibits different time scales, or different spatial phases, which can be analyzed separately. These techniques are however far too restrictive to be applied on a large scale in systems biology, and do not take into account abstractions other than time or phase decompositions. Our purpose here is to propose a general computational method for relating models together, by considering primarily the structure of the interactions and abstracting from their dynamics in a first step. We present a graph-theoretic formalism with node merge and delete operations, in which model reductions can be studied as graph matching problems. From this setting, we derive an algorithm for deciding whether there exists a reduction from one model to another, and evaluate it on the computation of the reduction relations between all SBML models of the biomodels.net repository. In particular, in the case of the numerous models of MAPK signalling, and of the circadian clock, biologically meaningful mappings between models of each class are automatically inferred from the structure of the interactions. We conclude on the generality of our graphical method, on its limits with respect to the representation of the structure of the interactions in SBML, and on some perspectives for dealing with the dynamics. The algorithms described in this article are implemented in the open-source software modeling platform BIOCHAM available at http

  15. Persistent organic pollutants and related biological responses measured in coastal fish using chemical and biological screening methods

    DEFF Research Database (Denmark)

    Tairova, Zhanna; Strand, Jakob; Bossi, Rossana

    2017-01-01

    The aim of this study was to investigate the spatial distribution, levels of dioxin-like compounds (DLC), and biological responses in two fish species. The viviparous eelpout (Zoarces viviparus) was collected from various locations in the Baltic Sea and in fjords of Kattegat and Skagerrak, while ...

  16. Biological availability of energy related effluent material in the coastal ecosystem

    International Nuclear Information System (INIS)

    Gibson, C.I.; Abel, K.H.; Ahlstrom, S.W.; Crecelius, E.A.; Schmidt, R.L.; Thatcher, T.O.; Wildung, R.E.

    1977-01-01

    In order to make the predictions necessary to forecast the ecological consequences of an energy-related technology, there must be an understanding of: the biogeochemical processes involved in the natural system; the manner in which an energy technology affects these processes and how, in turn, this affects the ecosystem as a whole. Direct biological effects such as lethality, behavioral changes, and physiological changes, are being studied under the program previously discussed. The biological availability and impact studies are investigating: the chemical, physical, and biological processes that occur in the natural marine ecosystem; how energy effluents affect these processes; and the factors involved in regulating the bioavailability of effluent material. This past year's effort has centered on defining the quantities and forms of metals and radioisotopes in nuclear power plant effluent streams, the chemical forms present in bioassay systems, the chemical and microbial processes controlling the forms of metals available from the sediments, and the uptake and control of copper in shrimp. In addition, several sites in Sequim Bay have been monitored for potential use in field verification studies

  17. Sequence-Related Amplified Polymorphism (SRAP Markers: A Potential Resource for Studies in Plant Molecular Biology

    Directory of Open Access Journals (Sweden)

    Daniel W. H. Robarts

    2014-07-01

    Full Text Available In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR, random-amplified polymorphic DNA (RAPD, and amplified fragment length polymorphism (AFLP to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use. highly variable marker with inherent biological significance.

  18. Relative biological effectiveness and radiation weighting factors in the context of animals and plants

    International Nuclear Information System (INIS)

    Higley, K.A.; Kocher, D.C.; Real, A.G.; Chambers, D.B.

    2012-01-01

    Radiation weighting factors have long been employed to modify absorbed dose as part of the process of evaluating radiological impact to humans. Their use represents an acknowledgement of the fundamental difference in energy deposition patterns of charged and uncharged particles, and how this can translate into varying degrees of biological impact. Weighting factors used in human radiation protection are derived from a variety of endpoints taken from in-vitro experiments that include human and animal cell lines, as well as in-vivo experiments with animals. Nonetheless, the application of radiation weighting factors in the context of dose assessment of animals and plants is not without some controversy. Specifically, radiation protection of biota has largely focused on limiting deterministic effects, such as reduced reproductive fitness. Consequently, the application of conventional stochastic-based radiation weighting factors (when used for human protection) appears inappropriate. While based on research, radiation weighting factors represent the parsing of extensive laboratory studies on relative biological effectiveness. These studies demonstrate that the magnitude of a biological effect depends not just on dose, but also on other factors including the rate at which the dose is delivered, the type and energy of the radiation delivering the dose, and, most importantly, the endpoint under consideration. This article discusses the efforts taken to develop a logical, transparent, and defensible approach to establishing radiation weighting factors for use in assessing impact to non-human biota, and the challenges found in differentiating stochastic from deterministic impacts.

  19. Radiation damage relative to transmission electron microscopy of biological specimens at low temperature: a review

    International Nuclear Information System (INIS)

    Glaeser, R.M.; Taylor, K.A.

    1978-01-01

    When biological specimens are irradiated by the electron beam in the electron microscope, the specimen structure is damaged as a result of molecular excitation, ionization, and subsequent chemical reactions. The radiation damage that occurs in the normal process of electron microscopy is known to present severe limitations for imaging high resolution detail in biological specimens. The question of radiation damage at low temperatures has therefore been investigated with the view in mind of reducing somewhat the rate at which damage occurs. The radiation damage protection found for small molecule (anhydrous) organic compounds is generally rather limited or even non-existent. However, large molecule, hydrated materials show as much as a 10-fold reduction at low temperature in the rate at which radiation damage occurs, relative to the damage rate at room temperature. In the case of hydrated specimens, therefore, low temperature electron microscopy offers an important advantage as part of the overall effort required in obtaining high resolution images of complex biological structures. (author)

  20. Studies with encapsulated 125I sources: dosimetry for determination of relative biological effectiveness

    International Nuclear Information System (INIS)

    Goldhagen, P.; Freeman, M.L.; Hall, E.J.

    1981-01-01

    During the past year, members of this laboratory have measured the Relative Biological Effectiveness (RBE) of photons from encapsulated 125 I sources (mean energy = 28.33 keV) using 661.6 keV 137 Cs gamma rays as a standard for comparison. These experiments were performed at clinically relevant dose rates and used reduction of the reproductive viability of mammalian cells as an endpoint. This section will discuss how dosimetry problems special to 125 I influence the design of the apparatus and will describe the ionization chamber to be used for measuring dose rates from both 125 I and 137 Cs photons

  1. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

    Science.gov (United States)

    Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

    2015-11-01

    Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

  2. Prediction of drug-related cardiac adverse effects in humans--B: use of QSAR programs for early detection of drug-induced cardiac toxicities.

    Science.gov (United States)

    Frid, Anna A; Matthews, Edwin J

    2010-04-01

    This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme, MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs. Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs. Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows, respectively: 70.7%, 91.7%, and 98.0% specificity; 74.7%, 47.2%, and 21.0% sensitivity; and 138.2, 206.3, and 144.2 chi(2). In addition, a prospective study using AE data from the U.S. Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity. Published by Elsevier Inc.

  3. Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

    Science.gov (United States)

    Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi

    2017-11-01

    Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

  4. Pattern of chemotherapy-related adverse effects among adult cancer patients treated at Gondar University Referral Hospital, Ethiopia: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Belachew SA

    2016-12-01

    chemotherapy-related ADRs among cancer patients is of concern. Setting up an effective ADR monitoring and reporting system (onco-pharmacovigilance and creating awareness among health care professionals regarding the importance of ADR reporting may help prevent the problem. Keywords: adverse drug reactions, causality, chemotherapy, Ethiopia, pharmacovigilance

  5. A case of nivolumab-related cholangitis and literature review: how to look for the right tools for a correct diagnosis of this rare immune-related adverse event.

    Science.gov (United States)

    Gelsomino, Francesco; Vitale, Giovanni; Ardizzoni, Andrea

    2018-02-01

    Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis.

  6. Role of soil biology and soil functions in relation to land use intensity.

    Science.gov (United States)

    Bondi, Giulia; Wall, David; Bacher, Matthias; Emmet-Booth, Jeremy; Graça, Jessica; Marongiu, Irene; Creamer, Rachel

    2017-04-01

    The delivery of the ecosystem's functions is predominantly controlled by soil biology. The biology found in a gram of soil contains more than ten thousand individual species of bacteria and fungi (Torsvik et al., 1990). Understanding the role and the requirements of these organisms is essential for the protection and the sustainable use of soils. Soil biology represents the engine of all the processes occurring in the soil and it supports the ecosystem services such as: 1) nutrient mineralisation 2) plant production 3) water purification and regulation and 4) carbon cycling and storage. During the last years land management type and intensity have been identified as major drivers for microbial performance in soil. For this reason land management needs to be appropriately studied to understand the role of soil biology within this complex interplay of functions. We aimed to study whether and how land management drives soil biological processes and related functions. To reach this objective we built a land use intensity index (LUI) able to quantify the impact of the common farming practices carried out in Irish grassland soils. The LUI is derived from a detailed farmer questionnaire on grassland management practices at 38 farms distributed in the five major agro-climatic regions of Ireland defined by Holden and Brereton (2004). Soils were classified based on their drainage status according to the Irish Soil Information System by Creamer et al. (2014). This detailed questionnaire is then summarised into 3 management intensity components: (i) intensity of Fertilisation (Fi), (ii) frequency of Mowing (Mi) and (iii) intensity of Livestock Grazing (Gi). Sites were sampled to assess the impact of land management intensity on microbial community structure and enzyme behaviour in relation to nitrogen, phosphorus and carbon cycling. Preliminary results for enzymes linked to C and N cycles showed higher activity in relation to low grazing pressure (low Gi). Enzymes linked to P

  7. Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study.

    Science.gov (United States)

    Pelletier, Roxanne; Bacon, Simon L; Arsenault, André; Dupuis, Jocelyn; Laurin, Catherine; Blais, Lucie; Lavoie, Kim L

    2015-12-15

    To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8 years, between 1998 and 2009. Depression and anxiety were assessed using a psychiatric interview (Primary Care Evaluation of Mental Disorders, PRIME-MD). Outcomes data were obtained from Quebec provincial databases. All-cause mortality and MACE. After adjustment for covariates, patients with depression were at increased risks of all-cause mortality (relative risk (RR)=2.84; 95% CI 1.25 to 6.49) compared with patients without depression. Anxiety was not associated with increased mortality risks (RR=0.86; 95% CI 0.31 to 2.36). When patients were stratified according to CAD status, depression increased the risk of mortality among patients with no CAD (RR=4.39; 95% CI 1.12 to 17.21), but not among patients with CAD (RR=2.32; 95% CI 0.78 to 6.88). Neither depression nor anxiety was associated with MACE among patients with or without CAD. Depression, but not anxiety, was an independent risk factor for all-cause mortality in patients without CAD. The present study contributes to a better understanding of the relative and unique role of depression versus anxiety among patients with versus without CAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Relative biological effectiveness (RBE) of alpha radiation in cultured porcine aortic endothelial cells.

    Science.gov (United States)

    Thomas, Patricia; Tracy, Bliss; Ping, Tilly; Baweja, Anar; Wickstrom, Mark; Sidhu, Narinder; Hiebert, Linda

    2007-03-01

    Northern peoples can receive elevated radiation doses (1- 10 mSv/y) from transfer of polonium-210 (210Po) through the lichen-caribou-human food chain. Ingested 210Po is primarily blood-borne and thus many of its short range alpha particles irradiate the endothelial cells lining the blood vessels. The relative biological effectiveness (RBE) of alpha particles vs. x-rays was examined in porcine aortic endothelial cells as a surrogate for understanding what might happen to human endothelial cells in northern populations consuming traditional foods. Cultured porcine aortic endothelial cells were exposed to x-ray and 210Po alpha particle radiation. Alpha irradiation was applied to the cell cultures internally via the culture medium and externally, using thin-bottomed culture dishes. The results given here are based on the external irradiation method, which was found to be more reliable. Dose-response curves were compared for four lethal endpoints (cell viability, live cell fraction, release of lactate dehydrogenase [LDH] and clonogenic survival) to determine the relative biological effectiveness (RBE) of alpha radiation. The alpha RBE for porcine cells varied from 1.6-21, depending on the endpoint: 21.2+/-4.5 for cell viability, 12.9+/-2.7 for decrease in live cell number, 5.3+/-0.4 for LDH release to the medium but only 1.6 +/-0.1 for clonogenic survival. The low RBE of 1.6 was due to x-ray hypersensitivity of endothelial cells at low doses.

  9. Biological nitrogen fixation in relation to energy forest production. Progress report, 1978-1980

    Energy Technology Data Exchange (ETDEWEB)

    Clarholm, M; Granhall, U

    1981-01-01

    Different pasture legumes, Alnus incana and Myrica gale have been tested in pot experiments and field trials with respect to their use as biological N-fertilizers in relation to energy forest production. So far experiments have been mainly concerned with their establishemnts as on intercrop with Galix at a mire site with ombrotrophic peat and in two clayish arable soils. Laboratory experiments have been made to determine optimal conditions for growth and nitrogen fixation of wild and Alaska lupines in relation to varous soil amendments in the form of lime, ash, NPKMo, and Fe. A pilot experiment of the terrelations between willows and grey alder growing together in peat has been started at Uppsala.

  10. Nectar sugar composition of European Caryophylloideae (Caryophyllaceae) in relation to flower length, pollination biology and phylogeny.

    Science.gov (United States)

    Witt, T; Jürgens, A; Gottsberger, G

    2013-10-01

    Floral nectar composition has been explained as an adaptation to factors that are either directly or indirectly related to pollinator attraction. However, it is often unclear whether the sugar composition is a direct adaptation to pollinator preferences. Firstly, the lower osmolality of sucrose solutions means that they evaporate more rapidly than hexose solutions, which might be one reason why sucrose-rich nectar is typically found in flowers with long tubes (adapted to long-tongued pollinators), where it is better protected from evaporation than in open or short-tubed flowers. Secondly, it can be assumed that temperature-dependent evaporation is generally lower during the night than during the day so that selection pressure to secrete nectar with high osmolality (i.e. hexose-rich solutions) is relaxed for night-active flowers pollinated at night. Thirdly, the breeding system may affect selection pressure on nectar traits; that is, for pollinator-independent, self-pollinated plants, a lower selective pressure on nectar traits can be assumed, leading to a higher variability of nectar sugar composition independent of pollinator preferences, nectar accessibility and nectar protection. To analyse the relations between flower tube length, day vs. night pollination and self-pollination, the nectar sugar composition was investigated in 78 European Caryophylloideae (Caryophyllaceae) with different pollination modes (diurnal, nocturnal, self-pollination) using high-performance liquid chromatography (HPLC). All Caryophylleae species (Dianthus and relatives) were found to have nectar with more than 50% sucrose, whereas the sugar composition of Sileneae species (Silene and relatives) ranged from 0% to 98.2%. In the genus Silene, a clear dichotomous distribution of sucrose- and hexose-dominant nectars is evident. We found a positive correlation between the flower tube length and sucrose content in Caryophylloideae, particularly in day-flowering species, using both conventional

  11. Adverse Outcome Pathway Networks II: Network Analytics.

    Science.gov (United States)

    Villeneuve, Daniel L; Angrish, Michelle M; Fortin, Marie C; Katsiadaki, Ioanna; Leonard, Marc; Margiotta-Casaluci, Luigi; Munn, Sharon; O'Brien, Jason M; Pollesch, Nathan L; Smith, L Cody; Zhang, Xiaowei; Knapen, Dries

    2018-02-28

    Toxicological responses to stressors are more complex than the simple one biological perturbation to one adverse outcome model portrayed by individual adverse outcome pathways (AOPs). Consequently, the AOP framework was designed to facilitate de facto development of AOP networks that can aid understanding and prediction of pleiotropic and interactive effects more common to environmentally realistic, complex exposure scenarios. The present paper introduces nascent concepts related to the qualitative analysis of AOP networks. First, graph theory-based approaches for identifying important topological features are illustrated using two example AOP networks derived from existing AOP descriptions. Second, considerations for identifying the most significant path(s) through an AOP network from either a biological or risk assessment perspective are described. Finally, approaches for identifying interactions among AOPs that may result in additive, synergistic, or antagonistic responses, or previously undefined emergent patterns of response, are introduced. Along with a companion article (Knapen et al. part I), these concepts set the stage for development of tools and case studies that will facilitate more rigorous analysis of AOP networks, and the utility of AOP network-based predictions, for use in research and regulatory decision-making. Collectively, this work addresses one of the major themes identified through a SETAC Horizon Scanning effort focused on advancing the AOP framework. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Epistemological Predictors of "Self Efficacy on Learning Biology" and "Test Anxiety Related to Evaluation of Learning on Biology" for Pre-Service Elementary Teachers

    Science.gov (United States)

    Koksal, Mustafa Serdar

    2011-01-01

    The degree to which pre-service teachers learn biology is related to both motivational factors of self-regulation and factors regarding epistemological beliefs. At the same time, self-regulation and epistemological beliefs are also associated with one another. Based on this relationship, the purpose of this study was to investigate the…

  13. Biological durability of wood in relation to end-use - Part 1. Towards a European standard for laboratory testing of the biological durability of wood

    NARCIS (Netherlands)

    Acker, Van J.; Stevens, M.; Carey, J.; Sierra-Alvarez, R.; Militz, H.; Bayon, Le I.; Kleist, G.; Peek, R.D.

    2003-01-01

    The determination of biological durability of wood is an issue requiring sufficient reliability regarding end-use related prediction of performance. Five test institutes joined efforts to check standard test methods and to improve methodology and data interpretation for assessment of natural

  14. "What kept me going": A qualitative study of avoidant responses to war-related adversity and perpetration of violence by former forcibly recruited children and youth in the Acholi region of northern Uganda.

    Science.gov (United States)

    Harnisch, Helle; Montgomery, Edith

    2017-09-01

    This qualitative study investigates what, according to 36 former forcibly recruited women and men, enabled them to "keep on going" during and after their forced recruitment in the twenty-year-long civil war in northern Uganda. Furthermore, the study conveys the ways most of the former forcibly recruited kept on going and today cope with ongoing war-related adversity and difficult reintegration processes without relying on psycho-social intervention. Thirty-five of the 36 women and men were forcibly recruited when they were children by the Lord's Resistance Army (LRA) from the Acholi region of northern Uganda. Over the course of five visits to the Acholi region from 2012 to 2016, 10 months of ethnographic fieldwork was carried out involving interviews and participant observation. The 36 Acholi women and men shared how they experienced and responded to suffering from brutal torture and being forced to perpetrate often lethal violence against fellow Acholi who had tried to escape the LRA. The article provides an overview of the responses to this war-related adversity and the results document how avoidant coping is the preferred and most common coping response among the 36 former forcibly recruited women and men in this study. We take an interdisciplinary approach to discussing how these avoidant coping responses resonate with psycho-traumatology research on responses to war-related trauma and with conceptualizations of resilience. We end with the argument that avoidant responses to war-related adversity, when faced in clinical and diagnostic settings, should not be understood exclusively from a biomedical perspective: Responses to war-related adversity must be carefully investigated in collaboration with the human beings who have experienced the war-related adversity and based on integrative and emic approaches that consider the locally situated notions of how to cope with adversity and "keep on going" in their own right. Copyright © 2017 The Authors. Published by

  15. A novel biological 'twin-father' temporal paradox of General Relativity in a Gödel universe - Where reproductive biology meets theoretical physics.

    Science.gov (United States)

    Ashrafian, Hutan

    2018-03-01

    Several temporal paradoxes exist in physics. These include General Relativity's grandfather and ontological paradoxes and Special Relativity's Langevin-Einstein twin-paradox. General relativity paradoxes can exist due to a Gödel universe that follows Gödel's closed timelike curves solution to Einstein's field equations. A novel biological temporal paradox of General Relativity is proposed based on reproductive biology's phenomenon of heteropaternal fecundation. Herein, dizygotic twins from two different fathers are the result of concomitant fertilization during one menstrual cycle. In this case an Oedipus-like individual exposed to a Gödel closed timelike curve would sire a child during his maternal fertilization cycle. As a consequence of heteropaternal superfecundation, he would father his own dizygotic twin and would therefore generate a new class of autofraternal superfecundation, and by doing so creating a 'twin-father' temporal paradox. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

    Science.gov (United States)

    Martini, Dylan J; Hamieh, Lana; McKay, Rana R; Harshman, Lauren C; Brandao, Raphael; Norton, Craig K; Steinharter, John A; Krajewski, Katherine M; Gao, Xin; Schutz, Fabio A; McGregor, Bradley; Bossé, Dominick; Lalani, Aly-Khan A; De Velasco, Guillermo; Michaelson, M Dror; McDermott, David F; Choueiri, Toni K

    2018-04-01

    The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients ( n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% ( n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR . ©2018 American Association for Cancer Research.

  17. Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

    Science.gov (United States)

    Läubli, Heinz; Balmelli, Catharina; Kaufmann, Lukas; Stanczak, Michal; Syedbasha, Mohammedyaseen; Vogt, Dominik; Hertig, Astrid; Müller, Beat; Gautschi, Oliver; Stenner, Frank; Zippelius, Alfred; Egli, Adrian; Rothschild, Sacha I

    2018-05-22

    Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

  18. Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

    2011-10-24

    Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. The Patient-Related Burden of Pegylated-Interferon-α Therapy and Adverse Events among Patients with Viral Hepatitis C in Japan.

    Science.gov (United States)

    Kumada, Hiromitsu; daCosta DiBonaventura, Marco; Yuan, Yong; Kalsekar, Anupama; Kopenhafer, Lewis; Tang, Ann; Victor, Timothy W; L'Italien, Gilbert; Chayama, Kazuaki; Toyota, Joji

    2014-05-01

    Pegylated-interferon-α (IFN-α)-based therapies for viral hepatitis C (HCV) are effective, but they are associated with several adverse events (AEs). The primary objectives of this study were to quantify the burden of IFN-α-based treatment and to measure the prevalence and burden of IFN-α-related AEs in Japan. A cross-sectional survey was administered online to patients with HCV in 2013. Patients who were currently taking IFN-α-based therapy (n = 188) were compared with patients who were taking a liver protectant but not IFN-α-based therapy (n = 180) and with patients who were untreated (n = 365) on measures of health-related quality of life (using the Hepatitis Quality of Life Questionnaire, version 2), work productivity, and health care resource use, controlling for sociodemographic characteristics and health history. Among patients taking IFN-α-based therapy, the prevalence and burden of AEs was examined on the same set of health outcomes as noted above along with treatment satisfaction and adherence. Compared with untreated patients, patients using IFN-α reported poorer health-related quality of life (physical component summary score, 50.13 vs. 52.04; mental component summary score, 44.12 vs. 47.97), more overall work impairment (32.73 vs. 25.64), more physician visits in the past 6 months (14.51 vs. 8.36), and an increased likelihood of an emergency room visit (odds ratio = 7.25) and hospitalization (odds ratio = 4.05) (all P < 0.05). The mean number of AEs was 6.05 for patients using IFN-α. All AEs were associated with poorer health outcomes (particularly the mental component summary score), and most were also associated with lower treatment satisfaction and medication adherence. A significant patient burden for IFN-α treatment itself and various AEs was observed. The results suggest that effective, non-IFN-α-based treatments may reduce the societal burden. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR

  20. Dissecting functions of the retinoblastoma tumor suppressor and the related pocket proteins by integrating genetic, cell biology, and electrophoretic techniques

    DEFF Research Database (Denmark)

    Hansen, Klaus; Lukas, J; Holm, K

    1999-01-01

    The members of the 'pocket protein' family, comprising the retinoblastoma tumor suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell proliferation and modulate fundamental biological processes including embryonic development, differentiation, homeostatic tissue renewal...

  1. Adverse Effects of Bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  2. Adverse effects of bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  3. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

    Directory of Open Access Journals (Sweden)

    Eliedonna Cacao

    Full Text Available The biological effects of high charge and energy (HZE particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10 are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

  4. Mastery of Content Representation (CoRes) Related TPACK High School Biology Teacher

    Science.gov (United States)

    Nasution, W. R.; Sriyati, S.; Riandi, R.; Safitri, M.

    2017-09-01

    The purpose of this study was to determine the mastery of Content Representation (CoRes) teachers related to the integration of technology and pedagogy in teaching Biology (TPACK). This research uses a descriptive method. The data were taken using instruments CoRes as the primary data and semi-structured interviews as supporting data. The subjects were biology teacher in class X MIA from four schools in Bandung. Teachers raised CoRes was analyzed using a scoring rubric CoRes with coding 1-3 then categorized into a group of upper, middle, or lower. The results showed that the two teachers in the lower category. This results means that the control of teachers in defining the essential concept in the CoRes has not been detailed and specific. Meanwhile, two other teachers were in the middle category. This means that the ability of teachers to determine the essential concepts in the CoRes are still inadequate so that still needs to be improved.

  5. The relative contributions of biological and abiotic processes to carbon dynamics in subarctic sea ice

    DEFF Research Database (Denmark)

    Søgaard, Dorte Haubjerg; Thomas, David; Rysgaard, Søren

    2013-01-01

    Knowledge on the relative effects of biological activity and precipitation/dissolution of calcium carbonate (CaCO3) in influencing the air-ice CO2 exchange in sea-ice-covered season is currently lacking. Furthermore, the spatial and temporal occurrence of CaCO3 and other biogeochemical parameters...... in sea ice are still not well described. Here we investigated autotrophic and heterotrophic activity as well as the precipitation/dissolution of CaCO3 in subarctic sea ice in South West Greenland. Integrated over the entire ice season (71 days), the sea ice was net autotrophic with a net carbon fixation...... and CaCO3 precipitation. The net biological production could only explain 4 % of this sea-ice-driven CO2 uptake. Abiotic processes contributed to an air-sea CO2 uptake of 1.5 mmol m(-2) sea ice day(-1), and dissolution of CaCO3 increased the air-sea CO2 uptake by 36 % compared to a theoretical estimate...

  6. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

    Directory of Open Access Journals (Sweden)

    Andrew T. Ludlow

    2011-01-01

    Full Text Available Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

  7. Unravelling the biology of human papillomavirus (HPV) related tumours to enhance their radiosensitivity

    International Nuclear Information System (INIS)

    Vozenin, M.C.; Lord, H.K.; Deutsch, E.; Vozenin, M.C.; Hartl, D.

    2010-01-01

    HPV infection is associated with most squamous cell carcinomas (SCC) of the uterine cervix and many head and neck SCC. While recent understanding of the mechanisms of HPV-induced carcinogenesis has lead to the development of prophylactic vaccines, the principal modality of treatment is radiotherapy and despite concurrent chemotherapy, outcomes remain suboptimal. Improving the radiotherapeutic index thus remains an important challenge as well as defining predictive assays for treatment outcome of HPV-related tumours. Therefore elucidating the influence of the HPV virus on tumour radiosensitivity is of major interest due to the prevalence of HPV-related tumours worldwide and due to evidence that head and neck HPV-tumours have markedly different clinical outcomes compared to non-HPV-related tumours. This difference may allow for different treatment strategies to be developed. The present review aims to summarize the current understanding of radiosensitivity and HPV-related tumour biology in order to subsequently develop new approaches to enhance the therapeutic index. This review also emphasizes the relevance of E6 and E7 onco-proteins to tumour cell response to radiotherapy suggesting that specific targeted approaches such as concomitant modulation of additional pathways using targeted therapies should offer new therapeutic avenues. (authors)

  8. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth?

    DEFF Research Database (Denmark)

    Putrik, Polina; Ramiro, Sofia; Kvien, Tore K

    2014-01-01

    To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare.......To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare....

  9. Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng-Fei Wang

    2017-10-01

    Full Text Available Background: Treatment of cancers with programmed cell death protein 1 (PD-1 pathway inhibitors can lead to immune-related adverse events (irAEs, which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs.Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence.Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC, colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis, endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency, digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin, respiratory system (pneumonitis, lung infiltration, and interstitial lung disease, and urinary system (increased creatinine, nephritis, and renal failure. In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73–32.61; I2, 92.80 in any grade and 6.10% (95% CI, 4.85–7.64; I2, 52.00 in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%.Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

  10. Relative biological effectiveness of tritiated water on cultured mammalian cells at molecular and cellular level

    International Nuclear Information System (INIS)

    Okada, S.; Sakai, K.; Nakamura, N.

    1986-01-01

    Factors that affect RBE values have been investigated in cultured cells. It was shown that: (1) Different RBE values were obtained with the same tritiated water treated cells depending upon the biological end-point; this may be related to target size. (2) The RBE value for one end-point (e.g. cell killing) in different cell types was often different. In some cells, the RBE value increased with reducing dose; in other cells, the value remained constant. (3) The RBE value for tritiated water seemed to fit a general RBE-LET relationship. These results suggest that although the RBE value might vary from 1 to 2 when cells are exposed to HTO, there are situations where the value becomes higher than 2; these are associated with low dose and low dose rate exposures in some cell types. (author)

  11. Single-dose relative biological effectiveness and toxicity studies under conditions of hypothermia and hyperbaric oxygen

    International Nuclear Information System (INIS)

    Hering, E.R.; Blekkenhorst, G.; Harrison, G.G.; Morrell, D.; Korrubel, J.; Gregory, A.; Phillips, J.; Manca, V.; Sealy, R.; Cape Town Univ.

    1986-01-01

    An approach to using hyperbaric oxygen with radiation in a clinical situation has been described in the preceding paper in this issue. To ascertain whether there might be a change in the relative biological effectiveness of radiation on normal mammalian tissue treated under conditions of hypothermia and hyperbaric oxygen, the acute reaction to radiation of pig skin was studied. A single dose enhancement ratio at the erythema reaction level of 1.4+-0.08 was obtained when compared with irradiation at normal body temperature in air. The authors studied also a series of antioxidant enzymes in rat liver and lung after exposure to hypothermia and hyperbaric oxygen. Enzyme changes were such as to combat oxygen toxicity which might develop as a result of the pre-treatment. (author)

  12. Sieve-based relation extraction of gene regulatory networks from biological literature.

    Science.gov (United States)

    Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko

    2015-01-01

    Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

  13. Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles

    Science.gov (United States)

    Maeda, Junko; Cartwright, Ian M.; Haskins, Jeremy S.; Fujii, Yoshihiro; Fujisawa, Hiroshi; Hirakawa, Hirokazu; Uesaka, Mitsuru; Kitamura, Hisashi; Fujimori, Akira; Thamm, Douglas H.; Kato, Takamitsu A.

    2016-01-01

    Heavy ions, characterized by high linear energy transfer (LET) radiation, have advantages compared with low LET protons and photons in their biological effects. The application of heavy ions within veterinary clinics requires additional background information to determine heavy ion efficacy. In the present study, comparison of the cell-killing effects of photons, protons and heavy ions was investigated in canine osteosarcoma (OSA) cells in vitro. A total of four canine OSA cell lines with various radiosensitivities were irradiated with 137Cs gamma-rays, monoenergetic proton beams, 50 keV/µm carbon ion spread out Bragg peak beams and 200 keV/µm iron ion monoenergetic beams. Clonogenic survival was examined using colony-forming as says, and relative biological effectiveness (RBE) values were calculated relative to gamma-rays using the D10 value, which is determined as the dose (Gy) resulting in 10% survival. For proton irradiation, the RBE values for all four cell lines were 1.0–1.1. For all four cell lines, exposure to carbon ions yielded a decreased cell survival compared with gamma-rays, with the RBE values ranging from 1.56–2.10. Iron ions yielded the lowest cell survival among tested radiation types, with RBE values ranging from 3.51–3.69 observed in the three radioresistant cell lines. The radiosensitive cell line investigated demonstrated similar cell survival for carbon and iron ion irradiation. The results of the present study suggest that heavy ions are more effective for killing radioresistant canine OSA cells when compared with gamma-rays and protons. This markedly increased efficiency of cell killing is an attractive reason for utilizing heavy ions for radioresistant canine OSA. PMID:27446477

  14. Scale relativity theory and integrative systems biology: 2. Macroscopic quantum-type mechanics.

    Science.gov (United States)

    Nottale, Laurent; Auffray, Charles

    2008-05-01

    In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, which aims at describing the effects of a non-differentiable and fractal (i.e., explicitly scale dependent) geometry of space-time. The first paper of this series was devoted, in this new framework, to the construction from first principles of scale laws of increasing complexity, and to the discussion of some tentative applications of these laws to biological systems. In this second review and perspective paper, we describe the effects induced by the internal fractal structures of trajectories on motion in standard space. Their main consequence is the transformation of classical dynamics into a generalized, quantum-like self-organized dynamics. A Schrödinger-type equation is derived as an integral of the geodesic equation in a fractal space. We then indicate how gauge fields can be constructed from a geometric re-interpretation of gauge transformations as scale transformations in fractal space-time. Finally, we introduce a new tentative development of the theory, in which quantum laws would hold also in scale space, introducing complexergy as a measure of organizational complexity. Initial possible applications of this extended framework to the processes of morphogenesis and the emergence of prokaryotic and eukaryotic cellular structures are discussed. Having founded elements of the evolutionary, developmental, biochemical and cellular theories on the first principles of scale relativity theory, we introduce proposals for the construction of an integrative theory of life and for the design and implementation of novel macroscopic quantum-type experiments and devices, and discuss their potential

  15. Chemical and Biological Significance of Oenothein B and Related Ellagitannin Oligomers with Macrocyclic Structure

    Directory of Open Access Journals (Sweden)

    Takashi Yoshida

    2018-03-01

    Full Text Available In 1990, Okuda et al. reported the first isolation and characterization of oenothein B, a unique ellagitannin dimer with a macrocyclic structure, from the Oenothera erythrosepala leaves. Since then, a variety of macrocyclic analogs, including trimeric–heptameric oligomers have been isolated from various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae. Among notable in vitro and in vivo biological activities reported for oenothein B are antioxidant, anti-inflammatory, enzyme inhibitory, antitumor, antimicrobial, and immunomodulatory activities. Oenothein B and related oligomers, and/or plant extracts containing them have thus attracted increasing interest as promising targets for the development of chemopreventive agents of life-related diseases associated with oxygen stress in human health. In order to better understand the significance of this type of ellagitannin in medicinal plants, this review summarizes (1 the structural characteristics of oenothein B and related dimers; (2 the oxidative metabolites of oenothein B up to heptameric oligomers; (3 the distribution of oenotheins and other macrocyclic analogs in the plant kingdom; and (4 the pharmacological activities hitherto documented for oenothein B, including those recently found by our laboratory.

  16. LGscore: A method to identify disease-related genes using biological literature and Google data.

    Science.gov (United States)

    Kim, Jeongwoo; Kim, Hyunjin; Yoon, Youngmi; Park, Sanghyun

    2015-04-01

    Since the genome project in 1990s, a number of studies associated with genes have been conducted and researchers have confirmed that genes are involved in disease. For this reason, the identification of the relationships between diseases and genes is important in biology. We propose a method called LGscore, which identifies disease-related genes using Google data and literature data. To implement this method, first, we construct a disease-related gene network using text-mining results. We then extract gene-gene interactions based on co-occurrences in abstract data obtained from PubMed, and calculate the weights of edges in the gene network by means of Z-scoring. The weights contain two values: the frequency and the Google search results. The frequency value is extracted from literature data, and the Google search result is obtained using Google. We assign a score to each gene through a network analysis. We assume that genes with a large number of links and numerous Google search results and frequency values are more likely to be involved in disease. For validation, we investigated the top 20 inferred genes for five different diseases using answer sets. The answer sets comprised six databases that contain information on disease-gene relationships. We identified a significant number of disease-related genes as well as candidate genes for Alzheimer's disease, diabetes, colon cancer, lung cancer, and prostate cancer. Our method was up to 40% more accurate than existing methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma

    NARCIS (Netherlands)

    Kerkhof, M.; Postma, D. S.; Brunekreef, B.; Reijmerink, N. E.; Wijga, A. H.; de Jongste, J. C.; Gehring, U.; Koppelman, G. H.

    Background Epidemiological studies have reported adverse effects of ambient air pollution on the prevalence of asthma. Laboratory studies have suggested that innate immune responses are involved. Objective A study was undertaken to determine whether the Toll-like receptor 2 and 4 genes (TLR2 and

  18. The relation of birth weight and gestational age to biological, occupational and socioeconomic factors.

    Science.gov (United States)

    Velonakis, E G; Maghiorakos, P; Tzonou, A; Barrat, J; Proteau, J; Ladopoulos, I

    1997-01-01

    The data of the 2,040 single births, born during 1987 at the "Saint Antoine" Hospital in Paris, were analysed in order to identify the impact of various biological, occupational, and socioeconomic factors on gestational age and birth weight. Birth weight is associated with the height of the mother and the weight gained during pregnancy. It is lower for mothers with preeclampsia during the current or previous pregnancies or with urogenital infections during the current pregnancy and for mothers with one or more induced abortions. Girls weigh less than boys. Parity has a positive relation to the baby's weight, while manual work seems to have a negative one. APGAR score and duration of the pregnancy are associated with the birth weight. Placenta previa, preeclampsia and urinary infections affect the gestational age. A short pause period in work is related to a shorter gestational age. Weight gain is associated with a prolonged duration of the pregnancy. Gestational age and birth weight are associated with the nationality of the mother, especially in some ethnic groups, and with marital status.

  19. Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

    International Nuclear Information System (INIS)

    Johnson, J.R.; Myers, D.K.; Jones, A.R.

    1995-01-01

    To help resolve uncertainties as to the most appropriate weighting factor for tritium β rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X-rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium β rays compared to X rays ranged from 1.0 ± to 1.3 ± 0.3. A w R value or 1 would thus appear to be more appropriate than a w R of 2 tritium β rays. 31 refs., 1 fig., 6 tabs

  20. Study of the Clinical Proton Beam Relative Biological Effectiveness at the JINR Phasotron, Dubna

    CERN Document Server

    Vitanova, A; Gaevskii, V N; Molokonov, A G; Spurny, F; Fadeeva, T A; Shmakova, N L

    2002-01-01

    Proton clinical beams contain particles with high linear energy transfer (LET). Secondary heavy charged particles produced from nuclear interactions and degraded protons at the Bragg peak region are particles with high LET. These particles could enhance the Relative Biological Effectiveness (RBE) of the proton beam. We have carried out two radiobiological experiments to investigate the RBE of 150 MeV clinical proton beam. The irradiation of the Chinese Hamster V79 cells were performed at two points of the depth-dose distribution - at the beam entrance and at the Bragg peak. The contribution of the high LET particles to dosimetric and microdosimetric characteristics in the various depth of proton beam was also experimentally studied using the CR-39 track etched detectors. The LET spectra between 10 and 700 keV/{\\mu}m were measured by means of track detectors and the automatic optical image analyzer LUCIA-II. The relative contribution of the high LET particles to ab! sorbed dose increases from several per cent ...

  1. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

    Science.gov (United States)

    Teoh, Seong Lin; Das, Srijit

    2016-11-01

    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

  2. Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

    International Nuclear Information System (INIS)

    Johnson, J.R.; Myers, D.K.; Jackson, J.S.; Dunford, D.W.; Gragtmans, N.J.; Wyatt, H.M.; Jones, A.R.; Percy, D.H.

    1995-01-01

    To help resolve uncertainties as to the most appropriate weighting factor for tritium β rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium 13 rays compared to X rays ranged from 1.0 ± 0.5 to 1.3 ± 0.3. A best estimate of the RBE for this experiment was about 1.2 ± 0.3. A w R value of 1 would thus appear to be more appropriate than a W R of 2 for tritium β rays. (author)

  3. Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.R. [Battelle Pacific Northwest Labs., Health Protection Branch, Health Div., Richland, WA (United States); Myers, D.K.; Jackson, J.S.; Dunford, D.W.; Gragtmans, N.J.; Wyatt, H.M.; Jones, A.R. [Atomic Energy of Canada Limited, Chalk River, Ontairo (Canada); Percy, D.H. [Univ. of Guelph, Ontario Veterinary College, Guelph, Ontario (Canada)

    1995-07-01

    To help resolve uncertainties as to the most appropriate weighting factor for tritium {beta} rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium 13 rays compared to X rays ranged from 1.0 {+-} 0.5 to 1.3 {+-} 0.3. A best estimate of the RBE for this experiment was about 1.2 {+-} 0.3. A w{sub R} value of 1 would thus appear to be more appropriate than a W{sub R} of 2 for tritium {beta} rays. (author)

  4. Relative biological effectiveness of tritium for induction of myeloid leukemia in CBA/H mice.

    Science.gov (United States)

    Johnson, J R; Myers, D K; Jackson, J S; Dunford, D W; Gragtmans, N J; Wyatt, H M; Jones, A R; Percy, D H

    1995-10-01

    To help resolve uncertainties as to the most appropriate weighting factor for tritium beta rays, a large experiment was carried out to measure the relative biological effectiveness (RBE) of tritiated water compared to X rays for the induction of myeloid leukemia in male mice of the CBA/H strain. The study was designed to estimate the lifetime incidence of myeloid leukemia in seven groups of about 750 mice each; radiation exposures were approximately 0, 1, 2 and 3 Gy both for tritiated water and for X rays. The lifetime incidence of leukemia in these mice increased from 0.13% in the control group to 6-8% in groups exposed to higher radiation doses. The results were fitted to various equations relating leukemia incidence to radiation dose, using both the raw data and data corrected for cumulative mouse-days at risk. The calculated RBE values for tritium beta rays compared to X rays ranged from 1.0 +/- 0.5 to 1.3 +/- 0.3. A best estimate of the RBE for this experiment was about 1.2 +/- 0.3. A wR value of 1 would thus appear to be more appropriate than a wR of 2 for tritium beta rays.

  5. The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

    2010-01-01

    % for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild......-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone...

  6. Relative associations between depression and anxiety on adverse cardiovascular events: does a history of coronary artery disease matter? A prospective observational study

    OpenAIRE

    Pelletier, Roxanne; Bacon, Simon L; Arsenault, Andr?; Dupuis, Jocelyn; Laurin, Catherine; Blais, Lucie; Lavoie, Kim L

    2015-01-01

    Objectives To assess whether depression and anxiety increase the risk of mortality and major adverse cardiovascular events (MACE), among patients with and without coronary artery disease (CAD). Design and setting, and patients DECADE (Depression Effects on Coronary Artery Disease Events) is a prospective observational study of 2390 patients referred at the Montreal Heart Institute. Patients were followed for 8.8?years, between 1998 and 2009. Depression and anxiety were assessed using a psychi...

  7. Adulthood personality correlates of childhood adversity

    OpenAIRE

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, whic...

  8. Adulthood Personality Correlates of Childhood Adversity

    OpenAIRE

    Charles S. Carver; Charles S. Carver; Sheri L Johnson; Sheri L Johnson; Michael E McCullough; Daniel E Forster; Jutta eJoormann

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which w...

  9. Newer biological agents in rheumatoid arthritis: impact on health-related quality of life and productivity.

    Science.gov (United States)

    Strand, Vibeke; Singh, Jasvinder A

    2010-01-01

    Health-related quality of life (HR-QOL) in patients with rheumatoid arthritis (RA) is significantly impaired as a result of pain, deficits in physical function and fatigue associated with this disease. Decrements in HR-QOL are also associated with an increased probability of no longer working, absence from work due to RA-associated sickness, and reduced productivity while at work or in the home, all of which have consequences for the patient as well as society. HR-QOL and productivity are thus important components in the assessment of outcomes in RA, and assessment of HR-QOL is now recommended in clinical trials that assess the efficacy of new treatments for RA. Measures to assess HR-QOL include the Medical Outcomes Study Short Form 36 (SF-36), EuroQol (EQ-5D) and the Health Utilities Index - Mark 3 (HUI3); these measures not only provide an indication of the clinical (i.e. statistical) efficacy of a treatment, but also provide information on whether this efficacy is truly 'meaningful' from a patient's perspective. These measures have been utilized in clinical trials of biological agents in patients with RA, including tumour necrosis factor inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol and golimumab), the co-stimulatory inhibitor molecule abatacept, the B-cell depletion agent rituximab and the interleukin-6 receptor antagonist tocilizumab, and have demonstrated that these agents can significantly improve HR-QOL. Assessment of work productivity in patients with RA and the impact of treatment is a practical way to measure disability from RA from individual and societal perspectives. As RA affects women three times more frequently than men, there is also a critical need for productivity assessment within the home as well as participation in family/social/leisure activities. Data from recent trials of biological agents demonstrate that these agents can reverse disease-related decrements in productivity and limitations in participation in family

  10. Review of relative biological effectiveness dependence on linear energy transfer for low-LET radiations

    International Nuclear Information System (INIS)

    Hunter, Nezahat; Muirhead, Colin R

    2009-01-01

    Information on Japanese A-bomb survivors exposed to gamma radiation has been used to estimate cancer risks for the whole range of photon (x-rays) and electron energies which are commonly encountered by radiation workers in the work place or by patients and workers in diagnostic radiology. However, there is some uncertainty regarding the radiation effectiveness of various low-linear energy transfer (low-LET) radiations (x-rays, gamma radiation and electrons). In this paper we review information on the effectiveness of low-LET radiations on the basis of epidemiological and in vitro radiobiological studies. Data from various experimental studies for chromosome aberrations and cell transformation in human lymphocytes and from epidemiological studies of the Japanese A-bomb survivors, patients medically exposed to radiation for diagnostic and therapeutic procedures, and occupational exposures of nuclear workers are considered. On the basis of in vitro cellular radiobiology, there is considerable evidence that the relative biological effectiveness (RBE) of high-energy low-LET radiation (gamma radiation, electrons) is less than that of low-energy low-LET radiation (x-rays, betas). This is a factor of about 3 to 4 for 29 kVp x-rays (e.g. as in diagnostic radiation exposures of the female breast) and for tritium beta-rays (encountered in parts of the nuclear industry) relative to Co-60 gamma radiation and 2-5 MeV gamma-rays (as received by the Japanese A-bomb survivors). In epidemiological studies, although for thyroid and breast cancer there appears to be a small tendency for the excess relative risks to decrease as the radiation energy increases for low-LET radiations, it is not statistically feasible to draw any conclusion regarding an underlying dependence of cancer risk on LET for the nominally low-LET radiations. (review)

  11. Relative biological effectiveness of 125I seeds for low-dose-rate irradiation of PANC-1

    International Nuclear Information System (INIS)

    Wang Jidong; Wang Junjie; Zhuang Hongqing; Liao Anyan; Zhao Yong

    2008-01-01

    Objective: To investigate the relative biological effectiveness(RBE) of National Model 6711 125 I seeds and the response patterns of PANC-1 exposed to 125 I seeds irradiation. Methods: PANC-1 cells in exponential growth were irradiated at initial dose rate of 2.59 cGy/h in vitro and exposed to 1, 2, 4, 6, 8 and 10 Gy. Meanwhile, the other part of cells were exposed to the same doses by 60 Co at dose rate of 2.21 Gy/min. After irradiation, the cells were stained by trypan blue to measure the cellular mortality rate and to compare the changes along with plating times of 12, 24, 48 and 72 h after 4 Gy. The colonies were counted to obtain the plating efficiencies by colony-forming assay and the cell surviving faction was calculated to plot cell survival curves, and RBE of 125 I seeds relative to 60 Co was determined. Results: The cell death rate for continuous low- dose-rate (LDR) irradiation by 125 I seeds was greater than 60 Co at the same doses above or equal to 4 Gy. After 4 Gy irradiation, the cellular mortality rates were increased with times. The difference was significant between 125 I seeds and 60 Co. The survival fractions of 125 I were lower than those of 60 Co, and the RBE of 125 I relative to 60 Co was determined to be 1.45. Conclusion: The cell-killing effects for continuous low-dose-rate (LDR) irradiation by 125 I seeds are greater than acute high-dose-rate of 60 Co. (authors)

  12. Child Development in the Context of Adversity: Experiential Canalization of Brain and Behavior

    Science.gov (United States)

    Blair, Clancy; Raver, C. Cybele

    2012-01-01

    The authors examine the effects of poverty-related adversity on child development, drawing upon psychobiological principles of experiential canalization and the biological embedding of experience. They integrate findings from research on stress physiology, neurocognitive function, and self-regulation to consider adaptive processes in response to…

  13. Level of Awareness of Biology and Geography Students Related to Recognizing Some Plants

    Science.gov (United States)

    Aladag, Caner; Kaya, Bastürk; Dinç, Muhittin

    2017-01-01

    The aim of this study is to investigate the awareness of the geography and biology students about recognizing some plants which they see frequently around them in accordance with the information they gained during their education process. The sample of the study consists of 37 biology and 40 geography students studying at the Ahmet Kelesoglu…

  14. Applications of Structural Biology and Bioinformatics in the Investigation of Oxidative Stress-Related Processes

    NARCIS (Netherlands)

    Bersch, Beate; Groves, Matthew; Johann, Klare; Torda, Andrew; Ortiz, Dario; Laher, I.

    2014-01-01

    Reactive oxygen species (ROS)-mediated dysfunction of certain biological processes is implicated in different diseases in humans, including cardiovascular, cancer, or neurodegenerative disorders. Not only human cells and tissues are affected by ROS but also all other biological systems, including

  15. Biological effectiveness of /sup 67/Ga relative to external x-rays

    International Nuclear Information System (INIS)

    Rao, D.V.; Mylavarapu, V.B.; Govelitz, G.F.; Sastry, K.S.R.; Howell, R.W.

    1987-01-01

    As a consequence of electron-capture decay, /sup 67/Ga emits several low energy electrons. The dosimetry of such Auger-emitters in vivo is of considerable interest. The effects of /sup 67/Ga-citrate are investigated using gametogenesis in male and female mice as the experimental models. Spermatogonial cells in mouse testes and primary oocytes in mouse ovary are very sensitive to radiation. Damage caused to spermatogonial cells can be observed as reduced number of sperm heads after a defined period of time, whereas the reduction in the primary oocytes can be readily counted following simple histological procedures. The sperm head survival curve with internally administered /sup 67/Ga-citrate gave a D/sub o/ value of 42 cGy. This value for primary oocyte survival is found to be 4.5 cGy. With external 120 kVp X-rays, the corresponding D/sub o/ values are 67 cGy for the testis and 8.5 cGy for the ovary. The values of relative biological effectiveness are therefore 1.6 and 1.9 respectively. These observed higher RBE values suggest that the conventional MIRD procedure to calculate the absorbed doses is insufficient and the localized deposition of energy at the cellular level must be taken into consideration

  16. Bauhinia forficata Link authenticity using flavonoids profile: relation with their biological properties.

    Science.gov (United States)

    Ferreres, Federico; Gil-Izquierdo, Angel; Vinholes, Juliana; Silva, Sara T; Valentão, Patrícia; Andrade, Paula B

    2012-09-15

    HPLC-DAD-ESI/MS(n) was used to ascertain the authenticity of two certified and two commercial Bauhinia forficata Link samples. Different flavonoids profiles were obtained, involving 39 compounds. Just kaempferol-3-O-(2-rhamnosyl)rutinoside was found in all analysed samples. Five compounds were common to the certified samples of B. forficata Link and B. forficata Link subsp. pruinosa (Vogel) Fortunato & Wunderlin, being kaempferol derivatives the most representative ones. The phenolic composition of B. forficata Link subsp. pruinosa (Vogel) Fortunato & Wunderlin is described herein for the first time, accounting for eight compounds, while 10 new compounds were identified in B. forficata Link. Commercial B. forficata Link showed higher contents of quercetin derivatives, in addition to the presence of myricetin derivatives and flavonoids-(galloyl)glycosides, for which the MS fragmentation pattern is reported for the first time. B. forficata Link and the two commercial samples were able to inhibit α-glucosidase, with EC(50) values lower than that found for acarbose. Mild effects on cholinesterases were observed with the certified samples, while commercial ones were more effective. The same behaviour was observed concerning the scavenging of DPPH, nitric oxide and superoxide radicals. The presence of high contents of quercetin derivatives in commercial samples seems to directly influence their biological properties. The differences between phenolic profiles and their relation with the authenticity of commercial samples are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. BRISK--research-oriented storage kit for biology-related data.

    Science.gov (United States)

    Tan, Alan; Tripp, Ben; Daley, Denise

    2011-09-01

    In genetic science, large-scale international research collaborations represent a growing trend. These collaborations have demanding and challenging database, storage, retrieval and communication needs. These studies typically involve demographic and clinical data, in addition to the results from numerous genomic studies (omics studies) such as gene expression, eQTL, genome-wide association and methylation studies, which present numerous challenges, thus the need for data integration platforms that can handle these complex data structures. Inefficient methods of data transfer and access control still plague research collaboration. As science becomes more and more collaborative in nature, the need for a system that adequately manages data sharing becomes paramount. Biology-Related Information Storage Kit (BRISK) is a package of several web-based data management tools that provide a cohesive data integration and management platform. It was specifically designed to provide the architecture necessary to promote collaboration and expedite data sharing between scientists. The software, documentation, Java source code and demo are available at http://genapha.icapture.ubc.ca/brisk/index.jsp. BRISK was developed in Java, and tested on an Apache Tomcat 6 server with a MySQL database. denise.daley@hli.ubc.ca.

  18. Relative biological effectiveness of high energy protons for a human melanoma

    International Nuclear Information System (INIS)

    Petrovic, I.; Ristic-Fira, A.; Todorovic, D.; Valastro, I.; Cirrone, P.; Cuttone, G.

    2005-01-01

    Relative biological effectiveness (RBE) for the survival of human melanoma cells induced by high linear energy transfer (LET) protons was investigated. Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons, as well as with 60 Co γ-rays, over single doses, ranging from 8-24 Gy. Clonogenic survival and cell viability were assessed up to 48 h post-irradiation, therefore considered as early inactivation effects. Dose dependent cell inactivation induced by high LET protons was observed. Surviving fractions have shown great overlapping with estimated cell viability, both with the increase of dose and with prolonged cell incubation. Evaluated RBEs were higher with the rise of dose, being in the range from 2 to 3. All analyzes performed have demonstrated a very radio-resistant nature of HTB140 melanoma cells. However, high LET protons are able to inactivate these cells in a larger extent compared to the effects of γ-rays. (author)

  19. Relative biological effectiveness of the therapeutic proton beams at NIRS and Tsukuba University

    International Nuclear Information System (INIS)

    Ando, Koichi; Koike, Sachiko; Kawachi, Kiyomitsu

    1985-01-01

    Relative biological effectiveness (RBE) of proton beams dedicated to radiotherapy was examined using a method of simultaneous irradiation. Mice received i.v. transplantation of syngeneic fibrosarcoma (NFSa) cells. These mice were divided into 3 groups on the following day, and thorax was simultaneously irradiated with one of the following beams: 70MeV proton beam at National Institute of Radiological Sciences (NIRS), 250 MeV Proton beam at Tsukuba University (PARMS) and 60 Co γ ray. Ten to 13 days thereafter, lungs were removed for colony counts to give dose-cell survival relationships. RBE of NIRS proton was ranging from 1.01 to 1.12 with an average of 1.06 while that of PARMS proton was ranging from 1.03 to 1.09 with an average of 1.06 at surviving fraction of 0.01. The simultaneous irradiation for RBE study was found to be reliable at large dose-low survival regions. (author)

  20. Biological effects of repeated inhalation exposure of beagle dogs to relatively insoluble aerosols of 144Ce

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1980-01-01

    Beagle dogs were exposed repeatedly to a relatively insoluble form of 144 Ce (in fused aluminosilicate particles) to study the deposition, retention, and long-term biological effects for comparison with data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every 8 weeks for 2 years (13 exposures) to achieve specified exposure goals. These goals were: to increase the lung burden by 2.5 μCi 144 Ce/kg body weight with each exposure; to reestablish lung burdens of 9 or 4.5 μCi 144 Ce/kg body weight and to expose controls to fused aluminosilicate particles containing nonradioactive cerium. To date, 19 exposed dogs and 2 control dogs have died or were euthanized. The most prevalent findings to date have been pulmonary carcinomas (7 dogs) and hemangiosarcomas in the tracheobronchial lymph nodes (3 dogs). Observations are continuing on the surviving 8 144 Ce-exposed and 7 control dogs who are now at approximately 2500 days (6.8 years) after the first exposure

  1. Biological Roles of Aberrantly Expressed Glycosphingolipids and Related Enzymes in Human Cancer Development and Progression

    Directory of Open Access Journals (Sweden)

    Dinghao Zhuo

    2018-05-01

    Full Text Available Glycosphingolipids (GSLs, which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition, and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains. Structures and functions of specific GSLs are also determined by their oligosaccharide chains. Different cells and tissues show differential expression of GSLs, and changes in structures of GSL glycan moieties occur during development of numerous types of human cancer. Association of GSLs and/or related enzymes with initiation and progression of cancer has been documented in 100s of studies, and many such GSLs are useful markers or targets for cancer diagnosis or therapy. In this review, we summarize (i recent studies on aberrant expression and distribution of GSLs in common human cancers (breast, lung, colorectal, melanoma, prostate, ovarian, leukemia, renal, bladder, gastric; (ii biological functions of specific GSLs in these cancers.

  2. Molecular biological approaches to the study of vectors in relation to malaria control

    Directory of Open Access Journals (Sweden)

    J. M. Crampton

    1992-01-01

    Full Text Available To a large extent, control of malaria vectors relies on the elimination of breeding sites and the application of chemical agents. There are increasing problems associated with the use of synthetic insecticides for vector control, including the evolution of resistance, the high cost of developing and registering new insecticides and an awareness of pollution from insecticide residues. These factors have stimulated interest in the application of molecular biology to the study of mosquito vectors of malaria; focussing primarily on two aspects. First, the improvement of existing control measures through the development of simplified DNA probe systems suitable for identification of vectors of malaria. The development of synthetic, non-radioactive DNA probes suitable for identification of species in the Anopheles gambiae complex is described with the aim of defining a simplified methodology wich is suitable for entomologist in the field. The second aspect to be considered is the development of completely novel strategies through the development of completely novel strategies through the genetic manipulation of insect vectors of malaria in order to alter their ability to transmit the disease. The major requirements for producing transgenic mosquitoes are outlined together with the progress wich has been made to date and discussed in relation to the prospects which this type of approach has for the future control of malaria.

  3. Behaviour of biological indicators of cadmium in relation to occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ghezzi, I; Toffoletto, F; Sesana, G; Fagioli, M G; Micheli, A; Di Silvestro, P; Zocchetti, C; Alessio, L

    1985-01-01

    Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determined in 83 male workers exposed to cadmium fumes. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroup of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.

  4. Variation of Phenolic Content in Globe Artichoke in Relation to Biological, Technical and Environmental Factors

    Directory of Open Access Journals (Sweden)

    Sara Lombardo

    2009-12-01

    Full Text Available In Italy, globe artichoke production is prevailingly concentrated in the South and islands, where it provides an important contribution to the agricultural economy. In recent years, there has been a renewed interest in this crop as a promising source of polyphenols, a heterogeneous class of secondary metabolites characterized by various healthy properties well-documented in literature. The phenolic fraction, present in the different artichoke plant parts, varies widely in relation to biotic and abiotic factors. Therefore, the present study aimed at evaluating the variation of phenolic content in globe artichoke in relation to biological, technical and environmental factors. Two field-experiments were carried out in Sicily (South Italy in two representative cultivation areas, in order to examine the effects of genotype, head fraction, season conditions, planting density and arrangement on the globe artichoke phenolic concentration. Both the total polyphenols and the individual phenolic compounds detected were notably genotype- dependent. Particularly, the high level of caffeoylquinic acids (chlorogenic acid, among others and apigenin 7- O-glucuronide, reported respectively by “Violetto di Sicilia” and “Romanesco clone C3”, could be used to encourage globe artichoke fresh consumption. Total polyphenols content also resulted more abundant in specific accumulation sites within the inflorescence, such as the floral stem and receptacle, and for most of genotypes it decreased during the second year in response to the different meteorological conditions. Additionally, total polyphenols content significantly and linearly increased as plant density increased from 1.0 to 1.8 plant m-2 and it significantly increased by 13% passing from single to twin rows plant arrangement.

  5. Variation of Phenolic Content in Globe Artichoke in Relation to Biological, Technical and Environmental Factors

    Directory of Open Access Journals (Sweden)

    Giovanni Mauromicale

    2011-02-01

    Full Text Available In Italy, globe artichoke production is prevailingly concentrated in the South and islands, where it provides an important contribution to the agricultural economy. In recent years, there has been a renewed interest in this crop as a promising source of polyphenols, a heterogeneous class of secondary metabolites characterized by various healthy properties well-documented in literature. The phenolic fraction, present in the different artichoke plant parts, varies widely in relation to biotic and abiotic factors. Therefore, the present study aimed at evaluating the variation of phenolic content in globe artichoke in relation to biological, technical and environmental factors. Two field-experiments were carried out in Sicily (South Italy in two representative cultivation areas, in order to examine the effects of genotype, head fraction, season conditions, planting density and arrangement on the globe artichoke phenolic concentration. Both the total polyphenols and the individual phenolic compounds detected were notably genotype- dependent. Particularly, the high level of caffeoylquinic acids (chlorogenic acid, among others and apigenin 7- O-glucuronide, reported respectively by “Violetto di Sicilia” and “Romanesco clone C3”, could be used to encourage globe artichoke fresh consumption. Total polyphenols content also resulted more abundant in specific accumulation sites within the inflorescence, such as the floral stem and receptacle, and for most of genotypes it decreased during the second year in response to the different meteorological conditions. Additionally, total polyphenols content significantly and linearly increased as plant density increased from 1.0 to 1.8 plant m-2 and it significantly increased by 13% passing from single to twin rows plant arrangement.

  6. WE-H-BRA-07: Mechanistic Modelling of the Relative Biological Effectiveness of Heavy Charged Particles

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, S [Massachusetts General Hospital, Boston, MA (United States); Queen’s University, Belfast, Belfast (United Kingdom); McNamara, A; Schuemann, J; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States); Prise, K [Queen’s University, Belfast, Belfast (United Kingdom)

    2016-06-15

    Purpose Uncertainty in the Relative Biological Effectiveness (RBE) of heavy charged particles compared to photons remains one of the major uncertainties in particle therapy. As RBEs depend strongly on clinical variables such as tissue type, dose, and radiation quality, more accurate individualised models are needed to fully optimise treatments. MethodsWe have developed a model of DNA damage and repair following X-ray irradiation in a number of settings, incorporating mechanistic descriptions of DNA repair pathways, geometric effects on DNA repair, cell cycle effects and cell death. Our model has previously been shown to accurately predict a range of biological endpoints including chromosome aberrations, mutations, and cell death. This model was combined with nanodosimetric models of individual ion tracks to calculate the additional probability of lethal damage forming within a single track. These lethal damage probabilities can be used to predict survival and RBE for cells irradiated with ions of different Linear Energy Transfer (LET). ResultsBy combining the X-ray response model with nanodosimetry information, predictions of RBE can be made without cell-line specific fitting. The model’s RBE predictions were found to agree well with empirical proton RBE models (Mean absolute difference between models of 1.9% and 1.8% for cells with α/β ratios of 9 and 1.4, respectively, for LETs between 0 and 15 keV/µm). The model also accurately recovers the impact of high-LET carbon ion exposures, showing both the reduced efficacy of ions at extremely high LET, as well as the impact of defects in non-homologous end joining on RBE values in Chinese Hamster Ovary cells.ConclusionOur model is predicts RBE without the inclusion of empirical LET fitting parameters for a range of experimental conditions. This approach has the potential to deliver improved personalisation of particle therapy, with future developments allowing for the calculation of individualised RBEs. SJM is

  7. Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma

    Science.gov (United States)

    Imataki, Osamu; Arai, Hidekazu; Kume, Tetsuo; Shiozaki, Hitomi; Katsumata, Naomi; Mori, Mariko; Ishide, Keiko; Ikeda, Takashi

    2018-01-01

    Background The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. Material/Methods We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. Results Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=−0.73, P=0.003; r=−0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). Conclusions Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation. PMID:29398693

  8. Adverse Weather Evokes Nostalgia.

    Science.gov (United States)

    van Tilburg, Wijnand A P; Sedikides, Constantine; Wildschut, Tim

    2018-03-01

    Four studies examined the link between adverse weather and the palliative role of nostalgia. We proposed and tested that (a) adverse weather evokes nostalgia (Hypothesis 1); (b) adverse weather causes distress, which predicts elevated nostalgia (Hypothesis 2); (c) preventing nostalgia exacerbates weather-induced distress (Hypothesis 3); and (d) weather-evoked nostalgia confers psychological benefits (Hypothesis 4). In Study 1, participants listened to recordings of wind, thunder, rain, and neutral sounds. Adverse weather evoked nostalgia. In Study 2, participants kept a 10-day diary recording weather conditions, distress, and nostalgia. We also obtained meteorological data. Adverse weather perceptions were positively correlated with distress, which predicted higher nostalgia. Also, adverse natural weather was associated with corresponding weather perceptions, which predicted elevated nostalgia. (Results were mixed for rain.) In Study 3, preventing nostalgia (via cognitive load) increased weather-evoked distress. In Study 4, weather-evoked nostalgia was positively associated with psychological benefits. The findings pioneer the relevance of nostalgia as source of comfort in adverse weather.

  9. Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

    Science.gov (United States)

    Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (pbystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

  10. Biological effects of repeated exposure of beagle dogs to relatively insoluble aerosols of 144Ce. IV

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Hanika-Rebar, C.; McClellan, R.O.; Mauderly, J.L.; Pickrell, J.A.

    1977-01-01

    This experiment is being conducted to study the behavior and long-term biological effects in Beagle dogs of 144 Ce inhaled in fused aluminosilicate particles in repeated inhalation exposures for comparison with similar data from dogs that were exposed only once to a similar aerosol. Four groups of nine dogs each were exposed once every eight weeks for two years (13 exposures) to achieve specified exposure goals. The 144 Ce-exposed dogs received increasing or relatively constant beta radiation dose rates in contrast to the steadily decreasing dose rate seen after a single inhalation exposure. Exposures in the first and second groups were planned to yield a cumulative absorbed dose to lung of approximately equal to 35,000 rads and those in the third group approximately equal to 17,000 rads within two years after the first exposure. Singly exposed dogs that had died with pulmonary tumors when this experiment was initiated had cumulative doses to death of 29,000 to 61,000 rads. All 13 exposures have been completed. One dog in the 4.5-μCi 144 Ce/kg body weight group died at 771 days after first exposure with emaciation, adrenal cortical degeneration and bone marrow aplasia. One control dog died accidentally during anesthesia. During the past year, two additional dogs have died. One dog in the repeated 2.5-μCi 144 Ce/kg body weight group died at 1256 days after the first exposure with radiation pneumonitis and pulmonary fibrosis and a control dog died at 1052 days with autoimmune hemolytic anemia. The remaining 32 dogs appear to be in good physical condition except for a persistent lymphopenia at approximately equal to 4 years after the first exposure. They are being maintained for life span observations

  11. SU-E-T-549: Modeling Relative Biological Effectiveness of Protons for Radiation Induced Brain Necrosis

    International Nuclear Information System (INIS)

    Mirkovic, D; Peeler, C; Grosshans, D; Titt, U; Taleei, R; Mohan, R

    2015-01-01

    Purpose: To develop a model of the relative biological effectiveness (RBE) of protons as a function of dose and linear energy transfer (LET) for induction of brain necrosis using clinical data. Methods: In this study, treatment planning information was exported from a clinical treatment planning system (TPS) and used to construct a detailed Monte Carlo model of the patient and the beam delivery system. The physical proton dose and LET were computed in each voxel of the patient volume using Monte Carlo particle transport. A follow-up magnetic resonance imaging (MRI) study registered to the treatment planning CT was used to determine the region of the necrosis in the brain volume. Both, the whole brain and the necrosis volumes were segmented from the computed tomography (CT) dataset using the contours drawn by a physician and the corresponding voxels were binned with respect to dose and LET. The brain necrosis probability was computed as a function of dose and LET by dividing the total volume of all necrosis voxels with a given dose and LET with the corresponding total brain volume resulting in a set of NTCP-like curves (probability as a function of dose parameterized by LET). Results: The resulting model shows dependence on both dose and LET indicating the weakness of the constant RBE model for describing the brain toxicity. To the best of our knowledge the constant RBE model is currently used in all clinical applications which may Result in increased rate of brain toxicities in patients treated with protons. Conclusion: Further studies are needed to develop more accurate brain toxicity models for patients treated with protons and other heavy ions

  12. Measurements of Relative Biological Effectiveness and Oxygen Enhancement Ratio of Fast Neutrons of Different Energies

    Energy Technology Data Exchange (ETDEWEB)

    Barendsen, G. W.; Broerse, J. J. [Radiobiological Institute of the Health Research Council TNO, Rijswijk (ZH) (Netherlands)

    1968-03-15

    Impairment of the reproductive capacity of cultured cells of human kidney origin (T-l{sub g} cells) has been measured by the Puck cloning technique. From the dose-survival curves obtained in these experiments by irradiation of cells in equilibrium with air and nitrogen, respectively, the relative biological effectiveness (RBE) and the oxygen enhancement ratios (OER) were determined for different beams of fast neutrons. Monoenergetic neutrons of 3 and 15 MeV energy, fission spectrum fast neutrons (mean energy about 1.5 MeV), neutrons produced by bombarding Be with cyclotron-accelerated 16 MeV deuterons (mean energy about 6 MeV) and neutrons produced by bombarding Be with cyclotron- accelerated 20 MeV {sup 3}He ions (mean energy about 10 MeV) have been compared with 250 kVp X-rays as a standard reference. The RBE for 50% cell survival varies from 4.7 for fission-spectrum fast neutrons to 2.7 for 15 MeV monoenergetic neutrons. The OER is not strongly dependent on the neutron energy for the various beams investigated. For the neutrons with the highest and lowest energies used OER values of 1.6 {+-} 0.2 and 1.5 {+-} 0.1 were measured. An interpretation of these data on the basis of the shapes of the LET spectra is proposed and an approximate verification of this hypothesis is provided from measurements in which secondary particle equilibrium was either provided for or deliberately eliminated. (author)

  13. Radiation biology using synchrotron radiation. In relation to radiation chemistry as an initial process

    International Nuclear Information System (INIS)

    Kobayashi, Katsumi

    1995-01-01

    Radiation biology using synchrotron radiation have been investigated, focusing on the mechanism of the formation of molecular damage. This paper introduces recent outcome of these studies. First, the process from imparted energy to the formation of molecular damage is outlined. The previous studies can be largely categorized as dealing with (1) biological effects of inner-shell ionization on elements composing the living body and (2) X-ray energy dependence of biological effects. Bromine and phosphorus are used as elements for the study of inner-cell ionization. In the study on lethal effects of monochromatic soft X-rays on the BrdUMP-incorporated yeast cells, Auger enhancement was found to occur. The first report on the effects of K-shell absorption of cellular phosphorus atoms has revealed that biological effects on cellular lethality and genetic changes was enhanced by 40%. Plasmid DNA and oligonucleotide have been used to study biological effects of vacuum ultraviolet rays to monochromatic soft X-ray, which makes it possible to study strand breaks. Because experimental production of energy required for the formation of double strand breaks has become possible, synchrotron radiation plays a very important role in radiation biological studies. Finally, future issues are presented. (N.K.)

  14. First International Conference on Lysophospholipids and Related Bioactive Lipids in Biology and Disease Sponsored by the Federation of American Societies of Experimental Biology

    Directory of Open Access Journals (Sweden)

    Edward J. Goetzl

    2001-01-01

    Full Text Available The First International Conference on “Lysophospholipids and Related Bioactive Lipids in Biology and Diseases” was held in Tucson, AZ on June 10�14, 2001, under the sponsorship of the Federation of American Societies of Experimental Biology (FASEB. More than 100 scientists from 11 countries discussed the recent results of basic and clinical research in the broad biology of this emerging field. Immense progress was reported in defining the biochemistry of generation and biology of cellular effects of the bioactive lysophospholipids (LPLs. These aspects of LPLs described at the conference parallel in many ways those of the eicosanoid mediators, such as prostaglandins and leukotrienes. As for eicosanoids, the LPLs termed lysophosphatidic acid (LPA and sphingosine 1-phosphate (S1P are produced enzymatically from phospholipid precursors in cell membranes and act on cells at nanomolar concentrations through subfamilies of receptors of the G protein–coupled superfamily. The rate-limiting steps in production of LPLs were reported to be controlled by specific phospholipases for LPA and sphingosine kinases for S1P. The receptor subfamilies formerly were designated endothelial differentiation gene-encoded receptors or Edg Rs for their original discovery in endothelial cells. A currently active nomenclature committee at this conference suggested the ligand-based names: S1P1 = Edg-1, S1P2 = Edg-5, S1P3 = Edg-3, S1P4 = Edg-6, and S1P5 = Edg-8; LPA1 = Edg-2, LPA2 = Edg-4, and LPA3 = Edg-7 receptors. Several families of lysophospholipid phosphatases (LPPs have been characterized, which biodegrade LPA, whereas S1P is inactivated with similar rapidity by both a lyase and S1P phosphatases.

  15. Spectroscopic characterisation of biological vaterite: relations to synthetic and geological vaterites

    Science.gov (United States)

    Jacob, D. E.; Wehrmeister, U.; Soldati, A. L.; Hofmeister, W.

    2009-04-01

    The pair aragonite and calcite are some of the most intensively studied polymorphous minerals. These CaCO3 polymorphs are most commonly observed in biological minerals produced by marine molluscs, whereas in freshwater molluscs mostly aragonite and vaterite, the third CaCO3 polymorph is identified (e.g. Wehrmeister et al., 2007). Vaterite is the thermodynamically most unstable CaCO3 polymorph and is often discussed as a precursor phase in the mineralization of aragonite or calcite by organisms. Apart from these biological parageneses, vaterite is also known as rare small polycrystalline aggregates from geological occurrences. In laboratory crystallisation experiments, vaterite can be stabilized either kinetically or with the help of organic macromolecules (e.g. Falini et al., 2005). Despite considerable research on vaterite, it is less well known that the crystal structure of vaterite is not unobjectionably determined. Due to the overall small crystal sizes, single crystal XRD analysis of vaterite is very difficult and this could be one of the reasons for the lack of a conclusive determination of the crystal structure. At least four different crystal structure proposals have to be considered: One proposed vaterite to be pseudo hexagonal and to crystallise in the orthorhombic space group Pnma (Meyer 1959). In addition, three crystal structures with hexagonal unit cells are proposed: Kamhi (1963) and Meyer (1969) proposed the same crystal space group: P63/mmc, whereas the site symmetry of the carbonate ion is proposed to be different with 2mm and m, respectively. Lastly, Lippmann (1973) proposed a structure based on the high-temperature modification of YbBO3 with space group 6322. Here, we present new and complete Raman spectra for biological, geological and synthetic vaterite. The spectroscopic results are evaluated in light of all published crystal structures for vaterite and are aimed at gaining more detailed information about the crystallographic features of

  16. Hospital deaths and adverse events in Brazil

    Directory of Open Access Journals (Sweden)

    Pavão Ana Luiza B

    2011-09-01

    Full Text Available Abstract Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103 and that related to preventable adverse events was 2.3% (25/1103. Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43 and the odds ratio adjusted for patient risk factors (OR 8.23 between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events.

  17. Childhood adversity, perceived discrimination, and coping strategies in relation to depressive symptoms among First Nations adults in Canada: The moderating role of unsupportive social interactions from ingroup and outgroup members.

    Science.gov (United States)

    McQuaid, Robyn Jane; Bombay, Amy; McInnis, Opal Arilla; Matheson, Kimberly; Anisman, Hymie

    2015-07-01

    Aboriginal peoples are at greater risk of experiencing early life adversity relative to non-Aboriginal peoples in Canada, and as adults frequently experience high levels of discrimination that act as a further stressor. Although these factors appear to contribute to high rates of depressive disorders and suicidality in Aboriginal peoples, the psychosocial factors that contribute to the relationship between childhood adversity and the development of depressive symptoms have hardly been assessed in this group. The present investigation explored potential mediators to help explain the relation between childhood trauma and depressive symptoms among a sample of First Nations adults from across Canada. These mediated relationships were further examined in the context of unsupportive social interactions from ingroup and outgroup members. In Study 1, (N = 225), the relationship between childhood trauma and depression scores was mediated by perceived discrimination, and this was particularly notable in the presence of unsupportive relations with outgroup members. In Study 2, (N = 134) the relationship between childhood trauma and depressive symptoms was mediated by emotion-focused coping that was specific to coping with experiences of ethnic discrimination, and this mediated effect was moderated by both outgroup and ingroup unsupportive social interactions. Thus, it seems that experiences of discrimination and unsupport might contribute to depressive symptoms among First Nations adults who had experienced early life adverse events. (c) 2015 APA, all rights reserved).

  18. Relation of Serum Adiponectin Levels to Number of Traditional Atherosclerotic Risk Factors and All-Cause Mortality and Major Adverse Cardiovascular Events (from the Copenhagen City Heart Study)

    DEFF Research Database (Denmark)

    Lindberg, Soren; Mogelvang, Rasmus; Pedersen, Sune H

    2013-01-01

    adiponectin has been associated with increased mortality and an increasing number of major adverse CV events (MACE). Because of these conflicting results, the true role of adiponectin remains to be elucidated. In the Copenhagen City Heart Study, we prospectively followed up 5,624 randomly selected men...... and women from the community without CV disease. Plasma adiponectin was measured at the beginning of the study. The median follow-up time was 7.8 years (interquartile range 7.3 to 8.3). The end point was all-cause mortality (n = 801), and the combined end point was MACE, consisting of CV mortality...... or nonfatal myocardial infarction or ischemic stroke (n = 502). High adiponectin was inversely associated with an increasing number of traditional CV risk factors (p...

  19. Epidemiological profile of work-related accidents with biological exposure among medical students in a surgical emergency room.

    Science.gov (United States)

    Reis, Phillipe Geraldo Teixeira de Abreu; Driessen, Anna Luiza; da Costa, Ana Claudia Brenner Affonso; Nasr, Adonis; Collaço, Iwan Augusto; Tomasich, Flávio Daniel Saavedra

    2013-01-01

    To evaluate the accidents with biological material among medical students interning in a trauma emergency room and identify key related situations, attributed causes and prevention. we conducted a study with a quantitative approach. Data were collected through a questionnaire applied via internet, with closed, multiple-choice questions regarding accidents with biological material. The sample comprised 100 students. thirty-two had accidents with biological material. Higher-risk activities were local anesthesia (39.47%), suture (18.42%) and needle recapping (15.79%). The main routes of exposure to biological material were the eyes or mucosa, with 34%, and syringe needle puncture, with 45%. After contamination, only 52% reported the accident to the responsible department. The main causes of accidents and routes of exposure found may be attributed to several factors, such as lack of training and failure to use personal protective equipment. Educational and preventive actions are extremely important to reduce the incidence of accidents with biological materials and improve the conduct of post-exposure. It is important to understand the main causes attributed and situations related, so as general and effective measures can be applied.

  20. Exposures to airborne particulate matter and adverse perinatal outcomes: a biologically plausible mechanistic framework for exploring potential Exposição à matéria particulada aérea e efeitos perinatais adversos: referencial mecanístico biologicamente plausível para exploração de potenciais

    Directory of Open Access Journals (Sweden)

    Srimathi Kannan

    2007-12-01

    Full Text Available This article has three objectives: to describe the biologically plausible mechanistic pathways by which exposure to particulate matter (PM may lead to adverse perinatal outcomes of low birth weight (LBW, intrauterine growth retardation (IUGR, and preterm delivery (PTD; review evidence showing that nutrition affects biologic pathways; and explain mechanisms by which nutrition may modify the impact of PM exposure on perinatal outcomes. We propose an interdisciplinary framework that brings together maternal and infant nutrition, air pollution exposure assessment, and cardiopulmonary and perinatal epidemiology. Five possible biologic mechanisms have been put forth in the emerging environmental sciences literature and provide corollaries for the proposed framework. The literature indicates that the effects of PM on LBW, PTD, and IUGR may manifest through the cardiovascular mechanisms of oxidative stress, inflammation, coagulation, endothelial function, and hemodynamic responses. PM exposure studies relating mechanistic pathways to perinatal outcomes should consider the likelihood that biologic responses and adverse birth outcomes may be derived from both PM and non-PM sources. We present strategies for empirically testing the proposed model and developing future research efforts.São três os objetivos deste artigo: descrever rotas mecanísticas biologicamente plausíveis pelas quais a exposição à matéria particulada (MP pode levar a efeitos perinatais adversos, como baixo peso ao nascer (BPN, retardo do crescimento intra-uterino (RCIU e nascimentos pré-termo (NPT; fazer uma revisão de evidências mostrando que a nutrição afeta rotas biológicas; explicar os mecanismos através dos quais a nutrição pode modificar o impacto da exposição a MP nos efeitos perinatais adversos. Propomos um referencial interdisciplinar que aproxime nutrição materna e infantil, avaliação de poluição do ar e epidemiologia cardiopulmonar e perinatal

  1. Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

    International Nuclear Information System (INIS)

    Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

    2006-01-01

    Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters (α=0.15 Gy -1 and α/β=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD 2 ) with respect to three effects: edema, RBE, and dose heterogeneity for 125 I and 103 Pd implants. The EUD 2 analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V 100 (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D 90 (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for 125 I and 103 Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for 125 I and 1.3-1.6 for 103 Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies

  2. Relative biological value of 1α-hydroxycholecalciferol to 25-hydroxycholecalciferol in broiler chicken diets.

    Science.gov (United States)

    Han, J C; Chen, G H; Zhang, J L; Wang, J G; Qu, H X; Yan, Y F; Yang, X J; Cheng, Y H

    2017-07-01

    This study was conducted to evaluate the relative biological value (RBV) of 1α-hydroxycholecalciferol (1α-OH-D3) to 25-hydroxycholecalciferol (25-OH-D3) in one- to 21-day-old broiler chickens fed calcium (Ca)- and phosphorus (P)-deficient diets. On the d of hatch, 450 male Ross 308 broiler chickens were weighed and randomly allotted to 9 treatments with 5 replicates of 10 birds per replicate. The basal diet contained 0.50% Ca and 0.25% non-phytate phosphorus (NPP) but was not supplemented with cholecalciferol (vitamin D3). The levels of Ca and NPP in basal diets were lower than those recommended by NRC (1994). 25-OH-D3 was fed at zero, 1.25, 2.5, 5.0, and 10.0 μg/kg, and 1α-OH-D3 was fed at 0.625, 1.25, 2.5, and 5.0 μg/kg. The RBV of 1α-OH-D3 to 25-OH-D3 based on vitamin D intake was determined by the slope ratio method. Results showed that 25-OH-D3 or 1α-OH-D3 improved the growth performance and decreased the mortality in one- to 21-day-old broilers. A linear relationship was observed between the level of 25-OH-D3 or 1α-OH-D3 and mineralization of the femur, tibia, or metatarsus. The RBV of 1α-OH-D3 to 25-OH-D3 were 234, 253, and 202% when the weight, ash weight, and Ca percentage of femur were used as criteria. The corresponding RBV of 1α-OH-D3 to 25-OH-D3 were 232 to 263% and 245 to 267%, respectively, when tibia and metatarsus mineralization were used as criteria. These data indicate that when directly feeding a hormonally active form of vitamin D as 1α-OH-D3 proportionally less is needed than when using the precursor (25-OH-D3) in diets deficient in Ca and P. © 2017 Poultry Science Association Inc.

  3. Biological, psychological and social processes that explain celebrities' influence on patients' health-related behaviors.

    Science.gov (United States)

    Hoffman, Steven J; Tan, Charlie

    2015-01-01

    Celebrities can have substantial influence as medical advisors. However, their impact on public health is equivocal: depending on the advice's validity and applicability, celebrity engagements can benefit or hinder efforts to educate patients on evidence-based practices and improve their health literacy. This meta-narrative analysis synthesizes multiple disciplinary insights explaining the influence celebrities have on people's health-related behaviors. Systematic searches of electronic databases BusinessSource Complete, Communication & Mass Media Complete, Humanities Abstracts, ProQuest Political Science, PsycINFO, PubMed, and Sociology Abstracts were conducted. Retrieved articles were used to inform a conceptual analysis of the possible processes accounting for the substantial influence celebrities may have as medical advisors. Fourteen mechanisms of celebrity influence were identified. According to the economics literature, celebrities distinguish endorsed items from competitors and can catalyze herd behavior. Marketing studies tell us that celebrities' characteristics are transferred to endorsed products, and that the most successful celebrity advisors are those viewed as credible, a perception they can create with their success. Neuroscience research supports these explanations, finding that celebrity endorsements activate brain regions involved in making positive associations, building trust and encoding memories. The psychology literature tells us that celebrity advice conditions people to react positively toward it. People are also inclined to follow celebrities if the advice matches their self-conceptions or if not following it would generate cognitive dissonance. Sociology explains how celebrities' advice spreads through social networks, how their influence is a manifestation of people's desire to acquire celebrities' social capital, and how they affect the ways people acquire and interpret health information. There are clear and deeply rooted biological

  4. Interaction between childhood adversity and functional polymorphisms in the dopamine pathway on first-episode psychosis.

    Science.gov (United States)

    Trotta, Antonella; Iyegbe, Conrad; Yiend, Jenny; Dazzan, Paola; David, Anthony S; Pariante, Carmine; Mondelli, Valeria; Colizzi, Marco; Murray, Robin M; Di Forti, Marta; Fisher, Helen L

    2018-04-10

    There is consistent evidence of a cumulative relationship between childhood adversity and psychosis, with number of adversities experienced increasing the probability of psychosis onset. It is possible that genetic factors moderate the association between childhood adversity and psychosis, potentially by influencing how an individual reacts biologically and/or psychologically following exposure to adversity, in such a way as to set them off on the path to psychosis. However, identifying the specific genetic variants involved and how they interact with childhood adversity remains challenging. We examined whether the association between cumulative exposure to childhood adversity and development of psychotic disorder was moderated by the COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect dopamine levels. Participants were 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetics and Psychosis (GAP) study. Childhood adversity was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived genotype data were collected. Our findings revealed no main effect of COMT Val 158 Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case status or reports of childhood adversity. Individuals reporting a history of multiple adversities were more likely to be psychosis patients than controls, regardless of their genetic risk. There was no evidence of candidate genotype by childhood adversity interactions in relation to psychosis onset. These findings did not provide evidence of a possible role of COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Adulthood Personality Correlates of Childhood Adversity

    Directory of Open Access Journals (Sweden)

    Charles S. Carver

    2014-11-01

    Full Text Available Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed Anger/Aggression, Extrinsic focus, Agreeableness, and Engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower Agreeableness and to higher Anger/Aggression and Extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection.

  6. OAE: The Ontology of Adverse Events.

    Science.gov (United States)

    He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

    2014-01-01

    A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e

  7. New improved method for evaluation of growth by food related fungi on biologically derived materials

    DEFF Research Database (Denmark)

    Bergenholtz, Karina P.; Nielsen, Per Væggemose

    2002-01-01

    Biologically derived materials, obtained as commercial and raw materials (Polylactate (PLA), Polyhydroxybutyrate (PHB), potato, wheat and corn starch) were tested for their ability to support fungal growth using a modified ASTM G21-96 (American Society for Testing and Materials) standard as well...

  8. Identification of Biological and Pharmaceutical Mast Cell- and Basophil-Related Targets

    Czech Academy of Sciences Publication Activity Database

    Klein, O.; Ngo-Nyekel, F.; Stefanache, T.; Torres, R.; Salomonsson, M.; Hallgren, J.; Radinger, M.; Bambousková, Monika; Campbell, M.; Cohen-Mor, S.; Dema, B.; Rose, C.G.; Abrink, M.; Charles, N.; Ainooson, G.; Paivandy, A.; Pavlova, V.G.; Serrano-Candelas, E.; Yu, Y.; Hellman, L.; Jensen, B.M.; Van Anrooij, B.; Grootens, J.; Gura, H.K.; Stylianou, M.; Tobio, A.; Blank, U.; Ohrvik, H.; Maurer, M.

    2016-01-01

    Roč. 83, č. 6 (2016), s. 465-472 ISSN 0300-9475 Institutional support: RVO:68378050 Keywords : tyrosine kinase inhibitors * fc-epsilon-ri * in-vivo * inflammatory diseases * dependent activation * midostaurin pkc412 * mediator release * murine basophils * animal-models * mouse models Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Immunology Impact factor: 2.256, year: 2016

  9. Biological lifestyle factors related to cognition and learning performance in adults in distance education

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2015-01-01

    An important part of learning performance is influenced by individual characteristics. One of those are the environmental influences determined by lifestyle. We call these influences biological lifestyle factors (BLFs). Physical activity, sleep and nutrition are such BLFs and they contribute to

  10. Plant ecdysteroids: plant sterols with intriguing distributions, biological effects and relations to plant hormones

    Czech Academy of Sciences Publication Activity Database

    Tarkowská, Danuše; Strnad, Miroslav

    2016-01-01

    Roč. 244, č. 3 (2016), s. 545-555 ISSN 0032-0935 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Phytoecdysteroids * Ecdysteroids * 20-Hydroxyecdysone Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.361, year: 2016

  11. Physics of Non-Newtonian Fluids and Interdisciplinary Relations (Biology and Criminology)

    Science.gov (United States)

    Holubova, R.

    2018-01-01

    The aim of the paper is the presentation of an interdisciplinary topic that allows applying content knowledge in physics, mathematics and biology in real life environment. Students use to play games and view crime scenes but in common they have little knowledge about the science used during crime scene investigation. In this paper the science…

  12. Biodegradation of chlorinated unsaturated hydrocarbons in relation to biological waste-gas treatment

    NARCIS (Netherlands)

    Hartmans, S.

    1993-01-01

    The original goal of the research described in this thesis was to develop a biological process for the removal of vinyl chloride from waste gases. The gaseous and carcinogenic vinyl chloride is used to produce the plastic polyvinyl chloride (PVC). During this production process waste gases

  13. [THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

    Science.gov (United States)

    Titov, V N

    2015-11-01

    The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

  14. Towards a multidisciplinary and integrated strategy in the assessment of adverse health effects related to air pollution: The case study of Cracow (Poland) and asthma

    International Nuclear Information System (INIS)

    Oudinet, Jean-Paul; Meline, Julie; Chelmicki, Wojciech; Sanak, Marek; Magdalena, Dutsch-Wicherek; Besancenot, Jean-Pierre; Wicherek, Stanislas; Julien-Laferriere, Bertrand; Gilg, Jean-Paul; Geroyannis, Helene; Szczeklik, Andrew; Krzemien, Kazimierz

    2006-01-01

    Complex interaction between anthropogenic activities, air quality and human health in urban areas, such as in Cracow sustains the need for the development of an interdisciplinary and integrated risk-assessment methodology. In such purpose, we propose a pilot study performed on asthmatics and based on a combined use of a biomarker, such as metallothionein 2A (MT-2A) in the characterization of human exposure to one or a mixture of pollutants and of Geographical Information Systems (G.I.S.) which integrates climatic and urban anthropogenic parameters in the assessment of spatio-temporal dispersion of air pollutants. Considering global incidence of air pollution on asthma and on peripheral blood lymphocytes MT-2A expression should provide a complementary information on biological risks linked to urban anthropogenic activities. Such study would help for the establishment of a sustainable development in urban areas that can maintain the integrity of air quality and preserve human health. - An integrative risk methodology based on both geographic and molecular biological approaches is proposed for the assessment of asthmatics exposure to urban air pollution

  15. Radiotoxicity of gadolinium-148 and radium-223 in mouse testes: Relative biological effectiveness of alpha-particle emitters in vivo

    International Nuclear Information System (INIS)

    Howell, R.W.; Goddu, S.M.; Narra, V.R.

    1997-01-01

    The biological effects of radionuclides that emit α particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of α-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy α particles (3.2 MeV) emitted by 148 Gd is investigated and determined to be 7.4 ± 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po and 212 Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for α particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE α = 9.14 - 0.510 E α , where 3 α 223 Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 ± 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E α relationship to predict the biological effects of α-particle emitters in vivo. 42 refs., 5 figs., 1 tab

  16. Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

    Science.gov (United States)

    Berger, Jean-Luc; Nguyen, Yohan; Lebrun, Delphine; Migault, Caroline; Hentzien, Maxime; Marty, Hélène; Bani-Sadr, Firouzé

    2017-01-01

    We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

  17. Review and needs in actinide chemistry in relation with biological purposes

    Energy Technology Data Exchange (ETDEWEB)

    Ansoborlo, E.; Moulin, V.; Bion, L.; Doizi, D.; Moulin, C.; Cote, G.; Madic, C.; Van der Lee, J

    2004-07-01

    In case of accidental release of radionuclides in the environment, actinides could occur and may present an healthy risk for human beings. In order to study their behavior in human organism (metabolism, retention, excretion), it is of prime importance to know solution actinide chemistry, and more particularly thermodynamic constants, which will allow to determine their speciation: speciation governs biological availability and toxicity of elements and is also of great interest for decorporation purposes. In this framework, a CEA working group on speciation has been created in order to share data both on thermodynamic constants and on speciation analytical methods, interesting chemists, environmentalists and biologists. It has been focused, in a first time, on actinides. The purpose of this paper is to present the state of the art on actinide speciation within biological media and to focus on the lack of information in order to orientate future research. (authors)

  18. Solid Phase Microextraction and Related Techniques for Drugs in Biological Samples

    OpenAIRE

    Moein, Mohammad Mahdi; Said, Rana; Bassyouni, Fatma; Abdel-Rehim, Mohamed

    2014-01-01

    In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from o...

  19. IAEA activities related to radiation biology and health effects of radiation

    International Nuclear Information System (INIS)

    Wondergem, Jan; Rosenblatt, Eduardo

    2012-01-01

    The IAEA is involved in capacity building with regard to the radiobiological sciences in its member states through its technical cooperation programme. Research projects/programmes are normally carried out within the framework of coordinated research projects (CRPs). Under this programme, two CRPs have been approved which are relevant to nuclear/radiation accidents: (1) stem cell therapeutics to modify radiation-induced damage to normal tissue, and (2) strengthening biological dosimetry in IAEA member states. (note)

  20. Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

    Science.gov (United States)

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

    2010-02-01

    The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell

  1. Elemental analysis of samples of biological origin relative to their protein content by means of charged particle bombardment

    International Nuclear Information System (INIS)

    Szoekefalvi-Nagy, Z.; Demeter, I.; Varga, L.; Hollos-Nagy, K.; Keszthelyi, L.

    1981-04-01

    The particle excited X-ray emission (PIXE) and the 14 N(d,p) 15 N nuclear reaction is combined for simultaneous elemental composition and nitrogen content determination in biological samples. Using the correlation between nitrogen and proton content the elemental composition is related to the protein content of the sample. The principles and main characteristics of the method are described and illustrative applications are also given. (author)

  2. Investigations in space-related molecular biology. [cryo-electron microscopic and diffraction studies on terrestrial and extraterrestrial specimens

    Science.gov (United States)

    Fernandez-Moran, H.; Pritzker, A. N.

    1974-01-01

    Improved instrumentation and preparation techniques for high resolution, high voltage cryo-electron microscopic and diffraction studies on terrestrial and extraterrestrial specimens are reported. Computer correlated ultrastructural and biochemical work on hydrated and dried cell membranes and related biological systems provided information on membrane organization, ice crystal formation and ordered water, RNA virus linked to cancer, lunar rock samples, and organometallic superconducting compounds. Apollo 11, 12, 14, and 15 specimens were analyzed

  3. Relative biological effectiveness in a proton spread-out Bragg peak formed by pencil beam scanning mode

    Czech Academy of Sciences Publication Activity Database

    Michaelidesová, Anna; Vachelová, Jana; Puchalská, M.; Pachnerová Brabcová, Kateřina; Vondráček, V.; Sihver, L.; Davídková, Marie

    2017-01-01

    Roč. 40, č. 2 (2017), s. 359-368 ISSN 0158-9938 R&D Projects: GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:61389005 Keywords : Relative biological effectiveness * Proton therapy * Clonogennic assay * Micronuclei assay * Monte Carlo simulations * Scanning beam Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders OBOR OECD: Nuclear physics Impact factor: 1.171, year: 2016

  4. [Biological contamination in office buildings related to ventilation/air conditioning system].

    Science.gov (United States)

    Bródka, Karolina; Sowiak, Małgorzata; Kozajda, Anna; Cyprowski, Marcin; Irena, Szadkowska-Stańczyk

    2012-01-01

    Indoor air is contaminated with microorganisms coming from both the atmospheric air and sources present in premises. The aim of this study was to analyze the concentrations of biological agents in office buildings, dependending on ventilation/air conditioning system and season. The study covered office buildings (different in the system of ventila-tion/air conditioning). Air samples for assessing the levels of inhalable dust, endotoxins and (1-->3)-beta-D-glucans, were taken at the selected stationary points of each building during summer and winter. The air was sampled for 6 h, using portable sets consisting of the GilAir 5 pump and the head filled with a filter of fiber glass. The samples for the presence of airborne bacteria and fungi were collected twice during the day using the impaction method. Average concentrations of inhalable dust, bacteria, fungi, endotoxins and (1-->3)-beta-D-glucans in office premises were 0.09 mg/m3, 6.00 x 10(2) cfu/m3, 4.59 x 10(1) cfu/m3, 0.42 ng/m3 and 3.91 ng/m3, respectively. Higher concentrations of the investigated agents were found in summer. In premises with air conditioning concentrations of airborne fungi, (1-->3)-beta-D-glucans and inhalable dust were significantly lower in winter. In summer the trend was reverse except for (1-->3)-beta-D-glucans. Concentrations of biological agents were affected by the season and the presence of air conditioning. Concentrations of inhalable dust, bacteria, fungi, endotoxins and (1-->3)-beta-D-glucans, observed inside the office buildings, were significantly higher in summer than in winter. The presence of the air conditioning system modified in various ways the levels of biological agents. Its influence was greater on the concentration of fungi and (1-->3)-beta-D-glucans than on that of bacteria and endotoxins.

  5. Ranking Adverse Drug Reactions With Crowdsourcing

    KAUST Repository

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel; Altman, Russ B

    2015-01-01

    Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs

  6. Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications.

    Science.gov (United States)

    Vaupel, Peter; Mayer, Arnulf

    2014-01-01

    Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.

  7. A radioimmunoassay for the detection of diethylstilboestrol and related stilbenes in biological fluids

    International Nuclear Information System (INIS)

    Hallahan, Cornelius; McGarry, Yvonne; Collins, J.D.

    1985-01-01

    A radioimmunoassay for the measurement of the synthetic anabolic agent diethylstilboestrol (DES) is described. It is based on a commercially available antiserum and a tritiated derivative of DES. The method can detect low concentrations of residues (less than 0.5 ng/ml) in small samples (0.05 to 0.2 ml) of biological fluids. DES was measured in plasma, bile and urine obtained from a calf slaughtered 22 days after subcutaneous implantation of 24 mg DES. The assay described is suitable as a rapid screening procedure for identifying animals treated with stilbene substances. (author)

  8. Physics of non-Newtonian fluids and interdisciplinary relations (biology and criminology)

    Science.gov (United States)

    Holubova, R.

    2018-03-01

    The aim of the paper is the presentation of an interdisciplinary topic that allows applying content knowledge in physics, mathematics and biology in real life environment. Students use to play games and view crime scenes but in common they have little knowledge about the science used during crime scene investigation. In this paper the science background of blood spatter analysis is presented—the physics of non-Newtonian fluids, the biology of blood and mathematics—the measurement and calculation of the angle of inpact, the relationship between height and spatter diameter. This topic was choosen according to the analysis of interviews with secondary and high school learners realized at four schools in Moravia, Czech Republic. The topic can be taught at secondary schools so as at a higher level at high schools. Hands-on activities are included. The teaching strategy supports group work. The appropriateness and reasonableness of the topic was checked in the real teaching process and the activities have had a positive feedback.

  9. Relative biological effectiveness of alpha-particle emitters in vivo at low doses

    International Nuclear Information System (INIS)

    Howell, R.W.; Azure, M.T.; Narra, V.R.; Rao, D.V.

    1994-01-01

    The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 - 6.1 x 10 -2 LET + 1.0 x 10 -3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by RBE α = 22 E α -0.73 . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters. 46 refs., 6 figs

  10. Exploring Biological and Geological Age-related Changes through Variations in Intra- and Intertooth Proteomes of Ancient Dentine.

    Science.gov (United States)

    Procopio, Noemi; Chamberlain, Andrew T; Buckley, Michael

    2018-03-02

    Proteomic analyses are becoming more widely used in archeology not only due to the greater preservation of proteins in ancient specimens than DNA but also because they can offer different information, particularly relating to compositional preservation and potentially a means to estimate biological and geological age. However, it remains unclear to what extent different burial environments impact these aspects of proteome decay. Teeth have to date been much less studied than bone but are ideal to explore how proteins decay with time due to the negligible turnover that occurs in dentine relative to bone. We investigated the proteome variability and deamidation levels of different sections of molar teeth from archeological bovine mandibles as well as their mandibular bone. We obtained a greater yield of proteins from the crown of the teeth but did not find differences between the different molars analyzed within each mandible. We also obtained the best variety of protein from a well-preserved mandible that was not the youngest one in terms of chronological age, showing the influence of the preservation conditions on the final proteomic outcome. Intriguingly, we also noticed an increase in abundance levels of fetuin-A in biologically younger mandibles as reported previously, but the opposite trend in tooth dentine. Interestingly, we observed higher glutamine deamidation levels in teeth from the geologically oldest mandible despite it being the biologically youngest specimen, showing that the archeological age strongly impacts on the level of deamidations observed, much more so than biological aging. This indicates that the glutamine deamidation ratio of selected peptides may act as a good predictor of the relative geochronological age of archeological specimens.

  11. Guidelines for submitting adverse event reports for publication

    NARCIS (Netherlands)

    Kelly, William; Arellano, Felix; Barnes, Joanne; Bergman, Ulf; Edwards, Ralph; Fernandez, Alina; Freedman, Stephen; Goldsmith, David; Huang, Kui; Jones, Judith; McLeay, Rachel; Moore, Nicholas; Stather, Rosie; Trenque, Thierry; Troutman, William; van Puijenbroek, Eugène; Williams, Frank; Wise, Robert

    2009-01-01

    Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these

  12. Estimation of relative biological effectiveness for low energy protons using cytogenetic end points in mammalian cells

    International Nuclear Information System (INIS)

    Bhat, N.N.; Nairy, Rajesh; Chaurasia, Rajesh; Desai, Utkarsha; Shirsath, K.B.; Anjaria, K.B.; Sreedevi, B.

    2013-01-01

    A facility has been designed and developed to facilitate irradiation of biological samples to proton beam using folded tandem ion accelerator (FOTIA) at BARC. The primary proton beam from the accelerator was diffused using gold foil and channelled through a drift tube. Scattered beam was monitored and calibrated. Uniformity and dosimetry studies were conducted to calibrate the setup for precise irradiation of mammalian cells. Irradiation conditions and geometry were optimized for mammalian cells and other biological samples in thin layer. The irradiation facility is housed in a clean air laminar flow to help exposure of samples in aseptic conditions. The set up has been used for studying various radiobiological endpoints in many biological model systems. CHO, MCF-7, A-549 and INT-407 cell lines were studied in the present investigation using micronucleus (MN) induction as an indicator of radiation damage. The mammalian cells grown on petri plates to about 40 % confluence (log phase) were exposed to proton beam of known doses in the range of 0.1 to 2 Gy. The dose estimation was done based on specific ionization in cell medium. Studies were also conducted using 60 Co gamma radiation to compare the results. Linear quadratic response was observed for all the cell lines when exposed to 60 Co gamma radiation. In contrast, linear response was observed for proton beam. In addition, very significant increase in the MN yield was observed for proton beam compared to 60 Co gamma radiation. Estimated α and β values for CHO cells is found to be 0.02±0.003 Gy-1 and 0.042±0.006 Gy-2 respectively for 60 Co gamma radiation. For proton beam, estimated α for linear fit is found to be 0.37±0.011 Gy-1. Estimated RBE was found to be in the range of 4-8 for all the cell lines and dose ranges studied. In conclusion, the proton irradiation facility developed for mammalian cells has helped to study various radiobiological endpoints. In this presentation, facility description, MN as

  13. Assessment of biological chromium among stainless steel and mild steel welders in relation to welding processes.

    Science.gov (United States)

    Edmé, J L; Shirali, P; Mereau, M; Sobaszek, A; Boulenguez, C; Diebold, F; Haguenoer, J M

    1997-01-01

    Air and biological monitoring were used for assessing external and internal chromium exposure among 116 stainless steel welders (SS welders) using manual metal arc (MMA), metal inert gas (MIG) and tungsten inert gas (TIG) welding processes (MMA: n = 57; MIG: n = 37; TIG: n = 22) and 30 mild steel welders (MS welders) using MMA and MIG welding processes (MMA: n = 14; MIG: n = 16). The levels of atmospheric total chromium were evaluated after personal air monitoring. The mean values for the different groups of SS welders were 201 micrograms/m3 (MMA) and 185 micrograms/m3 (MIG), 52 micrograms/m3 (TIG) and for MS welders 8.1 micrograms/m3 (MMA) and 7.3 micrograms/m3 (MIG). The curve of cumulative frequency distribution from biological monitoring among SS welders showed chromium geometric mean concentrations in whole blood of 3.6 micrograms/l (95th percentile = 19.9), in plasma of 3.3 micrograms/l (95th percentile = 21.0) and in urine samples of 6.2 micrograms/l (95th percentile = 58.0). Among MS welders, mean values in whole blood and plasma were rather more scattered (1.8 micrograms/l, 95th percentile = 9.3 and 1.3 micrograms/l, 95th percentile = 8.4, respectively) and in urine the value was 2.4 micrograms/l (95th percentile = 13.3). The analysis of variance of chromium concentrations in plasma previously showed a metal effect (F = 29.7, P process effect (F = 22.2, P process interaction (F = 1.3, P = 0.25). Concerning urinary chromium concentration, the analysis of variance also showed a metal effect (F = 30, P process effect (F = 72, P process interaction (F = 13.2, P = 0.0004). Throughout the study we noted any significant differences between smokers and non-smokers among welders. Taking in account the relationships between chromium concentrations in whole, plasma or urine and the different welding process. MMA-SS is definitely different from other processes because the biological values are clearly higher. These higher levels are due to the very significant

  14. Expression Profiling of Genes Related to Endothelial Cells Biology in Patients with Type 2 Diabetes and Patients with Prediabetes

    Directory of Open Access Journals (Sweden)

    Sara Moradipoor

    2016-01-01

    Full Text Available Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT2 Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.

  15. Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

    Science.gov (United States)

    Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

    2013-01-01

    A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

  16. Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Bassler, Niels; Nielsen, Steffen

    2017-01-01

    of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. RESULTS: The MDD50 values......, where LETd,z =1 was 3.3 keV/μm. CONCLUSIONS: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated....

  17. Quantitative global and gene-specific promoter methylation in relation to biological properties of neuroblastomas

    Directory of Open Access Journals (Sweden)

    Kiss Nimrod B

    2012-09-01

    Full Text Available Abstract Background In this study we aimed to quantify tumor suppressor gene (TSG promoter methylation densities levels in primary neuroblastoma tumors and cell lines. A subset of these TSGs is associated with a CpG island methylator phenotype (CIMP in other tumor types. Methods The study panel consisted of 38 primary tumors, 7 established cell lines and 4 healthy references. Promoter methylation was determined by bisulphate Pyrosequencing for 14 TSGs; and LINE-1 repeat element methylation was used as an indicator of global methylation levels. Results Overall mean TSG Z-scores were significantly increased in cases with adverse outcome, but were unrelated to global LINE-1 methylation. CIMP with hypermethylation of three or more gene promoters was observed in 6/38 tumors and 7/7 cell lines. Hypermethylation of one or more TSG (comprising TSGs BLU, CASP8, DCR2, CDH1, RASSF1A and RASSF2 was evident in 30/38 tumors. By contrast only very low levels of promoter methylation were recorded for APC, DAPK1, NORE1A, P14, P16, TP73, PTEN and RARB. Similar involvements of methylation instability were revealed between cell line models and neuroblastoma tumors. Separate analysis of two proposed CASP8 regulatory regions revealed frequent and significant involvement of CpG sites between exon 4 and 5, but modest involvement of the exon 1 region. Conclusions/significance The results highlight the involvement of TSG methylation instability in neuroblastoma tumors and cell lines using quantitative methods, support the use of DNA methylation analyses as a prognostic tool for this tumor type, and underscore the relevance of developing demethylating therapies for its treatment.

  18. Summary of biological investigations relating to surface-water quality in the Kentucky River Basin, Kentucky

    International Nuclear Information System (INIS)

    Bradfield, A.D.; Porter, S.D.

    1990-01-01

    The Kentucky River basin, an area of approximately 7,000 sq mi, is divided into five hydrologic units that drain parts of three physiographic regions. Data on aquatic biological resources were collected and reviewed to assess conditions in the major streams for which data were available. The North, Middle, and south Forks of the Kentucky River are in the Eastern Coal Field physiographic region. Streams in this region are affected by drainage from coal mines and oil and gas operations, and many support only tolerant biotic stream forms. The Kentucky River from the confluence of the three forks to the Red River, is in the Knobs physiographic region. Oil and gas production operations and point discharges from municipalities have affected many streams in this region. The Red River, a Kentucky Wild River, supported a unique flora and fauna but accelerated sedimentation has eliminated many species of mussels. The Millers Creek drainage is affected by brines discharged from oil and gas operations, and some reaches support only halophilic algae and a few fish. The Kentucky River from the Red River to the Ohio River is in the Bluegrass physiographic region. Heavy sediment loads and sewage effluent from urban centers have limited the aquatic biota in this region. Silver Creek and South Elkhorn Creek have been particularly affected and aquatic communities in these streams are dominated by organisms tolerant of low dissolved oxygen concentrations. Biological data for other streams indicate that habitat and water quality conditions are favorable for most commonly occurring aquatic organisms. 205 refs., 7 figs., 1 tab

  19. Neutron activation analysis studies of marine biological species and related marine sediments

    International Nuclear Information System (INIS)

    Guinn, V.P.; Di Casa, M.; de Goeij, J.J.M.; Young, D.R.

    1974-01-01

    To assess the effects, if any, of elemental pollution of the Pacific Ocean from the major Southern California sewage outfalls, samples of ocean sediments were obtained and specimens of Dover Sole were caught in a number of locations. Liver tissue samples from Dover Sole specimens were analyzed for 12 elements and sediment samples for 4 elements. Although a number of the elements were highly concentrated in the surface sediments in the heavily-polluted areas, the Dover Sole showed no evidence of picking up any of the 12 elements from these polluted sediments. Sediment profiles, versus depth, (0-34 cm) were also determined for As, Sb, Se, and Hg. Stemming partly from the results of the NSF Baseline Study, the Southern California Coastal Water Research Project (SCCWRP) became interested in a more intensive multi-element study of marine biological species and ocean sediments off the coast of Southern California. The purpose of this study was to assess the effects, if any, of a number of selected elements of interest being discharged into the Pacific Ocean from the principal sewage outfalls in the Southern California (Los Angeles) area upon marine biological species. The 12 elements selected for study were Cr, Fe, Co, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, and Hg. Since a number of these elements were not amenable to purely instrumental NAA measurements, a suitable post-irradiation radiochemical separation procedure was devised, thoroughly tested, and then applied to 39 samples of liver tissue from specimens of Dover Sole caught in non-polluted, slightly-polluted, fairly-polluted, and heavily-polluted areas along the coast. A number of surface sediment samples from these same locations were also analyzed, by both instrumental and radiochemical NAA. In the following sections, the samples analyzed are cited, the procedures developed and employed are described, the results obtained are presented, and the conclusions reached are discussed

  20. Endocrine active agents: implications of adverse and non-adverse changes.

    Science.gov (United States)

    Foster, Paul M D; McIntyre, Barry S

    2002-01-01

    The US Environmental Protection Agency (EPA) is currently in the process of developing screening and testing methodologies for the assessment of agents that may possess endocrine-like activity--the so-called endocrine disruptors. Moreover, the EPA has signaled its intention of placing information arising from such studies on the worldwide web. This has created significant interest in how such information may be used in risk assessment and by policymakers and the public in the potential regulation or deselection of specific chemical agents. The construction of lists of endocrine disruptors, although fulfilling the requirements of some parties, is really of little use when the nature of the response, the dose level employed, and the lifestage of the test species used are not given. Thus, we have already seen positive in vitro information available on the interaction with a receptor being used as a key indicator when the results of large, high quality in vivo studies showing no adverse changes have been ignored. Clearly a number of in vitro systems are available to ascertain chemical interaction with specific (mainly steroid) hormone receptors including a number of reporter gene assays. These assays only provide indicators of potential problems and should not be, in isolation, indicators of toxicity. Likewise, short-term in vivo screens such as the uterotrophic and Hershberger studies are frequently conducted in castrated animals and thus indicate the potential for a pharmacological response in vivo rather than an adverse effect. A number of new end points have been added to standard rodent testing protocols in the belief of providing more sensitivity to detect endocrine related changes. These include the measurement of anogenital distance (AGD), developmental landmarks [vaginal opening (VO), preputial separation (PPS)], and in some studies the counting of nipples and areolae on males. AGD, VO, and PPS are all affected by the size of the pup in which they are measured

  1. [Prevention of medical device-related adverse events in hospitals: Specifying the recommendations of the German Coalition for Patient Safety (APS) for users and operators of anaesthesia equipment].

    Science.gov (United States)

    Bohnet-Joschko, Sabine; Zippel, Claus; Siebert, Hartmut

    2015-01-01

    The use and organisation of medical technology has an important role to play for patient and user safety in anaesthesia. Specification of the recommendations of the German Coalition for Patient Safety (APS) for users and operators of anaesthesia equipment, explore opportunities and challenges for the safe use and organisation of anaesthesia devices. We conducted a literature search in Medline/PubMed for studies dealing with the APS recommendations for the prevention of medical device-related risks in the context of anaesthesia. In addition, we performed an internet search for reports and recommendations focusing on the use and organisation of medical devices in anaesthesia. Identified studies were grouped and assigned to the recommendations. The division into users and operators was maintained. Instruction and training in anaesthesia machines is sometimes of minor importance. Failure to perform functional testing seems to be a common cause of critical incidents in anaesthesia. There is a potential for reporting to the federal authority. Starting points for the safe operation of anaesthetic devices can be identified, in particular, at the interface of staff, organisation, and (anaesthesia) technology. The APS recommendations provide valuable information on promoting the safe use of medical devices and organisation in anaesthesia. The focus will be on risks relating to the application as well as on principles and materials for the safe operation of anaesthesia equipment. Copyright © 2015. Published by Elsevier GmbH.

  2. Setting the stage to advance the adverse outcome pathway (AOP) framework through horizon scanning

    Science.gov (United States)

    Recognizing the international interest surrounding the adverse outcome pathway framework, which captures existing information describing causal linkages between a molecular initiating event through levels of biological organization to an adverse outcome of regulatory significance...

  3. Speciation of trace elements in biological samples by nuclear analytical and related techniques coupled with chemical and biochemical separation

    International Nuclear Information System (INIS)

    Chen, C.Y.; Gao, Y.X.; Li, B.; Yu, H.W.; Li, Y.F.; Sun, J.; Chai, Z.F.

    2005-01-01

    In the past, most analytical problems relating to biological systems were addressed by measuring the total concentrations of elements. Now there is increasing interest of the importance of their chemical forms, in which an element is present in biological systems, e.g., the oxidation state, the binding state with macromolecules, or even the molecular structure. The biological effects of chromium, which is classified as an essential nutrient, are dependent upon its oxidation. state. In general, trivalent chromium is biochemically active, whereas hexavalent chromium is considered to be toxic. Mercury is one of serious environmental persistent pollutants. However, organic forms of mercury are known to possess much higher toxicity than inorganic mercury. Therefore, information on speciation is critically required in order to better understanding of their bioavailability, metabolism, transformation, and toxicity in vivo. Recently, chemical speciation of selenium, mercury, copper, zinc, iron, and so on, has been investigated by INAA, ICP-MS, XRF, EXAFS and related techniques combined with chemical and biochemical separation (extraction, chromatography, gel electrophoresis, etc.). INAA, XRF, and ICP-MS have superior advantages in aspect of multielemental analysis with high accuracy and sensitivity, which render the possibility of analyzing various elements of interest simultaneously. These offline or online techniques have been flexibly applied to different biological matrixes, such as human hair, serum, urine, various tissues and organs in our researches. In addition, EXAFS provides structural information about the moiety of metal centers up to a distance of approximately 4-5 Anstrom. For instance, hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Imbalance of elements, such as Se, Zn, Fe, Cu, Cd, Ca, etc., has been found in the whole blood or serum of patients with HCC. We found that the profiles of Se, Cd, Fe, Zn and Cu-containing proteins

  4. Change of School in Early Adolescence and Adverse Obesity-Related Dietary Behavior: A Longitudinal Cohort Study, Victoria, Australia, 2013-2014.

    Science.gov (United States)

    Marks, Jennifer; Barnett, Lisa M; Allender, Steven

    2015-09-10

    Environments that facilitate energy-dense, nutrient-poor diets are associated with childhood obesity. We examined the effect of a change of school environment on the prevalence of obesity and related dietary behavior in early adolescence. Fifteen schools in Victoria, Australia, were recruited at random from the bottom 2 strata of a 5-level socioeconomic scale. In 9 schools, students in grade 6 primary school transitioned to different schools for grade 7 secondary school, whereas in 6 schools, students remained in the same school from grade 6 to grade 7. Time 1 measures were collected from students (N = 245) in grade 6 (aged 11-13 y). Time 2 data were collected from 243 (99%) of the original cohort in grade 7. Data collected were dietary recall self-reported by students via questionnaire, measured height and weight of students, and aspects of the school food environment via school staff survey. Comparative and mixed model regression analyses were conducted. Of 243 students, 63% (n = 152) changed schools from time 1 to time 2, with no significant difference in weight status. Students who changed schools reported an increase in purchases of after-school snack food, greater sweetened beverage intake, fewer fruit-and-vegetable classroom breaks, and less encouragement for healthy eating compared with students who remained in the same school. School staff surveys showed that more primary than secondary schools had written healthy canteen policies and fewer days of canteen or food services operation. A change of school environment has negative effects on children's obesity-related dietary behavior. Consistent policy is needed across school types to support healthy eating in school environments.

  5. Adverse drug events in the oral cavity.

    Science.gov (United States)

    Yuan, Anna; Woo, Sook-Bin

    2015-01-01

    Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  7. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    Science.gov (United States)

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  8. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

    Science.gov (United States)

    Robarts, Daniel W H; Wolfe, Andrea D

    2014-07-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

  9. [Adverse events prevention ability].

    Science.gov (United States)

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools.

  10. Review: Improving our knowledge of male mosquito biology in relation to genetic control programmes.

    Science.gov (United States)

    Lees, Rosemary Susan; Knols, Bart; Bellini, Romeo; Benedict, Mark Q; Bheecarry, Ambicadutt; Bossin, Hervé Christophe; Chadee, Dave D; Charlwood, Jacques; Dabiré, Roch K; Djogbenou, Luc; Egyir-Yawson, Alexander; Gato, René; Gouagna, Louis Clément; Hassan, Mo'awia Mukhtar; Khan, Shakil Ahmed; Koekemoer, Lizette L; Lemperiere, Guy; Manoukis, Nicholas C; Mozuraitis, Raimondas; Pitts, R Jason; Simard, Frederic; Gilles, Jeremie R L

    2014-04-01

    The enormous burden placed on populations worldwide by mosquito-borne diseases, most notably malaria and dengue, is currently being tackled by the use of insecticides sprayed in residences or applied to bednets, and in the case of dengue vectors through reduction of larval breeding sites or larviciding with insecticides thereof. However, these methods are under threat from, amongst other issues, the development of insecticide resistance and the practical difficulty of maintaining long-term community-wide efforts. The sterile insect technique (SIT), whose success hinges on having a good understanding of the biology and behaviour of the male mosquito, is an additional weapon in the limited arsenal against mosquito vectors. The successful production and release of sterile males, which is the mechanism of population suppression by SIT, relies on the release of mass-reared sterile males able to confer sterility in the target population by mating with wild females. A five year Joint FAO/IAEA Coordinated Research Project brought together researchers from around the world to investigate the pre-mating conditions of male mosquitoes (physiology and behaviour, resource acquisition and allocation, and dispersal), the mosquito mating systems and the contribution of molecular or chemical approaches to the understanding of male mosquito mating behaviour. A summary of the existing knowledge and the main novel findings of this group is reviewed here, and further presented in the reviews and research articles that form this Acta Tropica special issue. Copyright © 2013 International Atomic Energy Agency 2013. Published by Elsevier B.V. All rights reserved.

  11. Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

    Directory of Open Access Journals (Sweden)

    Matej Mihelčić

    Full Text Available Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD. We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A, which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01 were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP in the non-amyloidogenic pathway

  12. Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

    Science.gov (United States)

    Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

    2017-01-01

    Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could be

  13. Assessing biological and chemical signatures related to nutrient removal by floating islands in stormwater mesocosms.

    Science.gov (United States)

    Chang, Ni-Bin; Islam, Kamrul; Marimon, Zachary; Wanielista, Martin P

    2012-07-01

    Aquatic floating plants on BioHaven mats were tested for their potential use as a Best Management Practice to be incorporated within existing stormwater detention ponds. Plants were analyzed for their capability to remove nutrient-pollution in parallel with the study of ecological dynamics. Experiments were carried out in cylindrical mesocosms of 5 m diameter and 1.2 m height, above-ground pools with a water volume of 14 m(3). The design parameters tested were for 5% and 10% vegetated floating island coverage of the mesocosm, both with and without shoreline plants called littoral zone. This littoral shelf was 0.5 m thick, graded at a downward slope of 1:5 toward the center using loamy soil with low organic matter content, excavated from below turf grass. Endemic plant species were chosen for the experimental location in central Florida based on a wetland identification manual by the Florida Department of Environmental Protection to ensure the study was not compromised by unique climate requirements of the plants. Nutrient and aquatic chemical conditions such as pH, dissolved oxygen, temperature, turbidity, and chlorophyll a were monitored to understand their relationships to the general wetland ecosystem. Real-time polymerase chain reaction analysis identified the microbial activity near the rhizospheric zone. Logistical placement considerations were made using spatial sampling across the horizontal plane of the mesocosms, beneath and around the root zone, to determine if nutrients tend to aggregate around the floating island. This study concluded that the application of floating islands as a stormwater technology can remove nutrients through plant uptake and biological activity. The most cost-effective size in the outdoor mesocosms was 5% surface area coverage of the mat. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Adverse Socioeconomic Conditions and Oocyst-Related Factors Are Associated with Congenital Toxoplasmosis in a Population-Based Study in Minas Gerais, Brazil

    Science.gov (United States)

    Carellos, Ericka Viana Machado; de Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Romanelli, Roberta Maia Castro; Abreu, Mery Natali Silva; da Silva, Fabiana Maria; Loures, Ivy Rosa Coelho; de Andrade, Juliana Queiroz; Caiaffa, Waleska Teixeira

    2014-01-01

    Objective Congenital toxoplasmosis is a public health problem in Brazil. This study aimed to determine risk factors associated with congenital toxoplasmosis in Minas Gerais which is the second largest Brazilian State based on number of inhabitants, and its territorial extension is larger than that of France. Methods: Population-based case-control study to assess the association between congenital toxoplasmosis and maternal exposure to infection risk factors. The study included mothers/children participating in the Minas Gerais Newborn Screening Program. The cases consisted of 175 mothers of infected children, and the controls consisted of 278 mothers of children without suspected infection. The associations were assessed through binomial logistic regression with p≤0.05. Results The variables associated with lower probability of toxoplasmosis were: older mother age (OR = 0.89; CI95% = 0.85–0.93), higher level of education (OR = 0.85; CI95% = 0.78–0.92), access to potable water (OR = 0.21; CI95% = 0.08–0.51), and home with flush toilet (OR = 0.18; CI95% = 0.04–078). The variables associated with higher probability of infection were: cats in the neighborhood (OR = 2.27; CI95% = 1.27–4.06), owning or visiting homes with domestic cats (OR = 1.90; CI95% = 1.09–3.31), handling the soil (OR = 2.29; CI95% = 1.32–3.96), and eating fresh meat not previously frozen (OR = 3.97; CI95% = 2.17–7.25). After stratification according region of residence (rural or urban/peri-urban), home with flush toilet and consumption of treated water were protective against the disease only in the rural stratum. Conclusions In Minas Gerais, congenital toxoplasmosis has been associated with poor socioeconomic conditions. Considering maternal exposure to sources of Toxoplasma gondii, the predominating risk factors were those related to the ingestion of oocysts. It is expected that these results will contribute to

  15. Wound induces changes in nitric oxide related biologies putatively modulating tuber healing

    Science.gov (United States)

    Wound-related losses in harvested potatoes and cut seed are a serious and costly problem (losses > $320 m/yr). Our understanding of the regulation and modulation of the processes involved in wound healing (WH) are advancing and showing promise in the development of new approaches and technologies t...

  16. Socioeconomic status and stress-related biological responses over the working day.

    NARCIS (Netherlands)

    Steptoe, A.; Kunz-Ebrecht, S.R.; Owen, N.; Feldman, P.J.; Willemsen, G.; Kirschbaum, C.; Marmot, M.

    2003-01-01

    Objectives: The influence of low socioeconomic status on cardiovascular disease may be mediated in part by sustained activation of stress-related autonomic and neuroendocrine processes. We hypothesized that low socio-economic status would be associated with heightened ambulatory blood pressure and

  17. Adverse outcome pathways (AOPs) to enhance EDC ...

    Science.gov (United States)

    Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway (AOP) framework, which organizes information concerning measureable changes that link initial biological interactions with a chemical to adverse effects that are meaningful to risk assessment and management, can aid this process. This presentation outlines the ways in which the AOP framework has already been employed to support EDSP and how it may further enhance endocrine disruptor assessments in the future. Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway

  18. Relating N2O emissions during biological nitrogen removal with operating conditions using multivariate statistical techniques.

    Science.gov (United States)

    Vasilaki, V; Volcke, E I P; Nandi, A K; van Loosdrecht, M C M; Katsou, E

    2018-04-26

    Multivariate statistical analysis was applied to investigate the dependencies and underlying patterns between N 2 O emissions and online operational variables (dissolved oxygen and nitrogen component concentrations, temperature and influent flow-rate) during biological nitrogen removal from wastewater. The system under study was a full-scale reactor, for which hourly sensor data were available. The 15-month long monitoring campaign was divided into 10 sub-periods based on the profile of N 2 O emissions, using Binary Segmentation. The dependencies between operating variables and N 2 O emissions fluctuated according to Spearman's rank correlation. The correlation between N 2 O emissions and nitrite concentrations ranged between 0.51 and 0.78. Correlation >0.7 between N 2 O emissions and nitrate concentrations was observed at sub-periods with average temperature lower than 12 °C. Hierarchical k-means clustering and principal component analysis linked N 2 O emission peaks with precipitation events and ammonium concentrations higher than 2 mg/L, especially in sub-periods characterized by low N 2 O fluxes. Additionally, the highest ranges of measured N 2 O fluxes belonged to clusters corresponding with NO 3 -N concentration less than 1 mg/L in the upstream plug-flow reactor (middle of oxic zone), indicating slow nitrification rates. The results showed that the range of N 2 O emissions partially depends on the prior behavior of the system. The principal component analysis validated the findings from the clustering analysis and showed that ammonium, nitrate, nitrite and temperature explained a considerable percentage of the variance in the system for the majority of the sub-periods. The applied statistical methods, linked the different ranges of emissions with the system variables, provided insights on the effect of operating conditions on N 2 O emissions in each sub-period and can be integrated into N 2 O emissions data processing at wastewater treatment plants

  19. Influence of Soils, Riparian Zones, and Hydrology on Nutrients, Herbicides, and Biological Relations in Midwestern Agricultural Streams

    Science.gov (United States)

    Porter, S.

    2001-12-01

    Chemical, biological, and habitat conditions were characterized in 70 streams in the upper Mississippi River basin during August 1997, as part of the U.S. Geological Survey's National Water-Quality Assessment (NAWQA) Program. The study was designed to evaluate algal and macroinvertebrate responses to high agricultural intensity in relation to nonpoint sources of nutrients and herbicides, characteristics of basin soils, wooded-riparian vegetation, and hydrology. Concentrations and forms of nutrients, herbicides and their metabolites, and seston constituents varied significantly with regional differences in soil properties, ground and surface water relations, density of riparian trees, and precedent rainfall-runoff conditions. Dissolved nitrate concentrations were relatively low in streams with high algal productivity; however, nitrate concentrations increased with basin water yield, which was associated with the regional distribution of rainfall during the month prior to the study. Stream productivity and respiration were positively correlated with seston (phytoplankton) chlorophyll concentrations, which were significantly larger in streams in areas with poorly drained soils and low riparian-tree density. Concentrations of dissolved phosphorus were low in streams where periphyton biomass was high. Periphyton biomass was relatively larger in streams with clear water and low abundance of macroinvertebrates that consume algae. Periphyton biomass decreased rapidly with modest increases in the abundance of scrapers such as snails and certain mayfly taxa. Differences in dissolved oxygen, organic carbon, stream velocity, and precedent hydrologic conditions explained much of the variance in macroinvertebrate community structure. The overall number of macroinvertebrate species and number of mayfly, caddisfly, and stonefly (EPT) taxa that are sensitive to organic enrichment were largest in streams with moderate periphyton biomass, in areas with moderately-well drained soils

  20. Biological, psychological and social processes that explain celebrities? influence on patients? health-related behaviors

    OpenAIRE

    Hoffman, Steven J; Tan, Charlie

    2015-01-01

    Background: Celebrities can have substantial influence as medical advisors. However, their impact on public health is equivocal: depending on the advice’s validity and applicability, celebrity engagements can benefit or hinder efforts to educate patients on evidence-based practices and improve their health literacy. This meta-narrative analysis synthesizes multiple disciplinary insights explaining the influence celebrities have on people’s health-related behaviors. Methods: Systematic searche...

  1. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

    OpenAIRE

    Andrew T. Ludlow; Stephen M. Roth

    2011-01-01

    Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and...

  2. International approach to assessing soil quality by ecologically-related biological parameters

    OpenAIRE

    Filip, Z.

    2002-01-01

    Metadata only record Soil quality represents an integral value of the compositional structures and natural functions of soil in relation to soil use and environmental conditions on site. Among the indigenous soil components, different organisms and especially microorganisms play a key role in ecologically important biogeochemical processes. In that way, soil microorganisms contribute to the maintenance of the matter and energy transfer in terrestrial environments. Under stress conditions c...

  3. Ventral striatal activity links adversity and reward processing in children

    NARCIS (Netherlands)

    Kamkar, N.H.; Lewis, D.J.; van den Bos, W.; Morton, J.B.

    2017-01-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive

  4. Altered brain processing of decision-making in healthy first-degree biological relatives of suicide completers.

    Science.gov (United States)

    Ding, Y; Pereira, F; Hoehne, A; Beaulieu, M-M; Lepage, M; Turecki, G; Jollant, F

    2017-08-01

    Suicidal behavior is heritable, with the transmission of risk being related to the transmission of vulnerability traits. Previous studies suggest that risky decision-making may be an endophenotype of suicide. Here, we aimed at investigating brain processing of decision-making in relatives of suicide completers in order to shed light on heritable mechanisms of suicidal vulnerability. Seventeen healthy first-degree biological relatives of suicide completers with no personal history of suicidal behavior, 16 relatives of depressed patients without any personal or family history of suicidal behavior, and 19 healthy controls were recruited. Functional 3 T magnetic resonance imaging scans were acquired while participants underwent the Iowa Gambling Task, an economic decision-making test. Whole-brain analyses contrasting activations during risky vs safe choices were conducted with AFNI and FSL. Individuals with a family history of suicide in comparison to control groups showed altered contrasts in left medial orbitofrontal cortex, and right dorsomedial prefrontal cortex. This pattern was different from the neural basis of familial depression. Moreover, controls in comparison to relatives showed increased contrast in several regions including the post-central gyrus, posterior cingulate and parietal cortices, and cerebellum (culmen) in familial suicide; and inferior parietal, temporal, occipital, anteromedial and dorsolateral prefrontal cortices, and cerebellum (vermis) in familial depression. These findings most likely represent a complex combination of vulnerability and protective mechanisms in relatives. They also support a significant role for deficient risk processing, and ventral and dorsal prefrontal cortex functioning in the suicidal diathesis.

  5. [Biological exposure-related injuries in workers in a health system of the health service of Galicia, Spain].

    Science.gov (United States)

    Cores Calvo, Juan; Muñiz Saborido, José Ramón; González Iglesias, Marta Clara

    2013-01-01

    The objective of this study was to describe the factors involved in biological exposure-related injuries occurring in worker from a health system in Galicia, Spain. The study was conducted in a health system of the Health Service of Galicia, that included four hospitals and 72 primary care centers, with nearly 6000 workers. The study used occupational injury data available o in the injury registry of the Health Service of Galicia for the year 2011. We identified 194 biohazard-related injuries. Exposures, locations, devices, tasks and causes of these incidents were analysed. The majority of biological exposures occurred through needlestick injuries (82%). The areas where more injuries occurred were in inpatient wards (37%) and operating rooms (25%). The devices most frequently involved were suture needles (15%) and insulin needles (15%). The most frequently recorded causes were lack of training and information, together with lack of biosafety devices. Worker training and information should be promoted along with the implementation of biosafety devices, as the latter measure alone does not seem sufficient to reduce the number of injuries. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

  6. Biological indicators in relation to coastal pollution along Karnataka coast, India

    Digital Repository Service at National Institute of Oceanography (India)

    Verlecar, X.N.; Desai, S.R.; Sarkar, A.; Dalal, S.G.

    pollutants in relation to planktonic and benthic organisms were examined at two locations along Karnataka coast, one at Kulai (740 47.74? E and 120 55.16? N) receiving huge amount of industrial effluents from fertilizer, petroleum and chemical plants along... with t 0 45? E and 130 10? N) is located 20 kms away, which is a typically agricultural and fishing village having no stress of industrial discharges. Although the concentrations of dissolved oxygen (DO), nutrients and trace metals in water and sediment...

  7. EBI2, GPR18 and GPR17--three structurally related, but biologically distinct 7TM receptors

    DEFF Research Database (Denmark)

    Nørregaard, Kristine; Benned-Jensen, Tau; Rosenkilde, Mette Marie

    2011-01-01

    7TM receptors constitute one of the largest superfamilies of proteins in the human genome. They are involved in a large number of physiological and pathological processes in the human body and thus represent major and important drug targets for the pharmaceutical industry. Although the majority...... have been deorphanized, many remain orphan, and these orphan receptors constitute a large pool of potential drug targets. This review focuses on one of these orphan targets, the Epstein-Barr Virus-induced receptor 2, EBI2 (or GPR183), together with two structurally related receptors, GPR17 and GPR18...

  8. Interest, Attitudes and Self-Efficacy Beliefs Explaining Upper-Secondary School Students' Orientation Towards Biology-Related Careers

    Science.gov (United States)

    Uitto, Anna

    2014-01-01

    The aim of the study was to discover the contribution of students' interest in school biology, as well as their self-efficacy and attitudes towards different science subjects and mathematics when explaining students' orientation towards biology-related careers at upper-secondary school. The data of 321 K-11 students (49% women) were…

  9. Development and evaluation of a radioimmunoassay for the detection of amphetamine and related compounds in biological fluids

    International Nuclear Information System (INIS)

    Mason, P.A.; Bal, T.S.; Law, B.; Moffat, A.C.

    1983-01-01

    A radioimmunoassay has been developed for the detection of amphetamine and its analogues in blood and urine without any pretreatment of the samples. It is based on a commercially available antiserum and a [ 125 I] iodinated derivative of amphetamine. The assay can detect low levels of amphetamine (less than 10 ng ml - 1 ) in very small samples (50 μl) of blood and urine. It is cheap (3 pence per test), rapid, simple to perform and is specific for compounds closely related to amphetamine. A high, positive correlation was obtained (r = 0.93) when results of the analyses of urine samples from volunteers who had ingested amphetamine were compared with those produced by gas chromatography - mass spectrometry. The assay has proved very useful for the detection of amphetamine and closely related compounds in biological fluids. (author)

  10. Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation.

    Science.gov (United States)

    Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean-Claude

    2006-06-15

    Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 microM), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties.

  11. Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2012-02-01

    Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

  12. Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2010-06-01

    Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

  13. Clever generation of rich SPARQL queries from annotated relational schema: application to Semantic Web Service creation for biological databases.

    Science.gov (United States)

    Wollbrett, Julien; Larmande, Pierre; de Lamotte, Frédéric; Ruiz, Manuel

    2013-04-15

    In recent years, a large amount of "-omics" data have been produced. However, these data are stored in many different species-specific databases that are managed by different institutes and laboratories. Biologists often need to find and assemble data from disparate sources to perform certain analyses. Searching for these data and assembling them is a time-consuming task. The Semantic Web helps to facilitate interoperability across databases. A common approach involves the development of wrapper systems that map a relational database schema onto existing domain ontologies. However, few attempts have been made to automate the creation of such wrappers. We developed a framework, named BioSemantic, for the creation of Semantic Web Services that are applicable to relational biological databases. This framework makes use of both Semantic Web and Web Services technologies and can be divided into two main parts: (i) the generation and semi-automatic annotation of an RDF view; and (ii) the automatic generation of SPARQL queries and their integration into Semantic Web Services backbones. We have used our framework to integrate genomic data from different plant databases. BioSemantic is a framework that was designed to speed integration of relational databases. We present how it can be used to speed the development of Semantic Web Services for existing relational biological databases. Currently, it creates and annotates RDF views that enable the automatic generation of SPARQL queries. Web Services are also created and deployed automatically, and the semantic annotations of our Web Services are added automatically using SAWSDL attributes. BioSemantic is downloadable at http://southgreen.cirad.fr/?q=content/Biosemantic.

  14. Clever generation of rich SPARQL queries from annotated relational schema: application to Semantic Web Service creation for biological databases

    Science.gov (United States)

    2013-01-01

    Background In recent years, a large amount of “-omics” data have been produced. However, these data are stored in many different species-specific databases that are managed by different institutes and laboratories. Biologists often need to find and assemble data from disparate sources to perform certain analyses. Searching for these data and assembling them is a time-consuming task. The Semantic Web helps to facilitate interoperability across databases. A common approach involves the development of wrapper systems that map a relational database schema onto existing domain ontologies. However, few attempts have been made to automate the creation of such wrappers. Results We developed a framework, named BioSemantic, for the creation of Semantic Web Services that are applicable to relational biological databases. This framework makes use of both Semantic Web and Web Services technologies and can be divided into two main parts: (i) the generation and semi-automatic annotation of an RDF view; and (ii) the automatic generation of SPARQL queries and their integration into Semantic Web Services backbones. We have used our framework to integrate genomic data from different plant databases. Conclusions BioSemantic is a framework that was designed to speed integration of relational databases. We present how it can be used to speed the development of Semantic Web Services for existing relational biological databases. Currently, it creates and annotates RDF views that enable the automatic generation of SPARQL queries. Web Services are also created and deployed automatically, and the semantic annotations of our Web Services are added automatically using SAWSDL attributes. BioSemantic is downloadable at http://southgreen.cirad.fr/?q=content/Biosemantic. PMID:23586394

  15. Psychological, Relational, and Biological Correlates of Ego-Dystonic Masturbation in a Clinical Setting.

    Science.gov (United States)

    Castellini, Giovanni; Fanni, Egidia; Corona, Giovanni; Maseroli, Elisa; Ricca, Valdo; Maggi, Mario

    2016-09-01

    Attitudes toward masturbation are extremely varied, and this practice is often perceived with a sense of guilt. To evaluate the prevalence of ego-dystonic masturbation (EM), defined as masturbation activity followed by a sense of guilt, in a clinical setting of sexual medicine and the impact of EM on psychological and relational well-being. A series of 4,211 men attending an andrology and sexual medicine outpatient clinic was studied retrospectively. The presence and severity of EM were defined according to ANDROTEST items related to masturbation, determined by the mathematical product of the frequency of masturbation and the sense of guilt after masturbation. Clinical, biochemical, and psychological parameters were studied using the Structured Interview on Erectile Dysfunction, ANDROTEST, and modified Middlesex Hospital Questionnaire. Three hundred fifty-two subjects (8.4%) reported any sense of guilt after masturbation. Subjects with EM were younger than the remaining sample (mean age ± SD = 51.27 ± 13.43 vs 48.31 ± 12.04 years, P < .0001) and had more psychiatric comorbidities. EM severity was positively associated with higher free-floating (Wald = 35.94, P < .001) and depressive (Wald = 16.85, P < .001) symptoms, and subjects with a higher EM score reported less phobic anxiety (Wald = 4.02, P < .05) and obsessive-compulsive symptoms (Wald = 7.6, P < .01). A higher EM score was associated with a higher alcohol intake. Subjects with EM more often reported the partner's lower frequency of climax and more problems achieving an erection during sexual intercourse. EM severity was positively associated with worse relational and intrapsychic domain scores. Clinicians should consider that some subjects seeking treatment in a sexual medicine setting might report compulsive sexual behaviors. EM represents a clinically relevant cause of disability, given the high level of psychological distress reported by subjects with this condition, and the severe impact on

  16. The use of biologically related model (Eclipse for the intensity-modulated radiation therapy planning of nasopharyngeal carcinomas.

    Directory of Open Access Journals (Sweden)

    Monica W K Kan

    Full Text Available Intensity-modulated radiation therapy (IMRT is the most common treatment technique for nasopharyngeal carcinoma (NPC. Physical quantities such as dose/dose-volume parameters are used conventionally for IMRT optimization. The use of biological related models has been proposed and can be a new trend. This work was to assess the performance of the biologically based IMRT optimization model installed in a popular commercial treatment planning system (Eclipse as compared to its dose/dose volume optimization model when employed in the clinical environment for NPC cases.Ten patients of early stage NPC and ten of advanced stage NPC were selected for this study. IMRT plans optimized using biological related approach (BBTP were compared to their corresponding plans optimized using the dose/dose volume based approach (DVTP. Plan evaluation was performed using both biological indices and physical dose indices such as tumor control probability (TCP, normal tissue complication probability (NTCP, target coverage, conformity, dose homogeneity and doses to organs at risk. The comparison results of the more complex advanced stage cases were reported separately from those of the simpler early stage cases.The target coverage and conformity were comparable between the two approaches, with BBTP plans producing more hot spots. For the primary targets, BBTP plans produced comparable TCP for the early stage cases and higher TCP for the advanced stage cases. BBTP plans reduced the volume of parotid glands receiving doses of above 40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were 8.0 ± 5.8 and 7.9 ± 8.7 for early and advanced stage cases, respectively, while those of DVTP were 21.3 ± 8.3 and 24.4 ± 12.8, respectively. There were no significant differences in the NTCP values between the two approaches for the serial organs.Our results showed that the BBTP approach could be a potential alternative approach to the DVTP approach for NPC.

  17. Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology

    Directory of Open Access Journals (Sweden)

    Jia-You Fang

    2009-01-01

    Full Text Available Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs. Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models.

  18. Urban-Related Environmental Variables and Their Relation with Patterns in Biological Community Structure in the Fountain Creek Basin, Colorado, 2003-2005

    Science.gov (United States)

    Zuellig, Robert E.; Bruce, James F.; Evans, Erin E.; Stogner, Sr., Robert W.

    2007-01-01

    In 2003, the U.S. Geological Survey, in cooperation with Colorado Springs City Engineering, began a study to evaluate the influence of urbanization on stream ecosystems. To accomplish this task, invertebrate, fish, stream discharge, habitat, water-chemistry, and land-use data were collected from 13 sites in the Fountain Creek basin from 2003 to 2005. The Hydrologic Index Tool was used to calculate hydrologic indices known to be related to urbanization. Response of stream hydrology to urbanization was evident among hydrologic variables that described stormflow. These indices included one measurement of high-flow magnitude, two measurements of high-flow frequency, and one measurement of stream flashiness. Habitat and selected nonstormflow water chemistry were characterized at each site. Land-use data were converted to estimates of impervious surface cover and used as the measure of urbanization annually. Correlation analysis (Spearman?s rho) was used to identify a suite of nonredundant streamflow, habitat, and water-chemistry variables that were strongly associated (rho > 0.6) with impervious surface cover but not strongly related to elevation (rho analysis (BIO-ENV, PRIMER ver 6.1, Plymouth, UK) was used to create subsets of eight urban-related environmental variables that described patterns in biological community structure. The strongest and most parsimonious subset of variables describing patterns in invertebrate community structure included high flood pulse count, lower bank capacity, and nutrients. Several other combinations of environmental variables resulted in competing subsets, but these subsets always included the three variables found in the most parsimonious list. This study found that patterns in invertebrate community structure from 2003 to 2005 in the Fountain Creek basin were associated with a variety of environmental characteristics influenced by urbanization. These patterns were explained by a combination of hydrologic, habitat, and water

  19. An interspecies comparison of the biological effects of an inhaled, relatively insoluble beta emitter

    International Nuclear Information System (INIS)

    Griffith, W.C.; Lundgren, D.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1986-01-01

    Mice, rats, Syrian hamsters, and beagle dogs were exposed by inhalation to graded levels of 144 Ce in relatively insoluble forms to demonstrate species similarities and differences regarding patterns of deposition, fate, dosimetry, and dose-response relationships. All animals were serially evaluated to determine lung burdens, held for life-span observation, necropsied at death, and examined histopathologically to characterize the lesions present and to determine the cause of death. The primary malignant lung tumors observed in rodents were predominantly squamous-cell carcinomas and adenocarcinomas, whereas those in dogs at earlier times were primarily hemangiosarcomas and those in dogs that died at later times were pulmonary carcinomas. The relationship between the incidence of lung cancer and absorbed beta dose to the lung differed among species. The results of modeling these data provide a better understanding of how the choice of species can influence the outcome of a life-span study. The data are used to estimate the risk of lung cancer in man from an inhaled beta-emitting radionuclide. 26 refs., 5 figs., 6 tabs

  20. Sand lance: A review of biology and predator relations and annotated bibliography

    Science.gov (United States)

    Robards, Martin D.; Willson, Mary F.; Armstrong, Robert H.; Piatt, John F.

    1999-01-01

    Six species of sand lance (Ammodytes) in temperate and boreal regions are currently recognized. Sand lance can occupy a wide range of environmental conditions, but all appear to be dormant predominantly in winter, and one species is in summer also. They lack a swim bladder and spend much of their time buried in specific substrates. Copepods are the primary food. Spawning usually occurs in fall or winter (although some species also spawn in spring), eggs are demersal, and larvae may hatch at times of low food abundance. Sand lance usually occur in schools and are regarded as a relatively high-quality forage fish.Sand lance constitute a major prey for at least some populations of over 100 species of consumer, including 40 species of birds, 12 species of marine mammals, 45 species of fishes, and some invertebrates. Variation in the availability of sand lance (and other forage fishes) can have major effects on the breeding success and survival of their predators. Commercial fishing and other pressures on sand lance populations potentially have ramifying effects on many species of wildlife.The bibliography contains over 1,700 references on the family Ammodytidae, with an emphasis on the genus Ammodytes. Keywords are provided for each reference and have been further organized into taxonomic, geographic, subject, and predator indexes.

  1. heat-induced biological changes as heat tolerance indices related to growth performance in buffaloes

    International Nuclear Information System (INIS)

    Kaldes, M.Z.N.

    2004-01-01

    the main objective of this study was to predict new heat tolerance indices related to hot summer growth performance, depending on heat - induced changes in some physiological and biochemical parameters of young water buffalo calves. the present study was carried out on 8 egyptian male buffalo calves of 6 months old and 106.8 kg mean body weight (B W), and on the same animals of 12 months old and 179.5 kg mean B W. the animals were maintained in a climatic chamber of the egyptian atomic energy authority. the animals were maintained in metabolic cages inside a climatic chamber for 3 weeks under mild climate (20-24 c and 50-60% Rh, equivalent to 62-72 THI) for 6 hours daily as adjustment period,followed by 5 and 7 days in the 6- and 12-month old calves, respectively at the same climatic conditions as a control period.this was followed by 6 hours of acute heat exposure period (33-43 c and 40-60% Rh, equivalent to 85-93 Thi), then by chronic heat exposure period of the same climatic conditions for 5 and 7 days in the 6- and 12- month old calves, respectively.Rectal temperature (RT) and respiration rate (RR) were estimated daily, whereas BW was estimated at the beginning and the end of each exposure period

  2. Biological functions of melatonin in relation to pathogenesis of oral lichen planus.

    Science.gov (United States)

    Chaiyarit, Ponlatham; Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda

    2017-07-01

    Oral lichen planus (OLP) is considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Accumulated data support the involvement of cell-mediated immune dysfunction in the development of OLP. However, the connection between neuroendocrine system and oral immune response in OLP patients has never been clarified. Melatonin is considered as a major chronobiotic hormone produced mainly by the pineal gland. This gland is recognized as a regulator of circadian rhythm and a sensor in the immune response through the NF-kB transduction pathway. It was suggested that pineal-derived melatonin and extra-pineal melatonin synthesized at the site of inflamed lesion might play a role in inflammatory response. According to our immunohistochemical study, expression of melatonin could be detected in human oral mucosa. In addition, increased levels of melatonin were observed in inflamed oral mucosa of OLP patients. We hypothesize that chronic inflammation possibly induces the local biosynthesis of melatonin in inflamed oral mucosa. We also speculate that melatonin in oral mucosa may play a cytoprotective role through its anti-oxidative and anti-inflammatory properties. Moreover, melatonin may play an immunomodulatory role in relation to pathogenesis of OLP. Our hypothesis provides a new implication for upcoming research on the connection between circadian neuroendocrine network and immune response in oral mucosal compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Nitric Oxide-Related Biological Pathways in Patients with Major Depression.

    Directory of Open Access Journals (Sweden)

    Andreas Baranyi

    Full Text Available Major depression is a well-known risk factor for cardiovascular diseases and increased mortality following myocardial infarction. However, biomarkers of depression and increased cardiovascular risk are still missing. The aim of this prospective study was to evaluate, whether nitric-oxide (NO related factors for endothelial dysfunction, such as global arginine bioavailability, arginase activity, L-arginine/ADMA ratio and the arginine metabolites asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA might be biomarkers for depression-induced cardiovascular risk.In 71 in-patients with major depression and 48 healthy controls the Global Arginine Bioavailability Ratio (GABR, arginase activity (arginine/ornithine ratio, the L-arginine/ADMA ratio, ADMA, and SDMA were determined by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at baseline at the time of in-patient admittance and at the time of hospital discharge.The ADMA concentrations in patients with major depression were significantly elevated and the SDMA concentrations were significantly decreased in comparison with the healthy controls. Even after a first improvement of depression, ADMA and SDMA levels remained nearly unchanged. In addition, after a first improvement of depression at the time of hospital discharge, a significant decrease in arginase activity, an increased L-arginine/ADMA ratio and a trend for increased global arginine bioavailability were observed.Our study results are evidence that in patients with major depression ADMA and SDMA might be biomarkers to indicate an increased cardiovascular threat due to depression-triggered NO reduction. GABR, the L-arginine/ADMA ratio and arginase activity might be indicators of therapy success and increased NO production after remission.

  4. The relative biological effectiveness of a high energy neutron beam for micronuclei induction in T-lymphocytes of different individuals

    Energy Technology Data Exchange (ETDEWEB)

    Slabbert, J.P., E-mail: jps@tlabs.ac.z [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Dept. of Medical Imaging and Clinical Oncology, University of Stellenbosch (South Africa); August, L. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa); Vral, A. [Dept. of Basic Medical Sciences, Ghent University (Belgium); Symons, J. [NRF iThemba LABS (Laboratory for Accelerated Based Sciences), Somerset West (South Africa)

    2010-12-15

    In assessing the radiation risk of personnel exposed to cosmic radiation fields as it pertains to radiological damage during travel in civilian aircrafts, it is particularly important to know the relative biological effectiveness (RBE) for high energy neutrons. It has been the subject of numerous investigations in recent years using different neutron energies and cytogenetic examinations. Variations in the radiosensitivity of white blood cells for different individuals are likely to influence the estimate of the relative biological effectiveness for high energy neutrons. This as such observations have been noted in the response of different cancer cell lines with varying inherent sensitivities. In this work the radiosensitivities of T-lymphocytes of different individuals to the p(66)/Be neutron beam at iThemba LABS were measured using micronuclei formations and compared to that noted following exposure to {sup 60}Co {gamma}-rays. The principle objective of this investigation was to establish if a relationship between neutron RBE and variation in biological response to {sup 60}Co {gamma}-rays for lymphocytes from different individuals could be determined. Peripheral blood samples were collected from four healthy donors and isolated lymphocytes were exposed to different doses of {sup 60}Co {gamma}-rays (1-5 Gy) and p(66)/Be neutrons (0.5-2.5 Gy). One sample per donor was not exposed to radiation and served as a control. Lymphocytes were stimulated using PHA and cultured to induce micronuclei in cytokinesis-blocked cells. Micronuclei yields were numerated using fluorescent microscopy. Radiosensitivities and RBE values were calculated from the fitted parameters describing the micronuclei frequency dose response data. Dissimilar dose response curves for different donors were observed reflecting varying inherent sensitivities to both neutron and gamma radiation. A clear reduction in the dose limiting RBE{sub M} is noted for donors with lymphocytes more sensitive to

  5. [Chorionicity and adverse perinatal outcome].

    Science.gov (United States)

    Ferreira, Isabel; Laureano, Carla; Branco, Miguel; Nordeste, Ana; Fonseca, Margarida; Pinheiro, Adelaide; Silva, Maria Isabel; Almeida, Maria Céu

    2005-01-01

    Considering the highest rate of morbidity and mortality in diamniotic monochorionic twins, the authors evaluated and compared the adverse obstetric and perinatal outcome in twin pregnancies according to chorionicity. A retrospective study was conducted in all twin deliveries that occurred in the Obstetric Unit of Maternidade Bissaya-Barreto, for a period of tree years (from the 1st of January 1999 until the 31st of December 2001). From de 140 diamniotic twin pregnancies studied, we considered two groups according to the chorionicity: monochorionic and dichorionic. We compared multiple parameters as, epidemiologic data, adverse obstetric outcome, gestacional delivery age, type of delivery and the morbidity, the mortality and the follow-up of the newborn. The statistic tests used were the X2 and the t student. From the 140 twin pregnancies included in the study, 66% (92 cases) presented dichorionic placentation and 34% (48 cases) were monochorionic. In the group of monochorionic pregnancies, we observed highly difference related to pathology of amniotic fluid (14.5% vs 2.2%), discordant fetal growth (41.6% vs 22.8%) and rate of preterm delivery (66.6% vs 32.6%). Related to the newborn we verified that they had a lower average birth weight (1988g vs 2295g), a highly rate of weight discordancy (23% vs 15.3%), intraventricular haemorrhage (2.2% vs 0%) and IUGR (6.6% vs 1.6%), statistically significant in the monochorionic group. Also the perinatal mortality rate was significantly higher in the monochorionic pregnancies (93.7 per thousand vs 21.7 per thousand). The high rate of morbidity and mortality related to the monochorionic twin pregnancies, implies the need of a correct identification of the type of chorionicity and also a high standard of prenatal surveillance in prenatal specialised health centers.

  6. Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system

    International Nuclear Information System (INIS)

    Yoshida, Yukari; Katoh, Hiroyuki; Nakano, Takashi; Suzuki, Yoshiyuki; Al-Jahdari, Wael S.; Shirai, Katsuyuki; Hamada, Nobuyuki; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2012-01-01

    The purpose of this study was to clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-μm-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer=108 keV/μm). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena. (author)

  7. Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.

    Science.gov (United States)

    Iwata, Hiromitsu; Ogino, Hiroyuki; Hashimoto, Shingo; Yamada, Maho; Shibata, Hiroki; Yasui, Keisuke; Toshito, Toshiyuki; Omachi, Chihiro; Tatekawa, Kotoha; Manabe, Yoshihiko; Mizoe, Jun-etsu; Shibamoto, Yuta

    2016-05-01

    To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (Pcells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The association between cumulative adversity and mental health: considering dose and primary focus of adversity.

    Science.gov (United States)

    Keinan, Giora; Shrira, Amit; Shmotkin, Dov

    2012-09-01

    The study addressed the dose-response model in the association of cumulative adversity with mental health. Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self-oriented adversity revealed no, or negative, association with well-being, other-oriented adversity revealed a positive association. The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other-oriented adversity.

  9. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence

    NARCIS (Netherlands)

    Soyka, Michael; Kranzler, Henry R.; van den Brink, Wim; Krystal, John; Möller, Hans-Jürgen; Kasper, Siegfried

    2011-01-01

    Objectives. To develop evidence-based practice guidelines for the pharmacological treatment of opioid abuse and dependence. Methods. An international task force of the World Federation of Societies of Biological Psychiatry (WFSBP) developed these practice guidelines after a systematic review of the

  10. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

    Directory of Open Access Journals (Sweden)

    Schlegel Karl A

    2010-10-01

    Full Text Available Abstract Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL; however, osteonecrosis of the jaw (ONJ is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP-related and denosumab (anti-RANKL antibody-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment. Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to

  11. The normal limits, subclinical significance, related metabolic derangements and distinct biological effects of body site-specific adiposity in relatively healthy population.

    Directory of Open Access Journals (Sweden)

    Chun-Ho Yun

    Full Text Available BACKGROUND: The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized. MATERIALS AND METHODS: In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF and thoracic peri-aortic (TAT adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan, coronary calcium score (CCS, serum insulin, high-sensitivity C-reactive protein (Hs-CRP level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines. RESULTS: TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05. Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05, serum insulin (ß-coef.:0.17, p<0.05 and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05. These relationships persisted after adjustment in multivariable models (all p<0.05. A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74-0.83 to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05. CONCLUSION: In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and

  12. The use of remote sensors to relate biological and physical indicators to environmental and public health problems

    Science.gov (United States)

    1972-01-01

    Relationships between biological, ecological and botanical structures, and disease organisms and their vectors which might be detected and measured by remote sensing are determined. In addition to the use of trees as indicators of disease or potential disease, an attempt is made to identify environmental factors such as soil moisture and soil and water temperatures as they relate to disease or health problems and may be detected by remote sensing. The following three diseases and one major health problem are examined: Malaria, Rocky Mountain spotted fever, Encephalitis and Red Tide. It is shown that no single species of vascular plant nor any one environmental factor can be used as the indicator of disease or health problems. Entire vegetation types, successional stages and combinations of factors must be used.

  13. The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd→Be) for normal tissues. Pt. 3

    International Nuclear Information System (INIS)

    Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R.; Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V.

    1990-01-01

    The effect of single and fractionated doses of fast neutrons (42 MeV d→Bc ) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133 Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 ± 0.94 for infinitely small X-ray doses per fraction. (author)

  14. Alkali Metal Ion Complexes with Phosphates, Nucleotides, Amino Acids, and Related Ligands of Biological Relevance. Their Properties in Solution.

    Science.gov (United States)

    Crea, Francesco; De Stefano, Concetta; Foti, Claudia; Lando, Gabriele; Milea, Demetrio; Sammartano, Silvio

    2016-01-01

    Alkali metal ions play very important roles in all biological systems, some of them are essential for life. Their concentration depends on several physiological factors and is very variable. For example, sodium concentrations in human fluids vary from quite low (e.g., 8.2 mmol dm(-3) in mature maternal milk) to high values (0.14 mol dm(-3) in blood plasma). While many data on the concentration of Na(+) and K(+) in various fluids are available, the information on other alkali metal cations is scarce. Since many vital functions depend on the network of interactions occurring in various biofluids, this chapter reviews their complex formation with phosphates, nucleotides, amino acids, and related ligands of biological relevance. Literature data on this topic are quite rare if compared to other cations. Generally, the stability of alkali metal ion complexes of organic and inorganic ligands is rather low (usually log K  Na(+) > K(+) > Rb(+) > Cs(+). For example, for citrate it is: log K ML = 0.88, 0.80, 0.48, 0.38, and 0.13 at 25 °C and infinite dilution. Some considerations are made on the main aspects related to the difficulties in the determination of weak complexes. The importance of the alkali metal ion complexes was also studied in the light of modelling natural fluids and in the use of these cations as probes for different processes. Some empirical relationships are proposed for the dependence of the stability constants of Na(+) complexes on the ligand charge, as well as for correlations among log K values of NaL, KL or LiL species (L = generic ligand).

  15. Managing adverse effects of immunotherapy.

    Science.gov (United States)

    Gerson, James N; Ramamurthy, Chethan; Borghaei, Hossein

    2018-05-01

    Remarkable efficacy has been achieved in a variety of cancer types by targeting immune checkpoints. The cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab, the programmed death 1 inhibitors nivolumab and pembrolizumab, and the programmed death ligand 1 inhibitors atezolizumab, avelumab, and durvalumab are the agents currently approved by the US Food and Drug Administration for the treatment of certain advanced malignancies. These agents mark a departure from both standard cytotoxic chemotherapy and targeted therapy. However, they are associated with a unique set of immune-related adverse events (irAEs), which can manifest as a wide range of autoimmune phenomena. The irAEs can affect any system in the body and in rare cases are life-threatening. It is critical for the practicing medical oncologist to recognize and promptly treat any irAEs that may develop.

  16. Fiber optics in adverse environments

    International Nuclear Information System (INIS)

    Lyous, P.B.

    1982-01-01

    Radiation effects in optical fibers are considered, taking into account recent progress in the investigation of radiation resistant optical fibers, radiation damage in optical fibers, radiation-induced transient absorption in optical fibers, X-ray-induced transient attenuation at low temperatures in polymer clad silica (PCS) fibers, optical fiber composition and radiation hardness, the response of irradiated optical waveguides at low temperatures, and the effect of ionizing radiation on fiber-optic waveguides. Other topics explored are related to environmental effects on components of fiber optic systems, and radiation detection systems using optical fibers. Fiber optic systems in adverse environments are also discussed, giving attention to the survivability of Army fiber optics systems, space application of fiber optics systems, fiber optic wavelength multiplexing for civil aviation applications, a new fiber optic data bus topology, fiber optics for aircraft engine/inlet control, and application of fiber optics in high voltage substations

  17. Childhood adversity, social support, and telomere length among perinatal women.

    Science.gov (United States)

    Mitchell, Amanda M; Kowalsky, Jennifer M; Epel, Elissa S; Lin, Jue; Christian, Lisa M

    2018-01-01

    Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum. Childhood SES was defined as perceived childhood social class and parental educational attainment. Measures included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, Multidimensional Scale of Perceived Social Support, and average telomere length in PBMCs. Per a linear mixed model, telomere length did not change across pregnancy and postpartum visits; thus, subsequent analyses defined telomere length as the average across all available timepoints. ANCOVAs showed group differences by perceived childhood social class, maternal and paternal educational attainment, and current family social support, with lower values corresponding with shorter telomeres, after adjustment for possible confounds. No effects of childhood trauma or social support from significant others or friends on telomere length were observed. Findings demonstrate that while current SES was not related to telomeres, low childhood SES, independent of current SES, and low family social support were distinct risk factors for cellular aging in women. These data have relevance for understanding potential mechanisms by which early life deprivation of socioeconomic and relationship resources affect maternal health. In turn, this has potential significance for intergenerational transmission of telomere length. The predictive value of

  18. Eventos adversos e motivos de descarte relacionados ao reuso de produtos médicos hospitalares em angioplastia coronária Adverse events and reasons for discard related to the reuse of cardiac catheters in percutaneous transluminal coronary angioplasty

    Directory of Open Access Journals (Sweden)

    Margarete Ártico Batista

    2006-09-01

    Full Text Available OBJETIVO: Descrever os eventos adversos ocorridos durante e após angioplastia coronária (ATC, possivelmente relacionados ao reuso de produtos médico-hospitalares, além de quantificar e identificar os motivos de descarte em relação ao primeiro uso e ao reuso. MÉTODO: Foram estudados 60 pacientes, sendo que 29 (48,3% apresentavam angina instável, 27 (45% IAM e quatro (6,7% outros diagnósticos. Durante o procedimento e na permanência na Unidade Intensiva Coronariana, atentou-se à possibilidade de ocorrência dos eventos adversos febre, hipertensão, hipotensão, calafrios, sudorese, sangramento, náuseas e vômitos. Foram avaliados sete produtos médico-hospitalares: introdutor, cateter-guia, fio-guia 0.35, fio-guia 0.014, cateter- balão para angioplastia, seringa com manômetro para insuflar balão (indeflator e torneira de três vias (manifold. No total de produtos (76 de primeiro uso e 410 reprocessados, verificou-se se houve descarte e se isto ocorreu antes ou durante o procedimento e quais os motivos para tanto. Utilizou-se o teste Qui Quadrado, admitindo-se erro alfa de 5%. RESULTADOS: Vinte e seis pacientes apresentaram eventos adversos. A hipotensão foi o evento mais prevalente e ocorreu em 11(18,3% casos. Não houve, porém, significância estatística entre o evento adverso hipotensão e reuso ou não dos produtos médico-hospitalares. Por não estarem íntegros, foram descartados três produtos de primeiro uso e 55 produtos dos reutilizados. CONCLUSÃO: Os eventos adversos apresentados pelos pacientes submetidos à angioplastia não estão associados ao reuso dos produtos médico-hospitalares. A integridade e funcionalidade foram os motivos principais de descarte.OBJECTIVE: To describe the adverse effects that occur during and after percutaneous transluminal coronary angioplasty (PTCA possibly related to the reuse of medical equipment. An additional objective is to quantify and identify the reasons of discard in respect to

  19. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

    Science.gov (United States)

    Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

    2010-10-13

    Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

  20. Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity

    Science.gov (United States)

    Flouri, Eirini; Tzavidis, Nikos

    2011-01-01

    This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

  1. Childhood adversity and behavioral health outcomes for youth: An investigation using state administrative data.

    Science.gov (United States)

    Lucenko, Barbara A; Sharkova, Irina V; Huber, Alice; Jemelka, Ron; Mancuso, David

    2015-09-01

    This study aimed to measure the relative contribution of adverse experiences to adolescent behavioral health problems using administrative data. Specifically, we sought to understand the predictive value of adverse experiences on the presence of mental health and substance abuse problems for youth receiving publicly funded social and health services. Medicaid claims and other service records were analyzed for 125,123 youth age 12-17 and their biological parents. Measures from administrative records reflected presence of parental domestic violence, mental illness, substance abuse, criminal justice involvement, child abuse and/or neglect, homelessness, and death of a biological parent. Mental health and substance abuse status of adolescents were analyzed as functions of adverse experiences and other youth characteristics using logistic regression. In multivariate analyses, all predictors except parental domestic violence were statistically significant for substance abuse; parental death, parental mental illness, child abuse or neglect and homelessness were statistically significant for mental illness. Odds ratios for child abuse/neglect were particularly high in both models. The ability to identify risks during childhood using administrative data suggests the potential to target prevention and early intervention efforts for children with specific family risk factors who are at increased risk for developing behavioral health problems during adolescence. This study illustrates the utility of administrative data in understanding adverse experiences on children and the advantages and disadvantages of this approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

    Science.gov (United States)

    Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

  3. Biologics in spine arthrodesis.

    Science.gov (United States)

    Kannan, Abhishek; Dodwad, Shah-Nawaz M; Hsu, Wellington K

    2015-06-01

    Spine fusion is a tool used in the treatment of spine trauma, tumors, and degenerative disorders. Poor outcomes related to failure of fusion, however, have directed the interests of practitioners and scientists to spinal biologics that may impact fusion at the cellular level. These biologics are used to achieve successful arthrodesis in the treatment of symptomatic deformity or instability. Historically, autologous bone grafting, including iliac crest bong graft harvesting, had represented the gold standard in spinal arthrodesis. However, due to concerns over potential harvest site complications, supply limitations, and associated morbidity, surgeons have turned to other bone graft options known for their osteogenic, osteoinductive, and/or osteoconductive properties. Current bone graft selection includes autograft, allograft, demineralized bone matrix, ceramics, mesenchymal stem cells, and recombinant human bone morphogenetic protein. Each pose their respective advantages and disadvantages and are the focus of ongoing research investigating the safety and efficacy of their use in the setting of spinal fusion. Rh-BMP2 has been plagued by issues of widespread off-label use, controversial indications, and a wide range of adverse effects. The risks associated with high concentrations of exogenous growth factors have led to investigational efforts into nanotechnology and its application in spinal arthrodesis through the binding of endogenous growth factors. Bone graft selection remains critical to successful fusion and favorable patient outcomes, and orthopaedic surgeons must be educated on the utility and limitations of various biologics in the setting of spine arthrodesis.

  4. Association of cetuximab with adverse pulmonary events in cancer patients: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Lu Jason

    2009-08-01

    Full Text Available Abstract Compounds derived from biologic sources, or biologicals, are increasingly utilized as therapeutic agents in malignancy. Development of anti-cancer targeted therapies from biologics is increasingly being utilized. Cetuximab, a chimeric monoclonal antibody, is one such anti-cancer targeted therapeutic that has shown efficacy in quelling the rate of patient decline in colorectal, head/neck, and non-small cell lung cancer. However, due to the relatively recent addition of biologic compounds to the therapeutic arsenal, information related to adverse reactions is less well known than those seen in traditional chemotherapeutics. Dermatologic reactions have been demonstrated as the most frequent side effect cited during cetuximab therapy for malignancy; however, other effects may lead to greater morbidity. In general, pulmonary complications of therapeutics can lead to significant morbidity and mortality. The purpose of this review is to compile the various pulmonary side effects seen in patients treated with cetuximab for various malignancies, and to compare the incidence of these adverse reactions to standard therapies.

  5. Race, racism, and racial disparities in adverse birth outcomes.

    Science.gov (United States)

    Dominguez, Tyan Parker

    2008-06-01

    While the biologic authenticity of race remains a contentious issue, the social significance of race is indisputable. The chronic stress of racism and the social inequality it engenders may be underlying social determinants of persistent racial disparities in health, including infant mortality, preterm delivery, and low birth weight. This article describes the problem of racial disparities in adverse birth outcomes; outlines the multidimensional nature of racism and the pathways by which it may adversely affect health; and discusses the implications for clinical practice.

  6. Three lifestyle-related issues of major significance for public health among the Inuit in contemporary Greenland: a review of adverse childhood conditions, obesity, and smoking in a period of social transition.

    Science.gov (United States)

    Bjerregaard, Peter; Larsen, Christina V L

    2018-01-01

    Greenland is a country in transition from a colonial past with subsistence hunting and fishing to an urban Nordic welfare state. Epidemiological transition from infectious to chronic diseases has been evident since the 1950s. Ninety percent of the population is Inuit. We studied three public health issues based on published literature, namely adverse childhood experiences, addictive behavior, and suicide; diet and obesity; and smoking. Alcohol consumption was high in the 1970s and 1980s with accompanying family and social disruption. This is still a cause of poor mental health and suicides in the generations most affected. The diet is changing from a traditional diet of fish and marine mammals to imported food including food items rich in sugar and fat from domestic animals, and the level of physical activity is decreasing with an ensuing epidemic rise in obesity. The prevalence of smoking is high at around 60% among both men and women and is only slowly decreasing. Smoking shows large social variation, and tobacco-related diseases are widespread. The diseases and conditions outlined above all contribute towards a low life expectancy at birth-69 years for men and 74 years for women in 2011-2015-compared with 78 and 84 years for men and women, respectively, on average in the European countries. The translation of government public health programs into local activities needs strengthening, and it must be realized that the improvement of public health is a long-term process.

  7. Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions.

    Science.gov (United States)

    Stewart, Robert D; Streitmatter, Seth W; Argento, David C; Kirkby, Charles; Goorley, John T; Moffitt, Greg; Jevremovic, Tatjana; Sandison, George A

    2015-11-07

    To account for particle interactions in the extracellular (physical) environment, information from the cell-level Monte Carlo damage simulation (MCDS) for DNA double strand break (DSB) induction has been integrated into the general purpose Monte Carlo N-particle (MCNP) radiation transport code system. The effort to integrate these models is motivated by the need for a computationally efficient model to accurately predict particle relative biological effectiveness (RBE) in cell cultures and in vivo. To illustrate the approach and highlight the impact of the larger scale physical environment (e.g. establishing charged particle equilibrium), we examined the RBE for DSB induction (RBEDSB) of x-rays, (137)Cs γ-rays, neutrons and light ions relative to γ-rays from (60)Co in monolayer cell cultures at various depths in water. Under normoxic conditions, we found that (137)Cs γ-rays are about 1.7% more effective at creating DSB than γ-rays from (60)Co (RBEDSB  =  1.017) whereas 60-250 kV x-rays are 1.1 to 1.25 times more efficient at creating DSB than (60)Co. Under anoxic conditions, kV x-rays may have an RBEDSB up to 1.51 times as large as (60)Co γ-rays. Fission neutrons passing through monolayer cell cultures have an RBEDSB that ranges from 2.6 to 3.0 in normoxic cells, but may be as large as 9.93 for anoxic cells. For proton pencil beams, Monte Carlo simulations suggest an RBEDSB of about 1.2 at the tip of the Bragg peak and up to 1.6 a few mm beyond the Bragg peak. Bragg peak RBEDSB increases with decreasing oxygen concentration, which may create opportunities to apply proton dose painting to help address tumor hypoxia. Modeling of the particle RBE for DSB induction across multiple physical and biological scales has the potential to aid in the interpretation of laboratory experiments and provide useful information to advance the safety and effectiveness of hadron therapy in the treatment of cancer.

  8. Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.

    Science.gov (United States)

    Schussler, Edith; Sobel, Jeremy; Hsu, Joy; Yu, Patricia; Meaney-Delman, Dana; Grammer, Leslie C; Nowak-Wegrzyn, Anna

    2017-12-27

    Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care. Published by Oxford

  9. Nature-Based Stress Management Course for Individuals at Risk of Adverse Health Effects from Work-Related Stress—Effects on Stress Related Symptoms, Workability and Sick Leave

    Directory of Open Access Journals (Sweden)

    Eva Sahlin

    2014-06-01

    Full Text Available Sick leave due to stress-related disorders is increasing in Sweden after a period of decrease. To avoid that individuals living under heavy stress develop more severe stress-related disorders, different stress management interventions are offered. Self-assessed health, burnout-scores and well-being are commonly used as outcome measures. Few studies have used sick-leave to compare effects of stress interventions. A new approach is to use nature and garden in a multimodal stress management context. This study aimed to explore effects on burnout, work ability, stress-related health symptoms, and sick leave for 33 women participating in a 12-weeks nature based stress management course and to investigate how the nature/garden activities were experienced. A mixed method approach was used. Measures were taken at course start and three follow-ups. Results showed decreased burnout-scores and long-term sick leaves, and increased work ability; furthermore less stress-related symptoms were reported. Tools and strategies to better handle stress were achieved and were widely at use at all follow-ups. The garden and nature content played an important role for stress relief and for tools and strategies to develop. The results from this study points to beneficial effects of using garden activities and natural environments in a stress management intervention.

  10. Nature-Based Stress Management Course for Individuals at Risk of Adverse Health Effects from Work-Related Stress—Effects on Stress Related Symptoms, Workability and Sick Leave

    Science.gov (United States)

    Sahlin, Eva; Ahlborg, Gunnar; Vega Matuszczyk, Josefa; Grahn, Patrik

    2014-01-01

    Sick leave due to stress-related disorders is increasing in Sweden after a period of decrease. To avoid that individuals living under heavy stress develop more severe stress-related disorders, different stress management interventions are offered. Self-assessed health, burnout-scores and well-being are commonly used as outcome measures. Few studies have used sick-leave to compare effects of stress interventions. A new approach is to use nature and garden in a multimodal stress management context. This study aimed to explore effects on burnout, work ability, stress-related health symptoms, and sick leave for 33 women participating in a 12-weeks nature based stress management course and to investigate how the nature/garden activities were experienced. A mixed method approach was used. Measures were taken at course start and three follow-ups. Results showed decreased burnout-scores and long-term sick leaves, and increased work ability; furthermore less stress-related symptoms were reported. Tools and strategies to better handle stress were achieved and were widely at use at all follow-ups. The garden and nature content played an important role for stress relief and for tools and strategies to develop. The results from this study points to beneficial effects of using garden activities and natural environments in a stress management intervention. PMID:25003175

  11. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Assessment of biological variation and analytical imprecision of CA 125, CEA, and TPA in relation to monitoring of ovarian cancer

    DEFF Research Database (Denmark)

    Tuxen, M.K.; Sölétormos, G.; Petersen, P.H.

    1999-01-01

    biological variation. The aim of the study was to assess (i) the analytical imprecision (CVA) and the average inherent intra- and interindividual biological variation (CVTI and CVG, respectively) for CA 125, CEA, and TPA in a group of healthy women; (ii) the significance of changes in serial results of each...

  13. Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

    Science.gov (United States)

    Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

  14. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-17

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  15. Reproductive biology, steroid and biochemical profiles of Dentex dentex ovaries in the Eastern Mediterranean in relation to histological structure

    Directory of Open Access Journals (Sweden)

    R.F. Ismail

    2016-06-01

    Full Text Available This study focuses on reproductive biology in female Dentex dentex, which is a summer multiple spawner with the spawning period extending from late April to June. Females with body length over 35 cm were mature. The GSI value had peak values during May and June. The ova diameter ranged over nine groups (50–700 μm. The relative fecundity ranged from 510 to 1276 eggs per g gutted weight and from 20,409 to 22,595 eggs per 1 cm total length. The histological appearance of the ovarian cycle was divided into five periods. The histological structure of the maturing and ripe oocyte wall shows the presence of five different layers. Baseline of testosterone and estradiol levels was found during the immature and spent, whereas the peak value was found in prespawning and ripe-spawning period. While the maximum total lipid content was in the maturing ovary, the minimum was in muscles of prespawning female. The main polyunsaturated fatty acids n-3 (PUFA for ovary, liver and muscles were docosahexaenoic (DHA, 22:6 n-3 and eicosapentaenoic (EPA, 20:5 n-3 acids, whereas n-6 (PUFA were linoleic (18:2 n-6 and arachidonic (20:4 n-6. All together, the present observations gave basic data of the reproductive cycle of female D. dentex required for its successful spawning.

  16. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  17. Bright versus dim ambient light affects subjective well-being but not serotonin-related biological factors.

    Science.gov (United States)

    Stemer, Bettina; Melmer, Andreas; Fuchs, Dietmar; Ebenbichler, Christoph; Kemmler, Georg; Deisenhammer, Eberhard A

    2015-10-30

    Light falling on the retina is converted into an electrical signal which stimulates serotonin synthesis. Previous studies described an increase of plasma and CNS serotonin levels after bright light exposure. Ghrelin and leptin are peptide hormones which are involved in the regulation of hunger/satiety and are related to serotonin. Neopterin and kynurenine are immunological markers which are also linked to serotonin biosynthesis. In this study, 29 healthy male volunteers were exposed to bright (5000lx) and dim (50lx) light conditions for 120min in a cross-over manner. Subjective well-being and hunger as well as various serotonin associated plasma factors were assessed before and after light exposure. Subjective well-being showed a small increase under bright light and a small decrease under dim light, resulting in a significant interaction between light condition and time. Ghrelin concentrations increased significantly under both light conditions, but there was no interaction between light and time. Correspondingly, leptin decreased significantly under both light conditions. Hunger increased significantly with no light-time interaction. We also found a significant decrease of neopterin, tryptophan and tyrosine levels, but no interaction between light and time. In conclusion, ambient light was affecting subjective well-being rather than serotonin associated biological factors. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Microdosimetric evaluation of relative biological effectiveness for 103PD, 125I, 241AM, and 192IR brachytherapy sources

    International Nuclear Information System (INIS)

    Wuu, C.S.; Kliauga, P.; Zaider, M.; Amols, H.I.

    1996-01-01

    Purpose: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103 Pd, 125 I, 241 Am, and 192 Ir brachytherapy sources at low doses and/or low dose rates. Methods and Materials: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). Results: Relative to 60 Co, the RBE values obtained from this study are: 2.3 for 103 Pd, 2.1 for 125 I, 2.1 for 241 Am, and 1.3 for 192 Ir. Conclusions: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radition quality and make reliable predictions of RBE in low dose rate brachytherapy

  19. Cross-species comparison of the gut: Differential gene expression sheds light on biological differences in closely related tenebrionids.

    Science.gov (United States)

    Oppert, Brenda; Perkin, Lindsey; Martynov, Alexander G; Elpidina, Elena N

    2018-04-01

    The gut is one of the primary interfaces between an insect and its environment. Understanding gene expression profiles in the insect gut can provide insight into interactions with the environment as well as identify potential control methods for pests. We compared the expression profiles of transcripts from the gut of larval stages of two coleopteran insects, Tenebrio molitor and Tribolium castaneum. These tenebrionids have different life cycles, varying in the duration and number of larval instars. T. castaneum has a sequenced genome and has been a model for coleopterans, and we recently obtained a draft genome for T. molitor. We assembled gut transcriptome reads from each insect to their respective genomes and filtered mapped reads to RPKM>1, yielding 11,521 and 17,871 genes in the T. castaneum and T. molitor datasets, respectively. There were identical GO terms in each dataset, and enrichment analyses also identified shared GO terms. From these datasets, we compiled an ortholog list of 6907 genes; 45% of the total assembled reads from T. castaneum were found in the top 25 orthologs, but only 27% of assembled reads were found in the top 25 T. molitor orthologs. There were 2281 genes unique to T. castaneum, and 2088 predicted genes unique to T. molitor, although improvements to the T. molitor genome will likely reduce these numbers as more orthologs are identified. We highlight a few unique genes in T. castaneum or T. molitor that may relate to distinct biological functions. A large number of putative genes expressed in the larval gut with uncharacterized functions (36 and 68% from T. castaneum and T. molitor, respectively) support the need for further research. These data are the first step in building a comprehensive understanding of the physiology of the gut in tenebrionid insects, illustrating commonalities and differences that may be related to speciation and environmental adaptation. Published by Elsevier Ltd.

  20. Nitrogen Retention in Coastal Marine Sediments—a Field Study of the Relative Importance of Biological and Physical Removal in a Danish Estuary

    DEFF Research Database (Denmark)

    Laurentius Nielsen, Søren; Risgaard-Petersen, Nils; Banta, Gary

    2017-01-01

    The aim of this study was to elucidate the relative importance of physical versus biological loss processes for the removal of microphytobenthic (MPB) bound nitrogen in a coastal environment at different times of the year via a dual isotope labeling technique. We used 51Cr, binding to inorganic...... were able to discern the relative importance of physical and biological processes. The isotope marking was supplemented with measurements of sediment chlorophyll biomass and oxygen fluxes, allowing us to evaluate MPB biomass as well as primary production vs. respiration in the sediment. In spring...... was physically dominated due to low MPB biomasses and activity combined with a significant storm event. Our data support the hypothesis that the relative balance between physical and biological processes in determining retention and removal of MPB-bound nitrogen changes seasonally....

  1. Impact of respiratory motion on variable relative biological effectiveness in 4D-dose distributions of proton therapy.

    Science.gov (United States)

    Ulrich, Silke; Wieser, Hans-Peter; Cao, Wenhua; Mohan, Radhe; Bangert, Mark

    2017-11-01

    Organ motion during radiation therapy with scanned protons leads to deviations between the planned and the delivered physical dose. Using a constant relative biological effectiveness (RBE) of 1.1 linearly maps these deviations into RBE-weighted dose. However, a constant value cannot account for potential nonlinear variations in RBE suggested by variable RBE models. Here, we study the impact of motion on recalculations of RBE-weighted dose distributions using a phenomenological variable RBE model. 4D-dose calculation including variable RBE was implemented in the open source treatment planning toolkit matRad. Four scenarios were compared for one field and two field proton treatments for a liver cancer patient assuming (α∕β) x  = 2 Gy and (α∕β) x  = 10 Gy: (A) the optimized static dose distribution with constant RBE, (B) a static recalculation with variable RBE, (C) a 4D-dose recalculation with constant RBE and (D) a 4D-dose recalculation with variable RBE. For (B) and (D), the variable RBE was calculated by the model proposed by McNamara. For (C), the physical dose was accumulated with direct dose mapping; for (D), dose-weighted radio-sensitivity parameters of the linear quadratic model were accumulated to model synergistic irradiation effects on RBE. Dose recalculation with variable RBE led to an elevated biological dose at the end of the proton field, while 4D-dose recalculation exhibited random deviations everywhere in the radiation field depending on the interplay of beam delivery and organ motion. For a single beam treatment assuming (α∕β) x  = 2 Gy, D 95 % was 1.98 Gy (RBE) (A), 2.15 Gy (RBE) (B), 1.81 Gy (RBE) (C) and 1.98 Gy (RBE) (D). The homogeneity index was 1.04 (A), 1.08 (B), 1.23 (C) and 1.25 (D). For the studied liver case, intrafractional motion did not reduce the modulation of the RBE-weighted dose postulated by variable RBE models for proton treatments.

  2. The Role of a Relative Age Effect in the 7 International Children’s Winter Games 2016 and the Influence of Biological Maturity Status on Selection

    Directory of Open Access Journals (Sweden)

    Lisa Müller, Carolin Hildebrandt, Christian Raschner

    2017-06-01

    Full Text Available The aim of this study was to analyse the role of a relative age effect (RAE and to investigate the influence of biological maturity status on the RAE at the 7th International Children`s Winter Games. The birth dates of all 572 participants (365 males, 207 females were analysed, and the biological maturity status of 384 athletes (243 males, 141 females was assessed by the age at peak height velocity (APHV method. A RAE was present in the total sample (χ2 = 67.81; p < 0.001, and among both male (χ2 = 49.02; p < 0.001 and female athletes (χ2 = 37.00; p < 0.001 as well as for strength- (χ2 = 56.46; p < 0.001, endurance- (χ2 = 20.48; p = 0.039 and technique-related types of sports (χ2 = 20.48; p = 0.041. No significant differences in biological maturity status were present between the male athletes of single relative age quarters. Among the female athletes a significant difference was present (F = 5.94, p < 0.001; relatively younger female athletes had significantly lower values in the APHV, which indicated that they were maturing earlier. However, when dividing the athletes into normal, early and late maturing athletes, it could be seen that among the relatively younger athletes, hardly any late maturing athletes were present. These findings revealed that relatively younger athletes seemed to only have a chance for selection if they were early maturing, whereas relatively older athletes had an increased likelihood for selection independent of their biological maturity status. In the future, the relative age and the biological maturity status should be considered in the talent development system for various types of winter sport, to contribute to more fairness and to not discriminate against relatively younger and less mature athletes.

  3. Childhood adversity and adult personality.

    Science.gov (United States)

    Rosenman, Stephen; Rodgers, Bryan

    2006-05-01

    To explore how recalled childhood adversity affects trait measures of personality in three age cohorts of an Australian adult population and to examine the effects of particular adversities on adult personality traits. A total of 7485 randomly selected subjects in the age bands of 20-24, 40-44 and 60-64 years were interviewed at the outset of a longitudinal community study of psychological health in the Canberra region of Australia. In the initial interview, subjects answered 17 questions about domestic adversity and three questions on positive aspects of upbringing to age 16 years. Personality traits were measured by Eysenck Personality Questionnaire, Behavioural Activation and Inhibition Scales, Positive and Negative Affect Scales and a measure of dissocial behaviours. Higher levels of childhood adversity substantially increase the risk of high neuroticism (OR = 2.6) and negative affect (OR = 2.6), less for behavioural inhibition (OR = 1.7) and for dissocial behaviour (OR = 1.7). No significant effect is seen for extraversion, psychoticism or behavioural activation. Age and gender had little effect on the pattern of risk. Maternal depression has significant and substantial independent effects on measures of neuroticism and negative affect as well as most other measures of personality. Childhood domestic adversity has substantial associations with clinically important aspects of personality: neuroticism and negative affect. Only small effects are seen on behavioural inhibition and dissocial behaviour, and no significant effect on extraversion and behavioural activation. These unexpected findings contradict clinical belief. Maternal psychological ill-health is pre-eminent among adversities predicting later disadvantageous traits, even for those traits that had only the slightest association with childhood adversity. Consequences of childhood adversity prevail throughout the lifespan in men and women equally. The study underlines the importance of childhood domestic

  4. Childhood Adversity and Pain Sensitization.

    Science.gov (United States)

    You, Dokyoung Sophia; Meagher, Mary W

    Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

  5. Epigenomic mechanisms of early adversity and HPA dysfunction: Considerations for PTSD research

    Directory of Open Access Journals (Sweden)

    Patrick O McGowan

    2013-09-01

    Full Text Available Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well known risk factors for post-traumatic stress disorder (PTSD, at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care – prime mediators of offspring neurodevelopment - in order to address several questions: (1 what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2 What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the Glucocorticoid Receptor (GR and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms.

  6. ChemProt: a disease chemical biology database

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Nielsen, Sonny Kim; Audouze, Karine Marie Laure

    2011-01-01

    Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network...... biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical-protein annotation resources, as well as disease-associated protein-protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30...... evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram...

  7. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma.

    Science.gov (United States)

    Weber, Jeffrey S; Dummer, Reinhard; de Pril, Veerle; Lebbé, Celeste; Hodi, F Stephen

    2013-05-01

    Ipilimumab 3 mg/kg was the first agent to demonstrate improved survival in previously treated patients with metastatic melanoma in a phase 3 trial (MDX010-20). Ipilimumab produced a characteristic spectrum of immune-related adverse events (irAEs) of special interest, consistent with its immune-based mechanism of action. In MDX010-20, 676 previously treated patients were randomized 3:1:1 to receive ipilimumab 3 mg/kg plus the glycoprotein 100 melanoma antigen vaccine (gp100), ipilimumab 3 mg/kg + placebo, or gp100 vaccine + placebo. For the current report, the authors conducted a detailed analysis of the time to onset and resolution of irAEs associated with ipilimumab therapy. Grade 2 through 5 irAEs generally developed during the induction phase of treatment (0-12 weeks). Most, including grade 3/4 irAEs, were reversible when managed with treatment guidelines using vigilant monitoring and corticosteroids. The median time to resolution (to grade 1 or 0 or to the grade at baseline) of irAEs that had an onset during the induction phase was approximately 6 weeks for grade 2 through 4 irAEs and 8 weeks for grade 3 and 4 irAEs. Across the entire study duration, most grade 2 through 4 irAEs resolved within 12 weeks. Most ipilimumab-associated irAEs, including grade 3/4 symptoms, developed within 12 weeks of initial dosing and resolved within 12 weeks of onset. IrAEs were well characterized in their evolution and could be managed using published algorithms. Copyright © 2013 American Cancer Society.

  8. The relation between histological, tumor-biological and clinical parameters in deep and superficial leiomyosarcoma and leiomyoma.

    NARCIS (Netherlands)

    Pijpe, Justin; Broers, Gerben H Torn; Plaat, Boudewijn E Ch; Hundeiker, M; Otto, F; Mastik, Mirjam F; Hoekstra, Harald J; Graaf, Winette T A van der; van den Berg, Eva; Molenaar, Willemina M

    2002-01-01

    Purpose: Leiomyosarcomas (LMS) of deep and superficial tissues were examined to identify prognostic markers explaining their different biological behaviour and to define differences between cutaneous and subcutaneous LMS. LMS and leiomyomas (LM) of the skin were compared to and consistent

  9. Early life adversity and telomere length: a meta-analysis.

    Science.gov (United States)

    Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

    2018-04-01

    Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

  10. Adverse Event Reporting System (AERS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Adverse Event Reporting System (AERS) is a computerized information database designed to support the FDA's post-marketing safety surveillance program for all...

  11. Organochlorine compounds in streambed sediment and in biological tissue from streams and their relations to land use, central Arizona

    Science.gov (United States)

    Gebler, Joseph B.

    2000-01-01

    Streambed-sediment samples from 13 sites and biological-tissue samples from 11 sites in the Gila River Basin in central Arizona were analyzed for 32 organochlorine compounds in streambed sediment and 28 compounds in biological tissue during 1996 as part of the U.S. Geological Survey's National Water-Quality Assessment program. The objectives of the study were to determine the occurrence and distribution of organochlorine compounds and their relation to land use. Sampling sites were categorized on the basis of major land uses in the basin or the source of water in the stream. Because land uses were mixed or had changed over time, some land-use categories were combined. Sites were categorized as forest/rangeland (6), forest/urban (1), urban (4), or agricultural/urban (2). Thirteen organochlorine compounds were detected in streambed-sediment samples, and 10 were detected in tissue samples. The number of compounds found in streambed-sediment samples from individual sites ranged from 0 to 10, and the range for individual tissue samples was 0 to 7. Comparison of the number of detections in streambed-sediment samples to the number of detections in tissue samples from particular sites where both were sampled yielded five instances where more compounds were detected in streambed sediment, six instances where more compounds were detected in tissue, and five instances where the number of detections in streambed sediment and tissue were equal. The frequency of detection of particular compounds for sites where both streambed sediment and tissue were sampled resulted in five compounds being detected more frequently in streambed sediment, five more frequently in tissue, and three compounds that were equally frequent in streambed sediment and in tissue. Few contaminants were detected in samples from the forest/rangeland sites; greater numbers of compounds were detected at the urban sites and at the forest/urban site. The greatest number of compounds and the highest concentrations

  12. Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

    Science.gov (United States)

    Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

    2015-01-01

    We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.

  13. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    International Nuclear Information System (INIS)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

    2015-01-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137 Cs γ-rays were used. To estimate the RBE of protons relative to 60 Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation

  14. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro; Tang, Shikui [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gheorghiu, Liliana [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Biggs, Peter; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  15. Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Underwood, Tracy S.A.; Kung, Jong [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Meng [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D.; Hong, Theodore S.; Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-05-01

    Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of ∼1.1. However, emerging data have suggested that Fanconi anemia (FA) and homologous recombination pathway defects can lead to a variable RBE, at least in vitro. We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response to proton irradiation. Methods and Materials: Isogenic cell pairs for the study of SLX4, XPF/ERCC1, MUS81, and SLX1 were irradiated at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer 2.5 keV/μm) or with 250 kVp x-rays, and the clonogenic survival fractions were determined. To estimate the RBE of the protons relative to cobalt-60 photons (Co60Eq), we assigned a RBE(Co60Eq) of 1.1 to x-rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor the damage responses, and the cell cycle distributions were assessed by flow cytometry. The poly(ADP-ribose) polymerase inhibitor olaparib was used for comparison. Results: Loss of SLX4 function resulted in an enhanced proton RBE(Co60Eq) of 1.42 compared with 1.11 for wild-type cells (at a survival fraction of 0.1; P<.05), which correlated with increased persistent DNA double-strand breaks in cells in the S/G{sub 2} phase. Genetic analysis identified the SLX4-binding partner MUS81 as a mediator of resistance to proton radiation. Both proton irradiation and olaparib treatment resulted in a similar prolonged accumulation of RAD51 foci in SLX4/MUS81-deficient cells, suggesting a common defect in the repair of DNA replication fork-associated damage. Conclusions: A defect in the FA pathway at the level of SLX4 results in hypersensitivity to proton radiation, which is, at least in part, due to impaired MUS81-mediated processing of replication forks that stall at clustered DNA damage. In vivo and clinical studies are needed to

  16. The Role of a Relative Age Effect in the 7th International Children’s Winter Games 2016 and the Influence of Biological Maturity Status on Selection

    Science.gov (United States)

    Müller, Lisa; Hildebrandt, Carolin; Raschner, Christian

    2017-01-01

    The aim of this study was to analyse the role of a relative age effect (RAE) and to investigate the influence of biological maturity status on the RAE at the 7th International Children`s Winter Games. The birth dates of all 572 participants (365 males, 207 females) were analysed, and the biological maturity status of 384 athletes (243 males, 141 females) was assessed by the age at peak height velocity (APHV) method. A RAE was present in the total sample (χ2 = 67.81; p < 0.001), and among both male (χ2 = 49.02; p < 0.001) and female athletes (χ2 = 37.00; p < 0.001) as well as for strength- (χ2 = 56.46; p < 0.001), endurance- (χ2 = 20.48; p = 0.039) and technique-related types of sports (χ2 = 20.48; p = 0.041). No significant differences in biological maturity status were present between the male athletes of single relative age quarters. Among the female athletes a significant difference was present (F = 5.94, p < 0.001); relatively younger female athletes had significantly lower values in the APHV, which indicated that they were maturing earlier. However, when dividing the athletes into normal, early and late maturing athletes, it could be seen that among the relatively younger athletes, hardly any late maturing athletes were present. These findings revealed that relatively younger athletes seemed to only have a chance for selection if they were early maturing, whereas relatively older athletes had an increased likelihood for selection independent of their biological maturity status. In the future, the relative age and the biological maturity status should be considered in the talent development system for various types of winter sport, to contribute to more fairness and to not discriminate against relatively younger and less mature athletes. Key points The relative age strongly influenced the participation rate at the 7th ICG in 2016. A highly significant RAE was present among male and female participants and among athletes of all three groups of sport

  17. How Does Biological Belief in Race Relate to Our Feelings towards In-Group and Out-Groups?: A Cognitive Dissonance Framework

    Science.gov (United States)

    Tawa, John; Kim, Grace S.

    2011-01-01

    This study considered the effect of belief in race as a biological construct (RACEBIO) and inter-group anxiety (IGA) on in-group racial salience (IGRS) and out-group discomfort (OGD). Participants included 66 racially and ethnically diverse high school boarding students. As hypothesized, RACEBIO was positively related to both IGRS and OGD. In…

  18. Ventral striatal activity links adversity and reward processing in children.

    Science.gov (United States)

    Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

    2017-08-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Ventral striatal activity links adversity and reward processing in children

    Directory of Open Access Journals (Sweden)

    Niki H. Kamkar

    2017-08-01

    Full Text Available Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain’s sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

  20. Adverse events associated with pediatric exposures to dextromethorphan.

    Science.gov (United States)

    Paul, Ian M; Reynolds, Kate M; Kauffman, Ralph E; Banner, William; Bond, G Randall; Palmer, Robert B; Burnham, Randy I; Green, Jody L

    2017-01-01

    Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.

  1. 3-12 Detection and Management of Adverse Drug React

    African Journals Online (AJOL)

    MINA SAN

    Detection and Management of Adverse Drug Reactions Related to Antiretroviral Drugs among. HIV/AIDS Patients in Kiambu ... of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care .... educational level, perception of ADRs, knowledge of ADRs, detection ...

  2. Adverse reactions in voluntary whole blood donors: Experience at ...

    African Journals Online (AJOL)

    Background: Whole blood donation, generally considered as a safe procedure, may be sometimes associated with adverse reactions and injuries of variable severity during or after the blood donation process. There are few reports of adverse events related to blood donation in the Democratic Republic of Congo.

  3. Adverse Selection in Health Insurance Markets: A Classroom Experiment

    Science.gov (United States)

    Hodgson, Ashley

    2014-01-01

    Adverse selection as it relates to health care policy will be a key economic issue in many upcoming elections. In this article, the author lays out a 30-minute classroom experiment designed for students to experience the kind of elevated prices and market collapse that can result from adverse selection in health insurance markets. The students…

  4. Chemoradiotherapy and molecular biology

    International Nuclear Information System (INIS)

    Hasegawa, Masatoshi; Mitsuhashi, Norio; Niibe, Hideo

    2000-01-01

    The current status of chemoradiotherapy was reviewed from the standpoint of molecular biology. Chemoradiotherapy was conducted to achieve systemic tumor control, to intensify the response to irradiation, and to reduce adverse reactions. The mechanisms of the efficacy of chemoradiotherapy were: modification of dose-response relationships, inhibition of tumor cell recovery from sublethal damage or potential lethal damage, effects on cell dynamics and the cell cycle, improvement of blood flow or reoxygenation, recruitment, improvement of drug uptake, increased cell damage. Cell death (necrosis and apoptosis) and cancer-related genes were described, as the essential points, because they are involved in the response to chemoradiotherapy. Cisplatin (platinum compound), 5-fluorouracil, etoposide, and taxoid (paclitaxel, docetaxel) were the principal anticancer agents used for chemoradiotherapy, and they enhanced the effects of irradiation. However, even when good responses or synergism between anticancer drug and radiotherapy was observed in in vitro studies, there was little therapeutic advantage clinically. Data from in vitro and in vivo studies should be collected and systemized, and ''molecular biology in chemotherapy'' that can be applied clinically may become established. (K.H.)

  5. Early menarche and childhood adversities in a nationally representative sample.

    Science.gov (United States)

    Henrichs, Kimberly L; McCauley, Heather L; Miller, Elizabeth; Styne, Dennis M; Saito, Naomi; Breslau, Joshua

    2014-01-01

    Epidemiological evidence suggests that early menarche, defined as onset of menses at age 11 or earlier, has increased in prevalence in recent birth cohorts and is associated with multiple poor medical and mental health outcomes in adulthood. There is evidence that childhood adversities occurring prior to menarche contribute to early menarche. Data collected in face-to-face interviews with a nationally representative sample of women age 18 and over (N = 3288), as part of the National Comorbidity Survey-Replication, were analyzed. Associations between pre-menarchal childhood adversities and menarche at age 11 or earlier were estimated in discrete time survival models with statistical adjustment for age at interview, ethnicity, and body mass index. Adversities investigated included physical abuse, sexual abuse, neglect, biological father absence from the home, other parent loss, parent mental illness, parent substance abuse, parent criminality, inter-parental viole