Processing speed and memory mediate age-related differences in decision making.

PubMed

Henninger, Debra E; Madden, David J; Huettel, Scott A

2010-06-01

Decision making under risk changes with age. Increases in risk aversion with age have been most commonly characterized, although older adults may be risk seeking in some decision contexts. An important, and unanswered, question is whether these changes in decision making reflect a direct effect of aging or, alternatively, an indirect effect caused by age-related changes in specific cognitive processes. In the current study, older adults (M = 71 years) and younger adults (M = 24 years) completed a battery of tests of cognitive capacities and decision-making preferences. The results indicated systematic effects of age upon decision quality-with both increased risk seeking and increased risk aversion observed in different tasks-consistent with prior studies. Path analyses, however, revealed that age-related effects were mediated by individual differences in processing speed and memory. When those variables were included in the model, age was no longer a significant predictor of decision quality. The authors conclude that the reduction in decision quality and associated changes in risk preferences commonly ascribed to aging are instead mediated by age-related changes in underlying cognitive capacities. (c) 2010 APA, all rights reserved

CANCER RISK ASSESSMENT FOR CHLOROFORM

EPA Science Inventory

Chloroform is a common chlorination by-product in drinking water. EPA has regulated chloroform as a probable human carcinogen under the Safe Drinking Water Act. The cancer risk estimate via ingestion was based on the 1985 Jorgenson study identifying kidney tumors in male Osborne ...

Fish Consumption Advisories: Toward a Unified, Scientifically Credible Approach

EPA Science Inventory

A model is proposed for fish consumption advisories based on consensus-derived risk assessment values for common contaminants in fish and the latest risk assessment methods. he model accounts in part for the expected toxicity to mixtures of chemicals, the underlying uncertainties...

Hemiplegic shoulder pain: a common clinical consequence of stroke.

PubMed

Coskun Benlidayi, Ilke; Basaran, Sibel

2014-04-01

Hemiplegic shoulder pain is common in stroke survivors, developing in up to 54% of patients. The underlying mechanisms include soft tissue lesions, impaired motor function and central nervous system-related phenomena. Hemiplegic shoulder pain has many underlying causes and is challenging to manage, requiring a team approach, including physicians, therapists and caregivers. The management strategy must target the underlying causes. Preventative measures, such as positioning and handling, can reduce the risk of developing hemiplegic shoulder pain. We have reviewed the literature on hemiplegic shoulder pain, and used this to categorise the underlying mechanisms, and to explore the best management strategies.

12 CFR Appendix B to Part 3 - Risk-Based Capital Guidelines; Market Risk

Code of Federal Regulations, 2014 CFR

2014-01-01

... 11Simplified Supervisory Formula Approach Section 12Market Risk Disclosures Section 1. Purpose, Applicability... respect to a company means any company that controls, is controlled by, or is under common control with... organization. Control A person or company controls a company if it: (1) Owns, controls, or holds with power to...

Dementia in the Oldest Old

PubMed Central

Bullain, Szófia S.; Corrada, María M.

2013-01-01

Purpose of Review: This article discusses some of the unique features of dementia in the oldest old, including some of the most common diagnostic challenges, and potential strategies to overcome them. Recent Findings: Advances include new insight into the role of common risk factors and the effects of multiple underlying neuropathologic features for dementia in the oldest old. In addition, this article contains the latest age-specific normative data for commonly used neuropsychological tests for the oldest old. Summary: The oldest old—people aged 90 years and older—are the fastest-growing segment of society and have the highest rates of dementia in the population. The risk factors, diagnostic challenges, and underlying neuropathologic features of dementia are strikingly different in the 90-years-and-older population compared to younger elderly. Special consideration of these unique features of dementia is necessary when evaluating oldest-old subjects with cognitive impairment. PMID:23558489

ENDANGERED SPECIES SENSITIVITY AND ECOLOGICAL RISK ASSESSMENT

EPA Science Inventory

he U.S. Environmental Protection Agency (EPA), U.S. Fish & Wildlife Service, and National Marine Fisheries Service share a common responsibility for the protection of our nation's aquatic species under the Endangered Species Act (ESA) of 1973. The EPA, under the Federal Insectici...

Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.

PubMed

Talmud, Philippa J; Hingorani, Aroon D; Cooper, Jackie A; Marmot, Michael G; Brunner, Eric J; Kumari, Meena; Kivimäki, Mika; Humphries, Steve E

2010-01-14

To assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes. Workplace based prospective cohort study with three 5 yearly medical screenings. 5535 initially healthy people (mean age 49 years; 33% women), of whom 302 developed new onset type 2 diabetes over 10 years. Non-genetic variables included in two established risk models-the Cambridge type 2 diabetes risk score (age, sex, drug treatment, family history of type 2 diabetes, body mass index, smoking status) and the Framingham offspring study type 2 diabetes risk score (age, sex, parental history of type 2 diabetes, body mass index, high density lipoprotein cholesterol, triglycerides, fasting glucose)-and 20 single nucleotide polymorphisms associated with susceptibility to type 2 diabetes. Cases of incident type 2 diabetes were defined on the basis of a standard oral glucose tolerance test, self report of a doctor's diagnosis, or the use of anti-diabetic drugs. A genetic score based on the number of risk alleles carried (range 0-40; area under receiver operating characteristics curve 0.54, 95% confidence interval 0.50 to 0.58) and a genetic risk function in which carriage of risk alleles was weighted according to the summary odds ratios of their effect from meta-analyses of genetic studies (area under receiver operating characteristics curve 0.55, 0.51 to 0.59) did not effectively discriminate cases of diabetes. The Cambridge risk score (area under curve 0.72, 0.69 to 0.76) and the Framingham offspring risk score (area under curve 0.78, 0.75 to 0.82) led to better discrimination of cases than did genotype based tests. Adding genetic information to phenotype based risk models did not improve discrimination and provided only a small improvement in model calibration and a modest net reclassification improvement of about 5% when added to the Cambridge risk score but not when added to the Framingham offspring risk score. The phenotype based risk models provided greater discrimination for type 2 diabetes than did models based on 20 common independently inherited diabetes risk alleles. The addition of genotypes to phenotype based risk models produced only minimal improvement in accuracy of risk estimation assessed by recalibration and, at best, a minor net reclassification improvement. The major translational application of the currently known common, small effect genetic variants influencing susceptibility to type 2 diabetes is likely to come from the insight they provide on causes of disease and potential therapeutic targets.

The Spectrum of Epidemiology Underlying Sudden Cardiac Death

PubMed Central

Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M.

2015-01-01

Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15–20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who suffer a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly due to inherited disorders. Coronary heart disease (CHD) is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. Over the past three decades, declines in SCD rates have not been as steep as for other causes of CHD deaths, and there is a growing fraction of SCDs not due to CHD and/or ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition prior to death. Multifaceted preventative approaches, which address risk factors in seemingly low risk and known high-risk populations will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies. PMID:26044246

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.

PubMed

Wen, Wanqing; Shu, Xiao-Ou; Guo, Xingyi; Cai, Qiuyin; Long, Jirong; Bolla, Manjeet K; Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Gao, Yu-Tang; Zheng, Ying; Dunning, Alison M; García-Closas, Montserrat; Brennan, Paul; Chen, Shou-Tung; Choi, Ji-Yeob; Hartman, Mikael; Ito, Hidemi; Lophatananon, Artitaya; Matsuo, Keitaro; Miao, Hui; Muir, Kenneth; Sangrajrang, Suleeporn; Shen, Chen-Yang; Teo, Soo H; Tseng, Chiu-Chen; Wu, Anna H; Yip, Cheng Har; Simard, Jacques; Pharoah, Paul D P; Hall, Per; Kang, Daehee; Xiang, Yongbing; Easton, Douglas F; Zheng, Wei

2016-12-08

Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

Mass media and risk factors for cancer: the under-representation of age.

PubMed

Macdonald, Sara; Cunningham, Yvonne; Patterson, Chris; Robb, Katie; Macleod, Una; Anker, Thomas; Hilton, Shona

2018-04-26

Increasing age is a risk factor for developing cancer. Yet, older people commonly underestimate this risk, are less likely to be aware of the early symptoms, and are more likely to be diagnosed with advanced stage cancer. Mass media are a key influence on the public's understanding health issues, including cancer risk. This study investigates how news media have represented age and other risk factors in the most common cancers over time. Eight hundred articles about the four most common cancers (breast, prostate, lung and colorectal) published within eight UK national newspapers in 2003, 2004, 2013 and 2014 were identified using the Nexis database. Relevant manifest content of articles was coded quantitatively and subjected to descriptive statistical analysis in SPSS to identify patterns across the data. Risk was presented in half of the articles but this was rarely discussed in any depth and around a quarter of all articles introduced more than one risk factor, irrespective of cancer site. Age was mentioned as a risk factor in approximately 12% of all articles and this varied by cancer site. Age was most frequently reported in relation to prostate cancer and least often in articles about lung cancer. Articles featuring personal narratives more frequently focused on younger people and this was more pronounced in non-celebrity stories; only 15% of non-celebrity narratives were about people over 60. Other common risks discussed were family history and genetics, smoking, diet, alcohol, and environmental factors. Family history and genetics together featured as the most common risk factors. Risk factor reporting varied by site and family history was most commonly associated with breast cancer, diet with bowel cancer and smoking with lung cancer. Age and older adults were largely obscured in media representation of cancer and cancer experience. Indeed common risk factors in general were rarely discussed in any depth. Our findings will usefully inform the development of future cancer awareness campaigns and media guidelines. It is important that older adults appreciate their heightened risk, particularly in the context of help-seeking decisions.

Young people's and stakeholders' perspectives of adolescent sexual risk behavior in Kilifi County, Kenya: A qualitative study.

PubMed

Ssewanyana, Derrick; Mwangala, Patrick N; Marsh, Vicki; Jao, Irene; van Baar, Anneloes; Newton, Charles R; Abubakar, Amina

2018-02-01

A lack of research exists around the most common forms of sexual risk behaviors among adolescents, including their underlying factors, in Sub-Saharan Africa. Using an Ecological Model of Adolescent Behavior, we explore the perceptions of 85 young people and 10 stakeholders on sexual risk behavior of adolescents in Kilifi County on the coast of Kenya. Our findings show that transactional sex, early sexual debut, coerced sex, and multiple sexual partnerships are prevalent. An urgent need exists to develop measures to counter sexual risk behaviors. The results contribute to understanding the range of risks and protective factors in differing contexts, tackling underlying issues at individual, family, local institutional, wider socio-economic, and political levels.

Young people’s and stakeholders’ perspectives of adolescent sexual risk behavior in Kilifi County, Kenya: A qualitative study

PubMed Central

Ssewanyana, Derrick; Mwangala, Patrick N; Marsh, Vicki; Jao, Irene; van Baar, Anneloes; Newton, Charles R; Abubakar, Amina

2017-01-01

A lack of research exists around the most common forms of sexual risk behaviors among adolescents, including their underlying factors, in Sub-Saharan Africa. Using an Ecological Model of Adolescent Behavior, we explore the perceptions of 85 young people and 10 stakeholders on sexual risk behavior of adolescents in Kilifi County on the coast of Kenya. Our findings show that transactional sex, early sexual debut, coerced sex, and multiple sexual partnerships are prevalent. An urgent need exists to develop measures to counter sexual risk behaviors. The results contribute to understanding the range of risks and protective factors in differing contexts, tackling underlying issues at individual, family, local institutional, wider socio-economic, and political levels. PMID:29076401

Role of risk factors and socio-economic status in pulmonary tuberculosis: a search for the root cause in patients in a tertiary care hospital, South India.

PubMed

Gupta, Soham; Shenoy, Vishnu Prasad; Mukhopadhyay, Chiranjay; Bairy, Indira; Muralidharan, Sethumadhavan

2011-01-01

To determine the frequency of underlying risk factors and the socio-economic impact based on occupation in the development of tuberculosis. Retrospective analysis of 207 clinically and microbiologically diagnosed patients with pulmonary tuberculosis (PTB) admitted to Kasturba Hospital in 2005 and 2006. Demographic details and underlying risk factors were statistically evaluated. Diabetes mellitus (DM) (30.9%) was the most prevalent condition and significantly more common than other risk factors like smoking (16.9%), alcoholism (12.6%), HIV (10.6%), malignancy (5.8%), chronic liver diseases (3.9%), history of contact with TB (3.4%), chronic corticosteroid therapy (2.9%), chronic kidney diseases and malnourishment (1.5%). There were 82 patients (39.6%) with no underlying risk factor. Men (M:F = 3.7:1) and patients older than 40 years had a higher incidence of co-existing conditions. PTB was significantly more common in blue-collar (44%) and white-collar (27.1%) workers than household workers (12.1%), students (10.6%) and retired/unemployed people (6.3%). Pulmonary tuberculosis had a significant impact and predominated in male patients co-existing with DM. Patients with DM and suggestive pulmonary symptoms should be screened for tuberculosis. More stringent health education and awareness programme should be implemented at the grass root level. © 2010 Blackwell Publishing Ltd.

Markers of visceral obesity and cardiovascular risk in patients with polycystic ovarian syndrome.

PubMed

Gateva, Antoaneta Trifonova; Kamenov, Zdravko Asenov

2012-10-01

Polycystic ovarian syndrome (PCOS) is one of most common endocrine disturbances in women of reproductive age. Besides its well known effects on reproductive health, it is also linked to increased cardiovascular risk in later life. The aim of this study was to investigate the link between some anthropometric indices of visceral obesity and surrogate markers of cardiovascular risk according to the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society consensus. The study included 36 normal weight (BMI<25 kg/m²) and 19 obese PCOS subjects (BMI ≥ 30 kg/m²), aged between 18 and 40 years. Different anthropometric markers were compared as predictors for an adverse cardiometabolic profile and composite cardiovascular risk factors as defined by the AE-PCOS consensus. Both waist-to-stature ratio (WSR) (area under the curve 0.75, p=0.002) and waist circumference (WC) (area under the curve 0.77, p=0.001) but not waist-to-hip ratio (WHR) (area under the curve 0.62, p=0.143) were shown to be good markers of increased cardiovascular risk, insulin resistance and dislipidemia in PCOS patients. The cut-off point for WSR of 0.50 is useful and the cut-off of 80 cm for WC is more appropriate than 88 cm in detecting cardiovascular risk in PCOS patients. Androgen levels and immunoreactive insulin during an oral glucose tolerance test had lower power for predicting increased cardiovascular risk than WC and WSR. The study indicates that WSR and WC are better associated with composite cardiovascular risk factors as defined by the AE-PCOS consensus than WHR, and that the commonly used cut-off for WSR of 0.5 is useful for detecting cardiovascular risk in PCOS patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Common Methods for Security Risk Analysis

DTIC Science & Technology

2005-01-12

recognized in the others. In Canada, three firms have been accredited as IT Security Evaluation and Testing (ITSET) Facility, under ISO / IEC 17025 -1999...harmonized security standards such as the Common Criteria and ISO 17799 may further increase the applicability of TRA approach. 3.4.8 MOST AUTOMATION...create something more suitable, the Common Criteria with Mutual Recognition Agreement (MRA) signed in October 1998. The CC became an ISO standard

How Does Sexual Minority Stigma "Get under the Skin"? A Psychological Mediation Framework

ERIC Educational Resources Information Center

Hatzenbuehler, Mark L.

2009-01-01

Sexual minorities are at increased risk for multiple mental health burdens compared with heterosexuals. The field has identified 2 distinct determinants of this risk, including group-specific minority stressors and general psychological processes that are common across sexual orientations. The goal of the present article is to develop a…

TESTING FOR ADDITIVITY IN THE LOW DOSE REGION OF AN ENVIRONMENTALLY RELEVANT MIXTURE OF 18 OLYHALOGENATED AROMATIC HYDROCARBONS.

EPA Science Inventory

A common default assumption in risk assessment of chemical mixtures is that the chemicals combine additively in the low dose region. Under additivity, with information from single chemical dose-response data, the risk associated with the mixture can be estimated. The objective ...

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

PubMed Central

Lin, Jhih-Rong; Cai, Ying; Zhang, Quanwei; Zhang, Wen; Nogales-Cadenas, Rubén; Zhang, Zhengdong D.

2016-01-01

Schizophrenia is a severe mental disorder with a large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, the underlying biological mechanisms are not clear. The critical first step for their elucidation is to identify the most likely disease genes as the source of the association signals. Here, we describe a general computational framework of post-GWAS analysis for complex disease gene prioritization. We identify 132 putative schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are outside the risk regions, likely under regulation of transcriptional regulatory elements contained therein. These putative schizophrenia risk genes are transcriptionally active in both brain and the immune system, and highly enriched among cellular pathways, consistent with leading pathophysiological hypotheses about the pathogenesis of schizophrenia. With their involvement in distinct biological processes, these putative schizophrenia risk genes, with different association strengths, show distinctive temporal expression patterns, and play specific biological roles during brain development. PMID:27754856

Correction to: Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study.

PubMed

Dennis, Michael; Shine, Laura; John, Ann; Marchant, Amanda; McGregor, Joanna; Lyons, Ronan A; Brophy, Sinead

2018-06-01

This article was originally published under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), but has now been made available under a Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The PDF and HTML versions of the paper have been modified accordingly.

Personalized Risk Prediction in Clinical Oncology Research: Applications and Practical Issues Using Survival Trees and Random Forests.

PubMed

Hu, Chen; Steingrimsson, Jon Arni

2018-01-01

A crucial component of making individualized treatment decisions is to accurately predict each patient's disease risk. In clinical oncology, disease risks are often measured through time-to-event data, such as overall survival and progression/recurrence-free survival, and are often subject to censoring. Risk prediction models based on recursive partitioning methods are becoming increasingly popular largely due to their ability to handle nonlinear relationships, higher-order interactions, and/or high-dimensional covariates. The most popular recursive partitioning methods are versions of the Classification and Regression Tree (CART) algorithm, which builds a simple interpretable tree structured model. With the aim of increasing prediction accuracy, the random forest algorithm averages multiple CART trees, creating a flexible risk prediction model. Risk prediction models used in clinical oncology commonly use both traditional demographic and tumor pathological factors as well as high-dimensional genetic markers and treatment parameters from multimodality treatments. In this article, we describe the most commonly used extensions of the CART and random forest algorithms to right-censored outcomes. We focus on how they differ from the methods for noncensored outcomes, and how the different splitting rules and methods for cost-complexity pruning impact these algorithms. We demonstrate these algorithms by analyzing a randomized Phase III clinical trial of breast cancer. We also conduct Monte Carlo simulations to compare the prediction accuracy of survival forests with more commonly used regression models under various scenarios. These simulation studies aim to evaluate how sensitive the prediction accuracy is to the underlying model specifications, the choice of tuning parameters, and the degrees of missing covariates.

Risk factors for gallbladder contractility after cholecystolithotomy in elderly high-risk surgical patients

PubMed Central

Wang, Tao; Luo, Hao; Yan, Hong-tao; Zhang, Guo-hu; Liu, Wei-hui; Tang, Li-jun

2017-01-01

Objective Cholecystolithiasis is a common disease in the elderly patient. The routine therapy is open or laparoscopic cholecystectomy. In the previous study, we designed a minimally invasive cholecystolithotomy based on percutaneous cholecystostomy combined with a choledochoscope (PCCLC) under local anesthesia. Methods To investigate the effect of PCCLC on the gallbladder contractility function, PCCLC and laparoscope combined with a choledochoscope were compared in this study. Results The preoperational age and American Society of Anesthesiologists (ASA) scores, as well as postoperational lithotrity rate and common biliary duct stone rate in the PCCLC group, were significantly higher than the choledochoscope group. However, the pre- and postoperational gallbladder ejection fraction was not significantly different. Univariable and multivariable logistic regression analyses indicated that the preoperational thickness of gallbladder wall (odds ratio [OR]: 0.540; 95% confidence interval [CI]: 0.317–0.920; P=0.023) and lithotrity (OR: 0.150; 95% CI: 0.023–0.965; P=0.046) were risk factors for postoperational gallbladder ejection fraction. The area under receiver operating characteristics curve was 0.714 (P=0.016; 95% CI: 0.553–0.854). Conclusion PCCLC strategy should be carried out cautiously. First, restricted by the diameter of the drainage tube, the PCCLC should be used only for small gallstones in high-risk surgical patients. Second, the usage of lithotrity should be strictly limited to avoid undermining the gallbladder contractility and increasing the risk of secondary common bile duct stones. PMID:28138229

Bacterial pneumonia in dogs and cats.

PubMed

Dear, Jonathan D

2014-01-01

Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less commonly in cats. Underlying causes include viral infection, aspiration injury, and foreign body inhalation. Identification of the organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management. Copyright © 2014 Elsevier Inc. All rights reserved.

Sub-clinical psychosis symptoms in young adults are risk factors for subsequent common mental disorders.

PubMed

Rössler, Wulf; Hengartner, Michael P; Ajdacic-Gross, Vladeta; Haker, Helene; Gamma, Alex; Angst, Jules

2011-09-01

Not all persons identified in the early stages to be at risk for psychosis eventually cross the threshold for a psychotic illness. However, sub-clinical symptoms may not only indicate a specific risk but also suggest a more general, underlying psychopathology that predisposes one to various common mental disorders. Analyzing data from the prospective Zurich Cohort Study, we used two psychosis subscales - "schizotypal signs" and "schizophrenia nuclear symptoms" - derived from the SCL-90-R checklist that measured sub-clinical psychosis symptoms in 1979. We also assessed 10 different diagnoses of common mental disorders through seven interview waves between 1979 and 2008. This 30-year span, covering participant ages of 19/20 to 49/50, encompasses the period of highest risk for the occurrence of such disorders. Both psychosis scales from 1979, but especially "schizotypal signs", were significantly correlated with most mental disorders over the subsequent test period. Higher values on both subscales were associated with an increasing number of co-occurring disorders. Our data demonstrate that sub-clinical psychosis generally represents a risk factor for the development of common mental disorders and a liability for co-occurring disorders. This refers in particular to dysthymia, bipolar disorder, social phobia, and obsessive-compulsive disorder. Proneness to psychosis could signal a fundamental tendency toward common mental disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

76 FR 802 - Florida Power and Light Company, Turkey Point, Units 3 and 4; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

..., health physics, chemistry, and security, to maintain the safe and secure operation of the facility. The... exemption is authorized by law. No Undue Risk to Public Health and Safety The underlying purposes of 10 CFR... previously evaluated. Therefore, there is no undue risk to public health and safety. Consistent With Common...

Basal cell carcinoma of the skin (part 1): epidemiology, pathology and genetic syndromes.

PubMed

Correia de Sá, Tiago Ribeiro; Silva, Roberto; Lopes, José Manuel

2015-11-01

Basal cell carcinoma (BCC) is the most common skin cancer worldwide with increasing incidence, but difficult to assess due to the current under registration practice. Despite the low mortality rate, BCC is a cause of great morbidity and an economic burden to health services. There are several risk factors that increase the risk of BCC and partly explain its incidence. Low-penetrance susceptibility alleles, as well as genetic alterations in signaling pathways, namely SHH pathway, also contribute to the carcinogenesis. BCC associate with several genetic syndromes, of which basal cell nevus syndrome is the most common.

Risk-dependent reward value signal in human prefrontal cortex

PubMed Central

Tobler, Philippe N.; Christopoulos, George I.; O'Doherty, John P.; Dolan, Raymond J.; Schultz, Wolfram

2009-01-01

When making choices under uncertainty, people usually consider both the expected value and risk of each option, and choose the one with the higher utility. Expected value increases the expected utility of an option for all individuals. Risk increases the utility of an option for risk-seeking individuals, but decreases it for risk averse individuals. In 2 separate experiments, one involving imperative (no-choice), the other choice situations, we investigated how predicted risk and expected value aggregate into a common reward signal in the human brain. Blood oxygen level dependent responses in lateral regions of the prefrontal cortex increased monotonically with increasing reward value in the absence of risk in both experiments. Risk enhanced these responses in risk-seeking participants, but reduced them in risk-averse participants. The aggregate value and risk responses in lateral prefrontal cortex contrasted with pure value signals independent of risk in the striatum. These results demonstrate an aggregate risk and value signal in the prefrontal cortex that would be compatible with basic assumptions underlying the mean-variance approach to utility. PMID:19369207

21 CFR 312.21 - Phases of an investigation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... are a follows: (a) Phase 1. (1) Phase 1 includes the initial introduction of an investigational new... under study and to determine the common short-term side effects and risks associated with the drug...

Longitudinal Links between Impulsivity, Gambling Problems and Depressive Symptoms: A Transactional Model from Adolescence to Early Adulthood

ERIC Educational Resources Information Center

Dussault, Frederic; Brendgen, Mara; Vitaro, Frank; Wanner, Brigitte; Tremblay, Richard E.

2011-01-01

Background: Research shows high co-morbidity between gambling problems and depressive symptoms, but the directionality of this link is unclear. Moreover, the co-occurrence of gambling problems and depressive symptoms could be spurious and explained by common underlying risk factors such as impulsivity and socio-family risk. The goals of the…

Cyber Insurance - Managing Cyber Risk

DTIC Science & Technology

2015-04-01

license under the clause at DFARS 252.227-7013 (a)(16) [Jun 2013]. Cyber Insurance – Managing Cyber Risk Data breaches involving...significant personal information losses and financial impact are becoming increasingly common. Whether the data breach has financial implications for...hundreds of millions of dollars depending on the type and size of the breach. Most states have some type of data breach law requiring notification

Significantly reduced health burden from ambient air pollution in the U.S. under emission reductions from 1990 to 2010

EPA Science Inventory

The recent 2013 Global Burden of Disease Study 2013 has attributed the ambient PM2.5 as the fifth-ranking mortality risk factor in 2015. While assessing the global or national burden of disease attributed to air pollution has become more common, fewer studies have tried to unders...

[The Common Risk Factor Approach - An Integrated Population- and Evidence-Based Approach for Reducing Social Inequalities in Oral Health].

PubMed

Heilmann, A; Sheiham, A; Watt, R G; Jordan, R A

2016-10-01

Worldwide, non-communicable diseases including dental caries and periodontal diseases, remain a major public health problem. Moreover, there is a social gradient in health across society that runs from the top to the bottom in a linear, stepwise fashion. Health promoting behaviours become more difficult to sustain further down the social ladder. Oral health inequalities also exist in Germany. Earlier explanations of social inequalities have mainly focused on individual lifestyle factors, ignoring the broader social determinants of health and disease. Until recently, the dominant approaches to general health promotion focused on actions to reduce specific diseases, separating oral health from general health. An alternative approach is the common risk factor approach (CRFA) where risk factors common to a number of major chronic diseases, including diseases of the mouth and teeth, are tackled. The CRFA focuses on the common underlying determinants of health to improve the overall health of populations, thereby reducing social inequalities. The main implication of the CRFA for oral health policies is to work in partnership with a range of other sectors and disciplines. Oral health issues need to be integrated with recommendations to promote general health. Improvements in oral health and a reduction in oral health inequalities are more likely by working in partnership across sectors and disciplines using strategies that focus upstream on the underlying determinants of oral diseases. © Georg Thieme Verlag KG Stuttgart · New York.

[Assessment on the yield loss risk of longan caused by cold damage in South China].

PubMed

Zhao, Jun-fang; Yu, Hui-kang

2016-02-01

Using daily climate variables gathered from 64 meteorological stations in South China from 1961 to 2012, recognized hazard indicators about disaster grades of cold damage for longan, and methods on agricultural meteorological disasters risk and simulation technology, the yield loss risks of longan caused by cold damage in South China during different developmental periods were assessed. The results showed that during the period of physiologic differentiation of flower bud, the disasters of longan affected by mild cold damage in South China were the most common, followed by severe cold damage and moderate cold damage. The hazards caused by cold damage under different grades varied. In particular, under mild cold damage, light disaster of longan was found in Fujian, followed by Guangdong and Hainan, and Guangxi was serious. Under moderate cold damage, light disaster of longan was found in Hainan, followed by Guangdong and Guangxi, and Fujian was serious. Under severe cold damage, light disaster of longan was found in Hainan, followed by Guangdong and Guangxi, Fujian was serious. During the period of morphologic differentiation of flower bud, the disasters of longan affected by mild cold damage in South China were the most common, followed by severe cold damage and moderate cold damage, while the disasters of longan under mild, moderate and severe cold damages within this period were similar. Specifically, light disasters of longan were all found in Hainan, followed by Guangdong, Guangxi and Fujian. During the period of dormancy, the disaster of longan affected by mild cold damage in South China was the most common, followed by severe cold damage and moderate cold damage. Under mild and severe cold damage, light disaster of longan was found in Fujian, followed by Guangdong and Hainan, and Guangxi was serious. However, under moderate cold damage, light disaster of longan was found in Hainan and Guangxi, followed by Guangdong, and Fujian was serious. At the same level of hazard, the largest risk indices of yield loss of longan during different developmental stages significantly differed. Under mild cold damage, serious disasters of longan were found in the period of physiologic differentiation of flower bud, followed by the period of morphologic differentiation of flower bud and the period of dormancy. However, under moderate and severe cold damage, serious disasters of longan were found in the period of physiologic differentiation of flower bud, followed by the period of dormancy and the period of morphologic differentiation of flower bud.

Risk in pediatric anesthesia.

PubMed

Paterson, Neil; Waterhouse, Peter

2011-08-01

Risk in pediatric anesthesia can be conveniently classified as minor or major. Major morbidity includes cardiac arrest, brain damage and death. Minor morbidity can be assessed by clinical audits with small patient samples. Major morbidity is rare. It is best assessed by very large clinical studies and by review of closed malpractice claims. Both minor and major morbidity occur most commonly in infants and children under three, especially those with severe co-morbidities. Knowledge of risk profiles in pediatric anesthesia is a starting point for the reduction of risk. © 2010 Blackwell Publishing Ltd.

Let Food Be Thy Medicine: Diet, Nutrition, and Biomarkers’ Risk of Alzheimer’s Disease

PubMed Central

Mosconi, Lisa; McHugh, Pauline F.

2015-01-01

Epidemiological evidence linking diet—one of the most important modifiable lifestyle factors—and risk of Alzheimer’s disease (AD)—the most common cause of dementia—is rapidly increasing. However, the biological mechanisms underlying the relationship between dietary nutrients, brain aging, and risk of AD are largely unexplored. Recent studies using brain imaging and biological markers of AD have begun to clarify how diet and nutrition modulate risk of AD in cognitively normal individuals, especially those at increased genetic risk. Such knowledge is critical prior to implementing dietary recommendations for prevention and treatment of disease. PMID:26167396

76 FR 62816 - Office of Biotechnology Activities; Recombinant DNA Research: Action Under the NIH Guidelines for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

... specify the risk group (RG) classification for several common attenuated strains of bacteria and viruses... minimum containment level required for experiments subject to the NIH Guidelines. The classification of...

Murder-suicide: a review of the recent literature.

PubMed

Eliason, Scott

2009-01-01

There has been recent widespread media coverage of events that involve murder-suicide. In this paper, the author does an extensive literature review of studies about murder-suicide. The purpose is to determine whether the incidence of murder-suicide is increasing and what its risk factors are. The results of this review show that the incidence of murder-suicide remains at under 0.001%. Risk factors for murder-suicide are based on relationship between perpetrator and victims, history of domestic violence, sex or perpetrator and victim, age of perpetrator, presence of divorce/separation, use of weapon, and history of mental illness. This paper shows that the incidence of murder-suicide is low, stable, and similar to what has been reported in the past. There are, however, some distinct risk factors for murder-suicide including: substance abuse (not as common), mostly male perpetrators, depression (more common), and older male caregivers are at risk.

Brief Report: Can Metrics of Reporting Bias Enhance Early Autism Screening Measures?

ERIC Educational Resources Information Center

Taylor, Cora M.; Vehorn, Alison; Noble, Hylan; Weitlauf, Amy S.; Warren, Zachary E.

2014-01-01

The goal of the current study was to develop and pilot the utility of two simple internal response bias metrics, over-reporting and under-reporting, in terms of additive clinical value within common screening practices for early detection of autism spectrum disorder risk. Participants were caregivers and children under 36 months of age (n = 145)…

Implementation of health risk assessments with family health history: barriers and benefits.

PubMed

Wu, R Ryanne; Orlando, Lori A

2015-09-01

Health risk assessments provide an opportunity to emphasise health promotion and disease prevention for individuals and populations at large. A key component of health risk assessments is the detailed collection of family health history information. This information is helpful in determining risk both for common chronic conditions and more rare diseases as well. While the concept of health risk assessments has been around since the Framingham Heart Study was launched in the 1950s, and such assessments are commonly performed in the workplace today, the US healthcare system has been slow to embrace them and the emphasis on prevention that they represent. Before wider implementation of health risk assessments within healthcare can be seen, several concerns must be addressed: (1) provider impact, (2) patient impact, (3) validity of patient-entered data and (4) health outcomes effect. Here, we describe recent developments in health risk assessment design that are helping to address these issues. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pulling a patient up in bed

MedlinePlus

... from rubbing can scrape or tear the person's skin. Common areas at risk for friction are the shoulders, back, buttocks, elbows, and heels. Never move patients up by grabbing them under their arms and pulling. This can injure their shoulders.

ORD PYRETHROIDS PROJECT

EPA Science Inventory

The Food Quality Protection Act (FQPA) of 1996 requires the Agency to consider the cumulative effects of pesticides and other substances that act by a common mechanism. Under the mandates of FQPA, the Agency conducted a cumulative risk assessment for the organophosphate pesticid...

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

PubMed

Day, Felix R; Ruth, Katherine S; Thompson, Deborah J; Lunetta, Kathryn L; Pervjakova, Natalia; Chasman, Daniel I; Stolk, Lisette; Finucane, Hilary K; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D; Elks, Cathy E; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A; Franke, Lude L; Huffman, Jennifer E; Keller, Margaux F; McArdle, Patrick F; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M; Schick, Ursula M; Smith, Jennifer A; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Arndt, Volker; Arnold, Alice M; Barbieri, Caterina; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J; Chapman, J Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J; Coviello, Andrea D; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eicher, John D; Fasching, Peter A; Faul, Jessica D; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E; García-Closas, Montserrat; Giles, Graham G; Girotto, Giorgia G; Goldberg, Mark S; González-Neira, Anna; Goodarzi, Mark O; Grove, Megan L; Gudbjartsson, Daniel F; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A; Hall, Per; Hamann, Ute; Henderson, Brian E; Hocking, Lynne J; Hofman, Albert; Homuth, Georg; Hooning, Maartje J; Hopper, John L; Hu, Frank B; Huang, Jinyan; Humphreys, Keith; Hunter, David J; Jakubowska, Anna; Jones, Samuel E; Kabisch, Maria; Karasik, David; Knight, Julia A; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian'an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B; Nordestgaard, Børge G; Olson, Janet E; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D P; Pirastu, Nicola N; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F; Sanna, Serena; Sawyer, Elinor J; Schlessinger, David; Schmidt, Marjanka K; Schmidt, Frank; Schmutzler, Rita K; Schoemaker, Minouk J; Scott, Robert A; Seynaeve, Caroline M; Simard, Jacques; Sorice, Rossella; Southey, Melissa C; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D; Thorsteinsdottir, Unnur; Toland, Amanda E; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F; Winqvist, Robert; Wolffenbuttel, Bruce B H R; Wright, Alan F; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I; Buring, Julie E; Ferrucci, Luigi; Montgomery, Grant W; Gudnason, Vilmundur; Spector, Tim D; van Duijn, Cornelia M; Alizadeh, Behrooz Z; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F; Gasparini, Paolo P; Gieger, Christian; Harris, Tamara B; Hayward, Caroline; Kardia, Sharon L R; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C; Reiner, Alex P; Ridker, Paul M; Rotter, Jerome I; Toniolo, Daniela; Uitterlinden, André G; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J; Weir, David R; Yerges-Armstrong, Laura M; Price, Alkes L; Stefansson, Kari; Visser, Jenny A; Ong, Ken K; Chang-Claude, Jenny; Murabito, Joanne M; Perry, John R B; Murray, Anna

2015-11-01

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Large-scale genomic analyses link reproductive ageing to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

PubMed Central

Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tõnu; Johnson, Andrew D.; Elks, Cathy E.; Franceschini, Nora; He, Chunyan; Altmaier, Elisabeth; Brody, Jennifer A.; Franke, Lude L.; Huffman, Jennifer E.; Keller, Margaux F.; McArdle, Patrick F.; Nutile, Teresa; Porcu, Eleonora; Robino, Antonietta; Rose, Lynda M.; Schick, Ursula M.; Smith, Jennifer A.; Teumer, Alexander; Traglia, Michela; Vuckovic, Dragana; Yao, Jie; Zhao, Wei; Albrecht, Eva; Amin, Najaf; Corre, Tanguy; Hottenga, Jouke-Jan; Mangino, Massimo; Smith, Albert V.; Tanaka, Toshiko; Abecasis, Goncalo; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arndt, Volker; Arnold, Alice M.; Barbieri, Caterina; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bernstein, Leslie; Bielinski, Suzette J.; Blomqvist, Carl; Boerwinkle, Eric; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Boutin, Thibaud S; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Campbell, Archie; Campbell, Harry; Chanock, Stephen J.; Chapman, J. Ross; Chen, Yii-Der Ida; Chenevix-Trench, Georgia; Couch, Fergus J.; Coviello, Andrea D.; Cox, Angela; Czene, Kamila; Darabi, Hatef; De Vivo, Immaculata; Demerath, Ellen W.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Eicher, John D.; Fasching, Peter A.; Faul, Jessica D.; Figueroa, Jonine; Flesch-Janys, Dieter; Gandin, Ilaria; Garcia, Melissa E.; García-Closas, Montserrat; Giles, Graham G.; Girotto, Giorgia G.; Goldberg, Mark S.; González-Neira, Anna; Goodarzi, Mark O.; Grove, Megan L.; Gudbjartsson, Daniel F.; Guénel, Pascal; Guo, Xiuqing; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Henderson, Brian E.; Hocking, Lynne J.; Hofman, Albert; Homuth, Georg; Hooning, Maartje J.; Hopper, John L.; Hu, Frank B.; Huang, Jinyan; Humphreys, Keith; Hunter, David J.; Jakubowska, Anna; Jones, Samuel E.; Kabisch, Maria; Karasik, David; Knight, Julia A.; Kolcic, Ivana; Kooperberg, Charles; Kosma, Veli-Matti; Kriebel, Jennifer; Kristensen, Vessela; Lambrechts, Diether; Langenberg, Claudia; Li, Jingmei; Li, Xin; Lindström, Sara; Liu, Yongmei; Luan, Jian’an; Lubinski, Jan; Mägi, Reedik; Mannermaa, Arto; Manz, Judith; Margolin, Sara; Marten, Jonathan; Martin, Nicholas G.; Masciullo, Corrado; Meindl, Alfons; Michailidou, Kyriaki; Mihailov, Evelin; Milani, Lili; Milne, Roger L.; Müller-Nurasyid, Martina; Nalls, Michael; Neale, Ben M.; Nevanlinna, Heli; Neven, Patrick; Newman, Anne B.; Nordestgaard, Børge G.; Olson, Janet E.; Padmanabhan, Sandosh; Peterlongo, Paolo; Peters, Ulrike; Petersmann, Astrid; Peto, Julian; Pharoah, Paul D.P.; Pirastu, Nicola N.; Pirie, Ailith; Pistis, Giorgio; Polasek, Ozren; Porteous, David; Psaty, Bruce M.; Pylkäs, Katri; Radice, Paolo; Raffel, Leslie J.; Rivadeneira, Fernando; Rudan, Igor; Rudolph, Anja; Ruggiero, Daniela; Sala, Cinzia F.; Sanna, Serena; Sawyer, Elinor J.; Schlessinger, David; Schmidt, Marjanka K.; Schmidt, Frank; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Robert A.; Seynaeve, Caroline M.; Simard, Jacques; Sorice, Rossella; Southey, Melissa C.; Stöckl, Doris; Strauch, Konstantin; Swerdlow, Anthony; Taylor, Kent D.; Thorsteinsdottir, Unnur; Toland, Amanda E.; Tomlinson, Ian; Truong, Thérèse; Tryggvadottir, Laufey; Turner, Stephen T.; Vozzi, Diego; Wang, Qin; Wellons, Melissa; Willemsen, Gonneke; Wilson, James F.; Winqvist, Robert; Wolffenbuttel, Bruce B.H.R.; Wright, Alan F.; Yannoukakos, Drakoulis; Zemunik, Tatijana; Zheng, Wei; Zygmunt, Marek; Bergmann, Sven; Boomsma, Dorret I.; Buring, Julie E.; Ferrucci, Luigi; Montgomery, Grant W.; Gudnason, Vilmundur; Spector, Tim D.; van Duijn, Cornelia M; Alizadeh, Behrooz Z.; Ciullo, Marina; Crisponi, Laura; Easton, Douglas F.; Gasparini, Paolo P.; Gieger, Christian; Harris, Tamara B.; Hayward, Caroline; Kardia, Sharon L.R.; Kraft, Peter; McKnight, Barbara; Metspalu, Andres; Morrison, Alanna C.; Reiner, Alex P.; Ridker, Paul M.; Rotter, Jerome I.; Toniolo, Daniela; Uitterlinden, André G.; Ulivi, Sheila; Völzke, Henry; Wareham, Nicholas J.; Weir, David R.; Yerges-Armstrong, Laura M.; Price, Alkes L.; Stefansson, Kari; Visser, Jenny A.; Ong, Ken K.; Chang-Claude, Jenny; Murabito, Joanne M.; Perry, John R.B.; Murray, Anna

2015-01-01

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damage-response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10−14), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms. PMID:26414677

Applying risk management strategies to strengthen an IDS's investment policy.

PubMed

Fine, R P

1998-11-01

The increased financial risk that not-for-profit integrated delivery systems have assumed to function under managed care has required them to become increasingly reliant on income and gains from their investment portfolios. This reliance underscores the need for these organizations to take steps to effectively manage their investment risk. Not-for-profit IDSs should establish a systematic approach to investment risk management that is based on maintaining a sound fiduciary infrastructure and having a clear understanding of risk exposures, the most important of which are policy and market risk. Applying reasonable and common-sense risk management strategies to investment policy will enhance an IDS's overall financial and competitive strength.

A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.

PubMed

Martin, Joanna; Walters, Raymond K; Demontis, Ditte; Mattheisen, Manuel; Lee, S Hong; Robinson, Elise; Brikell, Isabell; Ghirardi, Laura; Larsson, Henrik; Lichtenstein, Paul; Eriksson, Nicholas; Werge, Thomas; Mortensen, Preben Bo; Pedersen, Marianne Giørtz; Mors, Ole; Nordentoft, Merete; Hougaard, David M; Bybjerg-Grauholm, Jonas; Wray, Naomi R; Franke, Barbara; Faraone, Stephen V; O'Donovan, Michael C; Thapar, Anita; Børglum, Anders D; Neale, Benjamin M

2018-06-15

Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r g estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15). Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Central serous choroidopathy

MedlinePlus

... is unknown. Men are affected more often than women, and the condition is most common at around age 45. However, anyone can be affected. Stress appears to be a risk factor. Early studies found that people with aggressive, "type A" personalities who are under a lot ...

Reliability, return periods, and risk under nonstationarity

NASA Astrophysics Data System (ADS)

Read, Laura K.; Vogel, Richard M.

2015-08-01

Water resources design has widely used the average return period as a concept to inform management and communication of the risk of experiencing an exceedance event within a planning horizon. Even though nonstationarity is often apparent, in practice hydrologic design often mistakenly assumes that the probability of exceedance, p, is constant from year to year which leads to an average return period To equal to 1/p; this expression is far more complex under nonstationarity. Even for stationary processes, the common application of an average return period is problematic: it does not account for planning horizon, is an average value that may not be representative of the time to the next flood, and is generally not applied in other areas of water planning. We combine existing theoretical and empirical results from the literature to provide the first general, comprehensive description of the probabilistic behavior of the return period and reliability under nonstationarity. We show that under nonstationarity, the underlying distribution of the return period exhibits a more complex shape than the exponential distribution under stationary conditions. Using a nonstationary lognormal model, we document the increased complexity and challenges associated with planning for future flood events over a planning horizon. We compare application of the average return period with the more common concept of reliability and recommend replacing the average return period with reliability as a more practical way to communicate event likelihood in both stationary and nonstationary contexts.

HIV-risk characteristics in community corrections.

PubMed

Clark, C Brendan; McCullumsmith, Cheryl B; Waesche, Matthew C; Islam, M Aminul; Francis, Reginald; Cropsey, Karen L

2013-01-01

Individuals in the criminal justice system engage in behaviors that put them at high risk for HIV. This study sought to identify characteristics of individuals who are under community corrections supervision (eg, probation) and at risk for HIV. Approximately 25,000 individuals under community corrections supervision were assessed for HIV risk, and 5059 participants were deemed high-risk or no-risk. Of those, 1519 exhibited high sexual-risk (SR) behaviors, 203 exhibited injection drug risk (IVR), 957 exhibited both types of risk (SIVR), and 2380 exhibited no risk. Sociodemographic characteristics and drug of choice were then examined using univariate and binary logistic regression. Having a history of sexual abuse, not having insurance, and selecting any drug of choice were associated with all forms of HIV risk. However, the effect sizes associated with the various drugs of choice varied significantly by group. Aside from those common risk factors, very different patterns emerged. Female gender was a risk factor for the SR group but was less likely to be associated with IVR. Younger age was associated with SR, whereas older age was associated with IVR. Black race was a risk factor for SR but had a negative association with IVR and SIVR. Living in a shelter, living with relatives/friends, and being unemployed were all risk factors for IVR but were protective factors for SR. Distinct sociodemographic and substance use characteristics were associated with sexual versus injection drug use risk for individuals under community corrections supervision who were at risk for HIV. Information from this study could help identify high-risk individuals and allow tailoring of interventions.

The Genetics of Autism: Key Issues, Recent Findings and Clinical Implications

PubMed Central

El-Fishawy, Paul; State, Matthew W.

2010-01-01

Autism spectrum disorders (ASD’S) are highly heritable. Consequently, gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding important opportunities for the development of novel treatments and a more nuanced understanding of the natural history of these disorders. Although the underlying genetic architecture of ASD’s is not yet known, the literature demonstrates that it is not, writ large, a monogenic disorder with Mendelian inheritance, but rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. The widely accepted “Common Disease-Common Variant” hypothesis predicts that the risk alleles in ASD’s and other complex disorders will be common in the general population. However, recent evidence from gene discovery efforts in a wide range of diseases raises important questions regarding the overall applicability of the theory and the extent of its usefulness in explaining individual genetic liability. In contrast, considerable evidence points to the importance of rare alleles both with regard to their value in providing a foothold into the molecular mechanisms of ASD and their overall contribution to the population-wide risk. This chapter reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of both common and rare variant discoveries. PMID:20159341

A model-based analysis of decision making under risk in obsessive-compulsive and hoarding disorders.

PubMed

Aranovich, Gabriel J; Cavagnaro, Daniel R; Pitt, Mark A; Myung, Jay I; Mathews, Carol A

2017-07-01

Attitudes towards risk are highly consequential in clinical disorders thought to be prone to "risky behavior", such as substance dependence, as well as those commonly associated with excessive risk aversion, such as obsessive-compulsive disorder (OCD) and hoarding disorder (HD). Moreover, it has recently been suggested that attitudes towards risk may serve as a behavioral biomarker for OCD. We investigated the risk preferences of participants with OCD and HD using a novel adaptive task and a quantitative model from behavioral economics that decomposes risk preferences into outcome sensitivity and probability sensitivity. Contrary to expectation, compared to healthy controls, participants with OCD and HD exhibited less outcome sensitivity, implying less risk aversion in the standard economic framework. In addition, risk attitudes were strongly correlated with depression, hoarding, and compulsion scores, while compulsion (hoarding) scores were associated with more (less) "rational" risk preferences. These results demonstrate how fundamental attitudes towards risk relate to specific psychopathology and thereby contribute to our understanding of the cognitive manifestations of mental disorders. In addition, our findings indicate that the conclusion made in recent work that decision making under risk is unaltered in OCD is premature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease

PubMed Central

How, Joan; Zhou, Amy; Oh, Stephen T.

2016-01-01

Myeloproliferative neoplasms (MPNs) are the most common underlying prothrombotic disorder found in patients with splanchnic vein thrombosis (SVT). Clinical risk factors for MPN-associated SVTs include younger age, female sex, concomitant hypercoagulable disorders, and the JAK2 V617F mutation. These risk factors are distinct from those associated with arterial or deep venous thrombosis (DVT) in MPN patients, suggesting disparate disease mechanisms. The pathophysiology of SVT is thought to derive from local interactions between activated blood cells and the unique splanchnic endothelial environment. Other mutations commonly found in MPNs, including CALR and MPL, are rare in MPN-associated SVT. The purpose of this article is to review the clinical and molecular risk factors for MPN-associated SVT, with particular focus on the possible mechanisms of SVT formation in MPN patients. PMID:28246554

SOLVENT DESIGN UNDER VARYING ENVIRONMENTAL REQUIREMENTS

EPA Science Inventory

There is currently a great need to replace many solvents that are commonly used by industry and the public, but whose continued use entails a number of human health and environmental risks. One issue hampering solvent replacement is the general thought that replacement, particul...

The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

PubMed

Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

2014-04-25

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

Old and New Techniques as a Safe Hybrid Approach for Carotid Tandem Lesions.

PubMed

Barillà, David; Massara, Mafalda; Alberti, Antonino; Volpe, Alberto; Cutrupi, Andrea; Versace, Paolo; Volpe, Pietro

2016-04-01

Carotid revascularization is performed to prevent stroke. Carotid tandem lesions represent a challenge for treatment, and a hybrid approach may result effective. A high-risk 65-year-old woman presented with a "tandem lesion" of left common and internal carotid artery. She was deemed unfit for "simple" standard carotid endarterectomy (CEA). A "single-step" safe hybrid procedure was scheduled for the patient. A "Cormier" carotid vein graft bypass with a retrograde stenting was performed under local anesthesia. The "safe hybrid procedure" for tandem lesions of the common and internal carotid artery is effective and suitable in high-risk patients in a high-volume centers. Copyright © 2016 Elsevier Inc. All rights reserved.

Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis

PubMed Central

Li, Changzhao; Athar, Mohammad

2016-01-01

This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to ionizing radiation (IR). BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. Overall, this risk is higher in Caucasians than other races. People who were exposed early in life develop more BCCs. The enhanced IR correlation with BCC and not other common cutaneous malignancies is intriguing. The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology. PMID:26930381

Diabetes and Alzheimer's Disease: Can Tea Phytochemicals Play a Role in Prevention?

PubMed

Fernando, Warnakulasuriya M A D B; Somaratne, Geeshani; Goozee, Kathryn G; Williams, Shehan; Singh, Harjinder; Martins, Ralph N

2017-01-01

Dementia and diabetes mellitus are prevalent disorders in the elderly population. While recognized as two distinct diseases, diabetes has more recently recognized as a significant contributor to risk for developing dementia, and some studies make reference to type 3 diabetes, a condition resulting from insulin resistance in the brain. Alzheimer's disease, the most common form of dementia, and diabetes, interestingly, share underlying pathological processes, commonality in risk factors, and, importantly, pathways for intervention. Tea has been suggested to possess potent antioxidant properties. It is rich in phytochemicals including, flavonoids, tannins, caffeine, polyphenols, boheic acid, theophylline, theobromine, anthocyanins, gallic acid, and finally epigallocatechin-3-gallate, which is considered to be the most potent active ingredient. Flavonoid phytochemicals, known as catechins, within tea offer potential benefits for reducing the risk of diabetes and Alzheimer's disease by targeting common risk factors, including obesity, hyperlipidemia, hypertension, cardiovascular disease, and stroke. Studies also show that catechins may prevent the formation of amyloid-β plaques and enhance cognitive functions, and thus may be useful in treating patients who have Alzheimer's disease or dementia. Furthermore, other phytochemicals found within tea offer important antioxidant properties along with innate properties capable of modulating intracellular neuronal signal transduction pathways and mitochondrial function.

Establishing the role of rare coding variants in known Parkinson's disease risk loci.

PubMed

Jansen, Iris E; Gibbs, J Raphael; Nalls, Mike A; Price, T Ryan; Lubbe, Steven; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Williams, Nigel M; Brice, Alexis; Hardy, John; Wood, Nicholas W; Morris, Huw R; Gasser, Thomas; Singleton, Andrew B; Heutink, Peter; Sharma, Manu

2017-11-01

Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors

PubMed Central

Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei

2017-01-01

Objective: To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Methods: Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. Results: The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s−1; p < 0.01). Conclusion: The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population. PMID:27928926

Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors.

PubMed

Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei; Zhang, Weiguo

2017-02-01

To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s -1 ; p < 0.01). The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population.

Personality-dependent dispersal cancelled under predation risk

PubMed Central

Cote, Julien; Fogarty, Sean; Tymen, Blaise; Sih, Andrew; Brodin, Tomas

2013-01-01

Dispersal is a fundamental life-history trait for many ecological processes. Recent studies suggest that dispersers, in comparison to residents, display various phenotypic specializations increasing their dispersal inclination or success. Among them, dispersers are believed to be consistently more bold, exploratory, asocial or aggressive than residents. These links between behavioural types and dispersal should vary with the cause of dispersal. However, with the exception of one study, personality-dependent dispersal has not been studied in contrasting environments. Here, we used mosquitofish (Gambusia affinis) to test whether personality-dependent dispersal varies with predation risk, a factor that should induce boldness or sociability-dependent dispersal. Corroborating previous studies, we found that dispersing mosquitofish are less social than non-dispersing fish when there was no predation risk. However, personality-dependent dispersal is negated under predation risk, dispersers having similar personality types to residents. Our results suggest that adaptive dispersal decisions could commonly depend on interactions between phenotypes and ecological contexts. PMID:24197414

Management of a high risk epileptic patient under conscious sedation: A multidisciplinary approach

PubMed Central

Chellathurai, Burnice Nalina Kumari; Thiagarajan, Ramakrishnan; Jayakumaran, SelvaKumar; Devadoss, Pradeep; Elavazhagan

2016-01-01

Epilepsy, characterized by the risk of recurrent seizures, is a chronic disease that afflicts about 5% of the world's population. The main dental problems associated with epileptic patients include gingival hyperplasia, minor oral injuries, tooth trauma, and prosthodontic problems, which require the dental treatment. Stress and fear are the most common triggering factors for the epilepsy in dental chair. Therefore, a more appropriate method of treating such epileptic patients may be warranted. Conscious sedation is a technique of providing good anesthesia and analgesia to patients, the main advantage of which is the patient's rapid return to presentation levels. Midazolam used as a sedative agent has anticonvulsant properties. This case report highlights a case requiring multiple dental procedures carried out in a high risk epileptic patient under conscious sedation. PMID:27041847

On the Black-Scholes European Option Pricing Model Robustness and Generality

NASA Astrophysics Data System (ADS)

Takada, Hellinton Hatsuo; de Oliveira Siqueira, José

2008-11-01

The common presentation of the widely known and accepted Black-Scholes European option pricing model explicitly imposes some restrictions such as the geometric Brownian motion assumption for the underlying stock price. In this paper, these usual restrictions are relaxed using maximum entropy principle of information theory, Pearson's distribution system, market frictionless and risk-neutrality theories to the calculation of a unique risk-neutral probability measure calibrated with market parameters.

Risk perceptions of public health and food safety hazards in poultry husbandry by citizens, poultry farmers and poultry veterinarians.

PubMed

van Asselt, M; Poortvliet, P M; Ekkel, E D; Kemp, B; Stassen, E N

2018-02-01

Differences in risk perceptions of public health and food safety hazards in various poultry husbandry systems by various stakeholder groups, may affect the acceptability of those husbandry systems. Therefore, the objective was to gain insight into risk perceptions of citizens, poultry farmers, and poultry veterinarians regarding food safety and public health hazards in poultry husbandry systems, and into factors explaining these risk perceptions. We surveyed risk perceptions of Campylobacter contamination of broiler meat, avian influenza introduction in laying hens, and altered dioxin levels in eggs for the most commonly used broiler and laying hen husbandry systems in Dutch citizens (n = 2,259), poultry farmers (n = 100), and poultry veterinarians (n = 41). Citizens perceived the risks of the three hazards in the indoor systems higher and in the outdoor systems lower than did the professionals. Citizens reported higher concerns regarding aspects reflecting underlying psychological factors of risk perception compared to professionals. Professionals indicated a relatively low level of personal control, which might imply risk denial. Of the socio-demographic characteristics, gender and childhood residence were associated with risk perceptions. The influence of other factors of risks perception are discussed. It is suggested that risk perceptions of all stakeholder groups are influenced by affect, stigma, and underlying values. To adapt current or new husbandry systems that can count on societal support, views of key stakeholders and multiple aspects such as animal welfare, public health, food safety, and underlying values should be considered integrally. When trade-offs, such as between animal welfare and public health have to be made, insight into underlying values might help to find consensus among stakeholders. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

Risk perceptions of public health and food safety hazards in poultry husbandry by citizens, poultry farmers and poultry veterinarians

PubMed Central

Poortvliet, P M; Ekkel, E D; Kemp, B; Stassen, E N

2018-01-01

Abstract Differences in risk perceptions of public health and food safety hazards in various poultry husbandry systems by various stakeholder groups, may affect the acceptability of those husbandry systems. Therefore, the objective was to gain insight into risk perceptions of citizens, poultry farmers, and poultry veterinarians regarding food safety and public health hazards in poultry husbandry systems, and into factors explaining these risk perceptions. We surveyed risk perceptions of Campylobacter contamination of broiler meat, avian influenza introduction in laying hens, and altered dioxin levels in eggs for the most commonly used broiler and laying hen husbandry systems in Dutch citizens (n = 2,259), poultry farmers (n = 100), and poultry veterinarians (n = 41). Citizens perceived the risks of the three hazards in the indoor systems higher and in the outdoor systems lower than did the professionals. Citizens reported higher concerns regarding aspects reflecting underlying psychological factors of risk perception compared to professionals. Professionals indicated a relatively low level of personal control, which might imply risk denial. Of the socio-demographic characteristics, gender and childhood residence were associated with risk perceptions. The influence of other factors of risks perception are discussed. It is suggested that risk perceptions of all stakeholder groups are influenced by affect, stigma, and underlying values. To adapt current or new husbandry systems that can count on societal support, views of key stakeholders and multiple aspects such as animal welfare, public health, food safety, and underlying values should be considered integrally. When trade-offs, such as between animal welfare and public health have to be made, insight into underlying values might help to find consensus among stakeholders. PMID:29161444

Vertical Integration Spurs American Health Care Revolution.

ERIC Educational Resources Information Center

Phillips, Richard C.

1986-01-01

Under new "managed health care systems," the classical functional separation of risk taker, claims payor, and provider are vertically integrated into a common entity. This evolution should produce a competitive environment with medical care rendered to all Americans on a more cost-effective basis. (CJH)

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Can work make you mentally ill? A systematic meta-review of work-related risk factors for common mental health problems.

PubMed

Harvey, Samuel B; Modini, Matthew; Joyce, Sadhbh; Milligan-Saville, Josie S; Tan, Leona; Mykletun, Arnstein; Bryant, Richard A; Christensen, Helen; Mitchell, Philip B

2017-03-01

It has been suggested that certain types of work may increase the risk of common mental disorders, but the exact nature of the relationship has been contentious. The aim of this paper is to conduct the first comprehensive systematic meta-review of the evidence linking work to the development of common mental health problems, specifically depression, anxiety and/or work-related stress and to consider how the risk factors identified may relate to each other. MEDLINE, PsychInfo, Embase, the Cochrane Collaboration and grey literature databases were systematically searched for review articles that examined work-based risk factors for common mental health problems. All included reviews were subjected to a quality appraisal. 37 review studies were identified, of which 7 were at least moderate quality. 3 broad categories of work-related factors were identified to explain how work may contribute to the development of depression and/or anxiety: imbalanced job design, occupational uncertainty and lack of value and respect in the workplace. Within these broad categories, there was moderate level evidence from multiple prospective studies that high job demands, low job control, high effort-reward imbalance, low relational justice, low procedural justice, role stress, bullying and low social support in the workplace are associated with a greater risk of developing common mental health problems. While methodological limitations continue to preclude more definitive statements on causation between work and mental disorders, there is now a range of promising targets for individual and organisational-level interventions aimed at minimising mental health problems in the workplace. 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/.

Shared office space and the risk of the common cold.

PubMed

Jaakkola, J J; Heinonen, O P

1995-04-01

The common cold persists as a major economic and public health problem worldwide. Despite its long-established ubiquity, little is yet certain about the determinants of indoor environment in spreading of the infection, and even less about the role of indoor air quality as a mediator. The effect of sharing an office with one or more colleagues on the risk of the common cold was studied in a modern, mechanically ventilated, 8 story office building in central Helsinki. Data on respiratory infections and the relevant personal and environmental determinants were collected in a self-administered questionnaire (response rate 71.0%). The study population, one person from each office on floors 3 to 8, consisted of 893 workers, 493 males (49.2%) and 454 females (50.8%). In logistic regression analysis the adjusted odds ratio (OR) for more than two episodes of common cold during the past 12 months in subjects with one or more office colleagues vs those working alone was 1.35 (95% CI 1.00-1.82). Among all workers higher risk also emerged for those with young children (OR 1.46, 1.05-2.04) or a history of hay fever (OR 2.07, 1.47-2.92). Females (OR 1.25, 0.95-1.66) and all under 40 years of age (OR 1.15, 0.86-1.55) had non-significantly increased risk, while smokers did not differ essentially from non-smokers (OR 1.05, 0.76-1.42). The results suggest that sharing office space increases the risk of the common cold, although the primary mode of transmission-airborne, direct or indirect contact-remains controversial.

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

PubMed Central

Pardiñas, Antonio F.; Holmans, Peter; Pocklington, Andrew J.; Escott-Price, Valentina; Ripke, Stephan; Carrera, Noa; Legge, Sophie E.; Bishop, Sophie; Cameron, Darren; Hamshere, Marian L.; Han, Jun; Hubbard, Leon; Lynham, Amy; Mantripragada, Kiran; Rees, Elliott; MacCabe, James H.; McCarroll, Steven A.; Baune, Bernhard T.; Breen, Gerome; Byrne, Enda M.; Dannlowski, Udo; Eley, Thalia C.; Hayward, Caroline; Martin, Nicholas G.; McIntosh, Andrew M.; Plomin, Robert; Porteous, David J.; Wray, Naomi R.; Caballero, Armando; Geschwind, Daniel H.; Huckins, Laura M.; Ruderfer, Douglas M.; Santiago, Enrique; Sklar, Pamela; Stahl, Eli A.; Won, Hyejung; Agerbo, Esben; Als, Thomas D.; Andreassen, Ole A.; Bækvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Børglum, Anders D.; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giørtz; Golimbet, Vera; Grove, Jakob; Hougaard, David M.; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Søholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; Collier, David A.; Rujescu, Dan; Kirov, George; Owen, Michael J.; O’Donovan, Michael C.; Walters, James T. R.

2018-01-01

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population. PMID:29483656

Impact of task design on task performance and injury risk: case study of a simulated drilling task.

PubMed

Alabdulkarim, Saad; Nussbaum, Maury A; Rashedi, Ehsan; Kim, Sunwook; Agnew, Michael; Gardner, Richard

2017-06-01

Existing evidence is limited regarding the influence of task design on performance and ergonomic risk, or the association between these two outcomes. In a controlled experiment, we constructed a mock fuselage to simulate a drilling task common in aircraft manufacturing, and examined the effect of three levels of workstation adjustability on performance as measured by productivity (e.g. fuselage completion time) and quality (e.g. fuselage defective holes), and ergonomic risk as quantified using two common methods (rapid upper limb assessment and the strain index). The primary finding was that both productivity and quality significantly improved with increased adjustability, yet this occurred only when that adjustability succeeded in reducing ergonomic risk. Supporting the inverse association between ergonomic risk and performance, the condition with highest adjustability created the lowest ergonomic risk and the best performance while there was not a substantial difference in ergonomic risk between the other two conditions, in which performance was also comparable. Practitioner Summary: Findings of this study supported a causal relationship between task design and both ergonomic risk and performance, and that ergonomic risk and performance are inversely associated. While future work is needed under more realistic conditions and a broader population, these results may be useful for task (re)design and to help cost-justify some ergonomic interventions.

Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.

PubMed

Dalton, Christopher M; Tracy, Karen E; Hairston, Nelson G; Flecker, Alexander S

2018-03-01

Predators can alter nutrient cycles simply by inducing stress in prey. This stress accelerates prey's protein catabolism, nitrogen waste production, and nitrogen cycling. Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling. The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles. We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design. We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability. We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation. We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption. Guppies excreted substantially less under predation risk than they did under food deprivation or control conditions. These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion. We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction. Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk. Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey. © 2018 by the Ecological Society of America.

The Role of Psychological and Physiological Factors in Decision Making under Risk and in a Dilemma

PubMed Central

Fooken, Jonas; Schaffner, Markus

2016-01-01

Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV), which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context. PMID:26834591

Longitudinal histories as predictors of future diagnoses of domestic abuse: modelling study

PubMed Central

Kohane, Isaac S; Mandl, Kenneth D

2009-01-01

Objective To determine whether longitudinal data in patients’ historical records, commonly available in electronic health record systems, can be used to predict a patient’s future risk of receiving a diagnosis of domestic abuse. Design Bayesian models, known as intelligent histories, used to predict a patient’s risk of receiving a future diagnosis of abuse, based on the patient’s diagnostic history. Retrospective evaluation of the model’s predictions using an independent testing set. Setting A state-wide claims database covering six years of inpatient admissions to hospital, admissions for observation, and encounters in emergency departments. Population All patients aged over 18 who had at least four years between their earliest and latest visits recorded in the database (561 216 patients). Main outcome measures Timeliness of detection, sensitivity, specificity, positive predictive values, and area under the ROC curve. Results 1.04% (5829) of the patients met the narrow case definition for abuse, while 3.44% (19 303) met the broader case definition for abuse. The model achieved sensitive, specific (area under the ROC curve of 0.88), and early (10-30 months in advance, on average) prediction of patients’ future risk of receiving a diagnosis of abuse. Analysis of model parameters showed important differences between sexes in the risks associated with certain diagnoses. Conclusions Commonly available longitudinal diagnostic data can be useful for predicting a patient’s future risk of receiving a diagnosis of abuse. This modelling approach could serve as the basis for an early warning system to help doctors identify high risk patients for further screening. PMID:19789406

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention.

PubMed

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Students were recruited online (n=1047, age: M=21.8, SD=4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n=519) or a control intervention (n=528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p=.018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating. This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention. ControlledTrials.com ISRCTN14342225.

Targeted Prevention of Common Mental Health Disorders in University Students: Randomised Controlled Trial of a Transdiagnostic Trait-Focused Web-Based Intervention

PubMed Central

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

Background A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. Aims To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Method Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Results Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating. Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention. Trial Registration ControlledTrials.com ISRCTN14342225 PMID:24736388

COMPUTER AIDED DESIGN OF REPLACEMENT SOLVENTS UNDER VARYING ENVIRONMENTAL CONSTRAINTS

EPA Science Inventory

There is a great need to replace many solvents that are commonly used by industry and the public, but whose continued use entails a number of human health and environmental risks. One problem hampering solvent replacement is the thought that replacement, particularly for environm...

Sexual Misconduct by School Employees.

ERIC Educational Resources Information Center

Mawdsley, Ralph D.

1992-01-01

The recent United States Supreme Court decision in "Franklin v. Gwinnett County Public Schools" highlights the additional risks facing school districts and employees under federal statutes and the common law as a result of sexual misconduct by school employees. The "Franklin" case illustrates that damages could be available to…

Spread and development of Phytophthora ramorum in a California christmas tree farm

Treesearch

Gary A. Chastagner; Kathy Riley; Norm Dart

2008-01-01

The risk of conifers being infected by Phytophthora ramorum under natural conditions is poorly understood. In California, infected conifers commonly occur as understory plants beneath or adjacent to heavily infected plants like California bay laurel (Umbellularia californica). During wet periods, P. ramorum is...

Common genetic risk factors for coronary artery disease: new opportunities for prevention?

PubMed

Hamrefors, Viktor

2017-05-01

Atherosclerotic cardiovascular disease (CVD) is a leading cause of mortality and morbidity worldwide, with coronary artery disease (CAD) being the single leading cause of death. Better control of risk factors, enhanced diagnostic techniques and improved medical therapies have all substantially decreased the mortality of CAD in developed countries. However, CAD and other forms of atherosclerotic CVD are projected to remain the leading cause of death by 2030 and we face a number of challenges if the outcomes of CAD are to be further improved. The fact that a substantial fraction of high-risk subjects do not reach treatment goals for important risk factors is one of these challenges. At the same time, there is also a non-negotiable fraction of 'concealed' high-risk subjects who are not detected by current risk algorithms and diagnostic modalities. In recent years, we have started to rapidly increase our knowledge of the framework of common genetics underlying CAD and atherosclerotic CVD in the population. In conjunction with modern diagnostic and therapeutic options, this new genetic knowledge may provide a valuable tool for further improvements in prevention. This review summarizes the recent findings from the search for common genetic risk factors for CAD. Furthermore, the author discusses how such recent findings could potentially be used in a number of clinical applications within CAD prevention, including in clinical risk stratification, in prediction of drug treatment response and in the search for targets for novel preventive therapies. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Preoperative Nutritional Status and The Impact on Radical Cystectomy Recovery: An International Comparative Study.

PubMed

Jensen, Bente Thoft; Dalbagni, Guido; Borre, Michael; Love-Retinger, Nora

2016-01-01

In radical cystectomy, under-nutrition is common and has detrimental physiological and clinical effects, which can lead to increased complications and prolonged recovery. This article compares measurements and outcomes across continents in this patient population with advanced bladder cancer. The association of preoperative nutritional risk, nutritional status, and length of stay is equal across continents, and the results promote increased clinical awareness that women at severe risk should be identified preoperatively.

Psychological job demands as a risk factor for common cold in a Dutch working population.

PubMed

Mohren, D C; Swaen, G M; Borm, P J; Bast, A; Galama, J M

2001-01-01

We investigated the effect of Psychological Job Demands (PJD) on the occurrence of the clinical symptoms of common cold. Subjects, participating in a large prospective cohort study on psychological determinants of fatigue at work, were asked to fill in a questionnaire on the occurrence of common cold during the previous four months. High PJD were considered as a potential risk factor. Other factors such as age, gender, and having young children were considered as potential confounders. In logistic regression analysis, the adjusted odds ratio (OR) for having a recent cold in subjects reporting high PJD vs. those reporting low PJD was 1.20 (95% confidence interval (CI), 1.08-1.33). A higher risk emerged among those with young children (OR, 1.70; 95% CI, 1.47-1.96), those having a history of asthma (OR, 1.69; 95% CI, 1.28-2.22), or being under the age of 40 (OR, 1.28; 95% CI, 1.14-1.43) and among smokers (OR, 1.23; 95% CI, 1.09-1.38). The results support an association between PJD and common cold. In spite of the almost inevitable shortcoming of a large cohort study using questionnaires, this study gave us the opportunity to study the relationship between common cold and work-related factors in a nonexperimental setting with participants observed in a natural environment with all the normal everyday hassles.

Femoral head necrosis: A finite element analysis of common and novel surgical techniques.

PubMed

Cilla, Myriam; Checa, Sara; Preininger, Bernd; Winkler, Tobias; Perka, Carsten; Duda, Georg N; Pumberger, Matthias

2017-10-01

Femoral head necrosis is a common cause of secondary osteoarthritis. At the early stages, treatment strategies are normally based on core decompression techniques, where the number, location and diameter of the drilling holes varies depending on the selected approach. The purpose of this study was to investigate the risk of femoral head, neck and subtrochanteric fracture following six different core decompression techniques. Five common and a newly proposed techniques were analyzed in respect to their biomechanical consequences using finite element analysis. The geometry of a femur was reconstructed from computed-tomography images. Thereafter, the drilling configurations were simulated. The strains in the intact and drilled femurs were determined under physiological, patient-specific, muscle and joint contact forces. The following results were observed: i) - an increase in collapse and fracture risk of the femur head by disease progression ii) - for a single hole approach at the subtrochanteric region, the fracture risk increases with the diameter iii) - the highest fracture risks occur for an 8mm single hole drilling at the subtrochanteric region and approaches with multiple drilling at various entry points iv) - the proposed novel approach resulted in the most physiological strains (closer to the experienced by the healthy bone). Our results suggest that all common core decompression methods have a significant impact on the biomechanical competence of the proximal femur and impact its mechanical potential. Fracture risk increases with drilling diameter and multiple drilling with smaller diameter. We recommend the anterior approach due to its reduced soft tissue trauma and its biomechanical performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endowment Investing: Time for a Sustainability Play?

ERIC Educational Resources Information Center

Pelletier, Stephen G.

2010-01-01

Managers of university endowment funds are paying closer attention to investing in "green" industries, commonly bundled under the umbrella "cleantech." Cleantech offers the possibility of buying in while prices are low "and" making a "green" investment play, but it also harbors the risks inherent in any emerging industry. Cleantech has varying…

A Longitudinal Twin Study on the Association between ADHD Symptoms and Reading

ERIC Educational Resources Information Center

Greven, Corina U.; Rijsdijk, Fruhling V.; Asherson, Philip; Plomin, Robert

2012-01-01

Background: Attention deficit hyperactivity disorder (ADHD) and reading disability commonly co-occur because of shared genetic risk factors. However, the stability and change of these genetic influences and the predictive relationships underlying this association longitudinally remain unclear. Methods: ADHD symptoms and reading were assessed as…

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Workplace cluster of Bell’s palsy in Lima, Peru

PubMed Central

2014-01-01

Background We report on a workplace cluster of Bell’s palsy that occurred within a four-month period in 2011 among employees of a three-story office building in Lima, Peru and our investigation to determine the etiology and associated risk factors. Findings An outbreak investigation was conducted to identify possible common infectious or environmental exposures and included patient interviews, reviews of medical records, an epidemiologic survey, serological analysis for IgM and IgG antibodies to putative Bell’s palsy-inducing pathogens, and an environmental exposure assessment of the office building. Three cases of Bell’s palsy were reported among 65 at-risk employees, attack rate 4.6%. Although two patients had underlying risk factors, there was no clear association or common identifiable risk factor among all cases. Serologic analysis showed no evidence of recent infections, and air and water sample measures of all known chemical or neurotoxins were below maximum allowable concentrations for exposure. Conclusions An infection spread among workplace employees could not be excluded as a potential cause of this cluster; however, it was unlikely a pathogen commonly associated with individual cases of Bell’s palsy. Although a specific etiology was not identified among all cases, we believe this methodology will aid future outbreak investigations of Bell’s palsy and a better understanding of its etiology. While environmental assessments may be useful in their ability to ascertain the cause of clusters of Bell’s palsy, future investigations should prioritize focus on common infectious etiology. PMID:24885256

Understanding the Reasons Why Mothers Do or Do Not Have Their Adolescent Daughters Vaccinated Against Human Papillomavirus

PubMed Central

DEMPSEY, AMANDA F.; ABRAHAM, LEAH M.; DALTON, VANESSA; RUFFIN, MACK

2010-01-01

PURPOSE The objective of this study was to compare the reasons why mothers do or do not have their adolescent daughters vaccinated against HPV. METHODS Mothers of vaccinated and unvaccinated 11- to 17-year-old girls seen during preventive care visits in outpatient family medicine or pediatric clinics underwent an audiotaped structured telephone interview that used open-ended questions to assess the reasons underlying maternal decisions about HPV vaccination. Qualitative methods categorized maternal responses into themes. RESULTS Interviews of 52 mothers (19 declining vaccination, 33 accepting) identified several distinct factors underlying their decisions about HPV vaccination. Lack of knowledge about HPV, age-related concerns, and low perceived risk of infection were commonly cited reasons for declining vaccination. Desire to prevent illness, physician recommendation, and a high perceived risk of infection were commonly identified motivating factors. Both groups of mothers had significant concerns about vaccine safety. Locus of control (e.g., mother or daughter) of health-related decisions arose as a novel factor influencing this decision that had not been previously described in the context of HPV vaccination. CONCLUSIONS Addressing safety concerns, educating parents about the age-specific risk of HPV infection, and promoting strong physician recommendation for vaccination may be the most useful targets for future interventions to increase HPV vaccine utilization. PMID:19394865

Mean-variance model for portfolio optimization with background risk based on uncertainty theory

NASA Astrophysics Data System (ADS)

Zhai, Jia; Bai, Manying

2018-04-01

The aim of this paper is to develop a mean-variance model for portfolio optimization considering the background risk, liquidity and transaction cost based on uncertainty theory. In portfolio selection problem, returns of securities and assets liquidity are assumed as uncertain variables because of incidents or lacking of historical data, which are common in economic and social environment. We provide crisp forms of the model and a hybrid intelligent algorithm to solve it. Under a mean-variance framework, we analyze the portfolio frontier characteristic considering independently additive background risk. In addition, we discuss some effects of background risk and liquidity constraint on the portfolio selection. Finally, we demonstrate the proposed models by numerical simulations.

Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme

PubMed Central

Dhalla, F; da Silva, S P; Lucas, M; Travis, S; Chapel, H

2011-01-01

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immunodeficiencies in adults. They comprise a heterogeneous group of pathologies, with frequent non-infectious complications in addition to the bacterial infections that usually characterize their presentation. Complications include a high risk of malignancy, especially lymphoma and gastric cancer. Helicobacter pylori infection and pernicious anaemia are risk predictors for gastric cancer in the general population and probably in patients with CVIDs. Screening for gastric cancer in a high-risk population appears to improve survival. Given the increased risk of gastric cancer in patients with CVIDs and prompted by a case of advanced gastric malignancy in a patient with a CVID and concomitant pernicious anaemia, we performed a review of the literature for gastric cancer and conducted a cohort study of gastric pathology in 116 patients with CVIDs under long-term follow-up in Oxford. Regardless of the presence of pernicious anaemia or H. pylori infection, patients with CVIDs have a 10-fold increased risk of gastric cancer and are therefore a high-risk population. Although endoscopic screening of all patients with CVIDs could be considered, a more selective approach is appropriate and we propose a surveillance protocol that should reduce modifiable risk factors such as H. pylori, in order to improve the management of patients with CVIDs at risk of gastric malignancy. PMID:21470209

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015

PubMed Central

Bah, Elhadj Ibrahima; Haba, Nyankoye; Delamou, Alexandre; Camara, Bienvenu Salim; Olivier, Kadio Jean-Jacques; De Clerck, Hilde; Nordenstedt, Helena; Semple, Malcolm G.; Van Herp, Michel; Buyze, Jozefien; De Crop, Maaike; Van Den Broucke, Steven; Lynen, Lutgarde; De Weggheleire, Anja

2016-01-01

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90–0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death. PMID:27869610

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015.

PubMed

van Griensven, Johan; Bah, Elhadj Ibrahima; Haba, Nyankoye; Delamou, Alexandre; Camara, Bienvenu Salim; Olivier, Kadio Jean-Jacques; De Clerck, Hilde; Nordenstedt, Helena; Semple, Malcolm G; Van Herp, Michel; Buyze, Jozefien; De Crop, Maaike; Van Den Broucke, Steven; Lynen, Lutgarde; De Weggheleire, Anja

2016-12-01

By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at admission and their predictive value to stratify patients into risk groups. Patients underwent testing with a point-of-care device. We used logistic regression to construct a prognostic model and summarized the predictive value with the area under the receiver operating curve. Abnormalities were common among patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold value, renal dysfunction, low calcium levels, and low hemoglobin levels were independently associated with increased risk for death. A prognostic model using all 5 factors was highly discriminatory (area under the receiver operating curve 0.95; 95% CI 0.90-0.99) and enabled the definition of risk criteria to guide targeted care. Most patients had a very low (<5%) or very high (>80%) risk for death.

The Use of Object-Oriented Analysis Methods in Surety Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craft, Richard L.; Funkhouser, Donald R.; Wyss, Gregory D.

1999-05-01

Object-oriented analysis methods have been used in the computer science arena for a number of years to model the behavior of computer-based systems. This report documents how such methods can be applied to surety analysis. By embodying the causality and behavior of a system in a common object-oriented analysis model, surety analysts can make the assumptions that underlie their models explicit and thus better communicate with system designers. Furthermore, given minor extensions to traditional object-oriented analysis methods, it is possible to automatically derive a wide variety of traditional risk and reliability analysis methods from a single common object model. Automaticmore » model extraction helps ensure consistency among analyses and enables the surety analyst to examine a system from a wider variety of viewpoints in a shorter period of time. Thus it provides a deeper understanding of a system's behaviors and surety requirements. This report documents the underlying philosophy behind the common object model representation, the methods by which such common object models can be constructed, and the rules required to interrogate the common object model for derivation of traditional risk and reliability analysis models. The methodology is demonstrated in an extensive example problem.« less

Space Telecommunications Radio System (STRS) Architecture Standard. Release 1.02.1

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Kacpura, Thomas J.; Handler, Louis M.; Hall, C. Steve; Mortensen, Dale J.; Johnson, Sandra K.; Briones, Janette C.; Nappier, Jennifer M.; Downey, Joseph A.; Lux, James P.

2012-01-01

This document contains the NASA architecture standard for software defined radios used in space- and ground-based platforms to enable commonality among radio developments to enhance capability and services while reducing mission and programmatic risk. Transceivers (or transponders) with functionality primarily defined in software (e.g., firmware) have the ability to change their functional behavior through software alone. This radio architecture standard offers value by employing common waveform software interfaces, method of instantiation, operation, and testing among different compliant hardware and software products. These common interfaces within the architecture abstract application software from the underlying hardware to enable technology insertion independently at either the software or hardware layer.

Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals

PubMed Central

Dunlop, Malcolm G.; Tenesa, Albert; Farrington, Susan M.; Ballereau, Stephane; Brewster, David H.; Pharoah, Paul DP.; Schafmayer, Clemens; Hampe, Jochen; Völzke, Henry; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; von Holst, Susanna; Picelli, Simone; Lindblom, Annika; Jenkins, Mark A.; Hopper, John L.; Casey, Graham; Duggan, David; Newcomb, Polly; Abulí, Anna; Bessa, Xavier; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Niittymäki, Iina; Tuupanen, Sari; Karhu, Auli; Aaltonen, Lauri; Zanke, Brent W.; Hudson, Thomas J.; Gallinger, Steven; Barclay, Ella; Martin, Lynn; Gorman, Maggie; Carvajal-Carmona, Luis; Walther, Axel; Kerr, David; Lubbe, Steven; Broderick, Peter; Chandler, Ian; Pittman, Alan; Penegar, Steven; Campbell, Harry; Tomlinson, Ian; Houlston, Richard S.

2016-01-01

Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. In a large, multi-population study, we set out to assess the feasibility of CRC risk prediction using common genetic variant data, combined with other risk factors. We built a risk prediction model and applied it to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate colorectal cancer risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence colorectal cancer risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266), and in combination with gender, age and family history (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4,187 independent samples. 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. Results Median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10−16), confirmed in external validation sets (Sweden p=1.2×10−6, Finland p=2×10−5). Mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05–1.13). Discriminative performance was poor across the risk spectrum (area under curve (AUC) for genotypes alone - 0.57; AUC for genotype/age/gender/FH - 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion We show that genotype data provides additional information that complements age, gender and FH as risk factors. However, individualized genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential, since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance. PMID:22490517

Modeling logistic performance in quantitative microbial risk assessment.

PubMed

Rijgersberg, Hajo; Tromp, Seth; Jacxsens, Liesbeth; Uyttendaele, Mieke

2010-01-01

In quantitative microbial risk assessment (QMRA), food safety in the food chain is modeled and simulated. In general, prevalences, concentrations, and numbers of microorganisms in media are investigated in the different steps from farm to fork. The underlying rates and conditions (such as storage times, temperatures, gas conditions, and their distributions) are determined. However, the logistic chain with its queues (storages, shelves) and mechanisms for ordering products is usually not taken into account. As a consequence, storage times-mutually dependent in successive steps in the chain-cannot be described adequately. This may have a great impact on the tails of risk distributions. Because food safety risks are generally very small, it is crucial to model the tails of (underlying) distributions as accurately as possible. Logistic performance can be modeled by describing the underlying planning and scheduling mechanisms in discrete-event modeling. This is common practice in operations research, specifically in supply chain management. In this article, we present the application of discrete-event modeling in the context of a QMRA for Listeria monocytogenes in fresh-cut iceberg lettuce. We show the potential value of discrete-event modeling in QMRA by calculating logistic interventions (modifications in the logistic chain) and determining their significance with respect to food safety.

Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

When Changing from Merit Pay to Variable/Bonus Pay: What Do Employees Want?

ERIC Educational Resources Information Center

Fox, Jeremy B.; Donohue, Joan M.

2004-01-01

This study examines potential responses to a change in an employee reward system from permanent merit pay increases to one-time bonus payments. Removing long term risks associated with escalating pay is an increasingly common compensation strategy. Often overlooked, however, are employee perceptions of reward fairness under such conditions of…

Developmental Pathways to Conduct Disorder: Implications for Future Directions in Research, Assessment, and Treatment

ERIC Educational Resources Information Center

Frick, Paul J.

2012-01-01

Research has indicated that there are several common pathways through which children and adolescents develop conduct disorder, each with different risk factors and each with different underlying developmental mechanisms leading to the child's aggressive and antisocial behavior. The current article briefly summarizes research on these pathways,…

12 CFR 3.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Definitions. As used in this part: Additional tier 1 capital is defined in § 3.20(c). Advanced approaches... described in § 3.100(b)(1). Advanced approaches total risk-weighted assets means: (1) The sum of: (i) Credit... respect to a company, means any company that controls, is controlled by, or is under common control with...

Bone and glucocorticoids.

PubMed

Briot, Karine

2018-06-01

Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the most frequent cause of osteoporosis in young people. Bone loss and fracture risk increase rapidly after the initiation of corticosteroid therapy and are proportional to dose and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurement, as it is also related to impaired bone quality and increased risk of falls. Prevention should be considered in all patients beginning corticosteroid therapy, especially as the underlying inflammation in itself impairs bone quality. Bisphosphonates and teriparatide have shown efficacy in the treatment of corticosteroid-induced osteoporosis. Several national and international guidelines are available to improve management of corticosteroid-induced osteoporosis, which remains inadequate. Duration of anti-osteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the progression of the underlying inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

Introducing Triquetrum, A Possible Future for Kepler and Ptolemy II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooks, Christopher; Billings, Jay Jay

Triquetrum is an open platform for managing and executing scientific workflows that is under development as an Eclipse project. Both Triquetrum and Kepler use Ptolemy II as their execution engine. Triquetrum presents opportunities and risks for the Kepler community. The opportunities include a possibly larger community for interaction and a path for Kepler to move from Kepler's one-off ant-based build environment towards a more common OSGi-based environment and a way to maintain a stable Ptolemy II core. The risks include the fact that Triquetrum is a fork of Ptolemy II that would result in package name changes and other possiblemore » changes. In addition, Triquetrum is licensed under the Eclipse Public License v1.0, which includes a patent clause that could conflict with the University of California patent clause. This paper describes these opportunities and risks.« less

Ischemic brain injury in cerebral amyloid angiopathy

PubMed Central

van Veluw, Susanne J; Greenberg, Steven M

2016-01-01

Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

[Causation between occupational prolonged standing time during progestation and pregnancy related complications].

PubMed

Weng, Ting-ting; Xu, Ye-qing; Yan, Shuang-qin; Pan, Wei-jun; Tao, Fang-biao

2013-06-01

To describe the epidemiological characteristics of profession related long-standing behavior during preconception and progestation, and to probe the relationship between prolonged standing jobs and the common pregnancy related complications among pregnant women, in Ma' anshan city,Anhui province. In this cohort study, subjects who had their first antenatal examination at Ma' anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. Three questionnaires were filled in by subjects under the guidance of healthcare takers. In the study, the 75(th) percentile of prolonged-standing times were 4.0 h/d and 3.0 h/d respectively in preconception and progestation. The characteristics of pregnant women with low social/economic status, prone to be involved in stand-long occupation. Results in logistic regression analysis, prolonged-standing jobs during preconception was the risk factor of pregnancy-induced hypertension and severe anemia. The adjusted odds ratios were 2.05 (95%CI:1.26-3.31) and 1.38(95%CI:1.03-1.85)respectively. Prolonged standing jobs appeared to be common occupational exposure to and risks of both pregnant woman and their fetus. Exposure to these kinds of jobs during preconception could increase the risk of pregnancy-induced hypertension and severe anemia. In order to promote maternal health programs, all the related occupational risk factors should be valued and avoided during preconception and pregnancy.

Assessment of risky sexual behavior and practice among Aksum University students, Shire Campus, Shire Town, Tigray, Ethiopia, 2017.

PubMed

Kebede, Awoke; Molla, Bogale; Gerensea, Hadgu

2018-01-31

Having sex at early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs and unprotected sexual behaviors are the common characteristics of risky sexual behavior which increases risk of individuals to sexuality and reproductive health problems. Risky sexual behavior is the most common problem in adolescents and young adults which may expose individuals for permanent social, economical, psychological and physical problem. So that this study focus on assessment of risk sexual behavior using institution based cross-sectional study design on 287 randomly selected subjects among Aksum University students. Almost 60% students reported to have ever had sexual activity. Of which 86 (83.5%) and 112 (64.4%) reported having inconsistent condom use and multiple sexual partners respectively. Even though more than half of first sexual intercourse (61.5%) starts due to their desire but still peer pressure and alcohol have significant effect. Similarly the study indicated that a significant segment of students have risk sexual behaviors which increase individuals' risk of acquiring HIV/AIDS. Unless appropriate age and institutional targeted interventions exist, certain behaviors can place the university students at greater risk of HIV infection and sexually transmitted disease.

Risk of collective failure provides an escape from the tragedy of the commons.

PubMed

Santos, Francisco C; Pacheco, Jorge M

2011-06-28

From group hunting to global warming, how to deal with collective action may be formulated in terms of a public goods game of cooperation. In most cases, contributions depend on the risk of future losses. Here, we introduce an evolutionary dynamics approach to a broad class of cooperation problems in which attempting to minimize future losses turns the risk of failure into a central issue in individual decisions. We find that decisions within small groups under high risk and stringent requirements to success significantly raise the chances of coordinating actions and escaping the tragedy of the commons. We also offer insights on the scale at which public goods problems of cooperation are best solved. Instead of large-scale endeavors involving most of the population, which as we argue, may be counterproductive to achieve cooperation, the joint combination of local agreements within groups that are small compared with the population at risk is prone to significantly raise the probability of success. In addition, our model predicts that, if one takes into consideration that groups of different sizes are interwoven in complex networks of contacts, the chances for global coordination in an overall cooperating state are further enhanced.

Ciguatera fish poisoning in East Asia and southeast Asia.

PubMed

Chan, Thomas Y K

2015-06-02

In the coastal countries of East Asia and Southeast Asia, ciguatera should be common because of the extensive tropical and subtropical coral reefs along the coasts and in the neighboring seas with ciguatoxic fishes. An extensive search of journal databases, the Internet and the government websites was performed to identify all reports of ciguatera from the regions. Based on the official data and large published case series, the incidence of ciguatera was higher in the coastal cities (Hong Kong, Foshan, Zhongshan) of southern China than in Japan (Okinawa Prefecture). In Singapore, ciguatera appeared to be almost unknown. In other countries, only isolated cases or small case series were reported, but under-reporting was assumed to be common. Ciguatera may cause severe acute illness and prolonged neurological symptoms. Ciguatera represents an important public health issue for endemic regions, with significant socio-economic impact. Coordinated strategies to improve risk assessment, risk management and risk communication are required. The systematic collection of accurate data on the incidence and epidemiology of ciguatera should enable better assessment and management of its risk. Much more work needs to be done to define the size threshold for important coral reef fish species from different regions, above which the risk of ciguatera significantly increases.

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

Aspergillus otitis in small animals--a retrospective study of 17 cases.

PubMed

Goodale, Elizabeth C; Outerbridge, Catherine A; White, Stephen D

2016-02-01

Aspergillus spp. are saprophytic opportunistic fungal organisms and are a common cause of otomycosis in humans. Although there have been case reports of Aspergillus otitis externa in dogs, to the best of the authors' knowledge, this is the first retrospective case series describing Aspergillus otitis in dogs and cats. To characterize signalment, putative risk factors, treatments and outcomes of a case series of dogs and cats with Aspergillus otitis. Eight dogs and nine cats diagnosed with Aspergillus otitis. A retrospective review of medical records from 1989 to 2014 identified animals diagnosed with Aspergillus otitis based on culture. All dogs weighed greater than 23 kg. The most common putative risk factors identified in this study were concurrent diseases, therapy causing immunosuppression or a history of an otic foreign body. Aspergillus otitis was unilateral in all study dogs and most cats. Concurrent otitis media was confirmed in three dogs and one cat, and suspected in two additional cats. Aspergillus fumigatus was the most common isolate overall and was the dominant isolate in cats. Aspergillus niger and A. terreus were more commonly isolated from dogs. Animals received various topical and systemic antifungal medications; however, otic lavage under anaesthesia and/or surgical intervention increased the likelihood of resolution of the fungal infection. Aspergillus otitis is uncommon, typically seen as unilateral otitis externa in cats and larger breed dogs with possible risk factors that include immunosuppression and otic foreign bodies; previous antibiotic usage was common. © 2015 ESVD and ACVD.

The effect of exercise on prevention of the common cold: a meta-analysis of randomized controlled trial studies.

PubMed

Lee, Hyun Kun; Hwang, In Hong; Kim, Soo Young; Pyo, Se Young

2014-05-01

Because there is no specific treatment for the common cold, many previous studies have focused on prevention of the common cold. There were some studies reporting that regular, moderate-intensity exercise increases immunity and prevents the common cold. We conducted a meta-analysis to determine the effects of exercise on prevention of the common cold. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL for studies released through June 2013. We manually searched the references. Two authors independently extracted the data. To assess the risk of bias of included literature, Cochrane Collaboration's tool for assessing risk of bias was used. Review Manager ver. 5.2 (RevMan, Cochrane Collaboration) was used for statistical analysis. Four randomized controlled trials were identified. A total of 281 participants, 134 in the exercise group and 147 in the control group, were included. The effect of exercise on the prevention of the common cold had a relative risk (RR) of 0.73 (95% confidence interval [CI], 0.56 to 0.95; I(2) = 7%). The mean difference of mean illness days between exercise group and control group was -3.50 (95% CI, -6.06 to -0.94; I(2) = 93%). In the subgroup analysis, the RR of under 16 weeks exercise was 0.79 (95% CI, 0.58 to 1.08). In this meta-analysis, regular, moderate-intensity exercise may have an effect on the prevention of the common cold. But numbers of included studies and participants were too small and quality of included studies was relatively poor. Subsequent well-designed studies with larger sample size are needed to clarify the association.

The role of the general dental practitioner (GDP) in the management of abuse of vulnerable adults.

PubMed

Moore, Roisin; Newton, J Tim

2012-10-01

Abuse of vulnerable adults is largely under reported. The most common forms of abuse amongst this group are neglect and financial abuse, although an individual may be at risk of any or all forms of abuse. Certain individuals are at an increased risk of abuse due to their domestic environment and any physical or mental disability they may have. Vulnerable adults constitute a significant proportion of the population. GDPs should be aware of the signs of abuse, to be able to identify those individuals at risk, and how and when to raise concerns of abuse to social services.

Genetics of coronary artery disease: discovery, biology and clinical translation

PubMed Central

Khera, Amit V.; Kathiresan, Sekar

2018-01-01

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked about 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forward, genetic testing could enable precision medicine approaches, by identifying subgroups of patients at increased risk of CAD or those with a specific driving pathophysiology in whom a therapeutic or preventive approach is most useful. PMID:28286336

Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome.

PubMed

Srikanth, Sundararajan; Deedwania, Prakash

2016-10-01

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings. Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk. Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

[Chronic Pancreatitis and Pancreatic Cancer - Tumor Risk and Screening].

PubMed

Beyer, Georg; D'Haese, Jan G; Ormanns, Steffen; Mayerle, Julia

2018-06-01

Chronic pancreatitis is a fibroinflammatory syndrome of the exocrine pancreas, which is characterized by an increasing incidence, high morbidity and lethality. Common etiologies besides alcohol and nicotine consumption include genetic causes and risk factors. The life time risk for the development of pancreatic cancer is elevated 13- to 45-fold depending on the underlying etiology. In patients with chronic pancreatitis clinical, laboratory and imaging surveillance for early detection of complications, including pancreatic cancer, is recommended, although the available methods lack the desired sensitivity and specificity. In this article we review the epidemiology, etiologies and risk factors for chronic pancreatitis and pancreatic cancer and discuss current recommendations for screening and management of patients at risk for tumor development. © Georg Thieme Verlag KG Stuttgart · New York.

A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

PubMed

Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

2016-08-20

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

Age-Related Macular Degeneration: Genetics and Biology Coming Together

PubMed Central

Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Gonçalo R.; Curcio, Christine A.

2014-01-01

Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

Budd-Chiari syndrome

PubMed Central

Martens, Pieter

2015-01-01

Budd-Chiari syndrome (BCS) is a rare and potentially life-threatening disorder characterized by obstruction of the hepatic outflow tract at any level between the junction of the inferior vena cava with the right atrium and the small hepatic veins. In the West, BCS is a rare hepatic manifestation of one or more underlying prothrombotic risk factors. The most common underlying prothrombotic risk factor is a myeloproliferative disorder, although it is now recognized that almost half of patients have multiple underlying prothrombotic risk factors. Clinical manifestations can be diverse, making BCS a possible differential diagnosis of many acute and chronic liver diseases. The index of suspicion should be very low if there is a known underlying prothrombotic risk factor and new onset of liver disease. Doppler ultrasound is sufficient for confirming the diagnosis, although tomographic imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) is often necessary for further treatment and discussion with a multidisciplinary team. Anticoagulation is the cornerstone of the treatment. Despite the use of anticoagulation, the majority of patients need additional (more invasive) treatment strategies. Algorithms consisting of local angioplasty, TIPS and liver transplantation have been proposed, with treatment choice dictated by a lack of response to a less-invasive treatment regimen. The application of these treatment strategies allows for a five-year survival rate of 90%. In the long term the disease course of BCS can sometimes be complicated by recurrence, progression of the underlying myeloproliferative disorder, or development of post-transplant lymphoma in transplant patients. PMID:26668741

Integrating Household Risk Mitigation Behavior in Flood Risk Analysis: An Agent-Based Model Approach.

PubMed

Haer, Toon; Botzen, W J Wouter; de Moel, Hans; Aerts, Jeroen C J H

2017-10-01

Recent studies showed that climate change and socioeconomic trends are expected to increase flood risks in many regions. However, in these studies, human behavior is commonly assumed to be constant, which neglects interaction and feedback loops between human and environmental systems. This neglect of human adaptation leads to a misrepresentation of flood risk. This article presents an agent-based model that incorporates human decision making in flood risk analysis. In particular, household investments in loss-reducing measures are examined under three economic decision models: (1) expected utility theory, which is the traditional economic model of rational agents; (2) prospect theory, which takes account of bounded rationality; and (3) a prospect theory model, which accounts for changing risk perceptions and social interactions through a process of Bayesian updating. We show that neglecting human behavior in flood risk assessment studies can result in a considerable misestimation of future flood risk, which is in our case study an overestimation of a factor two. Furthermore, we show how behavior models can support flood risk analysis under different behavioral assumptions, illustrating the need to include the dynamic adaptive human behavior of, for instance, households, insurers, and governments. The method presented here provides a solid basis for exploring human behavior and the resulting flood risk with respect to low-probability/high-impact risks. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Older adults at high risk of falling need more time for anticipatory postural adjustment in the precrossing phase of obstacle negotiation.

PubMed

Uemura, Kazuki; Yamada, Minoru; Nagai, Koutatsu; Ichihashi, Noriaki

2011-08-01

Obstacles are a common cause of falls among older adults. Anticipatory motor planning for obstacle negotiation must be completed during the precrossing phase in order to step over the obstacle safely. This cognitive load may affect anticipatory postural adjustments (APAs) in older adults at high risk of falling. This study explored the effect of obstacle negotiation on APA during gait initiation in older adults at high risk of falling. Seventy-six elderly volunteers (mean age: 80.5 [7.6 years]) from the community participated in this study. Participants performed gait initiation tasks from a starting position on a force platform under the following two conditions: (1) unobstructed (smooth walkway) and (2) obstructed (walkway with an obstacle placed at 1 m from the initial position). The reaction and APA phases were measured from the data of center of pressure. Each participant was categorized as a high-risk or a low-risk individual according to the presence or absence of a fall experience within the past year. High-risk participants had significantly longer APA phases than low-risk participants under the obstructed condition even though there was no significant difference between groups under the unobstructed condition. Reaction phase was not significantly different between groups in either the unobstructed or the obstructed condition. Motor performance deterioration occurred in high-risk participants in the beginning of the precrossing phase of obstacle negotiation. A slow and inefficient APA at the precrossing phase of obstacle negotiation might be one of the causes of accidental falls.

[Epidemiology of nosocomial infections].

PubMed

Astagneau, P

1998-09-15

The frequency of nosocomial infections lies between 5 and 10%, and varies according to the type of hospital and service. Age, underlying disease invasive devices (such as catheters) or procedures are the main risk factors. Common nosocomial infections are urinary tract infections, pneumonia, surgical site infections, bacteremia/septicemia and intravascular catheter-related infections. Gram positive cocci and gram negative bacilli account for one third and two thirds of microorganisms respectively, Staphylococcus aureus being frequently resistant to antibiotics. Prevention is based on a better control of infection risk related to the use of invasive devices.

Rating Scale Analysis and Psychometric Properties of the Caregiver Self-Efficacy Scale for Transfers

ERIC Educational Resources Information Center

Cipriani, Daniel J.; Hensen, Francine E.; McPeck, Danielle L.; Kubec, Gina L. D.; Thomas, Julie J.

2012-01-01

Parents and caregivers faced with the challenges of transferring children with disability are at risk of musculoskeletal injuries and/or emotional stress. The Caregiver Self-Efficacy Scale for Transfers (CSEST) is a 14-item questionnaire that measures self-efficacy for transferring under common conditions. The CSEST yields reliable data and valid…

Cognition and dementia in older patients with epilepsy

PubMed Central

Sen, Arjune; Capelli, Valentina

2018-01-01

Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising the possibility that better understanding of shared mechanisms in these conditions might help to ameliorate not just seizures, but also epileptogenesis and cognitive dysfunction. PMID:29506031

Juvenile idiopathic arthritis-associated uveitis.

PubMed

Clarke, Sarah L N; Sen, Ethan S; Ramanan, Athimalaipet V

2016-04-27

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

Common Carotid Artery Diameter and Risk of Cardiovascular Events and Mortality: Pooled Analyses of Four Cohort Studies.

PubMed

Sedaghat, Sanaz; van Sloten, Thomas T; Laurent, Stéphane; London, Gérard M; Pannier, Bruno; Kavousi, Maryam; Mattace-Raso, Francesco; Franco, Oscar H; Boutouyrie, Pierre; Ikram, M Arfan; Stehouwer, Coen D A

2018-05-21

Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure-related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67±9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter <7 mm) had a higher incidence of stroke (hazard ratio, 1.5; 95% confidence interval, 1.1-2.0). From all estimates of processes underlying arterial remodeling, adjustment for carotid intima-media thickness attenuated this association (hazard ratio after adjustment for intima-media thickness, 1.2; 95% confidence interval, 0.9-1.6). Larger carotid diameter was associated with risk of CVD and mortality but not clearly with coronary heart disease risk. We showed that a larger carotid diameter is associated with incident stroke, CVD, and mortality. Carotid intima-media thickness, a measure of blood pressure-related media thickening, partially explained the association with stroke incidence. © 2018 American Heart Association, Inc.

Febrile neutropenia and refeeding syndrome.

PubMed

Jahn, H K; Barraclough, S; Currell, S; Tighe, M P

2016-12-01

We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues. 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/.

Management of acute anterior shoulder dislocation.

PubMed

Dala-Ali, Benan; Penna, Marta; McConnell, Jamie; Vanhegan, Ivor; Cobiella, Carlos

2014-08-01

Shoulder dislocation is the most common large joint dislocation in the body. Recent advances in radiological imaging and shoulder surgery have shown the potential dangers of traditional reduction techniques such as the Kocher's and the Hippocratic methods, which are still advocated by many textbooks. Many non-specialists continue to use these techniques, unaware of their potential risks. This article reviews the clinical and radiographic presentation of dislocation; some common reduction techniques; their risks and success rate; analgesia methods to facilitate the reduction; and postreduction management. Many textbooks advocate methods that have been superceded by safer alternatives. Trainees should learn better and safer relocation methods backed up by the current evidence available. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.

PubMed

Azboy, I; Barrack, R; Thomas, A M; Haddad, F S; Parvizi, J

2017-11-01

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a 'milder' agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420-30. ©2017 Azboy et al.

Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke.

PubMed

Adib-Samii, Poneh; Devan, William; Traylor, Matthew; Lanfranconi, Silvia; Zhang, Cathy R; Cloonan, Lisa; Falcone, Guido J; Radmanesh, Farid; Fitzpatrick, Kaitlin; Kanakis, Allison; Rothwell, Peter M; Sudlow, Cathie; Boncoraglio, Giorgio B; Meschia, James F; Levi, Chris; Dichgans, Martin; Bevan, Steve; Rosand, Jonathan; Rost, Natalia S; Markus, Hugh S

2015-02-01

Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses. A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (HSNP=0.23; P=0.0026). HSNP estimates were higher among hypertensive individuals (HSNP=0.45; P=7.99×10(-5)); this increase was greater than expected by chance (P=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (HSNP=0.13; P=0.13). A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wolters Kluwer.

Risk assessment models to predict caries recurrence after oral rehabilitation under general anaesthesia: a pilot study.

PubMed

Lin, Yai-Tin; Kalhan, Ashish Chetan; Lin, Yng-Tzer Joseph; Kalhan, Tosha Ashish; Chou, Chein-Chin; Gao, Xiao Li; Hsu, Chin-Ying Stephen

2018-05-08

Oral rehabilitation under general anaesthesia (GA), commonly employed to treat high caries-risk children, has been associated with high economic and individual/family burden, besides high post-GA caries recurrence rates. As there is no caries prediction model available for paediatric GA patients, this study was performed to build caries risk assessment/prediction models using pre-GA data and to explore mid-term prognostic factors for early identification of high-risk children prone to caries relapse post-GA oral rehabilitation. Ninety-two children were identified and recruited with parental consent before oral rehabilitation under GA. Biopsychosocial data collection at baseline and the 6-month follow-up were conducted using questionnaire (Q), microbiological assessment (M) and clinical examination (C). The prediction models constructed using data collected from Q, Q + M and Q + M + C demonstrated an accuracy of 72%, 78% and 82%, respectively. Furthermore, of the 83 (90.2%) patients recalled 6 months after GA intervention, recurrent caries was identified in 54.2%, together with reduced bacterial counts, lower plaque index and increased percentage of children toothbrushing for themselves (all P < 0.05). Additionally, meal-time and toothbrushing duration were shown, through bivariate analyses, to be significant prognostic determinants for caries recurrence (both P < 0.05). Risk assessment/prediction models built using pre-GA data may be promising in identifying high-risk children prone to post-GA caries recurrence, although future internal and external validation of predictive models is warranted. © 2018 FDI World Dental Federation.

Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

PubMed Central

Beaudin, Anna E.; Stover, Patrick J.

2015-01-01

Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

The risk of predation favors cooperation among breeding prey

PubMed Central

Krama, Tatjana; Berzins, Arnis; Rantala, Markus J

2010-01-01

Empirical studies have shown that animals often focus on short-term benefits under conditions of predation risk, which reduces the likelihood that they will cooperate with others. However, some theoretical studies predict that animals in adverse conditions should not avoid cooperation with their neighbors since it may decrease individual risks and increase long-term benefits of reciprocal help. We experimentally tested these two alternatives to find out whether increased predation risk enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behavior, among breeding pied flycatchers, Ficedula hypoleuca. Our results show that birds attended mobs initiated by their neighbors more often, approached the stuffed predator significantly more closely, and mobbed it at a higher intensity in areas where the perceived risk of predation was experimentally increased. This study demonstrates a positive impact of predation risk on cooperation in breeding songbirds, which might help to explain the emergence and evolution of cooperation. PMID:20714404

Risk factors of urinary tract infection in pregnancy.

PubMed

Haider, Gulfareen; Zehra, Nishat; Munir, Aftab Afroze; Haider, Ambreen

2010-03-01

To determine the frequency, risk factors and pattern of urinary complaints during pregnancy. A descriptive study was conducted in the Obstetric and Gynaecology Department of Isra University Hospital, Hyderabad from 1st January to 30th August 2008. Total 232 women were selected to ascertain the frequency and pattern of urinary symptoms as well as the risk factors of urinary tract infection (UTI) such as age, parity, education, past history of UTI and haemoglobin among women attending an antenatal clinic. All pregnant women irrespective of age, parity and gestational age were included, while women with known underlying renal pathology, chronic renal disease, renal transplant, diabetes or taking immunosuppressant therapy were excluded. Informed consent was taken and data collected on a self designed proforma. All the women underwent complete examination of urine. Dipstick test was performed on midstream urine and urine was cultured incase of positive dipstick test and women with urinary symptoms. Data was analyzed on SPSS version 11. Odds ratio and 95% confidence interval were calculated among the categorical parameters by applying the Fisher's exact test. Out of 232 women, 108(46.5%) reported urinary symptoms which were due to pregnancy induced changes on urinary system as no growth was obtained on urine culture, while 10 (4.3%) were due to underlying UTI. Most common urinary symptom in these women was abnormal voiding pattern 85 (40.3%) followed by irritative symptoms and voiding difficulties. Illiteracy, history of sexual activity, low socioeconomic (monthly income < Rs. 10,000 / month) group, past history of UTI and multiparity were found to be risk factors for UTI in these women. On complete urine examination, 222 (95.6%) patients either did not reveal any pus cells or had less than 5 WBC/HPF. Out of 108 cultures, only 10 (4.3%) specimens showed growth. E-coli was the most commonly detected organism 7 (3%) followed by S-aureus in 3 (1.3%). The common urinary symptoms encountered in the studied women were abnormal voiding pattern followed by irritative symptoms. Majority of urinary symptoms were due to pregnancy related changes in the urinary system. Past history of UTI, sexual activity, lower socioeconomic group and multi parity were significant risk factors for UTI.

Biomarkers to Stratify Risk Groups among Children with Malnutrition in Resource-Limited Settings and to Monitor Response to Intervention.

PubMed

McGrath, Christine J; Arndt, Michael B; Walson, Judd L

2017-01-01

Despite global efforts to reduce childhood undernutrition, current interventions have had little impact on stunting and wasting, and the mechanisms underlying growth faltering are poorly understood. There is a clear need to distinguish populations of children most likely to benefit from any given intervention and to develop tools to monitor response to therapy prior to the development of morbid sequelae. In resource-limited settings, environmental enteric dysfunction (EED) is common among children, contributing to malnutrition and increasing childhood morbidity and mortality risk. In addition to EED, early alterations in the gut microbiota can adversely affect growth through nutrient malabsorption, altered metabolism, gut inflammation, and dysregulation of the growth hormone axis. We examined the evidence linking EED and the gut microbiome to growth faltering and explored novel biomarkers to identify subgroups of children at risk of malnutrition due to underlying pathology. These and other biomarkers could be used to identify specific groups of children at risk of malnutrition and monitor response to targeted interventions. © 2017 S. Karger AG, Basel.

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Risk factors for child pneumonia - focus on the Western Pacific Region.

PubMed

Nguyen, T K P; Tran, T H; Roberts, C L; Fox, G J; Graham, S M; Marais, B J

2017-01-01

Pneumonia is a major cause of disease and death in infants and young children (aged <5 years) globally, as it is in the World Health Organization Western Pacific region. A better understanding of the underlying risk factors associated with child pneumonia is important, since pragmatic primary prevention strategies are likely to achieve major reductions in pneumonia-associated morbidity and mortality in children. This review focuses on risk factors with high relevance to the Western Pacific region, including a lack of exclusive breastfeeding, cigarette smoke and air pollution exposure, malnutrition and conditions of poverty, as well as common co-morbidities. Case management and vaccination coverage have been considered elsewhere. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ciguatera Fish Poisoning in East Asia and Southeast Asia

PubMed Central

Chan, Thomas Y. K.

2015-01-01

In the coastal countries of East Asia and Southeast Asia, ciguatera should be common because of the extensive tropical and subtropical coral reefs along the coasts and in the neighboring seas with ciguatoxic fishes. An extensive search of journal databases, the Internet and the government websites was performed to identify all reports of ciguatera from the regions. Based on the official data and large published case series, the incidence of ciguatera was higher in the coastal cities (Hong Kong, Foshan, Zhongshan) of southern China than in Japan (Okinawa Prefecture). In Singapore, ciguatera appeared to be almost unknown. In other countries, only isolated cases or small case series were reported, but under-reporting was assumed to be common. Ciguatera may cause severe acute illness and prolonged neurological symptoms. Ciguatera represents an important public health issue for endemic regions, with significant socio-economic impact. Coordinated strategies to improve risk assessment, risk management and risk communication are required. The systematic collection of accurate data on the incidence and epidemiology of ciguatera should enable better assessment and management of its risk. Much more work needs to be done to define the size threshold for important coral reef fish species from different regions, above which the risk of ciguatera significantly increases. PMID:26042615

Common variants identified in genome-wide association studies of testicular germ cell tumour: an update, biological insights and clinical application.

PubMed

Litchfield, K; Shipley, J; Turnbull, C

2015-01-01

Testicular germ cell tumour (TGCT) is the most common cause of cancer in young men (aged 15-45 years) in many populations. Multiple genome-wide association studies (GWAS) of TGCT have now been conducted, yielding over 25 disease-associated single-nucleotide polymorphism (SNP)s at 19 independent loci. The genes at these loci have provided rich biological and genetic insight into possible mechanisms underlying testicular germ cell oncogenesis. In this review, we summarize these mechanisms which can be grouped into five distinct categories: KIT/KITLG signalling, other pathways of male germ cell development/differentiation, telomerase function, microtubule assembly and DNA damage repair. The TGCT risk markers identified through GWAS include individual SNPs carrying per allele odds ratios (OR) in excess of 2.5. These ORs are among the highest reported in GWAS of any cancer type, hence suggesting a potential clinical utility in risk determination. Here, we present analysis of such an approach, using polygenic risk scores to calculate the combined effect of all risk loci on overall TGCT risk and discuss how a potential screening strategy may fit within a broader clinical context. © 2015 American Society of Andrology and European Academy of Andrology.

A Functional Model for the Integration of Gains and Losses under Risk: Implications for the Measurement of Subjective Value

ERIC Educational Resources Information Center

Viegas, Ricardo G.; Oliveira, Armando M.; Garriga-Trillo, Ana; Grieco, Alba

2012-01-01

In order to be treated quantitatively, subjective gains and losses (utilities/disutilities) must be psychologically measured. If legitimate comparisons are sought between them, measurement must be at least interval level, with a common unit. If comparisons of absolute magnitudes across gains and losses are further sought, as in standard…

Supporting Creative Responses in Design Education--The Development and Application of the Graphic Design Composition Method

ERIC Educational Resources Information Center

Lu, Hui-Ping; Chen, Jun-Hong; Lee, Chang-Franw

2016-01-01

Inspiration is the primary element of good design. Designers, however, also risk not being able to find inspiration. Novice designers commonly find themselves to be depressed during the conceptual design phase when they fail to find inspiration and the information to be creative. Accordingly, under the graphic design parameter, we have developed…

Overview of Diabetes in Children and Teens

ERIC Educational Resources Information Center

Kaufman, Francine R.; Gallivan, Joanne M.; Warren-Boulton, Elizabeth

2009-01-01

Type 1 and type 2 diabetes affect about 186,000 youth under age 20. Previously considered an adult disease, type 2 diabetes is becoming increasingly common in overweight minority youth over 10 years of age. Criteria help to identify young people at risk for type 2 diabetes as well as those with the disease. Prevention or delay of type 2 requires…

Nuclear Families and Nuclear Risks: The Effects of Gender, Geography, and Progeny on Attitudes toward a Nuclear Waste Facility

ERIC Educational Resources Information Center

Freudenburg, William R.; Davidson, Debra J.

2007-01-01

Studies of reactions to nuclear facilities have found consistent male/female differences, but the underlying reasons have never been well-clarified. The most common expectations involve traditional roles--with men focusing more on economic concerns and with women (especially mothers) being more concerned about family safety/health. Still, with…

75 FR 2564 - Virginia Electric and Power Company D/B/A Dominion Virginia Power and Old Dominion Electric...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-15

..., submit an annual update to the application's final safety analysis report (FSAR), which is a part of the... public health or safety, and are consistent with the common defense and security; and (2) special... is authorized by law. No Undue Risk to Public Health and Safety The underlying purpose of 10 CFR 50...

Development of a Model of Chronic Kidney Disease in the C57BL/6 Mouse with Properties of Progressive Human CKD

PubMed Central

Cruz, Gaile L.; Lu, Chao; Carlisle, Rachel E.; Werner, Kaitlyn E.; Ask, Kjetil; Dickhout, Jeffrey G.

2015-01-01

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers. PMID:26064882

Longitudinal Links Between Gambling Participation and Academic Performance in Youth: A Test of Four Models.

PubMed

Vitaro, Frank; Brendgen, Mara; Girard, Alain; Dionne, Ginette; Boivin, Michel

2018-01-11

Gambling participation and low academic performance are related during adolescence, but the causal mechanisms underlying this link are unclear. It is possible that gambling participation impairs academic performance. Alternatively, the link between gambling participation and low academic performance could be explained by common underlying risk factors such as impulsivity and socio-family adversity. It could also be explained by other current correlated problem behaviors such as substance use. The goal of the present study was to examine whether concurrent and longitudinal links between gambling participation and low academic performance exist from age 14 to age 17 years, net of common antecedent factors and current substance use. A convenience sample of 766 adolescents (50.6% males) from a longitudinal twin sample participated in the study. Analyses revealed significant, albeit modest, concurrent links at both ages between gambling participation and academic performance. There was also a longitudinal link between gambling participation at age 14 and academic performance at age 17, which persisted after controlling for age 12 impulsivity and socio-family adversity as well as current substance use. Gambling participation predicts a decrease in academic performance during adolescence, net of concurrent and antecedent personal and familial risk factors.

Central Sagittal Angle of the Sacrum as a New Risk Factor for Patients with Persistent Low Back Pain after Caesarean Section

PubMed Central

Kazdal, Hizir; Batcik, Osman Ersagun; Ozdemir, Bulent; Senturk, Senol; Yildirim, Murat; Kazancioglu, Leyla; Sen, Ahmet; Batcik, Sule; Balik, Mehmet Sabri

2017-01-01

Study Design Retrospective. Purpose This study investigated the possible association of persistent low back pain (LBP) with caesarean section (CS) under spinal anesthesia. Overview of Literature Many women suffer from LBP after CS, which is commonly performed under spinal anesthesia. However, this type of LBP is poorly understood, and there is poor consensus regarding increased risk after spinal anesthesia. Methods We examined two groups of patients who underwent cesarean delivery under spinal anesthesia. Group I included patients who presented to a neurosurgical clinic complaining of LBP for at least 6 months. Group II was a control group with patients without LBP. We analyzed clinical and sagittal angle parameters, including age, body mass index, parity, central sagittal angle of the sacrum (CSAS), and sacral slope (SS). Results Fifty-three patients participated in this study: 23 (43.1%) in Group I and 30 (56.9%) in Group II. Non-parametric Mann–Whitney U-tests showed that age, parity, and CSAS significantly differed between the two groups at 6 months. Conclusions Age, parity, and CSAS appear to be associated with increased risk for LBP after CS under spinal anesthesia. Future prospective studies on this subject may help validate our results. PMID:29093782

New developments in the use of prostatic stents

PubMed Central

Papatsoris, Athanasios G; Junaid, Islam; Zachou, Alexandra; Kachrilas, Stefanos; Zaman, Faruquz; Masood, Junaid; Buchholz, Noor

2011-01-01

Bladder outflow obstruction is a very common age-related clinical entity due to a variety of benign and malignant diseases of the prostate. Surgical treatment under general or regional anesthesia is not suitable for high-risk elderly patients who seek minimally invasive management. Unfortunately, for patients who are not fit for transurethral and/or laser prostatectomy, few treatment options remain, other than long-term catheterization and insertion (under local anesthesia) of a prostatic stent. In this review, we present developments in the use of prostatic stents. PMID:24198637

Further thoughts on the utility of risk matrices.

PubMed

Ball, David J; Watt, John

2013-11-01

Risk matrices are commonly encountered devices for rating hazards in numerous areas of risk management. Part of their popularity is predicated on their apparent simplicity and transparency. Recent research, however, has identified serious mathematical defects and inconsistencies. This article further examines the reliability and utility of risk matrices for ranking hazards, specifically in the context of public leisure activities including travel. We find that (1) different risk assessors may assign vastly different ratings to the same hazard, (2) even following lengthy reflection and learning scatter remains high, and (3) the underlying drivers of disparate ratings relate to fundamentally different worldviews, beliefs, and a panoply of psychosocial factors that are seldom explicitly acknowledged. It appears that risk matrices when used in this context may be creating no more than an artificial and even untrustworthy picture of the relative importance of hazards, which may be of little or no benefit to those trying to manage risk effectively and rationally. © 2013 Society for Risk Analysis.

Behaviour and physiology shape the growth accelerations associated with predation risk, high temperatures and southern latitudes in Ischnura damselfly larvae.

PubMed

Stoks, Robby; Swillen, Ine; De Block, Marjan

2012-09-01

1. To better predict effects of climate change and predation risk on prey animals and ecosystems, we need studies documenting not only latitudinal patterns in growth rate but also growth plasticity to temperature and predation risk and the underlying proximate mechanisms: behaviour (food intake) and digestive physiology (growth efficiency). The mechanistic underpinnings of predator-induced growth increases remain especially poorly understood. 2. We reared larvae from replicated northern and southern populations of the damselfly Ischnura elegans in a common garden experiment manipulating temperature and predation risk and quantified growth rate, food intake and growth efficiency. 3. The predator-induced and temperature-induced growth accelerations were the same at both latitudes, despite considerably faster growth rates in the southern populations. While the higher growth rates in the southern populations and the high rearing temperature were driven by both an increased food intake and a higher growth efficiency, the higher growth rates under predation risk were completely driven by a higher growth efficiency, despite a lowered food intake. 4. The emerging pattern that higher growth rates associated with latitude, temperature and predation risk were all (partly or completely) mediated by a higher growth efficiency has two major implications. First, it indicates that energy allocation trade-offs and the associated physiological costs play a major role both in shaping large-scale geographic variation in growth rates and in shaping the extent and direction of growth rate plasticity. Secondly, it suggests that the efficiency of energy transfer in aquatic food chains, where damselfly larvae are important intermediate predators, will be higher in southern populations, at higher temperatures and under predation risk. This may eventually contribute to the lengthening of food chains under these conditions and highlights that the prey identity may determine the influence of predation risk on food chain length. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

Effect of di-n-butyl phthalate (DBP) on the fruit quality of cucumber and the health risk.

PubMed

Wang, Lei; Sun, Xin; Chang, Qin; Tao, Yue; Wang, Lihua; Dong, Junwei; Lin, Yulong; Zhang, Ying

2016-12-01

Di-n-butyl phthalate (DBP) widely used as plastic films' plasticizer, can cause agricultural pollution which is of increasing concern because of the food safety issues. Cucumber ( Cucumis sativus Linn.), commonly cultured in greenhouse, was exposed to DBP stress to gain more information about the ecological risk of DBP in this study. Changes of DBP residues and fruit quality of cucumber at different DBP concentrations (0, 5, 10, 20, 40 mg/kg of dry soil) were investigated in pot experiments using an agricultural soil under greenhouse condition, respectively. DBP residue in cucumber fruits ranged from 0.5326 to 1.8938 mg/kg, and the quality of cucumber fruits (organic acids, vitamin C, soluble protein, and soluble sugar) were influenced by DBP stress. Moreover, the health risk assessment was evaluated by estimate daily intakes (EDI) and the target hazard quotient (THQ) was analyzed. Under 40 mg/kg DBP condition, the highest value of EDI was 2.49 μg/kg bw/day and the THQ ranged from 0.000700 to 0.0249. Although the risk of DBP in cucumber fruits was lower than the threshold limit value of risk, the potential health risk was not a negligible issue.

Hierarchical Bayesian modeling of spatio-temporal patterns of lung cancer incidence risk in Georgia, USA: 2000-2007

NASA Astrophysics Data System (ADS)

Yin, Ping; Mu, Lan; Madden, Marguerite; Vena, John E.

2014-10-01

Lung cancer is the second most commonly diagnosed cancer in both men and women in Georgia, USA. However, the spatio-temporal patterns of lung cancer risk in Georgia have not been fully studied. Hierarchical Bayesian models are used here to explore the spatio-temporal patterns of lung cancer incidence risk by race and gender in Georgia for the period of 2000-2007. With the census tract level as the spatial scale and the 2-year period aggregation as the temporal scale, we compare a total of seven Bayesian spatio-temporal models including two under a separate modeling framework and five under a joint modeling framework. One joint model outperforms others based on the deviance information criterion. Results show that the northwest region of Georgia has consistently high lung cancer incidence risk for all population groups during the study period. In addition, there are inverse relationships between the socioeconomic status and the lung cancer incidence risk among all Georgian population groups, and the relationships in males are stronger than those in females. By mapping more reliable variations in lung cancer incidence risk at a relatively fine spatio-temporal scale for different Georgian population groups, our study aims to better support healthcare performance assessment, etiological hypothesis generation, and health policy making.

Heightened aversion to risk and loss in depressed patients with a suicide attempt history.

PubMed

Baek, Kwangyeol; Kwon, JaeHyung; Chae, Jeong-Ho; Chung, Yong An; Kralik, Jerald D; Min, Jung-Ah; Huh, HyuJung; Choi, Kyung Mook; Jang, Kuk-In; Lee, Na-Bin; Kim, Sunyoung; Peterson, Bradley S; Jeong, Jaeseung

2017-09-11

Suicide attempters have been found to be impaired in decision-making; however, their specific biases in evaluating uncertain outcomes remain unclear. Here we tested the hypothesis that suicidal behavior is associated with heightened aversion to risk and loss, which might produce negative predictions about uncertain future events. Forty-five depressed patients with a suicide attempt history, 47 nonsuicidal depressed patients, and 75 healthy controls participated in monetary decision-making tasks assessing risk and loss aversion. Suicide attempters compared with the other groups exhibited greater aversion to both risk and loss during gambles involving potential loss. Risk and loss aversion correlated with each other in the depressed patients, suggesting that a common pathophysiological mechanism underlies these biases. In addition, emotion regulation via suppression, a detrimental emotional control strategy, was positively correlated with loss aversion in the depressed patients, also implicating impairment in regulatory processes. A preliminary fMRI study also found disrupted neural responses to potential gains and losses in the subgenual anterior cingulate cortex, insula cortex, and left amygdala, brain regions involved in valuation, emotion reactivity, and emotion regulation. The findings thus implicate heightened negative valuation in decision-making under risk, and impaired emotion regulation in depressed patients with a history of suicide attempts.

'In-between' and other reasonable ways to deal with risk and uncertainty: A review article.

PubMed

Zinn, Jens O

2016-11-16

How people deal with risk and uncertainty has fuelled public and academic debate in recent decades. Researchers have shown that common distinctions between rational and 'irrational' strategies underestimate the complexity of how people approach an uncertain future. I suggested in 2008 that strategies in-between do not follow standards of instrumental rationality nor they are 'irrational' but follow their own logic which works well under particular circumstances. Strategies such as trust, intuition and emotion are an important part of the mix when people deal with risk and uncertainty. In this article, I develop my original argument. It explores in-between strategies to deal with possible undesired outcomes of decisions. I examine 'non-rational strategies' and in particular the notions of active, passive and reflexive hope. Furthermore, I argue that my original typology should be seen as a triangular of reasonable strategies which work well under specific circumstances. Finally, I highlight a number of different ways in which these strategies combine.

‘In-between’ and other reasonable ways to deal with risk and uncertainty: A review article

PubMed Central

Zinn, Jens O.

2016-01-01

How people deal with risk and uncertainty has fuelled public and academic debate in recent decades. Researchers have shown that common distinctions between rational and ‘irrational’ strategies underestimate the complexity of how people approach an uncertain future. I suggested in 2008 that strategies in-between do not follow standards of instrumental rationality nor they are ‘irrational’ but follow their own logic which works well under particular circumstances. Strategies such as trust, intuition and emotion are an important part of the mix when people deal with risk and uncertainty. In this article, I develop my original argument. It explores in-between strategies to deal with possible undesired outcomes of decisions. I examine ‘non-rational strategies’ and in particular the notions of active, passive and reflexive hope. Furthermore, I argue that my original typology should be seen as a triangular of reasonable strategies which work well under specific circumstances. Finally, I highlight a number of different ways in which these strategies combine. PMID:28392747

Mandating responsible flagging practices as a strategy for reducing the risk of coastal oil spills.

PubMed

Miller, Dana D; Hotte, Ngaio; Sumaila, U Rashid

2014-04-15

As human civilization is becoming more aware of the negative impact our actions can inflict upon the natural world, the intensification of fossil fuel extraction and industrial development is being met with increasing opposition. In Western Canada, proposals that would increase the volume of petroleum transported by pipelines and by tankers through the coastal waters of British Columbia have engaged the province in debate. To ease public concern on the risk of a coastal oil spill, there are additional commitments that involved parties could make. There is evidence to show that the practice of registering vessels under foreign flags of states that have exhibited failure in compliance with international obligations is more common amongst petroleum tankers that have been involved in large-scale oil spills. To prove that they are committed to reducing the risk of oil spills, businesses need to stop registering their vessels under flags of foreign, non-compliant states. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of polygenic risk scores for predicting breast and prostate cancer risk.

PubMed

Machiela, Mitchell J; Chen, Chia-Yen; Chen, Constance; Chanock, Stephen J; Hunter, David J; Kraft, Peter

2011-09-01

Recently, polygenic risk scores (PRS) have been shown to be associated with certain complex diseases. The approach has been based on the contribution of counting multiple alleles associated with disease across independent loci, without requiring compelling evidence that every locus had already achieved definitive genome-wide statistical significance. Whether PRS assist in the prediction of risk of common cancers is unknown. We built PRS from lists of genetic markers prioritized by their association with breast cancer (BCa) or prostate cancer (PCa) in a training data set and evaluated whether these scores could improve current genetic prediction of these specific cancers in independent test samples. We used genome-wide association data on 1,145 BCa cases and 1,142 controls from the Nurses' Health Study and 1,164 PCa cases and 1,113 controls from the Prostate Lung Colorectal and Ovarian Cancer Screening Trial. Ten-fold cross validation was used to build and evaluate PRS with 10 to 60,000 independent single nucleotide polymorphisms (SNPs). For both BCa and PCa, the models that included only published risk alleles maximized the cross-validation estimate of the area under the ROC curve (0.53 for breast and 0.57 for prostate). We found no significant evidence that PRS using common variants improved risk prediction for BCa and PCa over replicated SNP scores. © 2011 Wiley-Liss, Inc.

Pathological patterns of primary nephrotic syndrome in Central China: a retrospective study of 627 cases.

PubMed

Chu, Fenfen; Chen, Guochun; Liu, Yinghong

2014-05-01

The pathological patterns underlying PNS in adult are poorly studied in Central China. This is a retrospective analysis of the clinical and pathologic data involving 627 adult patients with PNS who have been finished the renal biopsies from January 2009 to September 2012 in XiangYa 2nd Hospital of Central South University. Patients enrolled in our study were all from Central China. There were 379 males and 248 females, formed the ratio of 1.53:1. There existed three main sorts of pathological patterns underlying PNS: membranous nephropathy (MN) 26.63%, minimal change disease (MCD) 23.60%, IgA nephropathy (IgAN) 23.39%. Among all biopsies, the proportion of FSGS underlying PNS increased from 5.8% during the period from 2009 to 2010 to 14.7% during the period from 2011 to 2012. The most common complication of PNS was infectious diseases, and MCD underlying PNS ran a higher risk of encountering acute renal injury. IgAN had the highest incidence of hematuresis. The common pathological patterns of PNS differed in age-brackets: IgAN and MCD were the main pathological lesions in patients aged from 16 to 30 years; MN mostly occurs in patients over 30. MCD was the dominating pathological lesions underlying IgAN which expressed as PNS. (1) MN was the most frequent pathological pattern underlying PNS, the proportion of FSGS underlying PNS increased during the last 2 years. (2) The common pathological patterns of PNS differed in age-brackets and pathological patterns correlated to the complications or comorbidities of PNS to some extent.

Understanding genital warts: epidemiology, pathogenesis, and burden of disease of human papillomavirus.

PubMed

Bhatia, Neal; Lynde, Charles; Vender, Ronald; Bourcier, Marc

2013-12-01

As the most commonly sexually transmitted disease worldwide, human papillomavirus (HPV) infections are associated with significant morbidity and mortality. HPV infections most commonly affect young adults, women under 25 in particular. The most common risk factor for HPV infection in both sexes is a high number of lifetime sexual partners, whereas leading protective factors include circumcision, consistent condom use, and abstinence. Over 100 HPV types have been identified to date and are classified according to their level of oncogenic potential. HPV types 6 and 11 are responsible for approximately 90% of genital warts; HPV types 16 and 18 are responsible for 70% of invasive cervical cancers. External genital warts (EGWs) are the most common clinical manifestation of nononcogenic HPV infection. Coinfection with multiple HPV types is possible and may combine both low- and high-risk types, even in cases of genital warts. HPV infections are DNA viruses transmitted through skin-to-skin contact, invading the basal epithelial cells via microtears and evading the host immune response. Although non-life threatening, even low-risk HPV-type infections such as EGW carry a substantial psychosocial and economic burden. Stressors include the shame and embarrassment related to diagnosis, as well as the inconvenience and discomfort of treatment and the fear of recurrence, transmission, and the possible threat of cancer. Costs relate to routine screening for cervical cancer, treatment of genital warts, and the management and follow-up of malignancies.

[Epidemiology and risk factors in injuries due to fall in infants under one year-old].

PubMed

Jiménez de Domingo, Ana; Rubio García, Elena; Marañon Pardillo, Rafael; Arias Constanti, Vanessa; Frontado Haiek, Luis Alberto; Soriano Arola, Marta; Ripoll Oliveras, Francesc; Remón García, Cristina; Estopiña Ferrer, Gloria; Lorente Romero, Jorge

2017-06-01

To describe the epidemiological characteristics of unintentional injuries due to falls in children under one year and to analyse the risk factors associated with severe injuries. This multicentre, observational and cross-sectional study included all children less than one year treated for unintentional fall in the Emergency Departments of 8 Spanish Hospitals, belonging to the «Unintentional Paediatric Injury Workshop» of the Spanish Paediatric Emergency Society, between March 1st, 2014 and February 28th, 2015. Out of 289,887 emergency department cases, 1,022 were due to unintentional falls. The median age was 8 months and 52.5% were males. Fall injuries were more frequent among children aged 9-12 months (37.6%), and 83.5% occurred at home. The most common mechanism was fall from nursery equipment (69.4%), and 47.8% occurred from a height under 50cm. More than two-thirds (68%) of falls were witnessed, but in half of the cases (329) the caregiver was not in area. Serious injuries were seen in 12% of cases. In this study, a fall height greater than 50cm, falls in the street, from the arms of the carer, and from the stairs were identified as independent risk factors for worse outcomes. The most serious injuries occur in children <3 months and from a height of >50cm, though not related to unwitnessed falls. Because the most common serious injury mechanism is the fall from the arms of the carer, from stairs, and falls in the street, these facts should be highlighted in order to avoid morbidity. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics: Is Personalized Therapy in Sight?

PubMed

Darbar, Dawood

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide requiring therapy. Despite recent advances in catheter-based and surgical therapy, antiarrhythmic drugs (AADs) remain the mainstay of treatment for symptomatic AF. However, response in individual patients is highly variable with over half the patients treated with rhythm control therapy experiencing recurrence of AF within a year. Contemporary AADs used to suppress AF are incompletely and unpredictably effective and associated with significant risks of proarrhythmia and noncardiac toxicities. Furthermore, this "one-size" fits all strategy for selecting antiarrhythmics is based largely on minimizing risk of adverse effects rather than on the likelihood of suppressing AF. The limited success of rhythm control therapy is in part due to heterogeneity of the underlying substrate, interindividual differences in disease mechanisms, and our inability to predict response to AADs in individual patients. Genetic studies of AF over the past decade have revealed that susceptibility to and response to therapy for AF is modulated by the underlying genetic substrate. However, the bedside application of these new discoveries to the management of AF patients has thus far been disappointing. This may in part be related to our limited understanding about genetic predictors of drug response in general, the challenges associated with determining efficacy of response to AADs, and lack of randomized genotype-directed clinical trials. Nonetheless, recent studies have shown that common AF susceptibility risk alleles at the chromosome 4q25 locus modulated response to AADs, electrical cardioversion, and ablation therapy. This monograph discusses how genetic approaches to AF have not only provided important insights into underlying mechanisms but also identified AF subtypes that can be better targeted with more mechanism-based "personalized" therapy.

The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics – Is Personalized Therapy in Sight?

PubMed Central

Darbar, Dawood

2015-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide requiring therapy. Despite recent advances in catheter-based and surgical therapy, antiarrhythmic drugs (AAD) remain the mainstay of treatment for symptomatic AF. However, response in individual patients is highly variable with over half the patients treated with rhythm control therapy experiencing recurrence of AF within a year. Contemporary AADs used to suppress AF are incompletely and unpredictably effective and associated with significant risks of proarrhythmia and non-cardiac toxicities. Furthermore, this ‘one-size’ fits all strategy for selecting antiarrhythmics is based largely on minimizing risk of adverse effects rather than on the likelihood of suppressing AF. The limited success of rhythm-control therapy is in part due to heterogeneity of the underlying substrate, interindividual differences in disease mechanisms, and our inability to predict response to AADs in individual patients. Genetic studies of AF over the last decade have revealed that susceptibility to and response to therapy for AF is modulated by the underlying genetic substrate. However, the bedside application of these new discoveries to the management of AF patients has thus far been disappointing. This may in part be related to our limited understanding about genetic predictors of drug response in general, the challenges associated with determining efficacy of response to AADs and lack of randomized genotype-directed clinical trials. Nonetheless, recent studies have shown that common AF susceptibility risk alleles at the chromosome 4q25 locus modulated response to AADs, electrical cardioversion and ablation therapy. This monograph discusses how genetic approaches to AF have not only provided important insights into underlying mechanisms but also identified AF sub-types that can be better targeted with more mechanism-based ‘personalized’ therapy. PMID:25970841

The impact of socio-economic deprivation on burn injury: A nine-year retrospective study of 6441 patients.

PubMed

Marsden, N J; Battle, C E; Combellack, E J; Sabra, A; Morris, K; Dickson, W A; Whitaker, I S; Evans, P A

2016-03-01

Low socio-economic status is thought to be associated with increased burn risk, however the significance and generalisability across different populations and cultures has been questioned. A nine-year retrospective study of burn presentations to a large teaching hospital (2005-2014) was performed to investigate the association between socio-economic status and burns. Demographic and injury data was collected via the trust 'Information portal'. The Welsh Index of Multiple: Deprivation 2011 was used to score for socio-economic status. Chi-squared test and Odds Ratios were calculated and statistical significance defined as p<0.05 throughout. 6441 burns were identified, with 755 (11.7%) admitted. Overall incidence rates were the highest published in the UK (0.35/1000/year) with sub group analysis showing the highest rates in under fives and males. Significant relationships between both age and burn mechanism and gender and burn mechanism (p=0.0005) were identified. Scald (67.1%) was the most common mechanism with the upper limb (48%) most commonly burned. Chi square analysis demonstrated a significant relationship between socio-economic deprivation, age and burn incidence (p≤0.0005), with a disproportionately high number of burns in patients under the age of 16 in the most deprived quintile (OR 1.23; 95% CI 1.06-1.44). This study specifically highlights patients under the age of 16 living in poorer socio-economic areas as the most at risk of suffering burns receiving hospital attention. This study demonstrates burns as a significant public health issue, and the results should aid in designing specific burn prevention strategies to target high-risk groups. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Key to Prevention of Bradycardia: Be Relax Postoperatively: A Case Report.

PubMed

Chowdhury, Tumul; Schaller, Bernhard

2016-05-01

Hypotension and bradycardia are commonly observed after the spinal anesthesia and various mechanisms have been postulated for these hemodynamic changes.A middle-aged otherwise healthy male Caucasian patient developed several episodes of bradycardia postoperatively after the umbilical hernia repair under subarachnoid block (SAB) while trying to lean forward and move his legs. Episodes were aborted when patient was advised to relax in supine position.The common mechanism of bradycardia and hypotension under SAB is postulated as sympathetic blockade, decrease venous return, and parasympathetic over-dominance leading to a decrease in right arterial pressure and pressure in the great veins as they enter the right atrium. But over time, the parasympathetic inhibition is usually withdrawn first, leading to the risk of severe bradycardia that is probably favored by the reverse Trendelenburg position as described in our case.Postoperative severe hemodynamic changes can occur even under stable spinal anesthesia; however, can be prevented by vigilant monitoring and simple maneuver which includes maintenance of relax posture on the bed.

Recent developments in the treatment of anxiety disorders in children and adolescents.

PubMed

Creswell, Cathy; Waite, Polly

2016-08-01

Anxiety disorders are among the most common emotional difficulties experienced by children and young people. They cause significant disturbance to the lives of young people and their families and present a risk for lifelong psychological disturbance. Effective psychological (ie, cognitive-behaviour therapy (CBT)) and pharmacological interventions (eg, selective serotonin reuptake inhibitors (SSRIs)) have been established. However, the risk of adverse effects and unknown long-term effects of using SSRIs has led to recommendations that CBT is delivered as a first-line intervention. Recent innovations have included the development of low-intensity CBT programmes, delivered briefly via parents or online. These hold promise to increase access to psychological therapies for children and young people with these common and severe difficulties. 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/

New adolescent polycystic ovary syndrome perspectives.

PubMed

Alemzadeh, R; Kansra, A R

2011-02-01

Polycystic ovary syndrome (PCOS) is a common but heterogeneous disorder that usually arises during puberty. This endocrine disorder is associated with chronic anovulation and hyperandrogenemia with clinical manifestation of oligomenorrhea, hirsutism and acne. While the underlying etiology of PCOS remains unknown, it is commonly associated with obesity and insulin resistance leading to increased risk of cardiovascular disease, dyslipidemia and type 2 diabetes mellitus in hyperandrogenemic phenotypes. Menstrual irregularities and insulin resistance in obese adolescents are usually indistinguishable from the clinical manifestations of PCOS and pose a diagnostic dilemma due to higher circulating androgens during puberty. Consequently, a universal consensus on the definition of hyperandrogenemia in adolescents has been elusive. Nevertheless, hyperandrogenemia, independent of obesity, in postmenarchal adolescents is associated with increased risk of cardiometabolic syndrome. Therefore, treatment strategies including lifestyle changes and/or use of insulin-sensitizers, hormone replacement and antiandrogens should be utilized in order to delay long-term cardiovascular and metabolic complications of this endocrinopathy.

Velo-Cardio-Facial Syndrome

PubMed Central

Gothelf, Doron; Frisch, Amos; Michaelovsky, Elena; Weizman, Abraham; Shprintzen, Robert J.

2010-01-01

Velocardiofacial syndrome (VCFS) also known as DiGeorge, conotruncal anomaly face and Cayler syndromes is caused by a microdeletion in the long arm of chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the microdeletion region and the physical and neuropsychiatric phenotype of the syndrome. Velocardiofacial syndrome has a wide spectrum of more than 200 physical manifestations including palate and cardiac anomalies. Yet, the most challenging manifestations of VCFS are the learning disabilities and neuropsychiatric disorders. As VCFS is relatively common and as up to one third of the subjects with VCFS develop schizophrenia like psychotic disorder the syndrome is the most commonly known genetic risk factor to schizophrenia. Identifying the genetic, cognitive and psychiatric risk factors for VCFS-schizophrenia is under the focus of intensive research. PMID:20111667

Bacteremia and fungemia in pediatric versus adult cancer patients after chemotherapy: comparison of etiology, risk factors and outcome.

PubMed

Krupova, I; Kaiserova, E; Foltinova, A; Kovacicova, G; Kiskova, M; Krchnakova, A; Kunova, A; Trupl, J; West, D; Krcmery, V

1998-06-01

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Fracture Risk and Risk Factors for Osteoporosis.

PubMed

Schürer, Christian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry; Schober, Hans-Christof; Hannemann, Anke

2015-05-25

As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors.

Epidemiology of preeclampsia: Impact of obesity

PubMed Central

Jeyabalan, Arun

2013-01-01

Preeclampsia is a pregnancy-specific disorder that affects 2 to 8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Diagnosis is based on new onset of hypertension and proteinuria. Multiple organ systems can be affected with severe disease. The wide range of risk factors reflects the heterogeneity of preeclampsia. Obesity, which is increasing at an alarming rate, is also a risk factor for preeclampsia as well as for later life cardiovascular disease. Exploring common features may provide insight into the pathophysiologic mechanisms underlying preeclampsia among obese and overweight women. PMID:24147919

Management of atrial fibrillation.

PubMed

Moukabary, Talal; Gonzalez, Mario D

2015-07-01

Atrial fibrillation is a very common clinical problem with a high prevalence that is expected to rise over time because of increasing risk factors (eg, age, obesity, hypertension). This high prevalence is also associated with high cost, because atrial fibrillation represents about 1% of overall health care spending. The management of atrial fibrillation involves multiple facets: (1) management of underlying disease if present and the management of atrial fibrillation risk factors, (2) prevention of thromboembolism, (3) control of the ventricular rate during atrial fibrillation, and (4) restoration and maintenance of normal sinus rhythm. Copyright © 2015 Elsevier Inc. All rights reserved.

Infant botulism: advice on avoiding feeding honey to babies and other possible risk factors.

PubMed

Grant, Kathie A; McLauchlin, Jim; Amar, Corinne

2013-07-01

Botulism is a rare, but extremely serious, disease and Public Health England is responsible for its diagnosis and surveillance in the UK. Over the past five years (2008-2013), the most common form of the disease recognised in the UK has been infant botulism. The aim of this article is to raise awareness of infant botulism and highlight advice for parents and carers of infants that honey should not be fed to infants under 12 months old. Other possible risk factors for infant botulism are also discussed in this article, including household pet reptiles and herbal teas.

Innovations in vital signs measurement for the detection of hypertension and shock in pregnancy.

PubMed

Vousden, Nicola; Nathan, Hannah L; Shennan, Andrew H

2018-06-22

Approximately 820 women die in pregnancy and childbirth every day worldwide, with 99% of these occurring in low-resource settings. The most common causes of maternal mortality are haemorrhage, sepsis and hypertensive disorders. There are established, effective solutions to these complications, however challenges remain in identifying who is at greatest risk and ensuring that interventions are delivered early when they have the greatest potential to benefit. Measuring vital signs is the first step in identifying women at risk. Overstretched or poorly trained staff and inadequate access to accurate, reliable equipment to measure vital signs can potentially result in delayed treatment initiation. Early warning systems may help alert users to identify patients at risk, especially where novel technologies can improve usability by automating calculations and alerting users to abnormalities. This may be of greatest benefit in under-resourced settings where task-sharing is common and early identification of complications can allow for prioritisation of life-saving interventions. This paper highlights the challenges of accurate vital sign measurement in pregnancy and identifies innovations which may improve detection of pregnancy complications.

Predictive validity of the Hendrich fall risk model II in an acute geriatric unit.

PubMed

Ivziku, Dhurata; Matarese, Maria; Pedone, Claudio

2011-04-01

Falls are the most common adverse events reported in acute care hospitals, and older patients are the most likely to fall. The risk of falling cannot be completely eliminated, but it can be reduced through the implementation of a fall prevention program. A major evidence-based intervention to prevent falls has been the use of fall-risk assessment tools. Many tools have been increasingly developed in recent years, but most instruments have not been investigated regarding reliability, validity and clinical usefulness. This study intends to evaluate the predictive validity and inter-rater reliability of Hendrich fall risk model II (HFRM II) in order to identify older patients at risk of falling in geriatric units and recommend its use in clinical practice. A prospective descriptive design was used. The study was carried out in a geriatric acute care unit of an Italian University hospital. All over 65 years old patients consecutively admitted to a geriatric acute care unit of an Italian University hospital over 8-month period were enrolled. The patients enrolled were screened for the falls risk by nurses with the HFRM II within 24h of admission. The falls occurring during the patient's hospital stay were registered. Inter-rater reliability, area under the ROC curve, sensitivity, specificity, positive and negative predictive values and time for the administration were evaluated. 179 elderly patients were included. The inter-rater reliability was 0.87 (95% CI 0.71-1.00). The administration time was about 1min. The most frequently reported risk factors were depression, incontinence, vertigo. Sensitivity and specificity were respectively 86% and 43%. The optimal cut-off score for screening at risk patients was 5 with an area under the ROC curve of 0.72. The risk factors more strongly associated with falls were confusion and depression. As falls of older patients are a common problem in acute care settings it is necessary that the nurses use specific validate and reliable fall risk assessment tools in order to implement the most effective prevention measures. Our findings provided supporting evidence to the choice of the HFRM II to screen older patients at risk of falling in acute care settings. Copyright © 2010 Elsevier Ltd. All rights reserved.

Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

PubMed Central

Bleeker, Jonathan S.; Hogan, William J.

2011-01-01

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?

PubMed Central

Segev-Jacubovski, Orit; Herman, Talia; Yogev-Seligmann, Galit; Mirelman, Anat; Giladi, Nir; Hausdorff, Jeffrey M

2011-01-01

In this article, we briefly summarize the incidence and significant consequences of falls among older adults, the insufficient effectiveness of commonly used multifactorial interventions and the evidence linking falls and cognitive function. Recent pharmacologic and nonpharmacologic studies that evaluated the effects of cognitive therapy on fall risk are reviewed. The results of this article illustrate the potential utility of multiple, diverse forms of cognitive therapy for reducing fall risk. The article also indicates that large-scale, randomized controlled trials are warranted and that additional research is needed to better understand the pathophysiologic mechanisms underlying the interplay between human mobility, fall risk and cognitive function. Nonetheless, we suggest that multimodality interventions that combine motor and cognitive therapy should, eventually, be incorporated into clinical practice to enable older adults and patients to move safer and with a reduced fall risk. PMID:21721921

Case Study of the Minimum Provable Risk Considering the Variation in Background Risk: Effect of Residual Risk on Epidemiological Studies and a Comparative Assessment of Fatal Disease Risk Due to Radiation Exposure.

PubMed

Sasaki, Michiya; Ogino, Haruyuki; Hattori, Takatoshi

2018-06-08

In order to prove a small increment in a risk of concern in an epidemiological study, a large sample of a population is generally required. Since the background risk of an end point of interest, such as cancer mortality, is affected by various factors, such as lifestyle (diet, smoking, etc.), adjustment for such factors is necessary. However, it is impossible to inclusively and completely adjust for such factors; therefore, uncertainty in the background risk remains for control and exposed populations, indicating that there is a minimum limit to the lower bound for the provable risk regardless of the sample size. In this case study, we developed and discussed the minimum provable risk considering the uncertainty in background risk for hypothetical populations by referring to recent Japanese statistical information to grasp the extent of the minimum provable risk. Risk of fatal diseases due to radiation exposure, which has recently been the focus of radiological protection, was also examined by comparative assessment of the minimum provable risk for cancer and circulatory diseases. It was estimated that the minimum provable risk for circulatory disease mortality was much greater than that for cancer mortality, approximately five to seven times larger; circulatory disease mortality is more difficult to prove as a radiation risk than cancer mortality under the conditions used in this case study.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Utility of Respondent Driven Sampling to Reach Disadvantaged Emerging Adults for Assessment of Substance Use, Weight, and Sexual Behaviors.

PubMed

Tucker, Jalie A; Simpson, Cathy A; Chandler, Susan D; Borch, Casey A; Davies, Susan L; Kerbawy, Shatomi J; Lewis, Terri H; Crawford, M Scott; Cheong, JeeWon; Michael, Max

2016-01-01

Emerging adulthood often entails heightened risk-taking with potential life-long consequences, and research on risk behaviors is needed to guide prevention programming, particularly in under-served and difficult to reach populations. This study evaluated the utility of Respondent Driven Sampling (RDS), a peer-driven methodology that corrects limitations of snowball sampling, to reach at-risk African American emerging adults from disadvantaged urban communities. Initial "seed" participants from the target group recruited peers, who then recruited their peers in an iterative process (110 males, 234 females; M age = 18.86 years). Structured field interviews assessed common health risk factors, including substance use, overweight/obesity, and sexual behaviors. Established gender-and age-related associations with risk factors were replicated, and sample risk profiles and prevalence estimates compared favorably with matched samples from representative U.S. national surveys. Findings supported the use of RDS as a sampling method and grassroots platform for research and prevention with community-dwelling risk groups.

Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013.

PubMed

Khan, Fahmi Yousef; Abu-Khattab, Mohammed; Almaslamani, Eman Abdulrahman; Hassan, Abubaker Ahmed; Mohamed, Shehab Fareed; Elbuzdi, Abdurrahman Ali; Elmaki, Nada Yagoub; Anand, Deshmukh; Sanjay, Doiphode

2017-01-01

Bacterial meningitis is a common medical condition in Qatar. The aim of this study was to describe the clinical characteristics of bacterial meningitis, the frequency of each pathogen, and its sensitivity to antibiotics and risk factors for death. This retrospective study was conducted at Hamad General Hospital between January 1, 2009, and December 31, 2013. We identified 117 episodes of acute bacterial meningitis in 110 patients. Their mean age was 26.4 ± 22.3 years (range: 2-74) and 81 (69.2%) of them were male patients. Fifty-nine episodes (50.4%) were community-acquired infection and fever was the most frequent symptom (94%), whereas neurosurgery is the most common underlying condition. Coagulase-negative staphylococci were the most common causative agent, of which 95% were oxacillin-resistant, while 63.3% of Acinetobacter spp. showed resistance to meropenem. The in-hospital mortality was 14 (12%). Only the presence of underlying diseases, hypotension, and inappropriate treatment were found to be independent predictors of mortality. Acute bacterial meningitis predominantly affected adults and coagulase-negative staphylococci species were the common causative agent in Qatar with majority of infections occurring nosocomially. More than 90% of all implicated coagulase-negative staphylococci strains were oxacillin-resistant.

Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry.

PubMed

Palmer, Rohan H C; McGeary, John E; Heath, Andrew C; Keller, Matthew C; Brick, Leslie A; Knopik, Valerie S

2015-12-01

Genetic studies of alcohol dependence (AD) have identified several candidate loci and genes, but most observed effects are small and difficult to reproduce. A plausible explanation for inconsistent findings may be a violation of the assumption that genetic factors contributing to each of the seven DSM-IV criteria point to a single underlying dimension of risk. Given that recent twin studies suggest that the genetic architecture of AD is complex and probably involves multiple discrete genetic factors, the current study employed common single nucleotide polymorphisms in two multivariate genetic models to examine the assumption that the genetic risk underlying DSM-IV AD is unitary. AD symptoms and genome-wide single nucleotide polymorphism (SNP) data from 2596 individuals of European descent from the Study of Addiction: Genetics and Environment were analyzed using genomic-relatedness-matrix restricted maximum likelihood. DSM-IV AD symptom covariance was described using two multivariate genetic factor models. Common SNPs explained 30% (standard error=0.136, P=0.012) of the variance in AD diagnosis. Additive genetic effects varied across AD symptoms. The common pathway model approach suggested that symptoms could be described by a single latent variable that had a SNP heritability of 31% (0.130, P=0.008). Similarly, the exploratory genetic factor model approach suggested that the genetic variance/covariance across symptoms could be represented by a single genetic factor that accounted for at least 60% of the genetic variance in any one symptom. Additive genetic effects on DSM-IV alcohol dependence criteria overlap. The assumption of common genetic effects across alcohol dependence symptoms appears to be a valid assumption. © 2015 Society for the Study of Addiction.

Crime on Campus: Analyzing and Managing the Increasing Risk of Institutional Liability. The Publication Series.

ERIC Educational Resources Information Center

Burling, Philip

This monograph reviews a college or university's responsibility for incidents of crime occurring on its campus or in the course of its programs. Part 1 reviews the legal analyses which courts undertake in responding to claims that, under common tort law or contract theories, liability for the injuries suffered by a person ought to be shifted from…

Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

PubMed Central

Hernández-Díaz, Sonia; Levin, Michael

2014-01-01

Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

Motorcyclists' perceptions and experiences of riding and risk and their advice for safety.

PubMed

Simpson, Jean C; Wilson, Suzanne; Currey, Nandika

2015-01-01

To examine the knowledge, observations, and perceptions of motorcycle riders on the risks of on-road motorcycling and potential safety measures to give insight and guidance in developing policies, programs, and legislation to improve the safety of motorcyclists. Individual and focus group interviews were conducted with dealers and a cross section of motorcyclists from selected regions across New Zealand. The interviews were analyzed and coded to identify common themes and diverse perspectives on why people rode motorcycles, riders' perceptions on risk, and possible safety strategies for on-road motorcycling. Motorcycling has major benefits for riders, although most riders perceived that the risks could be severe and they were susceptible to injury. Their observations on the threats and barriers to safety focused on 3 components: the rider, the motorcycle, and the environment. Risks included inexperience, not riding to the conditions, choice of motorcycle, protective clothing and conspicuity, and speed. The underlying risk of being on 2 wheels was accentuated by the availability of high-power motorcycles. The threats perceived in the environment included the behavior of other road users, especially car drivers, and the poor road conditions and surrounds encountered. Riders identified risks that have been recognized in the road safety literature as well as risks for which there are no engineering or scientific solutions. To effectively increase motorcyclist safety, recognition of the commonalities and the differences between motorcyclists' perspectives and proposed strategies is needed. This approach is more likely to engage riders and thus support positive behavior change among riders and drivers.

Fall risk assessment and prevention.

PubMed

Kline, Nancy E; Davis, Mary Elizabeth; Thom, Bridgette

2011-02-01

Patient falls are a common cause of morbidity and are the leading cause of injury deaths in adults age 65 years and older. Injuries sustained as result of falls in a cancer hospital are often severe, regardless of patient age, due to the nature of the underlying cancer. Falls are a nursing-sensitive indicator and nurses are in a unique position to assess, design, implement, and evaluate programs for fall risk reduction. We analyzed our nursing processes related to falls and fall prevention in conjunction with an evidence-based review, a research study to improve our fall risk-assessment process, and development of a comprehensive fall-reduction program. This article outlines how our institution developed a fall risk assessment for the oncology patient population, and utilized this assessment in a comprehensive nursing approach to fall prevention in both inpatient and outpatient settings.

AHNS Series: Do you know your guidelines? Perioperative antithrombotic management in head and neck surgery.

PubMed

Meyer, Annika; Gross, Neil; Teng, Marita

2018-01-01

Head and neck surgeons are commonly faced with surgical patients who have underlying medical problems requiring antithrombotic therapy. It is difficult to achieve a balance between minimizing the risk of thromboembolism and hemorrhage in the perioperative period. Data from randomized, controlled trials are limited, and procedure-specific bleed rates are also difficult to pinpoint. The decision is made more difficult when patients with moderate-to-high risk for thromboembolic events undergo procedures that are high risk for bleeding. This is true for many head and neck oncologic surgeries. Furthermore, although elective procedures may be delayed for optimization of antithrombotic medication, emergent procedures cannot. Head and neck surgery often represents the most challenging of all these circumstances, given the potential risk of airway compromise from bleeding after head and neck surgery. © 2017 Wiley Periodicals, Inc.

Beyond Rational Decision-Making: Modelling the Influence of Cognitive Biases on the Dynamics of Vaccination Coverage

PubMed Central

Voinson, Marina; Billiard, Sylvain; Alvergne, Alexandra

2015-01-01

Background Theoretical studies predict that it is not possible to eradicate a disease under voluntary vaccination because of the emergence of non-vaccinating “free-riders” when vaccination coverage increases. A central tenet of this approach is that human behaviour follows an economic model of rational choice. Yet, empirical studies reveal that vaccination decisions do not necessarily maximize individual self-interest. Here we investigate the dynamics of vaccination coverage using an approach that dispenses with payoff maximization and assumes that risk perception results from the interaction between epidemiology and cognitive biases. Methods We consider a behaviour-incidence model in which individuals perceive actual epidemiological risks as a function of their opinion of vaccination. As a result of confirmation bias, sceptical individuals (negative opinion) overestimate infection cost while pro-vaccines individuals (positive opinion) overestimate vaccination cost. We considered a feedback between individuals and their environment as individuals could change their opinion, and thus the way they perceive risks, as a function of both the epidemiology and the most common opinion in the population. Results For all parameter values investigated, the infection is never eradicated under voluntary vaccination. For moderately contagious diseases, oscillations in vaccination coverage emerge because individuals process epidemiological information differently depending on their opinion. Conformism does not generate oscillations but slows down the cultural response to epidemiological change. Conclusion Failure to eradicate vaccine preventable disease emerges from the model because of cognitive biases that maintain heterogeneity in how people perceive risks. Thus, assumptions of economic rationality and payoff maximization are not mandatory for predicting commonly observed dynamics of vaccination coverage. This model shows that alternative notions of rationality, such as that of ecological rationality whereby individuals use simple cognitive heuristics, offer promising new avenues for modelling vaccination behaviour. PMID:26599688

Beyond Rational Decision-Making: Modelling the Influence of Cognitive Biases on the Dynamics of Vaccination Coverage.

PubMed

Voinson, Marina; Billiard, Sylvain; Alvergne, Alexandra

2015-01-01

Theoretical studies predict that it is not possible to eradicate a disease under voluntary vaccination because of the emergence of non-vaccinating "free-riders" when vaccination coverage increases. A central tenet of this approach is that human behaviour follows an economic model of rational choice. Yet, empirical studies reveal that vaccination decisions do not necessarily maximize individual self-interest. Here we investigate the dynamics of vaccination coverage using an approach that dispenses with payoff maximization and assumes that risk perception results from the interaction between epidemiology and cognitive biases. We consider a behaviour-incidence model in which individuals perceive actual epidemiological risks as a function of their opinion of vaccination. As a result of confirmation bias, sceptical individuals (negative opinion) overestimate infection cost while pro-vaccines individuals (positive opinion) overestimate vaccination cost. We considered a feedback between individuals and their environment as individuals could change their opinion, and thus the way they perceive risks, as a function of both the epidemiology and the most common opinion in the population. For all parameter values investigated, the infection is never eradicated under voluntary vaccination. For moderately contagious diseases, oscillations in vaccination coverage emerge because individuals process epidemiological information differently depending on their opinion. Conformism does not generate oscillations but slows down the cultural response to epidemiological change. Failure to eradicate vaccine preventable disease emerges from the model because of cognitive biases that maintain heterogeneity in how people perceive risks. Thus, assumptions of economic rationality and payoff maximization are not mandatory for predicting commonly observed dynamics of vaccination coverage. This model shows that alternative notions of rationality, such as that of ecological rationality whereby individuals use simple cognitive heuristics, offer promising new avenues for modelling vaccination behaviour.

Clinical picture and risk prediction of short-term mortality in cardiogenic shock.

PubMed

Harjola, Veli-Pekka; Lassus, Johan; Sionis, Alessandro; Køber, Lars; Tarvasmäki, Tuukka; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva-Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Tolppanen, Heli; Zeymer, Uwe; Thiele, Holger; Nieminen, Markku S; Mebazaa, Alexandre

2015-05-01

The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2 mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85). Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials. NCT01374867. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Development and evaluation of a brief self-completed family history screening tool for common chronic disease prevention in primary care

PubMed Central

Walter, Fiona M; Prevost, A Toby; Birt, Linda; Grehan, Nicola; Restarick, Kathy; Morris, Helen C; Sutton, Stephen; Rose, Peter; Downing, Sarah; Emery, Jon D

2013-01-01

Background Family history is an important risk factor for many common chronic diseases, but it remains underutilised for diagnostic assessment and disease prevention in routine primary care. Aim To develop and validate a brief self-completed family history questionnaire (FHQ) for systematic primary care assessment for family history of diabetes, ischaemic heart disease, breast cancer, and colorectal cancer. Design and setting Two-stage diagnostic validation study in 10 general practices in eastern England. Method Participants aged 18–50 years were identified via random sampling from electronic searches of general practice records. Participants completed a FHQ then had a three-generational ‘gold standard’ pedigree taken, to determine disease risk category. In stage 1, the FHQ comprised 12 items; in stage 2 the shorter 6-item FHQ was validated against the same ‘gold standard’. Results There were 1147 participants (stage 1: 618; stage 2: 529). Overall, 32% were at increased risk of one or more marker conditions (diabetes 18.9%, ischaemic heart disease 13.3%, breast cancer 6.2%, colorectal cancer 2.2%). The shorter 6-item FHQ performed very well for all four conditions: pooled data from both stages show diabetes, sensitivity = 98%, specificity = 94%; ischaemic heart disease, sensitivity = 93%, specificity = 81%; breast cancer, sensitivity = 81%, specificity = 83%; colorectal cancer, sensitivity = 96%, specificity = 88%, with an area under the receiver operating characteristic curve of 0.90 for males and 0.89 for females. Conclusion This brief self-completed FHQ shows good diagnostic accuracy for identifying people at higher risk of four common chronic diseases. It could be used in routine primary care to identify patients who would be most likely to benefit from a more detailed pedigree and risk assessment, and consequent management strategies. PMID:23735410

Analyzing risks of adverse pregnancy outcomes.

PubMed

Kramer, Michael S; Zhang, Xun; Platt, Robert W

2014-02-01

Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

[Vascular calcifications in subjects with and without chronic renal failure: types, sites and risk factors].

PubMed

Marinelli, Annibale; Di Napoli, Anteo

2017-04-01

Vascular calcifications worse outcomes in the general population and in patients on dialysis. We investigated 146 patients on chronic hemodialysis and 63 healthy controls with normal renal function under 65 years of age. All subjects underwent B-mode ultrasonography of common and internal carotid artery, abdominal aorta, common and superficial femoral artery and posterior tibial artery to assess the presence of intimal and medial calcifications. Intimal and media calcifications were present at the level of the carotid vessel, the abdominal aorta, the common femoral artery, the superficial femoral artery and the posterior tibial artery, respectively in 45%, 50%, 45%, 50%, 42% of patients on dialysis and in 5%, 15%, 24%, 5%, 2% of controls (p <0,01). On multivariate logistic analysis of regression, after adjustment for potential confounders, carotid intimal calcification, abdominal aortic calcification, medial calcification of the superficial femoral artery and posterior tibial artery calcification were associated with dialysis and with cardiovascular disease. Only intimal arterial calcification were associated with older age and smoking. Vascular calcifications are extremely common in middle-aged patients on chronic hemodialysis. Ultrasonography currently available in Nephrology, is a sensitive, reproducible, inexpensive imaging technique to identify arterial intimal and medial calcification in high-risk cardiovascular subjects. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

PubMed Central

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

2016-01-01

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.

PubMed

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Evans, D Gareth; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kjaer, Susanne Kruger; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F A G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M W; van Doorn, Helena C; van Rensburg, Elizabeth J; Van't Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

2016-09-07

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

PubMed

Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

2018-06-12

Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk patterns and correlated brain activities. Multidimensional statistical analysis of FMRI data in economic decision making study.

PubMed

van Bömmel, Alena; Song, Song; Majer, Piotr; Mohr, Peter N C; Heekeren, Hauke R; Härdle, Wolfgang K

2014-07-01

Decision making usually involves uncertainty and risk. Understanding which parts of the human brain are activated during decisions under risk and which neural processes underly (risky) investment decisions are important goals in neuroeconomics. Here, we analyze functional magnetic resonance imaging (fMRI) data on 17 subjects who were exposed to an investment decision task from Mohr, Biele, Krugel, Li, and Heekeren (in NeuroImage 49, 2556-2563, 2010b). We obtain a time series of three-dimensional images of the blood-oxygen-level dependent (BOLD) fMRI signals. We apply a panel version of the dynamic semiparametric factor model (DSFM) presented in Park, Mammen, Wolfgang, and Borak (in Journal of the American Statistical Association 104(485), 284-298, 2009) and identify task-related activations in space and dynamics in time. With the panel DSFM (PDSFM) we can capture the dynamic behavior of the specific brain regions common for all subjects and represent the high-dimensional time-series data in easily interpretable low-dimensional dynamic factors without large loss of variability. Further, we classify the risk attitudes of all subjects based on the estimated low-dimensional time series. Our classification analysis successfully confirms the estimated risk attitudes derived directly from subjects' decision behavior.

Simulating the Risk of Liver Fluke Infection using a Mechanistic Hydro-epidemiological Model

NASA Astrophysics Data System (ADS)

Beltrame, Ludovica; Dunne, Toby; Rose, Hannah; Walker, Josephine; Morgan, Eric; Vickerman, Peter; Wagener, Thorsten

2016-04-01

Liver Fluke (Fasciola hepatica) is a common parasite found in livestock and responsible for considerable economic losses throughout the world. Risk of infection is strongly influenced by climatic and hydrological conditions, which characterise the host environment for parasite development and transmission. Despite on-going control efforts, increases in fluke outbreaks have been reported in recent years in the UK, and have been often attributed to climate change. Currently used fluke risk models are based on empirical relationships derived between historical climate and incidence data. However, hydro-climate conditions are becoming increasingly non-stationary due to climate change and direct anthropogenic impacts such as land use change, making empirical models unsuitable for simulating future risk. In this study we introduce a mechanistic hydro-epidemiological model for Liver Fluke, which explicitly simulates habitat suitability for disease development in space and time, representing the parasite life cycle in connection with key environmental conditions. The model is used to assess patterns of Liver Fluke risk for two catchments in the UK under current and potential future climate conditions. Comparisons are made with a widely used empirical model employing different datasets, including data from regional veterinary laboratories. Results suggest that mechanistic models can achieve adequate predictive ability and support adaptive fluke control strategies under climate change scenarios.

Injury prevention in male youth soccer: Current practices and perceptions of practitioners working at elite English academies.

PubMed

Read, Paul J; Jimenez, Pablo; Oliver, Jon L; Lloyd, Rhodri S

2018-06-01

Forty-one practitioners inclusive of physiotherapists, sports scientists and strength and conditioning coaches from the academies of elite soccer clubs in the United Kingdom completed an on-line questionnaire which examined their: (1) background information; (2) perceptions of injury occurrence and risk factors; (3) screening and return to play; and (4) approach to designing and delivering injury prevention programmes with a response rate of 55% (41/75). Contact injuries were the most common mechanism reported and players between 13-16 years of age were perceived to be at the greatest risk. Pertinent risk factors included: reduced lower limb and eccentric hamstring strength, proprioception, muscle imbalances, and under developed foundational movement skills. Joint range of motion, jump tests, the functional movement screen, overhead and single leg squats were the most utilised screening methods. Training modalities rated in order of importance included: resistance training, flexibility development, agility, plyometrics and balance training. Training frequency was most commonly once or twice per week, during warm-ups, independent sessions or a combination of both. Injury prevention strategies in this cohort appear to be logical; however, the classification of injury occurrence and application of screening tools to identify "at risk" players do not align with existing research. The frequency and type of training used may also be insufficient to elicit an appropriate stimulus to address pertinent risk factors based on current recommendations.

A holistic food labelling strategy for preventing obesity and dental caries.

PubMed

Cinar, A B; Murtomaa, H

2009-05-01

Obesity and dental caries in childhood are among the major public health concerns described as a global pandemic because of their global distribution and severe consequences. A consensus has developed as to a recently emerging and alarming common risk factor that leads to the double burden of dental caries and obesity; energy-dense foods (sugar-coated cereals, high-sugar yogurt, soft drinks) are becoming very popular among children because of their dense marketing, cheaper price, increased supply and variety. Implementation of health-promoting and -supporting marketing strategies for healthy food can be one initial cornerstone for successful application of the common risk factor approach in prevention of obesity and dental caries, as also suggested by World Health Organization. Labelling healthy food with a 'health-friendly' logo, illustrating that the teeth and the heart are both parts of the whole body (standing side by side supporting each other as close friends), both happy and protected because of consumption of healthy food for the whole body, can promote the foods that are friendly to health of the whole body, implementing the common risk factor approach under a single theme. Labelling healthy food as 'health-friendly' based on an international consensus will provide a clear and uniform picture of what is healthy to eat and result in an international integrated programme for prevention of obesity and caries.

Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients.

PubMed

Gingerich, Morgan A; Smith, Joshua D; Michmerhuizen, Nicole L; Ludwig, Megan; Devenport, Samantha; Matovina, Chloe; Brenner, Chad; Chinn, Steven B

2018-05-01

The past 2 decades have seen an increased incidence of head and neck squamous cell carcinoma (HNSCC) in a nontraditional, low-risk patient population (ie, ≤45 years of age, no substance use history), owing to a combination of human papillomavirus (HPV) infection and individual genetic variation. Articles positing genetic variants as contributing factors in HNSCC incidence in low-risk, nontraditional patients were identified using a PubMed search, reviewed in detail, and concisely summarized herein. Recent data suggest that common polymorphisms in DNA repair enzymes, cell-cycle control proteins, apoptotic pathway members, and Fanconi anemia-associated genes likely modulate susceptibility to HNSCC development in low-risk, nontraditional patients. At present, there is a lack of robust, comprehensive data on genetic drivers of oncogenesis in low-risk patients and a clear need for further research on genetic alterations underlying the rising incidence of HNSCC in low-risk, nontraditional patients. © 2018 Wiley Periodicals, Inc.

Decision making under uncertainty, therapeutic inertia, and physicians' risk preferences in the management of multiple sclerosis (DIScUTIR MS).

PubMed

Saposnik, Gustavo; Sempere, Angel Perez; Raptis, Roula; Prefasi, Daniel; Selchen, Daniel; Maurino, Jorge

2016-05-04

The management of multiple sclerosis (MS) is rapidly changing by the introduction of new and more effective disease-modifying agents. The importance of risk stratification was confirmed by results on disease progression predicted by different risk score systems. Despite these advances, we know very little about medical decisions under uncertainty in the management of MS. The goal of this study is to i) identify whether overconfidence, tolerance to risk/uncertainty, herding influence medical decisions, and ii) to evaluate the frequency of therapeutic inertia (defined as lack of treatment initiation or intensification in patients not at goals of care) and its predisposing factors in the management of MS. This is a prospective study comprising a combination of case-vignettes and surveys and experiments from Neuroeconomics/behavioral economics to identify cognitive distortions associated with medical decisions and therapeutic inertia. Participants include MS fellows and MS experts from across Spain. Each participant will receive an individual link using Qualtrics platform(©) that includes 20 case-vignettes, 3 surveys, and 4 behavioral experiments. The total time for completing the study is approximately 30-35 min. Case vignettes were selected to be representative of common clinical encounters in MS practice. Surveys and experiments include standardized test to measure overconfidence, aversion to risk and ambiguity, herding (following colleague's suggestions even when not supported by the evidence), physicians' reactions to uncertainty, and questions from the Socio-Economic Panel Study (SOEP) related to risk preferences in different domains. By applying three different MS score criteria (modified Rio, EMA, Prosperini's scheme) we take into account physicians' differences in escalating therapy when evaluating medical decisions across case-vignettes. The present study applies an innovative approach by combining tools to assess medical decisions with experiments from Neuroeconomics that applies to common scenarios in MS care. Our results will help advance the field by providing a better understanding on the influence of cognitive factors (e.g., overconfidence, aversion to risk and uncertainty, herding) on medical decisions and therapeutic inertia in the management of MS which could lead to better outcomes.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.

PubMed

Zapata-Martín Del Campo, Carlos Manuel; Martínez-Rosas, Martín; Guarner-Lans, Verónica

2018-04-18

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease

PubMed Central

Zapata-Martín del Campo, Carlos Manuel; Martínez-Rosas, Martín

2018-01-01

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual. PMID:29670001

Predictive features of breast cancer on Mexican screening mammography patients

NASA Astrophysics Data System (ADS)

Rodriguez-Rojas, Juan; Garza-Montemayor, Margarita; Trevino-Alvarado, Victor; Tamez-Pena, José Gerardo

2013-02-01

Breast cancer is the most common type of cancer worldwide. In response, breast cancer screening programs are becoming common around the world and public programs now serve millions of women worldwide. These programs are expensive, requiring many specialized radiologists to examine all images. Nevertheless, there is a lack of trained radiologists in many countries as in Mexico, which is a barrier towards decreasing breast cancer mortality, pointing at the need of a triaging system that prioritizes high risk cases for prompt interpretation. Therefore we explored in an image database of Mexican patients whether high risk cases can be distinguished using image features. We collected a set of 200 digital screening mammography cases from a hospital in Mexico, and assigned low or high risk labels according to its BIRADS score. Breast tissue segmentation was performed using an automatic procedure. Image features were obtained considering only the segmented region on each view and comparing the bilateral di erences of the obtained features. Predictive combinations of features were chosen using a genetic algorithms based feature selection procedure. The best model found was able to classify low-risk and high-risk cases with an area under the ROC curve of 0.88 on a 150-fold cross-validation test. The features selected were associated to the differences of signal distribution and tissue shape on bilateral views. The model found can be used to automatically identify high risk cases and trigger the necessary measures to provide prompt treatment.

Cow-specific risk factors for clinical mastitis in Brazilian dairy cattle.

PubMed

Oliveira, C S F; Hogeveen, H; Botelho, A M; Maia, P V; Coelho, S G; Haddad, J P A

2015-10-01

Information related to mastitis risk factors is useful for the design and implementation of clinical mastitis (CM) control programs. The first objective of our study was to model the risk of CM under Brazilian conditions, using cow-specific risk factors. Our second objective was to explore which risk factors were associated with the occurrence of the most common pathogens involved in Brazilian CM infections. The analyses were based on 65 months of data from 9,789 dairy cows and 12,464 CM cases. Cow-specific risk factors that could easily be measured in standard Brazilian dairy farms were used in the statistical analyses, which included logistic regression and multinomial logistic regression. The first month of lactation, high somatic cell count, rainy season and history of clinical mastitis cases were factors associated with CM for both primiparous and multiparous cows. In addition, parity and breed were also associated risk factors for multiparous cows. Of all CM cases, 54% showed positive bacteriological culturing results from which 57% were classified as environmental pathogens, with a large percentage of coliforms (35%). Coagulase-negative Staphylococcus (16%), Streptococcus uberis (9%), Streptococcus agalactiae (7%) and other Streptococci (9%) were also common pathogens. Among the pathogens analyzed, the association of cow-specific risk factors, such as Zebu breed (OR=5.84, 95%CI 3.77-10.77) and accumulated history of SCC (1.76, 95%CI 1.37-2.27), was different for CM caused by Coagulase-negative Staphylococcus and S. agalactiae in comparison to CM caused by coliforms. Our results suggest that CM control programs in Brazil should specially consider the recent history of clinical mastitis cases and the beginning of the lactations, mainly during the rainy season as important risk factor for mastitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk Factors Associated with Injury and Mortality from Paediatric Low Speed Vehicle Incidents: A Systematic Review

PubMed Central

Paul Anthikkat, Anne; Page, Andrew; Barker, Ruth

2013-01-01

Objective. This study reviews modifiable risk factors associated with fatal and nonfatal injury from low-speed vehicle runover (LSVRO) incidents involving children aged 0–15 years. Data Sources. Electronic searches for child pedestrian and driveway injuries from the peer-reviewed literature and transport-related websites from 1955 to 2012. Study Selection. 41 studies met the study inclusion criteria. Data Extraction. A systematic narrative summary was conducted that included study design, methodology, risk factors, and other study variables. Results. The most commonly reported risk factors for LSVRO incidents included age under 5 years, male gender, and reversing vehicles. The majority of reported incidents involved residential driveways, but several studies identified other traffic and nontraffic locations. Low socioeconomic status and rental accommodation were also associated with LSVRO injury. Vehicles were most commonly driven by a family member, predominantly a parent. Conclusion. There are a number of modifiable vehicular, environmental, and behavioural factors associated with LSVRO injuries in young children that have been identified in the literature to date. Strategies relating to vehicle design (devices for increased rearward visibility and crash avoidance systems), housing design (physical separation of driveway and play areas), and behaviour (driver behaviour, supervision of young children) are discussed. PMID:23781251

Depression and Risk of Developing Dementia

PubMed Central

Byers, Amy L.; Yaffe, Kristine

2012-01-01

Depression is highly common throughout the life course and dementia is common in late life. The literature suggests an association between depression and dementia, and growing evidence implies that timing of depression may be important to defining the nature of the association. In particular, earlier-life depression or depressive symptoms consistently have been shown to be associated with a 2-fold or greater increase in risk of dementia. In contrast, studies of late-life depression have been more conflicting but the majority support an association; yet, the nature of this association is unclear (e.g., if depression is a prodrome or consequence or risk factor for dementia). The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroids and hippocampal atrophy, increased deposition of β-amyloid plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression might intervene on these pathways and in turn may alter risk for dementia. Given the projected increase of dementia in the coming decades, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize and analyze current evidence for late-life and earlier-life depression and their relationship to dementia, discuss the primary underlying mechanisms and implications for treatment. PMID:21537355

Preconception personality disorder and antenatal maternal mental health: A population-based cohort study.

PubMed

Hudson, Charlotte; Spry, Elizabeth; Borschmann, Rohan; Becker, Denise; Moran, Paul; Olsson, Craig; Coffey, Carolyn; Romaniuk, Helena; Bayer, Jordana K; Patton, George C

2017-02-01

Prior anxiety and depression have been identified as risk factors for maternal perinatal mental health problems, but other preconception mental disorders have not been prospectively examined. This study investigated prospectively whether women with preconception personality disorder have increased rates of antenatal anxiety and/or depressive symptoms. 244 women in a population cohort were assessed for personality disorder at age 24 using the Standardised Assessment of Personality. Five to twelve years later, women were screened with the Clinical Interview Schedule, Revised Anxiety Subscale and the Edinburgh Postnatal Depression Scale during the third trimester of 328 pregnancies. Preconception personality disorder was associated with a three-fold increase in the odds of antenatal anxiety symptoms, which remained with adjustment for preconception background factors and preconception common mental disorder (adjusted OR 2.84, 95% CI 1.31-6.15). Preconception personality disorder was associated with doubled odds of antenatal depressive symptoms, however this was attenuated with adjustment for preconception background factors and preconception common mental disorder (adjusted OR 1.98, 95% CI 0.81-4.81). Our findings are restricted to pregnant women aged 29-35 years. Anxiety and depression may have been under-identified because they were assessed at a single antenatal time point. Residual confounding of the associations by preconception common mental disorder at other time points may have occurred. Women with personality disorder are at heightened risk of anxiety symptoms in pregnancy, over and above risks associated with prior common mental disorder. This raises a possibility that pregnancy brings particular emotional challenges for women with personality disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-occurrence of behavioral risk factors of common non-communicable diseases among urban slum dwellers in Nairobi, Kenya.

PubMed

Haregu, Tilahun Nigatu; Oti, Samuel; Egondi, Thaddaeus; Kyobutungi, Catherine

2015-01-01

The four common non-communicable diseases (NCDs) account for 80% of NCD-related deaths worldwide. The four NCDs share four common risk factors. As most of the existing evidence on the common NCD risk factors is based on analysis of a single factor at a time, there is a need to investigate the co-occurrence of the common NCD risk factors, particularly in an urban slum setting in sub-Saharan Africa. To determine the prevalence of co-occurrence of the four common NCDs risk factors among urban slum dwellers in Nairobi, Kenya. This analysis was based on the data collected as part of a cross-sectional survey to assess linkages among socio-economic status, perceived personal risk, and risk factors for cardiovascular and NCDs in a population of slum dwellers in Nairobi, Kenya, in 2008-2009. A total of 5,190 study subjects were included in the analysis. After selecting relevant variables for common NCD risk factors, we computed the prevalence of all possible combinations of the four common NCD risk factors. The analysis was disaggregated by relevant background variables. The weighted prevalences of unhealthy diet, insufficient physical activity, harmful use of alcohol, and tobacco use were found to be 57.2, 14.4, 10.1, and 12.4%, respectively. Nearly 72% of the study participants had at least one of the four NCD risk factors. About 52% of the study population had any one of the four NCD risk factors. About one-fifth (19.8%) had co-occurrence of NCD risk factors. Close to one in six individuals (17.6%) had two NCD risk factors, while only 2.2% had three or four NCD risk factors. One out of five of people in the urban slum settings of Nairobi had co-occurrence of NCD risk factors. Both comprehensive and differentiated approaches are needed for effective NCD prevention and control in these settings.

International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis, Kristopher; Zhang Liying; Lutz, Stephen

Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately andmore » committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.« less

Effects of Acoustic Impulses on the Middle Ear

DTIC Science & Technology

2016-10-01

development of a MEMC detection algorithm for use with the National Health and Nutrition Examination Survey (NHANES) impedance traces. The second specific...Flamme GA, Deiters KK, Tasko SM, Ahroon WA (under review). Acoustic reflexes are common but not pervasive: Evidence from the National Health and Nutrition ...of new (or revising existing) damage risk criteria and health hazard assessment methods for exposure to high-level acoustic impulses such as

Posion Prevention in the Home

PubMed Central

Burnside, Sandra; Trepanier, Donna; McGuigan, Michael A.

1983-01-01

The Poison Control Centre at Toronto's Hospital for Sick Children received over 25,000 telephone inquiries in 1981. Those at greatest risk of accidental poisoning are children under age five. Education on poison prevention should begin at the first postnatal visit. This article lists the most common household poisons, including plants, resources that parents and physicians can use, and the telephone numbers of Canadian poison control centres. ImagesFig. 2Fig. 3Fig. 4

Adaptability in Crisis Management: The Role of Organizational Structure

DTIC Science & Technology

2013-06-01

individuals to make optimal decisions under constraints of high risk, uncertainty, high workload, and time pressure (see, e.g., Brehmer, 2007 ). There is...et al., 2003; Hallam & Stammers , 1981). For instance, Hallam and Stammers (1981) showed that the impact of variations in task complexity on team...each team member. FIRESCOPE, a commonly used crisis intervention plan developed in California (Office of Emergency Services, 2007 ) is a good

Biomarkers of Risk for Colorectal Neoplasia (Team Project #2) — EDRN Public Portal

Cancer.gov

The goal of this project is to evaluate biomarkers in normal colonic mucosa to determine their relationship to the occurrence of short- and long-term colorectal neoplasia. Candidate markers have been proposed by participating investigators based on promising preliminary data. The purpose of this team project is to evaluate these markers in a common, tissue-based reference set, under a uniform, structured protocol.

The genetics of pigment dispersion syndrome and pigmentary glaucoma.

PubMed

Lascaratos, Gerassimos; Shah, Ameet; Garway-Heath, David F

2013-01-01

We review the inheritance patterns and recent genetic advances in the study of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). Both conditions may result from combinations of mutations in more than one gene or from common variants in many genes, each contributing small effects. We discuss the currently known genetic loci that may be related with PDS/PG in humans, the role of animal models in expanding our understanding of the genetic basis of PDS, the genetic factors underlying the risk for conversion from PDS to PG and the relationship between genetic and environmental--as well as anatomical--risk factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014.

PubMed

Cooley, L; Dendle, C; Wolf, J; Teh, B W; Chen, S C; Boutlis, C; Thursky, K A

2014-12-01

Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Chronic Traumatic Encephalopathy: Known Causes, Unknown Effects.

PubMed

Iacono, Diego; Shively, Sharon B; Edlow, Brian L; Perl, Daniel P

2017-05-01

Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated. Published by Elsevier Inc.

Novel genetic predictors of venous thromboembolism risk in African Americans

PubMed Central

Hernandez, Wenndy; Gamazon, Eric R.; Smithberger, Erin; O’Brien, Travis J.; Harralson, Arthur F.; Tuck, Matthew; Barbour, April; Kittles, Rick A.; Cavallari, Larisa H.

2016-01-01

Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P < 6 × 10−7). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P = 9.87 × 10−6). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease. PMID:26888256

Ionising radiation risk disclosure: When should radiographers assume a duty to inform?

PubMed

Younger, C W E; Douglas, C; Warren-Forward, H

2018-05-01

Autonomy is a fundamental patient right for ethical practice, and informed consent is the mechanism by which health care professionals ensure this right has been respected. The ethical notion of informed consent has evolved alongside legal developments. Under Australian law, a provider who fails to disclose risk may be found to be in breach of a duty of disclosure, potentially facing legal consequences if the patient experiences harm that is attributable to an undisclosed risk. These consequences may include the common law tort of negligence. Ionising radiation, in the form of a medical imaging examination, has the potential to cause harm. However, stochastic effects cannot be attributable to a specific ionising radiation event. What then is the role of the Australian medical imaging service provider in disclosing ionising radiation risk? The ethical and legal principles of informed consent, and the duty of information provision to the patient are investigated. These general principles are then applied to the specific and unusual case of ionising radiation, and what responsibilities apply to the medical imaging provider. Finally, the legal, professional and ethical duties of the radiographer to disclose information to their patients are investigated. Australian law is unclear as to whether a radiographer has a common law responsibility to disclose radiation risk. There is ambiguity as to whether stochastic ionising radiation risk could be considered a legal disclosure responsibility. While it is unlikely that not disclosing risk will have medicolegal consequences, doing so represents sound ethical practice. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS – PART ONE

PubMed Central

Halle, Rob J.

2016-01-01

ABSTRACT Background Dry needling is an evidence-based treatment technique that is accepted and used by physical therapists in the United States. This treatment approach focuses on releasing or inactivating muscular trigger points to decrease pain, reduce muscle tension, and assist patients with an accelerated return to active rehabilitation. Issue While commonly used, the technique has some patient risk and value of the treatment should be based on benefit compared to the potential risk. Adverse effects (AEs) with dry needling can be mild or severe, with overall incidence rates varying from zero to rates of approximately 10 percent. While mild AEs are the rule, any procedure that involves a needle insertion has the potential for an AE, with select regions and the underlying anatomy increasing the risk. Known significant AEs from small diameter needle insertion include pneumothorax, cardiac tamponade, hematoma, infection, central nervous system injury, and other complications. Purpose/Objective Underlying anatomy across individuals has variability, requiring an in-depth knowledge of anatomy prior to any needle placement. This commentary is an overview of pertinent anatomy in the region of the thorax, with a ‘part two’ that addresses the abdomen, pelvis, back, vasovagal response, informed consent and other pertinent issues. The purpose of the commentary is to minimize the risk of a dry needling AE. Conclusions/Implications Dry needling is an effective adjunct treatment procedure that is within the recognized scope of physical therapy practice. Physical therapy education and training provides practitioners with the anatomy, basic sciences, and clinical foundation to use this intervention safely and effectively. A safe and evidenced-based implementation of the procedure is based on a thorough understanding of the underlying anatomy and the potential risks, with risks coordinated with patients via informed consent. Levels of Evidence Level 5 PMID:27525188

Prevalence of vaginitis in different age groups among females in Greece.

PubMed

Sianou, Argiri; Galyfos, George; Moragianni, Dimitra; Baka, Stavroula

2017-08-01

Patients with vaginitis were classified into four groups: Group A (prepubertal under-aged females); Group B (pubertal under-aged females); Group C (reproductive age adult females); Group D (postmenopausal adult females). All vaginal specimens underwent microscopy, amine testing, Gram staining and culturing. Overall, 163 patients were included (33, 14, 81 and 35 patients, respectively). The most common infection was bacterial vaginosis (BV), followed by Ureaplasma infection, aerobic vaginitis (AV) and candidiasis. The most common AV-associated organism was Escherichia coli and the most common BV-associated organism was Gardnerella vaginalis. AV was more frequent in Group A, BV in Group C and Ureaplasma infections in Groups C/D. Decreased lactobacilli concentrations were associated with BV in fertile patients (Groups B-C). Although presentation of vaginitis is similar among females of different age in Greece, type and prevalence of pathogens differ. Normal vaginal flora changes are associated with higher risk of vaginitis in specific age groups. Impact Statement The worldwide incidence of reproductive tract infections has been increasing, with specific pathogens being associated with significant risk of morbidity and complications. However, literature data on the distribution of such infections in different age groups is limited. Therefore, the aim of this study was to provide data on the prevalence and causes of vaginitis in adult and non-adult females of all ages. This study has shown that although presentation of vaginitis is similar among females of different age groups and menstrual status in Greece, type and prevalence of responsible pathogens are different among groups. Changes in normal vaginal flora seem to be associated with higher risk of vaginitis in specific age-groups as well. These findings could contribute in adjusting diagnostic and therapeutic strategies for each age group according to the prevailing pathogens. Further research on antibiotic resistance and treatment outcomes for each age group should be conducted.

Nearest Neighbor Algorithms for Pattern Classification

NASA Technical Reports Server (NTRS)

Barrios, J. O.

1972-01-01

A solution of the discrimination problem is considered by means of the minimum distance classifier, commonly referred to as the nearest neighbor (NN) rule. The NN rule is nonparametric, or distribution free, in the sense that it does not depend on any assumptions about the underlying statistics for its application. The k-NN rule is a procedure that assigns an observation vector z to a category F if most of the k nearby observations x sub i are elements of F. The condensed nearest neighbor (CNN) rule may be used to reduce the size of the training set required categorize The Bayes risk serves merely as a reference-the limit of excellence beyond which it is not possible to go. The NN rule is bounded below by the Bayes risk and above by twice the Bayes risk.

[Risk Management: concepts and chances for public health].

PubMed

Palm, Stefan; Cardeneo, Margareta; Halber, Marco; Schrappe, Matthias

2002-01-15

Errors are a common problem in medicine and occur as a result of a complex process involving many contributing factors. Medical errors significantly reduce the safety margin for the patient and contribute additional costs in health care delivery. In most cases adverse events cannot be attributed to a single underlying cause. Therefore an effective risk management strategy must follow a system approach, which is based on counting and analysis of near misses. The development of defenses against the undesired effects of errors should be the main focus rather than asking the question "Who blundered?". Analysis of near misses (which in this context can be compared to indicators) offers several methodological advantages as compared to the analysis of errors and adverse events. Risk management is an integral element of quality management.

Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants.

PubMed

Hernández-Díaz, Sonia; Levin, Michael

2014-08-01

Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations has been controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. We propose that development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

Uncertainty-accounting environmental policy and management of water systems.

PubMed

Baresel, Christian; Destouni, Georgia

2007-05-15

Environmental policies for water quality and ecosystem management do not commonly require explicit stochastic accounts of uncertainty and risk associated with the quantification and prediction of waterborne pollutant loads and abatement effects. In this study, we formulate and investigate a possible environmental policy that does require an explicit stochastic uncertainty account. We compare both the environmental and economic resource allocation performance of such an uncertainty-accounting environmental policy with that of deterministic, risk-prone and risk-averse environmental policies under a range of different hypothetical, yet still possible, scenarios. The comparison indicates that a stochastic uncertainty-accounting policy may perform better than deterministic policies over a range of different scenarios. Even in the absence of reliable site-specific data, reported literature values appear to be useful for such a stochastic account of uncertainty.

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

Identifying balance and fall risk in community-dwelling older women: the effect of executive function on postural control.

PubMed

Muir-Hunter, Susan W; Clark, Jennifer; McLean, Stephanie; Pedlow, Sam; Van Hemmen, Alysia; Montero Odasso, Manuel; Overend, Tom

2014-01-01

The mechanisms linking cognition, balance function, and fall risk among older adults are not fully understood. An evaluation of the effect of cognition on balance tests commonly used in clinical practice to assess community-dwelling older adults could enhance the identification of at-risk individuals. The study aimed to determine (1) the association between cognition and clinical tests of balance and (2) the relationship between executive function (EF) and balance under single- and dual-task testing. Participants (24 women, mean age of 76.18 [SD 16.45] years) completed six clinical balance tests, four cognitive tests, and two measures of physical function. Poor balance function was associated with poor performance on cognitive testing of EF. In addition, the association with EF was strongest under the dual-task timed up-and-go (TUG) test and the Fullerton Advanced Balance Scale. Measures of global cognition were associated only with the dual-task performance of the TUG. Postural sway measured with the Standing Balance Test, under single- or dual-task test conditions, was not associated with cognition. Decreased EF was associated with worse performance on functional measures of balance. The relationship between EF and balance was more pronounced with dual-task testing using a complex cognitive task combined with the TUG.

Utility of Ward-Based Retinal Photography in Stroke Patients.

PubMed

Frost, Shaun; Brown, Michael; Stirling, Verity; Vignarajan, Janardhan; Prentice, David; Kanagasingam, Yogesan

2017-03-01

Improvements in acute care of stroke patients have decreased mortality, but survivors are still at increased risk of future vascular events and mitigation of this risk requires thorough assessment of the underlying factors leading to the stroke. The brain and eye share a common embryological origin and numerous similarities exist between the small vessels of the retina and brain. Recent population-based studies have demonstrated a close link between retinal vascular changes and stroke, suggesting that retinal photography could have utility in assessing underlying stroke risk factors and prognosis after stroke. Modern imaging equipment can facilitate precise measurement and monitoring of vascular features. However, use of this equipment is a challenge in the stroke ward setting as patients are frequently unable to maintain the required seated position, and pupil dilatation is often not feasible as it could potentially obscure important neurological signs of stroke progression. This small study investigated the utility of a novel handheld, nonmydriatic retinal camera in the stroke ward and explored associations between retinal vascular features and stroke risk factors. This camera circumvented the practical limitations of conducting retinal photography in the stroke ward setting. A positive correlation was found between carotid disease and both mean width of arterioles (r = .40, P = .00571) and venules (r = .30, P = .0381). The results provide further evidence that retinal vascular features are clinically informative about underlying stroke risk factors and demonstrate the utility of handheld retinal photography in the stroke ward. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Risk factors for complicated varicella infection in pediatric oncology patients at a tertiary health care facility in Pakistan.

PubMed

Alam, Muhammad Matloob; Qamar, Farah Naz; Khan, Zalan Wahid; Kumar, Vikram; Mushtaq, Naureen; Fadoo, Zehra

2014-02-13

Varicella zoster infection (VZI) is well recognized as a potential cause of morbidity and mortality in immunocompromised pediatric oncology patients (POP). The purpose of this study was to describe the clinical profile and risk factors for complications and outcomes of VZI in POP treated with acyclovir. Medical records of all POP with a discharge diagnosis of VZI over a period of seven years (2005-2011) were reviewed. The demographic features, underlying malignancy, risk factors for VZI, complications, and outcomes were recorded. Thirty-six POP with VZI were identified. Leukemia was the most common underlying malignancy (n = 20, 58.8%), followed by lymphoma (n = 7, 20.6%) and solid organ tumors (n = 7, 20.6%). Most of the cases (41%) were observed in children under five. All patients were treated with acyclovir. Varicella-related complications developed in 10 (29%) patients. The most frequent complication was bloodstream infection (n = 3, 8.8%), followed by pneumonia (n = 2, 5.9%), skin infection (n = 2, 5.9%), hepatitis, renal failure, and encephalitis. Independent risk factors associated with complications were age < five years, weight for age < fifth percentile, delay in seeking care (> seven days after onset of symptoms) and severe neutropenia (ANC < 500/cm). One child died secondary to varicella encephalitis. Our data suggests that young age, poor health-seeking behavior, severe neutropenia, and being underweight are the major risk factors for the development of varicella-related complications in POP in developing countries. These complications could be favorably modified through active immunization of immunocompetent children.

Transfer Efficiency of Bacteria and Viruses from Porous and Nonporous Fomites to Fingers under Different Relative Humidity Conditions

PubMed Central

Gerba, Charles P.; Tamimi, Akrum H.; Kitajima, Masaaki; Maxwell, Sheri L.; Rose, Joan B.

2013-01-01

Fomites can serve as routes of transmission for both enteric and respiratory pathogens. The present study examined the effect of low and high relative humidity on fomite-to-finger transfer efficiency of five model organisms from several common inanimate surfaces (fomites). Nine fomites representing porous and nonporous surfaces of different compositions were studied. Escherichia coli, Staphylococcus aureus, Bacillus thuringiensis, MS2 coliphage, and poliovirus 1 were placed on fomites in 10-μl drops and allowed to dry for 30 min under low (15% to 32%) or high (40% to 65%) relative humidity. Fomite-to-finger transfers were performed using 1.0 kg/cm2 of pressure for 10 s. Transfer efficiencies were greater under high relative humidity for both porous and nonporous surfaces. Most organisms on average had greater transfer efficiencies under high relative humidity than under low relative humidity. Nonporous surfaces had a greater transfer efficiency (up to 57%) than porous surfaces (<6.8%) under low relative humidity, as well as under high relative humidity (nonporous, up to 79.5%; porous, <13.4%). Transfer efficiency also varied with fomite material and organism type. The data generated can be used in quantitative microbial risk assessment models to assess the risk of infection from fomite-transmitted human pathogens and the relative levels of exposure to different types of fomites and microorganisms. PMID:23851098

Respiratory inflammation and infections in high-performance athletes.

PubMed

Gleeson, Maree; Pyne, David B

2016-02-01

Upper respiratory illness is the most common reason for non-injury-related presentation to a sports medicine clinic, accounting for 35-65% of illness presentations. Recurrent or persistent respiratory illness can have a negative impact on health and performance of athletes undertaking high levels of strenuous exercise. The cause of upper respiratory symptoms (URS) in athletes can be uncertain but the majority of cases are related to common respiratory viruses, viral reactivation, allergic responses to aeroallergens and exercise-related trauma to the integrity of respiratory epithelial membranes. Bacterial respiratory infections are uncommon in athletes. Undiagnosed or inappropriately treated asthma and/or allergy are common findings in clinical assessments of elite athletes experiencing recurrent URS. High-performance athletes with recurrent episodes of URS should undergo a thorough clinical assessment to exclude underlying treatable conditions of respiratory inflammation. Identifying athletes at risk of recurrent URS is important in order to prescribe preventative clinical, training and lifestyle strategies. Monitoring secretion rates and falling concentrations of salivary IgA can identify athletes at risk of URS. Therapeutic interventions are limited by the uncertainty of the underlying cause of inflammation. Topical anti-inflammatory sprays can be beneficial for some athletes. Dietary supplementation with bovine colostrum, probiotics and selected antioxidants can reduce the incidence or severity of URS in some athletes. Preliminary studies on athletes prone to URS indicate a genetic predisposition to a pro-inflammatory response and a dysregulated anti-inflammatory cytokine response to intense exercise as a possible mechanism of respiratory inflammation. This review focuses on respiratory infections and inflammation in elite/professional athletes.

Prevalence of Sexually Transmitted Diseases and Risk Behaviors from the NIMH Collaborative HIV/STD Prevention Trial.

PubMed

Celentano, David D; Mayer, Kenneth H; Pequegnat, Willo; Abdala, Nadia; Green, Annette M; Handsfield, H Hunter; Hartwell, Tyler D

2010-01-01

This cross-sectional study describes the baseline prevalence and correlates of common bacterial and viral sexually transmitted diseases (STDs) and risk behaviors among individuals at high risk for HIV recruited in five low- and middle-income countries. Correlations of risk behaviors and demographic factors with prevalent STDs and the association of STDs with HIV prevalence are examined. Between 2,212 and 5,543 participants were recruited in each of five countries (China, India, Peru, Russia, and Zimbabwe). Standard protocols were used to collect behavioral risk information and biological samples for STD testing. Risk factors for HIV/STD prevalence were evaluated using logistic regression models. STD prevalence was significantly higher for women than men in all countries, and the most prevalent STD was Herpes simplex virus-type 2 (HSV-2). HIV prevalence was generally low (below 5%) except in Zimbabwe (30% among women, 11.7% among men). Prevalence of bacterial STDs was generally low (below 5% for gonorrhea and under 7% for syphilis in all sites), with the exception of syphilis among female sex workers in India. Behavioral and demographic risks for STDs varied widely across the five study sites. Common risks for STDs included female gender, increasing number of recent sex partners, and in some sites, older age, particularly for chronic STDs (i.e., HSV-2 and HIV). Prevalence of HIV was not associated with STDs except in Zimbabwe, which showed a modest correlation between HIV and HSV-2 prevalence (Pearson coefficient = .55). These findings underscore the heterogeneity of global STD and HIV epidemics and suggest that local, focused interventions are needed to achieve significant declines in these infections.

5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis.

PubMed

Pereira, Tiago Veiga; Rudnicki, Martina; Pereira, Alexandre Costa; Pombo-de-Oliveira, Maria S; Franco, Rendrik França

2006-10-01

There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies investigating an association between the C677T or A1298C polymorphisms and risk of ALL were included. We applied both fixed-effects and random-effects models to combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used to assess publication bias. The meta-analysis of the C677T polymorphism and risk of childhood ALL included 13 studies with a total of 4,894 individuals. Under a fixed-effects model, the TT genotype failed to be associated with a statistically significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI, 0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45; 95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was observed. No association between the A1298C variant and susceptibility to both adult and childhood ALL was disclosed. Our findings support the proposal that the common genetic C677T polymorphism in the MTHFR contributes to the risk of adult ALL, but not to the childhood ALL susceptibility.

The Common Risk Model for Dams: A Portfolio Approach to Security Risk Assessments

DTIC Science & Technology

2013-06-01

and threat estimates in a way that accounts for the relationships among these variables. The CRM -D can effectively quantify the benefits of...consequence, vulnerability, and threat estimates in a way that properly accounts for the relationships among these variables. The CRM -D can effectively...Common RiskModel ( CRM ) for evaluating and comparing risks associated with the nation’s critical infrastructure. This model incorporates commonly used risk

A review of electroencephalographic changes in diabetes mellitus in relation to major depressive disorder.

PubMed

Baskaran, Anusha; Milev, Roumen; McIntyre, Roger S

2013-01-01

A bidirectional relationship exists between diabetes mellitus (DM) and major depressive disorder (MDD), with depression commonly reported in both type 1 DM (T1DM) and type 2 DM (T2DM), and depressive symptoms associated with a higher incidence of diabetes. However, how the two conditions are pathologically connected is not completely understood. Similar neurophysiological abnormalities have been reported in both DM and MDD, including elevated electroencephalographic (EEG) activity in low-frequency slow waves and increased latency and/or reduced amplitude of event-related potentials. It is possible that this association reflects some common underlying pathology, and it has been proposed that diabetes may place patients at risk for depression through a biological mechanism linking the metabolic changes of DM to changes in the central nervous system. In this review we will discuss EEG abnormalities in DM, as well as the biological mechanisms underlying various EEG parameters, in order to evaluate whether or not a common EEG biosignature exists between DM and MDD. Identifying such commonalities could significantly inform the current understanding of the mechanisms that subserve the development of the two conditions. Moreover, this new insight may provide the basis for informing new drug discovery capable of mitigating and possibly even preventing both conditions.

Morbidity and mortality of women and men with intellectual and developmental disabilities newly initiating antipsychotic drugs.

PubMed

Vigod, Simone N; Lunsky, Yona; Cobigo, Virginie; Wilton, Andrew S; Somerton, Sarah; Seitz, Dallas P

2016-03-01

While up to 45% of individuals with intellectual and developmental disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are commonly prescribed, gender differences in the safety of antipsychotics have rarely been studied in this population. To compare men and women with IDD on medical outcomes after antipsychotic initiation. Our population-based study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly initiating antipsychotic medication on risk for diabetes mellitus, hypertension, venous thromboembolism, myocardial infarction, stroke and death, with up to 4 years of follow-up. Women were older and more medically complex at baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15-2.59) and death (HR 1.46, 95% CI 1.02-2.10) in crude analyses; but only thromboembolism risk was greater for women after covariate adjustment (aHR 1.58, 95% CI 1.05-2.38). Gender should be considered in decision-making around antipsychotic medications for individuals with IDD. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Colorectal Cancer and Alcohol Consumption—Populations to Molecules

PubMed Central

Rossi, Marco; Usman, Ahmad; Keshavarzian, Ali; Bishehsari, Faraz

2018-01-01

Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the third most common cancer diagnosed in both men and women in the world. Several environmental and habitual factors have been associated with the CRC risk. Alcohol intake, a common and rising habit of modern society, is one of the major risk factors for development of CRC. Here, we will summarize the evidence linking alcohol with colon carcinogenesis and possible underlying mechanisms. Some epidemiologic studies suggest that even moderate drinking increases the CRC risk. Metabolism of alcohol involves ethanol conversion to its metabolites that could exert carcinogenic effects in the colon. Production of ethanol metabolites can be affected by the colon microbiota, another recently recognized mediating factor to colon carcinogenesis. The generation of acetaldehyde and alcohol’s other metabolites leads to activation of cancer promoting cascades, such as DNA-adduct formation, oxidative stress and lipid peroxidation, epigenetic alterations, epithelial barrier dysfunction, and immune modulatory effects. Not only does alcohol induce its toxic effect through carcinogenic metabolites, but alcoholics themselves are predisposed to a poor diet, low in folate and fiber, and circadian disruption, which could further augment alcohol-induced colon carcinogenesis. PMID:29385712

Bilateral oblique facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk.

PubMed

Shanske, Alan L

2012-09-10

Congenital anomalies may be caused by genetic or environmental factors or a combination of both. Oblique facial clefts are very rare congenital deformities. The occurrence of facial clefts and an extremity anomaly suggests a common underlying cause. Lateral oro-ocular clefts do not occur along normal developmental planes and may be part of the amnion disruption complex sequence. Our objective was to report a case of this very event, which also followed an unusual intrauterine exposure and review the literature on the teratogenic risk of efavirenz. We report a case of amniotic rupture sequence after fetal HIV and antiretroviral exposure. Teratogenic exposure has been rarely reported and never after antiretroviral exposure. By reporting and registering more cases, we will be able to better assess the risks such medications pose to the developing fetus. The publication of a single case report has the potential to contribute to our knowledge of the significance of prenatal exposure to antiretrovirals and other medications for common HIV-associated disorders. It also generates a hypothesis that can be tested with further clinical data, animal models and epidemiologic studies.

Worldwide prevalence and risk factors for feline hyperthyroidism: A review.

PubMed

McLean, Joanne L; Lobetti, Remo G; Schoeman, Johan P

2014-11-14

Since first reported in the late 1970s, there has been a steady but dramatic increase in the worldwide prevalence of hyperthyroidism in cats. It is now regarded as the most common feline endocrine disorder, with diabetes mellitus coming a close second. Not only is there evidence for an increased worldwide prevalence of feline hyperthyroidism, but also for geographical variation in the prevalence of the disease. Despite its frequency, the underlying cause(s) of this common disease is or are not known, and therefore prevention of the disease is not possible. Due to the multiple risk factors that have been described for feline hyperthyroidism, however, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid-disruptor chemicals or goitrogens in food or water, acting together or in an additive fashion, may lead to euthyroid goitre and ultimately to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism. This review aims to summarise the available published evidence for the changes observed in the worldwide prevalence of the disease, as well as risk factors that may contribute to development of hyperthyroidism in susceptible cats.

Current and future role of genetic screening in gynecologic malignancies.

PubMed

Ring, Kari L; Garcia, Christine; Thomas, Martha H; Modesitt, Susan C

2017-11-01

The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic outcomes following childhood non-specific abdominal pain: a record-linkage study.

PubMed

Thornton, G C D; Goldacre, M J; Goldacre, R; Howarth, L J

2016-04-01

Non-specific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood. Our aim was to determine the risk of subsequent hospital diagnosis of organic and functional gastroenterological conditions following a diagnosis of NSAP, and to assess the persistence of this risk. An NSAP cohort of 268,623 children aged 0-16 years was constructed from linked English Hospital Episode Statistics from 1999 to 2011. The control cohort (1,684,923 children, 0-16 years old) comprised children hospitalised with unrelated conditions. Clinically relevant outcomes were selected and standardised rate ratios were calculated. From the NSAP cohort, 15,515 (5.8%) were later hospitalised with bowel pathology and 13,301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95% CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23 (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional disorder (unspecified) were significantly increased in all age groups except <2-year-olds. The risk of underlying bowel pathology remained raised up to 10 years after first diagnosis with NSAP. Only a small proportion of those with NSAP go on to be hospitalised with underlying bowel pathology. However, their risk is increased even at 10 years after the first hospital admission with NSAP. Diagnostic strategies need to be assessed and refined and active surveillance employed for children with NSAP. 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/

Real-data comparison of data mining methods in prediction of diabetes in iran.

PubMed

Tapak, Lily; Mahjub, Hossein; Hamidi, Omid; Poorolajal, Jalal

2013-09-01

Diabetes is one of the most common non-communicable diseases in developing countries. Early screening and diagnosis play an important role in effective prevention strategies. This study compared two traditional classification methods (logistic regression and Fisher linear discriminant analysis) and four machine-learning classifiers (neural networks, support vector machines, fuzzy c-mean, and random forests) to classify persons with and without diabetes. The data set used in this study included 6,500 subjects from the Iranian national non-communicable diseases risk factors surveillance obtained through a cross-sectional survey. The obtained sample was based on cluster sampling of the Iran population which was conducted in 2005-2009 to assess the prevalence of major non-communicable disease risk factors. Ten risk factors that are commonly associated with diabetes were selected to compare the performance of six classifiers in terms of sensitivity, specificity, total accuracy, and area under the receiver operating characteristic (ROC) curve criteria. Support vector machines showed the highest total accuracy (0.986) as well as area under the ROC (0.979). Also, this method showed high specificity (1.000) and sensitivity (0.820). All other methods produced total accuracy of more than 85%, but for all methods, the sensitivity values were very low (less than 0.350). The results of this study indicate that, in terms of sensitivity, specificity, and overall classification accuracy, the support vector machine model ranks first among all the classifiers tested in the prediction of diabetes. Therefore, this approach is a promising classifier for predicting diabetes, and it should be further investigated for the prediction of other diseases.

Prevention of non-contact anterior cruciate ligament injuries in soccer players. Part 1: Mechanisms of injury and underlying risk factors.

PubMed

Alentorn-Geli, Eduard; Myer, Gregory D; Silvers, Holly J; Samitier, Gonzalo; Romero, Daniel; Lázaro-Haro, Cristina; Cugat, Ramón

2009-07-01

Soccer is the most commonly played sport in the world, with an estimated 265 million active soccer players by 2006. Inherent to this sport is the higher risk of injury to the anterior cruciate ligament (ACL) relative to other sports. ACL injury causes the most time lost from competition in soccer which has influenced a strong research focus to determine the risk factors for injury. This research emphasis has afforded a rapid influx of literature defining potential modifiable and non-modifiable risk factors that increase the risk of injury. The purpose of the current review is to sequence the most recent literature that reports potential mechanisms and risk factors for non-contact ACL injury in soccer players. Most ACL tears in soccer players are non-contact in nature. Common playing situations precluding a non-contact ACL injury include: change of direction or cutting maneuvers combined with deceleration, landing from a jump in or near full extension, and pivoting with knee near full extension and a planted foot. The most common non-contact ACL injury mechanism include a deceleration task with high knee internal extension torque (with or without perturbation) combined with dynamic valgus rotation with the body weight shifted over the injured leg and the plantar surface of the foot fixed flat on the playing surface. Potential extrinsic non-contact ACL injury risk factors include: dry weather and surface, and artificial surface instead of natural grass. Commonly purported intrinsic risk factors include: generalized and specific knee joint laxity, small and narrow intercondylar notch width (ratio of notch width to the diameter and cross sectional area of the ACL), pre-ovulatory phase of menstrual cycle in females not using oral contraceptives, decreased relative (to quadriceps) hamstring strength and recruitment, muscular fatigue by altering neuromuscular control, decreased "core" strength and proprioception, low trunk, hip, and knee flexion angles, and high dorsiflexion of the ankle when performing sport tasks, lateral trunk displacement and hip adduction combined with increased knee abduction moments (dynamic knee valgus), and increased hip internal rotation and tibial external rotation with or without foot pronation. The identified mechanisms and risk factors for non-contact ACL injuries have been mainly studied in female soccer players; thus, further research in male players is warranted. Non-contact ACL injuries in soccer players likely has a multi-factorial etiology. The identification of those athletes at increased risk may be a salient first step before designing and implementing specific pre-season and in-season training programs aimed to modify the identified risk factors and to decrease ACL injury rates. Current evidence indicates that this crucial step to prevent ACL injury is the only option to effectively prevent the sequelae of osteoarthritis associated with this traumatic injury.

Medical comorbidity and late life depression: what is known and what are the unmet needs?

PubMed

Charlson, Mary; Peterson, Janey C

2002-08-01

Depression is an important problem in older patients with multiple medical problems, where the under-recognition and undertreatment of depression is especially common. A large number of studies assessing the relationship between depression and medical burden have focused on patients with cardiac disease, and recent research has focused on the role of depression as an independent risk factor for cardiac disease, mortality, and functional status in elderly patients. In particular, among coronary bypass surgery patients, depressive symptoms were found to occur most commonly in those with the highest comorbidity. In the treatment of depression in older adults, both pharmacologic and psychosocial interventions have shown promise, but such treatments need to be tested to determine whether mortality and functional status are affected. From a methodological perspective, new studies will need to control for comorbid disease, as many previous studies suggesting depression as a risk factor for mortality in cardiovascular patients have not consistently done so.

Preparation for Testing, Safe Packing and Shipping of Spent Nuclear Fuel from IFIN-HH, Bucharest-Magurele to Russian Federation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dragolici, C.A.; Zorliu, A.; Popa, V.

2007-07-01

The Russian Research Reactor Fuel Return (RRRFR) program is promoted by IAEA and DOE in order to repatriate of irradiated research reactor fuel originally supplied by Russia to facilities outside the country. Developed under the framework of the Global Threat Reduction Initiative (GTRI) the take-back program [1] common goal is to reduce both proliferation and security risks by eliminating or consolidating inventories of high-risk material. The main objective of this program is to support the return to Russian Federation of fresh or irradiated HEU and LEU fuel. Being part of this project, Romania is fulfilling its tasks by examining transportmore » and transfer cask options, assessment of transport routes, and providing cost estimates for required equipment and facility modifications. Spent Nuclear Fuel (SNF) testing, handling, packing and shipping are the most common interests on which the National Institute of Research and Development for Physics and Nuclear Engineering 'Horia Hulubei' (IFIN-HH) is focusing at the moment. (authors)« less

Ecohydrology of agroecosystems: probabilistic description of yield reduction risk under limited water availability

NASA Astrophysics Data System (ADS)

Vico, Giulia; Porporato, Amilcare

2013-04-01

Supplemental irrigation represents one of the main strategies to mitigate the effects of climate variability and stabilize yields. Irrigated agriculture currently provides 40% of food production and its relevance is expected to further increase in the near future, in face of the projected alterations of rainfall patterns and increase in food, fiber, and biofuel demand. Because of the significant investments and water requirements involved in irrigation, strategic choices are needed to preserve productivity and profitability, while maintaining a sustainable water management - a nontrivial task given the unpredictability of the rainfall forcing. To facilitate decision making under uncertainty, a widely applicable probabilistic framework is proposed. The occurrence of rainfall events and irrigation applications are linked probabilistically to crop development during the growing season and yields at harvest. Based on these linkages, the probability density function of yields and corresponding probability density function of required irrigation volumes, as well as the probability density function of yields under the most common case of limited water availability are obtained analytically, as a function of irrigation strategy, climate, soil and crop parameters. The full probabilistic description of the frequency of occurrence of yields and water requirements is a crucial tool for decision making under uncertainty, e.g., via expected utility analysis. Furthermore, the knowledge of the probability density function of yield allows us to quantify the yield reduction hydrologic risk. Two risk indices are defined and quantified: the long-term risk index, suitable for long-term irrigation strategy assessment and investment planning, and the real-time risk index, providing a rigorous probabilistic quantification of the emergence of drought conditions during a single growing season in an agricultural setting. Our approach employs relatively few parameters and is thus easily and broadly applicable to different crops and sites, under current and future climate scenarios. Hence, the proposed probabilistic framework provides a quantitative tool to assess the impact of irrigation strategy and water allocation on the risk of not meeting a certain target yield, thus guiding the optimal allocation of water resources for human and environmental needs.

Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis.

PubMed

Li, Chen; Yichao, Jin; Jiaxin, Lin; Yueting, Zhang; Qin, Lu; Tonghua, Yang

2015-01-01

Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42-4.36, p=0.001), but this did not apply in Caucasian populations. The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML.

Rethinking the Clinically Based Thresholds of TransCelerate BioPharma for Risk-Based Monitoring.

PubMed

Zink, Richard C; Dmitrienko, Anastasia; Dmitrienko, Alex

2018-01-01

The quality of data from clinical trials has received a great deal of attention in recent years. Of central importance is the need to protect the well-being of study participants and maintain the integrity of final analysis results. However, traditional approaches to assess data quality have come under increased scrutiny as providing little benefit for the substantial cost. Numerous regulatory guidance documents and industry position papers have described risk-based approaches to identify quality and safety issues. In particular, the position paper of TransCelerate BioPharma recommends defining risk thresholds to assess safety and quality risks based on past clinical experience. This exercise can be extremely time-consuming, and the resulting thresholds may only be relevant to a particular therapeutic area, patient or clinical site population. In addition, predefined thresholds cannot account for safety or quality issues where the underlying rate of observing a particular problem may change over the course of a clinical trial, and often do not consider varying patient exposure. In this manuscript, we appropriate rules commonly utilized for funnel plots to define a traffic-light system for risk indicators based on statistical criteria that consider the duration of patient follow-up. Further, we describe how these methods can be adapted to assess changing risk over time. Finally, we illustrate numerous graphical approaches to summarize and communicate risk, and discuss hybrid clinical-statistical approaches to allow for the assessment of risk at sites with low patient enrollment. We illustrate the aforementioned methodologies for a clinical trial in patients with schizophrenia. Funnel plots are a flexible graphical technique that can form the basis for a risk-based strategy to assess data integrity, while considering site sample size, patient exposure, and changing risk across time.

Probabilistic human health risk assessment of degradation-related chemical mixtures in heterogeneous aquifers: Risk statistics, hot spots, and preferential channels

NASA Astrophysics Data System (ADS)

Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

2015-06-01

The increasing presence of toxic chemicals released in the subsurface has led to a rapid growth of social concerns and the need to develop and employ models that can predict the impact of groundwater contamination on human health risk under uncertainty. Monitored natural attenuation is a common remediation action in many contamination cases. However, natural attenuation can lead to the production of daughter species of distinct toxicity that may pose challenges in pollution management strategies. The actual threat that these contaminants pose to human health depends on the interplay between the complex structure of the geological media and the toxicity of each pollutant byproduct. This work addresses human health risk for chemical mixtures resulting from the sequential degradation of a contaminant (such as a chlorinated solvent) under uncertainty through high-resolution three-dimensional numerical simulations. We systematically investigate the interaction between aquifer heterogeneity, flow connectivity, contaminant injection model, and chemical toxicity in the probabilistic characterization of health risk. We illustrate how chemical-specific travel times control the regime of the expected risk and its corresponding uncertainties. Results indicate conditions where preferential flow paths can favor the reduction of the overall risk of the chemical mixture. The overall human risk response to aquifer connectivity is shown to be nontrivial for multispecies transport. This nontriviality is a result of the interaction between aquifer heterogeneity and chemical toxicity. To quantify the joint effect of connectivity and toxicity in health risk, we propose a toxicity-based Damköhler number. Furthermore, we provide a statistical characterization in terms of low-order moments and the probability density function of the individual and total risks.

Computed tomography, magnetic resonance, and ultrasound imaging: basic principles, glossary of terms, and patient safety.

PubMed

Cogbill, Thomas H; Ziegelbein, Kurt J

2011-02-01

The basic principles underlying computed tomography, magnetic resonance, and ultrasound are reviewed to promote better understanding of the properties and appropriate applications of these 3 common imaging modalities. A glossary of frequently used terms for each technique is appended for convenience. Risks to patient safety including contrast-induced nephropathy, radiation-induced malignancy, and nephrogenic systemic fibrosis are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Incidence, prevalence and risk factors for post-surgical hypocalcaemia and hypoparathyroidism

PubMed Central

Edafe, Ovie

2017-01-01

Hypocalcaemia following thyroid surgery is common and is associated with significant short and long term morbidity. Damage to or devascularisation of parathyroid glands is the predominant underlying mechanism; although other factors such as hungry bone syndrome may occasionally contribute to it in the immediate post-operative period. The reported incidence of post-surgical hypocalcaemia and/or hypoparathyroidism (PoSH) varies significantly in the literature; the variation thought to be at least partly due to differences in the definitions used. Figures on the prevalence of chronic or long term post-surgical hypocalcaemia in the population are unclear. Risk factors for PoSH have been extensively studied in recent years and may be classified into patient, disease and surgery related factors. Some risk factors are modifiable; but both modifiable and non-modifiable factors help in generating a risk profile that may be used to select patients for preventative measures and/or changes in surgical strategy. This narrative review discusses recent literature on the incidence, prevalence and risk factors for PoSH. PMID:29322023

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

PubMed

Wray, Naomi R; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M; Abdellaoui, Abdel; Adams, Mark J; Agerbo, Esben; Air, Tracy M; Andlauer, Till M F; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan F T; Bigdeli, Tim B; Binder, Elisabeth B; Blackwood, Douglas R H; Bryois, Julien; Buttenschøn, Henriette N; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan I R; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E; Crowley, Cheynna A; Dashti, Hassan S; Davies, Gail; Deary, Ian J; Degenhardt, Franziska; Derks, Eske M; Direk, Nese; Dolan, Conor V; Dunn, Erin C; Eley, Thalia C; Eriksson, Nicholas; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K; Forstner, Andreas J; Frank, Josef; Gaspar, Héléna A; Gill, Michael; Giusti-Rodríguez, Paola; Goes, Fernando S; Gordon, Scott D; Grove, Jakob; Hall, Lynsey S; Hannon, Eilis; Hansen, Christine Søholm; Hansen, Thomas F; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M; Hu, Ming; Hyde, Craig L; Ising, Marcus; Jansen, Rick; Jin, Fulai; Jorgenson, Eric; Knowles, James A; Kohane, Isaac S; Kraft, Julia; Kretzschmar, Warren W; Krogh, Jesper; Kutalik, Zoltán; Lane, Jacqueline M; Li, Yihan; Li, Yun; Lind, Penelope A; Liu, Xiaoxiao; Lu, Leina; MacIntyre, Donald J; MacKinnon, Dean F; Maier, Robert M; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E; Mehta, Divya; Middeldorp, Christel M; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mill, Jonathan; Mondimore, Francis M; Montgomery, Grant W; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G; Nyholt, Dale R; O'Reilly, Paul F; Oskarsson, Hogni; Owen, Michael J; Painter, Jodie N; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E; Pettersson, Erik; Peyrot, Wouter J; Pistis, Giorgio; Posthuma, Danielle; Purcell, Shaun M; Quiroz, Jorge A; Qvist, Per; Rice, John P; Riley, Brien P; Rivera, Margarita; Saeed Mirza, Saira; Saxena, Richa; Schoevers, Robert; Schulte, Eva C; Shen, Ling; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Sinnamon, Grant B C; Smit, Johannes H; Smith, Daniel J; Stefansson, Hreinn; Steinberg, Stacy; Stockmeier, Craig A; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A; Thorgeirsson, Thorgeir E; Tian, Chao; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M; Viktorin, Alexander; Visscher, Peter M; Wang, Yunpeng; Webb, Bradley T; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Witt, Stephanie H; Wu, Yang; Xi, Hualin S; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T; Berger, Klaus; Boomsma, Dorret I; Cichon, Sven; Dannlowski, Udo; de Geus, E C J; DePaulo, J Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grabe, Hans J; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Kendler, Kenneth S; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S; Lucae, Susanne; Madden, Pamela F A; Magnusson, Patrik K; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Paciga, Sara A; Pedersen, Nancy L; Penninx, Brenda W J H; Perlis, Roy H; Porteous, David J; Potash, James B; Preisig, Martin; Rietschel, Marcella; Schaefer, Catherine; Schulze, Thomas G; Smoller, Jordan W; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M; Werge, Thomas; Winslow, Ashley R; Lewis, Cathryn M; Levinson, Douglas F; Breen, Gerome; Børglum, Anders D; Sullivan, Patrick F

2018-05-01

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child.

PubMed

Catalano, Patrick M; Shankar, Kartik

2017-02-08

Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Open Architecture Standard for NASA's Software-Defined Space Telecommunications Radio Systems

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Johnson, Sandra K.; Kacpura, Thomas J.; Hall, Charles S.; Smith, Carl R.; Liebetreu, John

2008-01-01

NASA is developing an architecture standard for software-defined radios used in space- and ground-based platforms to enable commonality among radio developments to enhance capability and services while reducing mission and programmatic risk. Transceivers (or transponders) with functionality primarily defined in software (e.g., firmware) have the ability to change their functional behavior through software alone. This radio architecture standard offers value by employing common waveform software interfaces, method of instantiation, operation, and testing among different compliant hardware and software products. These common interfaces within the architecture abstract application software from the underlying hardware to enable technology insertion independently at either the software or hardware layer. This paper presents the initial Space Telecommunications Radio System (STRS) Architecture for NASA missions to provide the desired software abstraction and flexibility while minimizing the resources necessary to support the architecture.

Mucormycosis in Australia: contemporary epidemiology and outcomes.

PubMed

Kennedy, K J; Daveson, K; Slavin, M A; van Hal, S J; Sorrell, T C; Lee, A; Marriott, D J; Chapman, B; Halliday, C L; Hajkowicz, K; Athan, E; Bak, N; Cheong, E; Heath, C H; Morrissey, C O; Kidd, S; Beresford, R; Blyth, C; Korman, T M; Robinson, J O; Meyer, W; Chen, S C-A

2016-09-01

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Common carotid artery intima-media thickness is as good as carotid intima-media thickness of all carotid artery segments in improving prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Nambi, Vijay; Chambless, Lloyd; He, Max; Folsom, Aaron R; Mosley, Tom; Boerwinkle, Eric; Ballantyne, Christie M

2012-01-01

Carotid intima-media thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intima-media thickness (CCA-IMT) is relatively more reliable and easier to measure. We evaluated whether CCA-IMT is comparable to A-CIMT when added to TRF and plaque information in improving CHD risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. Ten-year CHD risk prediction models using TRF alone, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque were developed for the overall cohort, men, and women. The area under the receiver operator characteristic curve (AUC), per cent individuals reclassified, net reclassification index (NRI), and model calibration by the Grønnesby-Borgan test were estimated. There were 1722 incident CHD events in 12 576 individuals over a mean follow-up of 15.2 years. The AUC for TRF only, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque models were 0.741, 0.754, and 0.753, respectively. Although there was some discordance when the CCA-IMT + plaque- and A-CIMT + plaque-based risk estimation was compared, the NRI and clinical NRI (NRI in the intermediate-risk group) when comparing the CIMT models with TRF-only model, per cent reclassified, and test for model calibration were not significantly different. Coronary heart disease risk prediction can be improved by adding A-CIMT + plaque or CCA-IMT + plaque information to TRF. Therefore, evaluating the carotid artery for plaque presence and measuring CCA-IMT, which is easier and more reliable than measuring A-CIMT, provide a good alternative to measuring A-CIMT for CHD risk prediction.

The Hip in Ice Hockey: A Current Concepts Review.

PubMed

Kuhn, Andrew W; Noonan, Benjamin C; Kelly, Bryan T; Larson, Christopher M; Bedi, Asheesh

2016-09-01

Ice hockey is a fast, physical sport with unique associated biomechanical demands often placing the hip in forced and repetitive supraphysiological ranges of motion. Ice hockey players commonly endure and are sidelined by nebulous groin injury or hip pain. Underlying causes can be chronic or acute and extra-articular, intra-articular, or "hip-mimicking." This article serves to review common hip-related injuries in ice hockey. For each, we define the particular condition; comment on risk factors and preventive strategies; discuss key historical, physical examination, and imaging findings; and finally, suggest nonoperative and/or operative treatment plans. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Stress--the battle for hearts and minds: links between depression, stress and ischemic heart disease.

PubMed

Korszun, Ania; Frenneaux, Michael P

2006-09-01

Depression and ischemic heart disease (IHD) are strongly related common disorders. Depression itself is an independent cardiac risk factor and is associated with a two- to threefold increase in IHD mortality. Attention has now shifted to identifying the common underlying mechanisms that could make individuals susceptible to both disorders. Abnormalities that have been implicated in this relationship include abnormal platelet activation, decreased baroreceptor sensitivity and endothelial dysfunction. Depression and IHD both have a high association with environmental stress, and depression is characterized by abnormalities of the stress-hormone axis. This review provides a brief overview of some recent developments in our understanding of the pathophysiological links between stress, depression and IHD.

From anomalies to forecasts: Toward a descriptive model of decisions under risk, under ambiguity, and from experience.

PubMed

Erev, Ido; Ert, Eyal; Plonsky, Ori; Cohen, Doron; Cohen, Oded

2017-07-01

Experimental studies of choice behavior document distinct, and sometimes contradictory, deviations from maximization. For example, people tend to overweight rare events in 1-shot decisions under risk, and to exhibit the opposite bias when they rely on past experience. The common explanations of these results assume that the contradicting anomalies reflect situation-specific processes that involve the weighting of subjective values and the use of simple heuristics. The current article analyzes 14 choice anomalies that have been described by different models, including the Allais, St. Petersburg, and Ellsberg paradoxes, and the reflection effect. Next, it uses a choice prediction competition methodology to clarify the interaction between the different anomalies. It focuses on decisions under risk (known payoff distributions) and under ambiguity (unknown probabilities), with and without feedback concerning the outcomes of past choices. The results demonstrate that it is not necessary to assume situation-specific processes. The distinct anomalies can be captured by assuming high sensitivity to the expected return and 4 additional tendencies: pessimism, bias toward equal weighting, sensitivity to payoff sign, and an effort to minimize the probability of immediate regret. Importantly, feedback increases sensitivity to probability of regret. Simple abstractions of these assumptions, variants of the model Best Estimate and Sampling Tools (BEAST), allow surprisingly accurate ex ante predictions of behavior. Unlike the popular models, BEAST does not assume subjective weighting functions or cognitive shortcuts. Rather, it assumes the use of sampling tools and reliance on small samples, in addition to the estimation of the expected values. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Bacterial Pneumonia in Older Adults.

PubMed

Henig, Oryan; Kaye, Keith S

2017-12-01

The incidence of pneumonia increases with age, and is particularly high in patients who reside in long-term care facilities (LTCFs). Mortality rates for pneumonia in older adults are high and have not decreased in the last decade. Atypical symptoms and exacerbation of underlying illnesses should trigger clinical suspicion of pneumonia. Risk factors for multidrug-resistant organisms are more common in older adults, particularly among LTCF residents, and should be considered when making empiric treatment decisions. Monitoring of clinical stability and underlying comorbid conditions, potential drug-drug interactions, and drug-related adverse events are important factors in managing elderly patients with pneumonia. Copyright © 2017 Elsevier Inc. All rights reserved.

Missing heritability and strategies for finding the underlying causes of complex disease

PubMed Central

Eichler, Evan E.; Flint, Jonathan; Gibson, Greg; Kong, Augustine; Leal, Suzanne M.; Moore, Jason H.; Nadeau, Joseph H.

2010-01-01

Although recent genome-wide studies have provided valuable insights into the genetic basis of human disease, they have explained relatively little of the heritability of most complex traits, and the variants identified through these studies have small effect sizes. This has led to the important and hotly debated issue of where the ‘missing heritability’ of complex diseases might be found. Here, seven leading geneticists offer their opinion about where this heritability is likely to lie, what this could tell us about the underlying genetic architecture of common diseases and how this could inform research strategies for uncovering genetic risk factors. PMID:20479774

Association between genetic risk scoring for schizophrenia and bipolar disorder with regional subcortical volumes.

PubMed

Caseras, X; Tansey, K E; Foley, S; Linden, D

2015-12-08

Previous research has shown coincident abnormal regional brain volume in patients with schizophrenia (SCZ) and bipolar disorder (BD) compared with controls. Whether these abnormalities are genetically driven or explained by secondary effects of the disorder or environmental factors is unknown. We aimed to investigate the association between genetic risk scoring (GRS) for SCZ and BD with volume of brain areas previously shown to be different between these clinical groups and healthy controls. We obtained subcortical brain volume measures and GRS for SCZ and BD from a sample of 274 healthy volunteers (71.4% females, mean age 24.7 (s.d. 6.9)). Volume of the globus pallidus was associated with the shared GRS between SCZ and BD, and also with the independent GRS for each of these disorders. Volume of the amygdala was associated with the non-shared GRS between SCZ and BD, and with the independent GRS for BD. Our results for volume of the globus pallidus support the idea of SCZ and BD sharing a common underlying neurobiological abnormality associated with a common genetic risk for both these disorders. Results for volume of the amygdala, though, would suggest the existence of a distinct mechanism only associated with genetic risk for BD. Finally, the lack of association between genetic risk and volume of most subcortical structures suggests that the volumetric differences reported in patient-control comparisons may not be genetically driven, but a consequence of the disorder or co-occurring environmental factors.

Environmental risk and toxicology of human and veterinary waste pharmaceutical exposure to wild aquatic host-parasite relationships.

PubMed

Morley, Neil J

2009-03-01

Pollution of the aquatic environment by human and veterinary waste pharmaceuticals is an increasing area of concern but little is known about their ecotoxicological effects on wildlife. In particular the interactions between pharmaceuticals and natural stressors of aquatic communities remains to be elucidated. A common natural stressor of freshwater and marine organisms are protozoan and metazoan parasites, which can have significant effects on host physiology and population structure, especially under the influence of many traditional kinds of toxic pollutants. However, little is known about the effects of waste pharmaceuticals to host-parasite dynamics. In order to assess the risk waste pharmaceuticals pose to aquatic wildlife it has been suggested the use of toxicological data derived from mammals during the product development of pharmaceuticals may be useful for predicting toxic effects. An additional similar source of information is the extensive clinical studies undertaken with numerous classes of drugs against parasites of human and veterinary importance. These studies may form the basis of preliminary risk assessments to aquatic populations and their interactions with parasitic diseases in pharmaceutical-exposed habitats. The present article reviews the effects of the most common classes of pharmaceutical medicines to host-parasite relationships and assesses the risk they may pose to wild aquatic organisms. In addition the effects of pharmaceutical mixtures, the importance of sewage treatment, and the risk of developing resistant strains of parasites are also assessed. Copyright © 2008 Elsevier B.V. All rights reserved.

Psychological Violence and Sexual Risk Behavior Among Predominantly African American Women.

PubMed

Ali, Bina; Mittal, Mona; Schroder, Allison; Ishman, Najah; Quinton, Sylvia; Boekeloo, Bradley

2017-07-01

Physical and sexual violence are commonly researched as risk factors for human immunodeficiency virus (HIV). However, psychological violence and its relationship with HIV risk behaviors have received limited attention among African American/Black (Black) women. This study examined (a) the frequency of recent (past 3 months) psychological violence, physical violence, and sexual violence and (b) the association of HIV risk behaviors, including unprotected sex, sex under the influence of alcohol/drugs, and sex exchange for money/drugs/shelter, with psychological violence. Participants included 191 women (89.2% Black), who were recruited through information sessions held at community centers, Parent Teacher Association meetings, substance use and HIV counseling centers, radio public service announcements, and word of mouth. Interested women participated in a multisession HIV and substance use prevention program and completed a self-reported assessment at program baseline. The current study utilized baseline data collected for a longitudinal study. Results from descriptive analysis indicated that the rate of psychological violence was higher than physical violence or sexual violence, and it was strongly associated with physical and sexual violence. Furthermore, hierarchical logistic regression analysis showed that unprotected sex was significantly associated with recent psychological violence after controlling for covariates. Findings suggest that recent psychological violence is more common than physical or sexual violence and it relates to sexual risk behaviors among Black women. Recent psychological violence may indicate psychosocial and sexual vulnerability for HIV and warrants particular attention among Black women.

Patterns of population differentiation and natural selection on the celiac disease background risk network.

PubMed

Sams, Aaron; Hawks, John

2013-01-01

Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

Improving Access to Mental Health Care by Delivering Psychotherapeutic Care in the Workplace: A Cross-Sectional Exploratory Trial.

PubMed

Rothermund, Eva; Kilian, Reinhold; Rottler, Edit; Mayer, Dorothea; Hölzer, Michael; Rieger, Monika A; Gündel, Harald

2017-01-01

Common mental disorders like mood and anxiety disorders and somatoform disorders have high costs, yet under-treatment is still frequent. Many people with common mental disorders are employed, so the workplace is potentially a suitable context in which to provide early treatment. Our study investigates whether a change of setting (workplace versus standard care) improves access to treatment for common mental disorders. Conditional latent profile analysis was applied to identify user profiles for work ability (WAI), clinical symptoms like depression (patient health questionnaire depression, PHQ-9), health-related quality of life (QoL, SF-12), and work-related stress (Maslach Burnout Inventory, irritation scale). Patients were recruited consecutively, via psychotherapeutic consultation in the workplace (n = 174) or psychotherapeutic consultation in outpatient care (n = 193). We identified four user profiles in our model: 'severe' (n = 99), 'moderate I-low QoL' (n = 88), 'moderate II-low work ability' (n = 83), and 'at risk' (n = 97). The 'at risk' profile encompassed individuals with reduced work ability (36.0, 34.73 to 37.37), only mild clinical symptoms (PHQ-9 5.7, 4.92 to 6.53), no signs of work-related stress and good quality of life. A higher proportion of the 'at risk' group than of the 'severe' group sought help via the psychotherapeutic consultation in the workplace (OR 0.287, P < 0.01); this effect remained after controlling for gender. Offering secondary mental health care in the workplace is feasible and accepted by users. Offering treatment in the workplace as an alternative to standard outpatient settings is a viable strategy for improving access to treatment for common mental disorders.

The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results.

PubMed

Ismail, Yasmin; Ismail, Abbas A; Ismail, Adel A A

2010-03-01

A major use of serum magnesium measurements in clinical practice is to identify patients with deficiency. However, numerous studies have shown that magnesium deficiency is common and may be present in over 10% of hospitalized patients, as well as in the general population. An important cause for under diagnosis of deficiency is that serum magnesium, the most commonly used test, can be normal despite negative body stores. This article focuses on the limitations of "normal" magnesium results and highlights the importance of lifestyle or "modus vivendi" as a pragmatic means of identifying those individuals potentially at risk for negative body magnesium stores. Researched peer reviewed articles on magnesium published between 1990 and 2008 in MEDLINE and EMBASE, using database keywords "magnesium, deficiency, diagnosis, treatment and hypomagnesaemia". Bibliographies of retrieved articles have been searched and followed. We have also performed a manual search of each individual issue in which most of these reports have appeared. In 183 peer reviewed studies published from 1990 to 2008, magnesium deficiency was associated with increased prevalence and risk in 11 major conditions. Similarly, in 68 studies performed over the same period, magnesium deficiency was found to predict adverse events and a decreased risk of pathology was noted when supplementation or treatment was instituted. The perception that "normal" serum magnesium excludes deficiency is common among clinicians. This perception is probably enforced by the common laboratory practice of highlighting only abnormal results. A health warning is therefore warranted regarding potential misuse of "normal" serum magnesium because restoration of magnesium stores in deficient patients is simple, tolerable, inexpensive and can be clinically beneficial.

Workplace violence against resident doctors in a tertiary care hospital in Delhi.

PubMed

Anand, Tanu; Grover, Shekhar; Kumar, Rajesh; Kumar, Madhan; Ingle, Gopal Krishna

2016-01-01

Healthcare workers particularly doctors are at high risk of being victims of verbal and physical violence perpetrated by patients or their relatives. There is a paucity of studies on work-related violence against doctors in India. We aimed to assess the exposure of workplace violence among doctors, its consequences among those who experienced it and its perceived risk factors. This study was done among doctors working in a tertiary care hospital in Delhi. Data were collected by using a self-administered questionnaire containing items for assessment of workplace violence against doctors, its consequences among those who were assaulted, reporting mechanisms and perceived risk factors. Of the 169 respondents, 104 (61.4%) were men. The mean (SD) age of the study group was 28.6 (4.2) years. Sixty-nine doctors (40.8%) reported being exposed to violence at their workplace in the past 12 months. However, there was no gender-wise difference in the exposure to violence (p=0.86). The point of delivery of emergency services was reported as the most common place for experiencing violence. Verbal abuse was the most common form of violence reported (n=52; 75.4%). Anger, frustration and irritability were the most common symptoms experienced by the doctors who were subjected to violence at the workplace. Only 44.2% of doctors reported the event to the authorities. 'Poor communication skills' was considered to be the most common physician factor responsible for workplace violence against doctors. A large proportion of doctors are victims of violence by their patients or relatives. Violence is being under-reported. There is a need to encourage reporting of violence and prepare healthcare facilities to tackle this emerging issue for the safety of physicians.

Parent driver characteristics associated with sub-optimal restraint of child passengers.

PubMed

Winston, Flaura K; Chen, Irene G; Smith, Rebecca; Elliott, Michael R

2006-12-01

To identify parent driver demographic and socioeconomic characteristics associated with the use of sub-optimal restraints for child passengers under nine years. Cross-sectional study using in-depth, validated telephone interviews with parent drivers in a probability sample of 3,818 vehicle crashes involving 5,146 children. Sub-optimal restraint was defined as use of forward-facing child safety seats for infants under one or weighing under 20 lbs, and any seat-belt use for children under 9. Sub-optimal restraint was more common among children under one and between four and eight years than among children aged one to three years (18%, 65%, and 5%, respectively). For children under nine, independent risk factors for sub-optimal restraint were: non-Hispanic black parent drivers (with non-Hispanic white parents as reference, adjusted relative risk, adjusted RR = 1.24, 95% CI: 1.09-1.41); less educated parents (with college graduate or above as reference: high school, adjusted RR = 1.27, 95% CI: 1.12-1.44; less than high school graduate, adjusted RR = 1.36, 95% CI: 1.13-1.63); and lower family income (with $50,000 or more as reference: <$20,000, adjusted RR = 1.23, 95% CI: 1.07-1.40). Multivariate analysis revealed the following independent risk factors for sub-optimal restraint among four-to-eight-year-olds: older parent age, limited education, black race, and income below $20,000. Parents with low educational levels or of non-Hispanic black background may require additional anticipatory guidance regarding child passenger safety. The importance of poverty in predicting sub-optimal restraint underscores the importance of child restraint and booster seat disbursement and education programs, potentially through Medicaid.

Driving under the influence behaviours among high school students who mix alcohol with energy drinks.

PubMed

Wilson, Maria N; Cumming, Tammy; Burkhalter, Robin; Langille, Donald B; Ogilvie, Rachel; Asbridge, Mark

2018-06-01

Alcohol and energy drinks are commonly used substances by youth in Canada, and are often mixed (AmED). While several studies have shown that AmED can have dangerous effects, less well understood is how AmED is associated with driving under the influence of either alcohol or drugs. This study sought to determine whether youth who use AmED were more likely to engage in driving, or being a passenger of a driver, under the influence of alcohol or cannabis compared to youth who use either alcohol or energy drinks alone. This study used data from grade 10-12 students who took part in the 2014/2015 Canadian Student Tobacco, Alcohol and Drugs Survey (N=17,450). The association of past-year AmED use with past-30day: driving under the influence of alcohol or cannabis, and riding with an alcohol- or cannabis-influenced driver, was assessed using logistic regression. One in four youth had consumed AmED in the previous 12months. AmED users were more likely to engage in all risk behaviours except riding with a drinking driver, relative to youth who only consumed alcohol. No association was observed for youth who consumed alcohol and energy drinks on separate occasions. Youth who use AmED demonstrate a higher risk profile for driving under the influence of alcohol or cannabis, than youth who use alcohol alone. Future research should explore the biopsychosocial pathways that may explain why using energy drinks enhances the already heightened risk posed by alcohol on other health-related behaviours such as driving under the influence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Injury patterns of child abuse: Experience of two Level 1 pediatric trauma centers.

PubMed

Yu, Yangyang R; DeMello, Annalyn S; Greeley, Christopher S; Cox, Charles S; Naik-Mathuria, Bindi J; Wesson, David E

2018-05-01

This study examines non-accidental trauma (NAT) fatalities as a percentage of all injury fatalities and identifies injury patterns in NAT admissions to two level 1 pediatric trauma centers. We reviewed all children (<5years old) treated for NAT from 2011 to 2015. Patient demographics, injury sites, and survival were obtained from both institutional trauma registries. Of 4623 trauma admissions, 557 (12%) were due to NAT. However, 43 (46%) of 93 overall trauma fatalities were due to NAT. Head injuries were the most common injuries sustained (60%) and led to the greatest increased risk of death (RR 5.1, 95% CI 2.0-12.7). Less common injuries that increased the risk of death were facial injuries (14%, RR 2.9, 95% CI 1.6-5.3), abdominal injuries (8%, RR 2.8, 95% CI 1.4-5.6), and spinal injuries (3%, RR 3.9, 95% CI 1.8-8.8). Although 76% of head injuries occurred in infants <1year, children ages 1-4years old with head injuries had a significantly higher case fatality rate (27% vs. 6%, p<0.001). Child abuse accounts for a large proportion of trauma fatalities in children under 5years of age. Intracranial injuries are common in child abuse and increase the risk of death substantially. Preventing NAT in infants and young children should be a public health priority. Retrospective Review. II. Copyright © 2018. Published by Elsevier Inc.

Developmental effects of antiepileptic drugs and the need for improved regulations

PubMed Central

Loring, David W.

2016-01-01

Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis. PMID:26519545

Psoriasis as a cardiovascular risk factor: updates and algorithmic approach.

PubMed

Cozzani, Emanuele; Rosa, Gianmarco; Burlando, Martina; Parodi, Aurora

2018-04-19

Although psoriasis is predominantly a chronic inflammatory skin disorder, it has been known to be associated with cardiovascular disease. Patients with psoriasis, particularly with moderate to severe forms, present an increased rate of cardiovascular mortality, myocardial infarction and stroke. However the pathophysiology of the relationship between psoriasis and cardiovascular risk and comorbidities has not yet completely known. Chronic inflammation may be considered a solid link between psoriasis and related cardiovascular events. Several cytokines and inflammatory cells play a pivotal role in the development of psoriatic lesions, resulting in angiogenesis and endothelial dysfunction. Furthermore, the imbalance between oxidative stress and anti-oxidant mechanisms in psoriatic patients may contribute to explain the pathogenesis of increased reactive oxygen species and the formation of atherosclerotic plaque. Other mechanistic pathways which may be involved in this relationship include cardiovascular effects of medications, a common genetic background and a higher prevalence of cardiovascular risk factors, which are often under-diagnosed and under-treated in psoriatic patients. Indeed, the early detection of specific markers of cardiovascular impairment, such as N-terminal pro B-type natriuretic peptide, homocysteine and YKL-40, may enable psoriatic patients at higher cardiovascular risk to be identified as soon as possible. This review examines the increased cardiovascular risk profile and high prevalence of cardiovascular disease associated with psoriasis, focusing on pathogenic links between psoriasis and atherosclerosis, serological markers of cardiovascular involvement and the implications of anti-psoriatic therapies on cardiovascular risk and proposes a flow chart, that every dermatologist should follow to screen psoriatic patients.

Risk factors associated with unintentional house fire incidents, injuries and deaths in high-income countries: a systematic review.

PubMed

Turner, Samantha L; Johnson, Rhodri D; Weightman, Alison L; Rodgers, Sarah E; Arthur, Geri; Bailey, Rowena; Lyons, Ronan A

2017-04-01

To identify the distinguishing risk factors associated with unintentional house fire incidents, injuries and deaths. Systematic review. A range of bibliographical databases and grey literature were searched from their earliest records to January 2016. To ensure the magnitude of risk could be quantified, only those study types which contained a control group, and undertook appropriate statistical analyses were included. A best evidence synthesis was conducted instead of a meta-analysis due to study heterogeneity. Eleven studies investigating a variety of risk factors and outcomes were identified. Studies ranged from medium to low quality with no high quality studies identified. Characteristics commonly associated with increased risk of house fire incidents, injuries and fatalities included: higher numbers of residents, male, children under the age of 5 years, non-working households, smoking, low income, non-privately owned properties, apartments and buildings in poor condition. Several risk factors were only associated with one outcome (eg, living alone was only associated with increased risk of injurious fires), and households with older residents were at increased risk of injurious fires, but significantly less likely to experience a house fire in the first place. This best evidence synthesis indicates that several resident and property characteristics are associated with risk of experiencing house fire incidents, injuries or death. These findings should be considered by the Fire and Rescue Services and others with a role in fire prevention. Future research should adopt robust, standardised study designs to permit meta-analyses and enable stronger conclusions to be drawn. 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/.

Positive Traits in the Bipolar Spectrum: The Space between Madness and Genius

PubMed Central

Greenwood, Tiffany A.

2017-01-01

Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment. Creativity is a complex, multidimensional construct with both cognitive and affective components, many of which appear to reflect a shared genetic vulnerability with bipolar disorder. It is suggested that a subset of bipolar risk variants confer advantages as positive traits according to an inverted-U-shaped curve with clinically unaffected allele carriers benefitting from the positive traits and serving to maintain the risk alleles in the population. The association of risk genes with creativity in healthy individuals (e.g., NRG1), as well as an overall sharing of common genetic variation between bipolar patients and creative individuals, provides support for this model. Current findings are summarized from a multidisciplinary perspective to demonstrate the feasibility of research in this area to reveal the mechanisms underlying illness. PMID:28277566

Association of common variants in JAK2 gene with reduced risk of metabolic syndrome and related disorders

PubMed Central

2011-01-01

Background Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects. Methods A total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis. Results rs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis. Conclusions It was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling. PMID:22185674

Risk assessment of pesticides and other stressors in bees: Principles, data gaps and perspectives from the European Food Safety Authority.

PubMed

Rortais, Agnès; Arnold, Gérard; Dorne, Jean-Lou; More, Simon J; Sperandio, Giorgio; Streissl, Franz; Szentes, Csaba; Verdonck, Frank

2017-06-01

Current approaches to risk assessment in bees do not take into account co-exposures from multiple stressors. The European Food Safety Authority (EFSA) is deploying resources and efforts to move towards a holistic risk assessment approach of multiple stressors in bees. This paper describes the general principles of pesticide risk assessment in bees, including recent developments at EFSA dealing with risk assessment of single and multiple pesticide residues and biological hazards. The EFSA Guidance Document on the risk assessment of plant protection products in bees highlights the need for the inclusion of an uncertainty analysis, other routes of exposures and multiple stressors such as chemical mixtures and biological agents. The EFSA risk assessment on the survival, spread and establishment of the small hive beetle, Aethina tumida, an invasive alien species, is provided with potential insights for other bee pests such as the Asian hornet, Vespa velutina. Furthermore, data gaps are identified at each step of the risk assessment, and recommendations are made for future research that could be supported under the framework of Horizon 2020. Finally, the recent work conducted at EFSA is presented, under the overarching MUST-B project ("EU efforts towards the development of a holistic approach for the risk assessment on MUltiple STressors in Bees") comprising a toolbox for harmonised data collection under field conditions and a mechanistic model to assess effects from pesticides and other stressors such as biological agents and beekeeping management practices, at the colony level and in a spatially complex landscape. Future perspectives at EFSA include the development of a data model to collate high quality data to calibrate and validate the model to be used as a regulatory tool. Finally, the evidence collected within the framework of MUST-B will support EFSA's activities on the development of a holistic approach to the risk assessment of multiple stressors in bees. In conclusion, EFSA calls for collaborative action at the EU level to establish a common and open access database to serve multiple purposes and different stakeholders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Physicians' fears of malpractice lawsuits are not assuaged by tort reforms.

PubMed

Carrier, Emily R; Reschovsky, James D; Mello, Michelle M; Mayrell, Ralph C; Katz, David

2010-09-01

Physicians contend that the threat of malpractice lawsuits forces them to practice defensive medicine, which in turn raises the cost of health care. This argument underlies efforts to change malpractice laws through legislative tort reform. We evaluated physicians' perceptions about malpractice claims in states where more objective indicators of malpractice risk, such as malpractice premiums, varied considerably. We found high levels of malpractice concern among both generalists and specialists in states where objective measures of malpractice risk were low. We also found relatively modest differences in physicians' concerns across states with and without common tort reforms. These results suggest that many policies aimed at controlling malpractice costs may have a limited effect on physicians' malpractice concerns.

Trade Study of Multiple Thruster Options for the Mars Airplane Concept

NASA Technical Reports Server (NTRS)

Kuhl, Christopher A.; Gayle, Steven W.; Hunter, Craig A.; Kenney, Patrick S.; Scola, Salvatore; Paddock, David A.; Wright, Henry S.; Gasbarre, Joseph F.

2009-01-01

A trade study was performed at NASA Langley Research Center under the Planetary Airplane Risk Reduction (PARR) project (2004-2005) to examine the option of using multiple, smaller thrusters in place of a single large thruster on the Mars airplane concept with the goal to reduce overall cost, schedule, and technical risk. The 5-lbf (22N) thruster is a common reaction control thruster on many satellites. Thousands of these types of thrusters have been built and flown on numerous programs, including MILSTAR and Intelsat VI. This study has examined the use of three 22N thrusters for the Mars airplane propulsion system and compared the results to those of the baseline single thruster system.

Fifty years of stroke researches in India

PubMed Central

Banerjee, Tapas Kumar; Das, Shyamal Kumar

2016-01-01

Currently, the stroke incidence in India is much higher than Western industrialized countries. Large vessel intracranial atherosclerosis is the commonest cause of ischemic stroke in India. The common risk factors, that is, hypertension, diabetes, smoking, and dyslipidemia are quite prevalent and inadequately controlled; mainly because of poor public awareness and inadequate infrastructure. Only a small number of ischemic stroke cases are able to have the benefit of thrombolytic therapy. Benefits from stem cell therapy in established stroke cases are under evaluation. Presently, prevention of stroke is the best option considering the Indian scenario through control and/or avoiding risk factors of stroke. Interventional studies are an important need for this scenario. PMID:27011621

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies

PubMed Central

Chawla, Anita J; Mytelka, Daniel S; McBride, Stephan D; Nellesen, Dave; Elkins, Benjamin R; Ball, Daniel E; Kalsekar, Anupama; Towse, Adrian; Garrison, Louis P

2014-01-01

Purpose To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. Methods We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. Results The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was −1.80 million LYs, attributable to delayed access to diabetes therapies (−0.18 million LYs) and fewer drugs (−1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. Conclusion The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or forgone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24892175

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies.

PubMed

Chawla, Anita J; Mytelka, Daniel S; McBride, Stephan D; Nellesen, Dave; Elkins, Benjamin R; Ball, Daniel E; Kalsekar, Anupama; Towse, Adrian; Garrison, Louis P

2014-03-01

To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result. Copyright © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Suicide and sleep: Is it a bad thing to be awake when reason sleeps?

PubMed

Perlis, Michael L; Grandner, Michael A; Chakravorty, Subhajit; Bernert, Rebecca A; Brown, Gregory K; Thase, Michael E

2016-10-01

Suicide is the second leading cause of death, worldwide, for those between the ages of 24 and 44 y old. In 2013, more than 41,000 suicides occurred in the United States. These statistics underscore the need to 1) understand why people die by suicide and 2) identify risk factors that are potentially modifiable. While it has been posited that sleep disturbance may represent one such factor, systematic research in this arena did not begin until the 2000s. Since that time, sleep disturbance has been reliably identified as a risk factor for suicidal ideation, suicide attempts, and suicide. While insomnia, nightmares, and other sleep disorders have each been found to contribute to the risk for suicidal ideation and behavior, it is also possible that these factors share some common variance. One possibility is that sleep disturbance results in being awake at night, and being awake at night also confers risk. The hypothesis proffered here is that being awake when one is not biologically prepared to be so results in "hypofrontality" and diminished executive function, and that this represents a common pathway to suicidal ideation and behavior. Such a proposition is highly testable under a variety of possible protocols. The current review summarizes the extant literature on suicide rates by time-of-day, and discusses circadian, psychosocial, and neurocognitive explanations of risk. Such a focus promises to enhance our understanding of how sleep disturbance may confer risk, allows for the identification of future lines of research, and further justifies the need for interventions that promote good sleep continuity among at-risk individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fall Risk Assessment Tools for Elderly Living in the Community: Can We Do Better?

PubMed

Palumbo, Pierpaolo; Palmerini, Luca; Bandinelli, Stefania; Chiari, Lorenzo

2015-01-01

Falls are a common, serious threat to the health and self-confidence of the elderly. Assessment of fall risk is an important aspect of effective fall prevention programs. In order to test whether it is possible to outperform current prognostic tools for falls, we analyzed 1010 variables pertaining to mobility collected from 976 elderly subjects (InCHIANTI study). We trained and validated a data-driven model that issues probabilistic predictions about future falls. We benchmarked the model against other fall risk indicators: history of falls, gait speed, Short Physical Performance Battery (Guralnik et al. 1994), and the literature-based fall risk assessment tool FRAT-up (Cattelani et al. 2015). Parsimony in the number of variables included in a tool is often considered a proxy for ease of administration. We studied how constraints on the number of variables affect predictive accuracy. The proposed model and FRAT-up both attained the same discriminative ability; the area under the Receiver Operating Characteristic (ROC) curve (AUC) for multiple falls was 0.71. They outperformed the other risk scores, which reported AUCs for multiple falls between 0.64 and 0.65. Thus, it appears that both data-driven and literature-based approaches are better at estimating fall risk than commonly used fall risk indicators. The accuracy-parsimony analysis revealed that tools with a small number of predictors (~1-5) were suboptimal. Increasing the number of variables improved the predictive accuracy, reaching a plateau at ~20-30, which we can consider as the best trade-off between accuracy and parsimony. Obtaining the values of these ~20-30 variables does not compromise usability, since they are usually available in comprehensive geriatric assessments.

A long-term comparative assessment of human health risk to leachate-contaminated groundwater from heavy metal with different liner systems.

PubMed

Mishra, Harshit; Karmakar, Subhankar; Kumar, Rakesh; Kadambala, Praneeth

2018-01-01

The handling and management of municipal solid waste (MSW) are major challenges for solid waste management in developing countries. Open dumping is still the most common waste disposal method in India. However, landfilling also causes various environmental, social, and human health impacts. The generation of heavily polluted leachate is a major concern to public health. Engineered barrier systems (EBSs) are commonly used to restrict potentially harmful wastes by preventing the leachate percolation to groundwater and overflow to surface water bodies. The EBSs are made of natural (e.g., soil, clay) and/or synthetic materials such as polymeric materials (e.g., geomembranes, geosynthetic clay liners) by arranging them in layers. Various studies have estimated the human health risk from leachate-contaminated groundwater. However, no studies have been reported to compare the human health risks, particularly due to the leachate contamination with different liner systems. The present study endeavors to quantify the human health risk to contamination from MSW landfill leachate using multiple simulations for various EBSs. To quantify the variation in health risks to groundwater consumption to the child and adult populations, the Turbhe landfill of Navi Mumbai in India has been selected. The leachate and groundwater samples were collected continuously throughout January-September in 2015 from the landfill site, and heavy metal concentrations were analyzed using an inductively coupled plasma system. The LandSim 2.5 Model, a landfill simulator, was used to simulate the landfill activities for various time slices, and non-carcinogenic human health risk was determined for selected heavy metals. Further, the uncertainties associated with multiple input parameters in the health risk model were quantified under a Monte Carlo simulation framework.

Suicide and sleep: Is it a bad thing to be awake when reason sleeps?

PubMed Central

Perlis, Michael L.; Grandner, Michael A.; Chakravorty, Subhajit; Bernert, Rebecca A.; Brown, Gregory K.; Thase, Michael E.

2016-01-01

Suicide is the second leading cause of death, worldwide, for those between the ages of 24 and 44 y old. In 2013, more than 41,000 suicides occurred in the United States. These statistics underscore the need to 1) understand why people die by suicide and 2) identify risk factors that are potentially modifiable. While it has been posited that sleep disturbance may represent one such factor, systematic research in this arena did not begin until the 2000s. Since that time, sleep disturbance has been reliably identified as a risk factor for suicidal ideation, suicide attempts, and suicide. While insomnia, nightmares, and other sleep disorders have each been found to contribute to the risk for suicidal ideation and behavior, it is also possible that these factors share some common variance. One possibility is that sleep disturbance results in being awake at night, and being awake at night also confers risk. The hypothesis proffered here is that being awake when one is not biologically prepared to be so results in “hypofrontality” and diminished executive function, and that this represents a common pathway to suicidal ideation and behavior. Such a proposition is highly testable under a variety of possible protocols. The current review summarizes the extant literature on suicide rates by time-of-day, and discusses circadian, psychosocial, and neuro-cognitive explanations of risk. Such a focus promises to enhance our understanding of how sleep disturbance may confer risk, allows for the identification of future lines of research, and further justifies the need for interventions that promote good sleep continuity among at-risk individuals. PMID:26706755

[Classical cardiovascular risk factors: predictive value and treatment of the elderly. The rocky road to evidence-based medicine].

PubMed

Thomas, H P

2001-04-01

Coronary heart disease and cerebrovascular disease are still the most common causes of death in Western countries. A number of risk factors have been identified in young and middle-aged adults, such as dyslipidemia, hypertension and diabetes. Their prevalence and importance, however, are less clear in the elderly. In terms of dyslipedemia it is questionable whether hypercholesterolemia is a definite risk factor. On the other hand, mortality can be reduced by lowering LDL cholesterol, but the benefit in the oldest old is not yet known. Systolic blood pressure rises with age and is discussed controversely as a potential risk factor in the elderly. Some large trials could show a clear relationship between high blood pressure while others did not see any association. Similar to the treatment of hypercholesterolemia, antihypertensive drugs showed beneficial effects in elderly people until the age of 80. But the treatment of the oldest old cannot be recommended in general. Diabetes and impaired glucose tolerance are some of the most common diseases in elderly people. They are considered to be an important risk factor until the age of 75. Their role in the oldest old is still under debate. Until now, we do not know anything about possible treatment effects because of the lack of controlled trials. Elderly people seem to have a risk profile different from younger people; especially in extreme ages the predictive role of classical risk factors is unclear. On the other hand, drug treatment could reduce mortality and morbidity in patients with hypercholesterolemia or hypertension. There are no studies which investigated the effects of blood glucose control in the elderly. The collection of sufficient data is a geriatric challange in order to decide whether treatment is useful or not.

Low plasma eicosapentaenoic acid concentration as a possible risk factor for intracerebral hemorrhage.

PubMed

Ikeya, Yoshimori; Fukuyama, Naoto; Mori, Hidezo

2015-03-01

N-3 fatty acids, including eicosapentaenoic acid (EPA), prevent ischemic stroke. The preventive effect has been attributed to an antithrombic effect induced by elevated EPA and reduced arachidonic acid (AA) levels. However, the relationship between intracranial hemorrhage and N-3 fatty acids has not yet been elucidated. In this cross-sectional study, we compared common clinical and lifestyle parameters between 70 patients with intracranial hemorrhages and 66 control subjects. The parameters included blood chemistry data, smoking, alcohol intake, fish consumption, and the incidences of underlying diseases. The comparisons were performed using the Mann-Whitney U test followed by multiple logistic regression analysis. Nonparametric tests revealed that the 70 patients with intracerebral hemorrhages exhibited significantly higher diastolic blood pressures and alcohol intakes and lower body mass indices, high-density lipoprotein (HDL) cholesterol levels, EPA concentrations, EPA/AA ratios, and vegetable consumption compared with the 66 control subjects. A multiple logistic regression analysis revealed that higher diastolic blood pressure and alcohol intake and lower body mass index, HDL cholesterol, EPA/AA ratio, and vegetable consumption were relative risk factors for intracerebral hemorrhage. High HDL cholesterol was a common risk factor in both of the sex-segregated subgroups and the <65-year-old subgroup. However, neither EPA nor the EPA/AA ratio was a risk factor in these subgroups. Eicosapentaenoic acid was relative risk factor only in the ≥65-year-old subgroup. Rather than higher EPA levels, lower EPA concentrations and EPA/AA ratios were found to be risk factors for intracerebral hemorrhage in addition to previously known risk factors such as blood pressure, alcohol consumption, and lifestyle. Copyright © 2015 Elsevier Inc. All rights reserved.

Familial Hypercholesterolaemia in the Era of Genetic Testing.

PubMed

Hughes, D P; Viljoen, A; Wierzbicki, A S

2016-05-01

Familial hypercholesterolaemia (FH) is a relatively common autosomal dominant genetic condition leading to premature ischaemic vascular disease and mortality if left untreated. Currently, a universal consensus on the diagnostic criteria of FH does not exist but the diagnosis of FH largely relies on the evaluation of low density lipoprotein-cholesterol (LDL-C) levels, a careful documentation of family history, and the identification of clinical features. Diagnosis based purely on lipid levels remains common but there are several limitations to this method of diagnosis both practically and in the proportion of false-negatives and false-positives detected, resulting in substantial under-diagnosis of FH. In some countries, diagnostic algorithms are supplemented with genetic testing of the index case as well as genetic and lipid testing of relatives of the index case. Such "cascade" screening of families following identification of index cases appears to not only improve the rate of diagnosis but is also cost-effective. Currently, we observe a great variation in the excess mortality among patients with FH, which likely reflects a combination of additional genetic and environmental effects on risk overlaid on the risk associated with FH. Current accepted drug therapies for FH include statins and PSCK9 inhibitors. Further work is required to evaluate the cardiovascular disease risk in patients with genetically diagnosed FH and to determine whether a risk-based approach to the treatment of FH is appropriate.

Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management.

PubMed

Zantomio, D; Grigg, A P; MacGregor, L; Panek-Hudson, Y; Szer, J; Ayton, R

2006-10-01

Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and co-morbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

Current Management of NAFLD

PubMed Central

MUNTEANU, MIHAI ALEXANDRU; NAGY, GEORGIANA ANCA; MIRCEA, PETRU ADRIAN

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. It affects about 1 billion individuals worldwide. While people with simple steatosis have no higher risk of death than the general population, people with non-alcoholic steatohepatitis are at increased risk of death compared to general population. Current management for NAFLD includes diet and lifestyle changes, management of underlying metabolic risk factors and pharmacological therapies. The objective of therapy is to prevent the complications. The problem with dietary and lifestyle interventions is that they are hard to implement. Compliance is the key. Until now, there is still no approved drug for the treatment of NAFLD. Insulin resistance is the main target of pharmacological therapy, but the question that we ask ourselves as physicians is who should receive medical treatment among NAFLD patients and for how long. PMID:27004021

Sleep patterns and the risk for unipolar depression: a review

PubMed Central

Wiebe, Sabrina T; Cassoff, Jamie; Gruber, Reut

2012-01-01

Psychological disorders, particularly mood disorders, such as unipolar depression, are often accompanied by comorbid sleep disturbances, such as insomnia, restless sleep, and restricted sleep duration. The nature of the relationship between unipolar depression and these sleep disturbances remains unclear, as sleep disturbance may be a risk factor for development, an initial manifestation of the disorder, or a comorbid condition affected by similar mechanisms. Various studies have examined the impact of sleep deprivation on the presence of (or exacerbation of) depressive symptoms, and have examined longitudinal and concurrent associations between different sleep disturbances and unipolar depression. This review examines the evidence for sleep disturbances as a risk factor for the development and presence of depression, as well as examining common underlying mechanisms. Clinical implications pertaining to the comorbid nature of various sleep patterns and depression are considered. PMID:23620679

Diet components can suppress inflammation and reduce cancer risk.

PubMed

Hardman, W Elaine

2014-06-01

Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.

Diet components can suppress inflammation and reduce cancer risk

PubMed Central

2014-01-01

Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases. PMID:24944766

Relative impacts of mitigation, temperature, and precipitation on 21st-Century megadrought risk in the American Southwest.

NASA Astrophysics Data System (ADS)

Ault, T.; Mankin, J. S.; Cook, B.; Smerdon, J. E.

2016-12-01

Megadroughts are comparable in severity to the worst droughts of the 20th Century, but of much longer duration. A megadrought in the American Southwest would impose unprecedented stress on the limited water resources of the area, making it critical to evaluate future risks under different climate change mitigation scenarios, as well as for different aspects of regional hydroclimate. We find changes in the mean hydroclimate state, rather than its variability, determine megadrought risk in the American Southwest. Estimates of megadrought probability based on precipitation alone tend to underestimate risk. Furthermore, business-as-usual emissions of greenhouse gases will drive regional warming and drying, despite the high uncertainty regarding precipitation. We find regional temperature increases alone push megadrought risk above 70%, 90%, or 99% by the end of the century, even if precipitation increases moderately, does not change, or decreases, respectively. While each outcome is supported by some climate models, the latter is the most common projection for the American Southwest. An aggressive reduction in global greenhouse gas emissions cuts these risks nearly in half.

A hidden curriculum: gambling and problem gambling among high school students in Auckland.

PubMed

Sullivan, Sean

2005-12-01

Participation in gambling by young people aged 13-18 years. During 2001, prior to the passing of legislation to minimise gambling harm, more than 500 students from six high schools completed a survey of their participation in gambling during the previous 12 months, and completed three problem gambling screens. Gambling, including under-age gambling, was a common event. Up to one in five were identified as at risk for problem gambling on at least one screen. Students who were non-European, or were from low socioeconomic areas, were more likely to be at risk for problem gambling. Help for gambling problems was preferred from friends and family rather than others, while inclusion of information in the education curriculum about risk of gambling problems was supported. The survey provided evidence for pre-legislation baseline gambling behaviour, and risk for problem gambling, of students attending high schools in Auckland. Levels of risk for problem gambling paralleled the elevated risk found for youth in many countries. Raising awareness, through a school curriculum, of risk for gambling problems among adolescents may be explored as a strategy to reduce the high levels of risk for gambling problems identified.

Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

PubMed

Kalderstam, Jonas; Edén, Patrik; Ohlsson, Mattias

2015-01-01

We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN) are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox) is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart), which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

A spatial scan statistic for nonisotropic two-level risk cluster.

PubMed

Li, Xiao-Zhou; Wang, Jin-Feng; Yang, Wei-Zhong; Li, Zhong-Jie; Lai, Sheng-Jie

2012-01-30

Spatial scan statistic methods are commonly used for geographical disease surveillance and cluster detection. The standard spatial scan statistic does not model any variability in the underlying risks of subregions belonging to a detected cluster. For a multilevel risk cluster, the isotonic spatial scan statistic could model a centralized high-risk kernel in the cluster. Because variations in disease risks are anisotropic owing to different social, economical, or transport factors, the real high-risk kernel will not necessarily take the central place in a whole cluster area. We propose a spatial scan statistic for a nonisotropic two-level risk cluster, which could be used to detect a whole cluster and a noncentralized high-risk kernel within the cluster simultaneously. The performance of the three methods was evaluated through an intensive simulation study. Our proposed nonisotropic two-level method showed better power and geographical precision with two-level risk cluster scenarios, especially for a noncentralized high-risk kernel. Our proposed method is illustrated using the hand-foot-mouth disease data in Pingdu City, Shandong, China in May 2009, compared with two other methods. In this practical study, the nonisotropic two-level method is the only way to precisely detect a high-risk area in a detected whole cluster. Copyright © 2011 John Wiley & Sons, Ltd.

Multiple sclerosis decreases explicit counterfactual processing and risk taking in decision making.

PubMed

Simioni, Samanta; Schluep, Myriam; Bault, Nadège; Coricelli, Giorgio; Kleeberg, Joerg; Du Pasquier, Renaud A; Gschwind, Markus; Vuilleumier, Patrik; Annoni, Jean-Marie

2012-01-01

Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished. We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded. In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (p<0.005) and greater risk aversion (p<0.001). They reported less negative affect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains). The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients.

Do Health Professionals Need Additional Competencies for Stratified Cancer Prevention Based on Genetic Risk Profiling?

PubMed Central

Chowdhury, Susmita; Henneman, Lidewij; Dent, Tom; Hall, Alison; Burton, Alice; Pharoah, Paul; Pashayan, Nora; Burton, Hilary

2015-01-01

There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention. PMID:26068647

Shared and unique common genetic determinants between pediatric and adult celiac disease.

PubMed

Senapati, Sabyasachi; Sood, Ajit; Midha, Vandana; Sood, Neena; Sharma, Suresh; Kumar, Lalit; Thelma, B K

2016-07-22

Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done. The database included basic demographic characteristics, clinical presentations, associated diseases and complications, if any. The genotype dataset was acquired for children (n = 217) and adult CD patients (n = 340) and controls (n = 736) using Immunochip. Association analysis was performed using logistic regression model to identify susceptibility genetic variants. The predominant form of CD was classical CD in both pediatric and adult CD groups. There was remarkable similarity between pediatric and adult CD except for quantitative differences between the two groups such as female preponderance, non-classical presentation, co-occurrence of other autoimmune diseases being more common amongst adult CD. Notably, same HLA-DQ2 and -DQ8 haplotypes were established as the major risk factors in both types of CD. In addition, a few suggestively associated (p < 5 × 10(-4)) non-HLA markers were identified of which only ANK3 (rs4948256-A; rs10994257-T) was found to be shared and explain risk for ~45 % of CD patients with HLA allele. Overall phenotypic similarity between pediatric and adult CD groups can be explained by contribution of same HLA risk alleles. Different non-HLA genes/loci with minor risk seem to play crucial role in disease onset and extra intestinal manifestation of CD. None of the non-HLA risk variants reached genome-wide significance, however most of them were shown to have functional implication to disease pathogenesis. Functional relevance of our findings needs to be investigated to address clinical heterogeneity of CD. This present study is the first comparative study based on common genetic markers to suggest that CD in pediatric age group and in adults are the spectrum of the same disease with novel and shared genetic risk determinants. Follow-up fine mapping studies with larger study cohorts are warranted for further genetic investigation.

Estimating the burden of disease attributable to four selected environmental risk factors in South Africa.

PubMed

Norman, Rosana; Bradshaw, Debbie; Lewin, Simon; Cairncross, Eugene; Nannan, Nadine; Vos, Theo

2010-01-01

The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure. The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty. Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease. This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels.

Pyrrolizidine alkaloid-containing toxic plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.).

PubMed

Stegelmeier, Bryan L

2011-07-01

Pyrrolizidine alkaloid (PA)-containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife, and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. This article briefly introduces high-risk North American PA-containing plants, summarizing their toxicity and subsequent pathology. Current diagnostic techniques, treatments, and strategies to avoid losses to PA poisoning are also reviewed. Published by Elsevier Inc.

Risky business: focus-group analysis of sexual behaviors, drug use and victimization among incarcerated women in St. Louis.

PubMed

Millay, Tamara A; Satyanarayana, Veena A; O'Leary, Catina C; Crecelius, Robert; Cottler, Linda B

2009-09-01

Incarcerated women report multiple vulnerabilities and, yet, are under-represented in research. This study used focus-group methodology to explore high-risk sexual behaviors, drug use, and victimization among female offenders in St. Louis. Inmates of the St. Louis Medium Security Institution (MSI) were invited to participate in one of five focus groups between May and September 2005 in preparation for an NIH/NINR HIV-prevention intervention study among female offenders in Drug Court. The focus group sample of 30 women was 70% African-American, with a mean age of 36 years. Results indicated that oral sex was the most common sex trade activity. Consistent with the literature, condom usage was described as irregular. In terms of drug use, participants reported that crack was most commonly used, with binges often lasting for several days. Regarding victimization, women frequently reported sexual abuse in childhood, and some described abusive relationships as adults. Participants also reported being beaten and raped by customers, which led to their concealing knives in purses and razors under the tongue. Consequently, perpetrated violence, including murder, was reported as protection against further violence. These findings confirm the vulnerability of this population of women who are at high risk for HIV. Effective HIV-prevention interventions are needed to assist these incarcerated women in making lifestyle changes during incarceration and sustaining them after release.

Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia.

PubMed

Rodriguez-Murillo, Laura; Xu, Bin; Roos, J Louw; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2014-03-01

We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32-34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32-34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case-control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case-control data sets of European descent highlighted a region across introns 2-6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia.

Science For Sendai - Bridging the gap between research and application

NASA Astrophysics Data System (ADS)

Rees, J.

2015-12-01

Disasters have an enormous cost in lives and livelihoods, but the use of rigorous evidence-based scientific approaches to minimise their impact remains poor. Vast amounts of science which could be readily applied for disaster risk reduction (DRR) is under-utilised, if used at all. Previous international agreements have failed to change this picture, but there is a clear call from the international community that the 2015 Sendai framework should make a difference; it is thus re-appraising how to bridge the chasm that exists between DRR relevant scientists and potential users of their research. There is widespread recognition of the need for risk affected countries and communities to engage in science-based decision-making, but several barriers, such as a lack of infrastructure or necessary skills, institutions, and enforcement of science-based policies require significant attention. There are now incentives for governments to respond: the framework has science embedded throughout and it sets-out national targets against which science uptake can be monitored; similarly, widening access to insurance also demands sound science. Advances such as open-data and models, increasing computational capacity, expanding networks, evolving diverse mobile technologies and the other multiple facets of the big data agenda, also should drive change. So, how does the scientific community need to adapt? Whilst vast amounts of 'DRR-relevant' science has been produced, too little of it can be readily used in DRR science. Much remains highly disciplinary and focused on analysis of limited distributions or single processes with a small number of agents; by contrast real-world DRR problems are commonly complex, with multiple drivers and uncertainties. There is a major need for a trans-disciplinary DRR-focused risk research agenda to evolve. Not only do research funders need to develop and resource risk research, but researchers themselves need to identify that focussing on the bigger risk picture is commonly more important than addressing the traditional disciplinary topics that they have commonly engaged.

Positioning patients for spine surgery: Avoiding uncommon position-related complications

PubMed Central

Kamel, Ihab; Barnette, Rodger

2014-01-01

Positioning patients for spine surgery is pivotal for optimal operating conditions and operative-site exposure. During spine surgery, patients are placed in positions that are not physiologic and may lead to complications. Perioperative peripheral nerve injury (PPNI) and postoperative visual loss (POVL) are rare complications related to patient positioning during spine surgery that result in significant patient disability and functional loss. PPNI is usually due to stretch or compression of the peripheral nerve. PPNI may present as a brachial plexus injury or as an isolated injury of single nerve, most commonly the ulnar nerve. Understanding the etiology, mechanism and pattern of injury with each type of nerve injury is important for the prevention of PPNI. Intraoperative neuromonitoring has been used to detect peripheral nerve conduction abnormalities indicating peripheral nerve stress under general anesthesia and to guide modification of the upper extremity position to prevent PPNI. POVL usually results in permanent visual loss. Most cases are associated with prolonged spine procedures in the prone position under general anesthesia. The most common causes of POVL after spine surgery are ischemic optic neuropathy and central retinal artery occlusion. Posterior ischemic optic neuropathy is the most common cause of POVL after spine surgery. It is important for spine surgeons to be aware of POVL and to participate in safe, collaborative perioperative care of spine patients. Proper education of perioperative staff, combined with clear communication and collaboration while positioning patients in the operating room is the best and safest approach. The prevention of uncommon complications of spine surgery depends primarily on identifying high-risk patients, proper positioning and optimal intraoperative management of physiological parameters. Modification of risk factors extrinsic to the patient may help reduce the incidence of PPNI and POVL. PMID:25232519

The use of general anesthesia to facilitate dental treatment in adult patients with special needs.

PubMed

Lim, Mathew Albert Wei Ting; Borromeo, Gelsomina Lucia

2017-06-01

General anesthesia is commonly used to facilitate dental treatment in patients with anxiety or challenging behavior, many of whom are children or patients with special needs. When performing procedures under general anesthesia, dental surgeons must perform a thorough pre-operative assessment, as well as ensure that the patients are aware of the potential risks and that informed consent has been obtained. Such precautions ensure optimal patient management and reduce the frequency of morbidities associated with this form of sedation. Most guidelines address the management of pediatric patients under general anesthesia. However, little has been published regarding this method in patients with special needs. This article constitutes a review of the current literature regarding management of patients with special needs under general anesthesia.

Different type 2 diabetes risk assessments predict dissimilar numbers at 'high risk': a retrospective analysis of diabetes risk-assessment tools.

PubMed

Gray, Benjamin J; Bracken, Richard M; Turner, Daniel; Morgan, Kerry; Thomas, Michael; Williams, Sally P; Williams, Meurig; Rice, Sam; Stephens, Jeffrey W

2015-12-01

Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under-reported, however, whether a different risk tool alters the predicted risk of an individual. This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. Cross-sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes(®), Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at 'high risk' followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes. © British Journal of General Practice 2015.

Understanding the complex relationships underlying hot flashes: a Bayesian network approach.

PubMed

Smith, Rebecca L; Gallicchio, Lisa M; Flaws, Jodi A

2018-02-01

The mechanism underlying hot flashes is not well-understood, primarily because of complex relationships between and among hot flashes and their risk factors. We explored those relationships using a Bayesian network approach based on a 2006 to 2015 cohort study of hot flashes among 776 female residents, 45 to 54 years old, in the Baltimore area. Bayesian networks were fit for each outcome (current hot flashes, hot flashes before the end of the study, hot flash severity, hot flash frequency, and age at first hot flashes) separately and together with a list of risk factors (estrogen, progesterone, testosterone, body mass index and obesity, race, income level, education level, smoking history, drinking history, and activity level). Each fitting was conducted separately on all women and only perimenopausal women, at enrollment and 4 years after enrollment. Hormone levels, almost always interrelated, were the most common variable linked to hot flashes; hormone levels were sometimes related to body mass index, but were not directly related to any other risk factors. Smoking was also frequently associated with increased likelihood of severe symptoms, but not through an antiestrogenic pathway. The age at first hot flashes was related only to race. All other factors were either not related to outcomes or were mediated entirely by race, hormone levels, or smoking. These models can serve as a guide for design of studies into the causal network underlying hot flashes.

Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc.

PubMed

Shinno, Yuki; Kage, Hidenori; Chino, Haruka; Inaba, Atsushi; Arakawa, Sayaka; Noguchi, Satoshi; Amano, Yosuke; Yamauchi, Yasuhiro; Tanaka, Goh; Nagase, Takahide

2018-01-01

Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis. © 2017 Asian Pacific Society of Respirology.

Live and non-live pregnancy outcomes among women with depression and anxiety: a population-based study.

PubMed

Ban, Lu; Tata, Laila J; West, Joe; Fiaschi, Linda; Gibson, Jack E

2012-01-01

Women taking antidepressant or anti-anxiety medications during early pregnancy have high risks of non-live pregnancy outcomes, although the contribution of the underlying illnesses to these risks remains unclear. We examined the impacts of antenatal depression and anxiety and of commonly prescribed treatments on the risks of non-live pregnancy outcomes. We identified all pregnancies and their outcome (live birth, perinatal death, miscarriage or termination) among women aged 15-45 years between 1990 and 2009 from a large primary care database in the United Kingdom. Women were grouped according to whether they had no history of depression and anxiety, a diagnosis of such illness prior to pregnancy, illness during pregnancy and illness during pregnancy with use of medication (stratified by medication type). Multinomial logistic regression models were used to compare risks of non-live outcomes among these groups, adjusting for major socio-demographic and lifestyle characteristics. Among 512,574 pregnancies in 331,414 women, those with antenatal drug exposure showed the greatest increased risks for all non-live pregnancy outcomes, relative to those with no history of depression or anxiety, although women with prior (but not currently medicated) illness also showed modest increased risks. Compared with un-medicated antenatal morbidity, there was weak evidence of an excess risk in women taking tricyclic antidepressants, and stronger evidence for other medications. Women with depression or anxiety have higher risks of miscarriage, perinatal death and decisions to terminate a pregnancy if prescribed psychotropic medication during early pregnancy than if not. Although underlying disease severity could also play a role, avoiding or reducing use of these drugs during early pregnancy may be advisable.

Fatty liver and drugs: the two sides of the same coin.

PubMed

Miele, L; Liguori, A; Marrone, G; Biolato, M; Araneo, C; Vaccaro, F G; Gasbarrini, A; Grieco, A

2017-03-01

Drug-induced liver injury (DILI) is a common and underestimated cause of liver disease. Several drugs and other xenobiotics can be the cause of different clinicopathologic patterns of liver disease. Steatosis and steatohepatitis are rare but well-documented types of DILI. Over the past decades commonly used drugs like amiodarone, tamoxifen, irinotecan, methotrexate, valproic acid and glucocorticoids have been recognized to be associated with steatosis. Even though the pathophysiological pathways are still only partially understood, inhibition of mitochondrial beta-oxidation, reduced very low-density lipoprotein secretion, insulin resistance induction and increased de novo synthesis or increased liver uptake of fatty acids are considered the main pathogenic mechanisms through which drugs can lead to hepatic steatosis. On the other hand, fatty liver itself is a very common clinical condition, and there is a growing awareness of the potential risk factors for DILI due to the underlying metabolic condition itself.

Lumbosacral Transitional Vertebrae and Its Prevalence in the Australian Population

PubMed Central

French, Heath D.; Somasundaram, Arjuna J.; Schaefer, Nathan R.; Laherty, Richard W.

2014-01-01

Study Design Retrospective cohort study. Objective Lumbosacral transitional vertebrae (LSTV) are a common congenital anomaly, and they can be accurately identified on anteroposterior (AP) radiographs of the lumbosacral spine. This study attempts to determine the prevalence of this congenital anomaly and to increase awareness among all clinicians to reduce the risk of surgical and procedural errors in patients with LSTV. Methods A retrospective review of 5,941 AP and lateral lumbar radiographs was performed. Transitional vertebrae were identified and categorized under the Castellvi classification. Results The prevalence of LSTV in the study population was 9.9%. Lumbarized S1 and sacralized L5 were seen in 5.8 and 4.1% of patients, respectively. Conclusion LSTV are a common normal variant and can be a factor in spinal surgery at incorrect levels. It is essential that all clinicians are aware of this common congenital anomaly. PMID:25396103

Imported melioidosis in Japan: a review of cases.

PubMed

Hadano, Yoshiro

2018-01-01

Fourteen cases of reported melioidosis in Japan were reviewed. The mean age was 52.4 years (33-69 years), and all patients were male. All of the presumed exposures originated in Southeast Asia. The most common underlying disease was diabetes mellitus, including those patients with impaired glucose tolerance (n=8). As for mode of onset, 13 patients had acute infections and one had chronic infection. Of these 14 patients, the most common infection site on admission was lung (n=8), followed by bone (n=5), skin (n=4), gastrointestinal abscess formation (n=3), urinary tract (n=3), aorta (n=2), mediastinal lymph node swelling (n=1), and central nervous system (n=1). Bacteremia was observed in nine patients, and Burkholderia pseudomallei isolates were mostly susceptible to ceftazidime and carbapenem. Overall mortality was 14.3%. Melioidosis is a rare infection in Japan, with all known cases to date having been imported from Southeast Asia. Diabetes was a common risk factor.

Association between Body Mass Index and Dental Caries among Anganwadi Children of Belgaum City, India.

PubMed

Aluckal, Eby; Anzil, Ksa; Baby, Mathews; George, Eldhose K; Lakshmanan, Sanju; Chikkanna, Shilpa

2016-10-01

Body mass index (BMI) is an index that measures height for weight, which is commonly used to categorize underweight, overweight, and obese individuals. Deviation from normal weight results from an imbalance between caloric consumption and energy expenditure. Childhood obesity and childhood dental caries are coincidental in many populations, probably due to common confounding risk factors, such as intake frequency, cariogenic diet, and poor oral hygiene. So the aim of the present study was to assess the BMI status and to corelate between dental caries and BMI among the Anganwadi children of Belgaum city, Karnataka, India. Four hundred and thirty three children from 20 Anganwadi's belonging to the age group of 2 to 6 years of both sexes were measured for BMI and dental caries status. The caries index was measured as the number of decayed (d) and filled (f) teeth (t) (dft). The BMI in units of kg/m 2 was determined and children were categorized according to age-and gender-specific criteria as underweight (<5th percentile), normal (5th-85th percentile), at risk for overweight (85th- 95th percentile), and overweight (>95th percentile). The data were subjected to statistical analysis using Student's t-test, analysis of variance (ANOVA), and Karl Pearson's correlation coefficient test with the help of Statistical Package for the Social Sciences (SPSS) version 18.0. The proportion of subjects in Centre for Disease Control (CDC) weight categories was: 5% underweight, 79% normal, 9% under the risk for overweight, and 6% overweight. A significant association was found between children with normal BMI and those who were underweight, overweight, and under the risk for overweight. Children with overweight/obese or underweight/malnourished children had higher decayed and filled surfaces compared to children with normal weight. Nutritional status has a profound effect on dental caries. Both underweight/malnutrition and overweight/ obesity have significant adverse implications for health. Childhood obesity and childhood dental caries are coincidental in many populations.

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians.

PubMed

Scott, William R; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S; Bozaoglu, Kiymet; Sanghera, Dharambir K; Elliott, Paul; Scott, James; Chambers, John C; Kooner, Jaspal S

2016-01-01

South Asians are 1/4 of the world's population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10-6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

PubMed Central

Scott, William R.; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S.; Bozaoglu, Kiymet; Sanghera, Dharambir K.; Elliott, Paul; Scott, James; Chambers, John C.; Kooner, Jaspal S.

2016-01-01

South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans. PMID:27195708

Classification of Cough as a Symptom in Adults and Management Algorithms: CHEST Guideline and Expert Panel Report.

PubMed

Irwin, Richard S; French, Cynthia L; Chang, Anne B; Altman, Kenneth W

2018-01-01

We performed systematic reviews using the population, intervention, comparison, outcome (PICO) format to answer the following key clinical question: Are the CHEST 2006 classifications of acute, subacute and chronic cough and associated management algorithms in adults that were based on durations of cough useful? We used the CHEST Expert Cough Panel's protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patient values and preferences and the clinical context were used to form recommendations or suggestions. Delphi methodology was used to obtain the final grading. With respect to acute cough (< 3 weeks), only three studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 CHEST Cough Guidelines, the most common causes were respiratory infections, most likely of viral cause, followed by exacerbations of underlying diseases such as asthma and COPD and pneumonia. The subjects resided on three continents: North America, Europe, and Asia. With respect to subacute cough (duration, 3-8 weeks), only two studies met our criteria for quality assessment, and both had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were postinfectious cough and exacerbation of underlying diseases such as asthma, COPD, and upper airway cough syndrome (UACS). The subjects resided in countries in Asia. With respect to chronic cough (> 8 weeks), 11 studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were UACS from rhinosinus conditions, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, combinations of these four conditions, and, less commonly, a variety of miscellaneous conditions and atopic cough in Asian countries. The subjects resided on four continents: North America, South America, Europe, and Asia. Although the quality of evidence was low, the published literature since 2006 suggests that CHEST's 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Complexity of mechanisms among human proprotein convertase subtilisin-kexin type 9 variants.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2017-04-01

There are many reports of human variants in proprotein convertase subtilisin-kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated. GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol-raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts. In contrast, LOF variants can be either ultrarare mutations or relatively more common polymorphisms seen in populations, affect all domains of the protein, act to increase LDL receptor expression through several mechanisms, have variable LDL cholesterol-lowering effects, and have been associated with decreased CVD risk mainly through Mendelian randomization studies in epidemiologic populations. There is considerable complexity underlying the clinical concept of both LOF and GOF variants of PCSK9. But despite the underlying mechanistic heterogeneity, altered PCSK9 secretion or function is ultimately correlated with plasma LDL cholesterol level, which is also the driver of CVD outcomes.

Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

PubMed

Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

2011-03-01

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible. Copyright © 2011 Elsevier Inc. All rights reserved.

Renal diagnosis of chronic hemodialysis patients with urinary tract transitional cell carcinoma in Taiwan.

PubMed

Chang, Chung-Hsin; Yang, Cheng-Ming; Yang, An-Hang

2007-04-15

Transitional cell carcinoma (TCC) is the most common malignancy in dialysis patients of Taiwan. The reason for such a high incidence of TCC is undetermined. The correlation between the underlying renal disease and the development of TCC was investigated. The authors retrospectively reviewed the clinical data and outcome of 1537 chronic hemodialysis (HD) patients from 1993 to 2002. The incidence of TCC was computed. The Cox regression method was used to analyze the role of potential risk factors. After a mean dialysis duration of 46.5 months, 26 (1.69%) patients with TCC were diagnosed. The standardized incidence ratio (SIR) of TCC was 48.2 as compared with the general population and the SIR of TCC seemed higher in women (65.1) and in the age group 50 to 54 years (173.6). Of them, most cases showed no definite etiology. All these cases showed bilateral contracted kidneys. Nonnephrotic proteinuria was found in all cases and trace glucosuria was found in 17 (65%). Painless gross hematuria was the cardinal symptom and distant metastasis was rare. Also, TCC in upper urinary tracts were common and found in 14 (54%) of patients. Age at the time of dialysis, female sex, compound analgesic use, and Chinese herb use had statistical significance as risk factors (P < .05). Chronic HD patients have a high risk of TCC in Taiwan, especially in female and middle-aged patients. The study indicated that chronic tubulointerstitial nephritis (CTIN) is the most likely underlying renal disease in HD patients with TCC, a high percentage of the CTIN related to the usage of Chinese herbs or compound analgesics may contribute to the development of TCC, whereas diabetes or chronic glomerulonephritis play only a minor role.

Increasing URM Undergraduate Student Success through Assessment-Driven Interventions: A Multiyear Study Using Freshman-Level General Biology as a Model System.

PubMed

Carmichael, Mary C; St Clair, Candace; Edwards, Andrea M; Barrett, Peter; McFerrin, Harris; Davenport, Ian; Awad, Mohamed; Kundu, Anup; Ireland, Shubha Kale

2016-01-01

Xavier University of Louisiana leads the nation in awarding BS degrees in the biological sciences to African-American students. In this multiyear study with ∼5500 participants, data-driven interventions were adopted to improve student academic performance in a freshman-level general biology course. The three hour-long exams were common and administered concurrently to all students. New exam questions were developed using Bloom's taxonomy, and exam results were analyzed statistically with validated assessment tools. All but the comprehensive final exam were returned to students for self-evaluation and remediation. Among other approaches, course rigor was monitored by using an identical set of 60 questions on the final exam across 10 semesters. Analysis of the identical sets of 60 final exam questions revealed that overall averages increased from 72.9% (2010) to 83.5% (2015). Regression analysis demonstrated a statistically significant correlation between high-risk students and their averages on the 60 questions. Additional analysis demonstrated statistically significant improvements for at least one letter grade from midterm to final and a 20% increase in the course pass rates over time, also for the high-risk population. These results support the hypothesis that our data-driven interventions and assessment techniques are successful in improving student retention, particularly for our academically at-risk students. © 2016 M. C. Carmichael et al. CBE—Life Sciences Education © 2016 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).

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

PubMed

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-09-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). © 2015 British Society for Immunology.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

PubMed Central

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-01-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; http://www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; http://www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). PMID:25959571

Supervised learning for infection risk inference using pathology data.

PubMed

Hernandez, Bernard; Herrero, Pau; Rawson, Timothy Miles; Moore, Luke S P; Evans, Benjamin; Toumazou, Christofer; Holmes, Alison H; Georgiou, Pantelis

2017-12-08

Antimicrobial Resistance is threatening our ability to treat common infectious diseases and overuse of antimicrobials to treat human infections in hospitals is accelerating this process. Clinical Decision Support Systems (CDSSs) have been proven to enhance quality of care by promoting change in prescription practices through antimicrobial selection advice. However, bypassing an initial assessment to determine the existence of an underlying disease that justifies the need of antimicrobial therapy might lead to indiscriminate and often unnecessary prescriptions. From pathology laboratory tests, six biochemical markers were selected and combined with microbiology outcomes from susceptibility tests to create a unique dataset with over one and a half million daily profiles to perform infection risk inference. Outliers were discarded using the inter-quartile range rule and several sampling techniques were studied to tackle the class imbalance problem. The first phase selects the most effective and robust model during training using ten-fold stratified cross-validation. The second phase evaluates the final model after isotonic calibration in scenarios with missing inputs and imbalanced class distributions. More than 50% of infected profiles have daily requested laboratory tests for the six biochemical markers with very promising infection inference results: area under the receiver operating characteristic curve (0.80-0.83), sensitivity (0.64-0.75) and specificity (0.92-0.97). Standardization consistently outperforms normalization and sensitivity is enhanced by using the SMOTE sampling technique. Furthermore, models operated without noticeable loss in performance if at least four biomarkers were available. The selected biomarkers comprise enough information to perform infection risk inference with a high degree of confidence even in the presence of incomplete and imbalanced data. Since they are commonly available in hospitals, Clinical Decision Support Systems could benefit from these findings to assist clinicians in deciding whether or not to initiate antimicrobial therapy to improve prescription practices.

Space-time variation of respiratory cancers in South Carolina: a flexible multivariate mixture modeling approach to risk estimation.

PubMed

Carroll, Rachel; Lawson, Andrew B; Kirby, Russell S; Faes, Christel; Aregay, Mehreteab; Watjou, Kevin

2017-01-01

Many types of cancer have an underlying spatiotemporal distribution. Spatiotemporal mixture modeling can offer a flexible approach to risk estimation via the inclusion of latent variables. In this article, we examine the application and benefits of using four different spatiotemporal mixture modeling methods in the modeling of cancer of the lung and bronchus as well as "other" respiratory cancer incidences in the state of South Carolina. Of the methods tested, no single method outperforms the other methods; which method is best depends on the cancer under consideration. The lung and bronchus cancer incidence outcome is best described by the univariate modeling formulation, whereas the "other" respiratory cancer incidence outcome is best described by the multivariate modeling formulation. Spatiotemporal multivariate mixture methods can aid in the modeling of cancers with small and sparse incidences when including information from a related, more common type of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Hot ash burns in the children of Western Australia: how and why they happen.

PubMed

Martin, L; Rea, S; McWilliams, T; Wood, F

2014-08-01

Burns from hot ash are common in the paediatric population in Western Australia. Fifty children were admitted to the paediatric burn centre with hot ash contact burns to the feet in 2011 and 2012. It is important to examine the extent of the problem, seasonal variations, and identify those at risk to determine strategies for prevention campaigns. Retrospective review of medical notes for all admissions to the paediatric burns unit was undertaken for 2011 and 2012. Data were collected for patient demographics, time, circumstance of injury, burn severity and treatment. Hot ash burns accounted for 8.6% of admissions but 16.1% of burns sustained in non-metro areas. Median age was just under 3 years, male or female. Median burn TBSA was 2%, and 44% of children required surgery. The burns were less common in summer, more common on non-school days and in children who were on camping trips away from home. Previous work has shown the value of targeted campaigns. The group for targeted prevention campaigns are the carers of very young children who go camping. Information distributed at camping shows and stores about the principles of campfire safety would reach the people at risk. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Different type 2 diabetes risk assessments predict dissimilar numbers at ‘high risk’: a retrospective analysis of diabetes risk-assessment tools

PubMed Central

Gray, Benjamin J; Bracken, Richard M; Turner, Daniel; Morgan, Kerry; Thomas, Michael; Williams, Sally P; Williams, Meurig; Rice, Sam; Stephens, Jeffrey W

2015-01-01

Background Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under-reported, however, whether a different risk tool alters the predicted risk of an individual. Aim This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. Design and setting Cross-sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. Method Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes®, Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. Results Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at ‘high risk’ followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). Conclusion The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes. PMID:26541180

Estimates of auditory risk from outdoor impulse noise. II: Civilian firearms.

PubMed

Flamme, Gregory A; Wong, Adam; Liebe, Kevin; Lynd, James

2009-01-01

Firearm impulses are common noise exposures in the United States. This study records, describes and analyzes impulses produced outdoors by civilian firearms with respect to the amount of auditory risk they pose to the unprotected listener under various listening conditions. Risk estimates were obtained using three contemporary damage risk criteria (DRC) including a waveform parameter-based approach (peak SPL and B-duration), an energy-based criterion (A-weighted SEL and equivalent continuous level) and a physiological model (AHAAH). Results from these DRC were converted into a number of maximum permissible unprotected exposures to facilitate interpretation. Acoustic characteristics of firearm impulses differed substantially across guns, ammunition, and microphone location. The type of gun, ammunition and the microphone location all significantly affected estimates of auditory risk from firearms. Vast differences in maximum permissible exposures were observed; the rank order of the differences varied with the source of the impulse. Unprotected exposure to firearm noise is not recommended, but people electing to fire a gun without hearing protection should be advised to minimize auditory risk through careful selection of ammunition and shooting environment. Small-caliber guns with long barrels and guns loaded with the least powerful ammunition tend to be associated with the least auditory risk.

Reaction of N,N-Dimethyltryptamine with Dichloromethane Under Common Experimental Conditions.

PubMed

Dunlap, Lee E; Olson, David E

2018-05-31

A large number of clinically used drugs and experimental pharmaceuticals possess the N , N -dimethyltryptamine (DMT) structural core. Previous reports have described the reaction of this motif with dichloromethane (DCM), a common laboratory solvent used during extraction and purification, leading to the formation of an undesired quaternary ammonium salt byproduct. However, the kinetics of this reaction under various conditions have not been thoroughly described. Here, we report a series of experiments designed to simulate the exposure of DMT to DCM that would take place during extraction from plant material, biphasic aqueous work-up, or column chromatography purification. We find that the quaternary ammonium salt byproduct forms at an exceedingly slow rate, only accumulates to a significant extent upon prolonged exposure of DMT to DCM, and is readily extracted into water. Our results suggest that DMT can be exposed to DCM under conditions where contact times are limited (<30 min) with minimal risk of degradation and that this byproduct is not observed following aqueous extraction. However, alternative solvents should be considered when the experimental conditions require longer contact times. Our work has important implications for preparing a wide-range of pharmaceuticals bearing the DMT structural motif in high yields and purities.

Implications of cost-effectiveness analysis of medical technology. background paper number 5. four common x-ray procedures: problems and prospects for economic evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, J.L.; Krieger, M.J.

This paper is about the economic evaluation of diagnostic procedures. The issue of economic evaluation is explored in the context of four common diagnostic X-ray procedures: the chest X-ray, the skull X-ray, the barium enema study, and the excretory urogram. The paper is divided into two parts. The first part summarizes the different evaluative models underlying studies of the four diagnostic X-ray procedures and to lay out the strengths and weaknesses of each method. The second part contains four separate chapters summarizing what is known about the utilization, costs, risks, and benefits of each procedure, with particular emphasis on themore » evaluative methods employed.« less

Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe.

PubMed

Cortinovis, Cristina; Caloni, Francesca

2015-12-08

Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed.

[Obesity and cardiac cachexia in chronic heart failure].

PubMed

Clauser, M; Altenberger, J

2013-09-01

Obesity as well as cardiac cachexia in heart failure patients are not fully understood and therefore of high scientific interest. Obesity as a common risk factor for cardiovascular disease is associated with a high mortality. In contrast obesity in patients suffering from chronic heart failure seems to be accompanied with a favorable outcome in contrast to people with normal weight, known as the obesity paradox. In the last decade there has been growing interest in cachexia, which is common in advanced stages of chronic diseases, such as heart failure, chronic obstructive pulmonary disease (COPD), cancer and renal failure and is associated with a poor prognosis. Until now cachexia has been underdiagnosed and undertreated. This review discusses the complex underlying pathomechanisms as well as potential therapeutic approaches.

Leptospirosis in a British soldier after travel to Borneo.

PubMed

Burns, Daniel S; Clay, K A; Bailey, M S

2016-12-01

Undifferentiated febrile illness in a returning soldier is a common problem encountered by serving medical officers. A 32-year-old soldier presented to Birmingham Heartlands Hospital with fever and acute kidney injury after return from Borneo. Leptospirosis was suspected and empirical antibiotics were started before subsequent confirmation by serology and PCR. Leptospirosis is common in South-East Asia, and troops exercising in jungle areas, and in the UK, are at risk. Advice, including inpatient management when appropriate, is available from the UK Role 4 Military Infectious Diseases and Tropical Medicine Service. 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/.

Morbidity and mortality of women and men with intellectual and developmental disabilities newly initiating antipsychotic drugs

PubMed Central

Lunsky, Yona; Cobigo, Virginie; Wilton, Andrew S.; Somerton, Sarah; Seitz, Dallas P.

2016-01-01

Background While up to 45% of individuals with intellectual and developmental disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are commonly prescribed, gender differences in the safety of antipsychotics have rarely been studied in this population. Aims To compare men and women with IDD on medical outcomes after antipsychotic initiation. Method Our population-based study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly initiating antipsychotic medication on risk for diabetes mellitus, hypertension, venous thromboembolism, myocardial infarction, stroke and death, with up to 4 years of follow-up. Results Women were older and more medically complex at baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15–2.59) and death (HR 1.46, 95% CI 1.02–2.10) in crude analyses; but only thromboembolism risk was greater for women after covariate adjustment (aHR 1.58, 95% CI 1.05–2.38). Conclusions Gender should be considered in decision-making around antipsychotic medications for individuals with IDD. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703773

Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus☆

PubMed Central

Cannon, Michael J.; Westbrook, Kyresa; Levis, Denise; Schleiss, Mark R.; Thackeray, Rosemary; Pass, Robert F.

2015-01-01

Objective Congenital cytomegalovirus (CMV) infection is a common cause of hearing loss and intellectual disability. We assessed CMV knowledge and the frequency of women's behaviors that may enable CMV transmission to inform strategies for communicating prevention messages to women. Methods We analyzed survey responses from 4184 participants (2181 women, 2003 men) in the 2010 HealthStyles survey, a national mail survey designed to be similar to the United States population. Results Only 7% of men and 13% of women had heard of congenital CMV. Women with children under age 19 (n=918) practiced the following risk behaviors at least once per week while their youngest child was still in diapers: kissing on the lips (69%), sharing utensils (42%), sharing cups (37%), and sharing food (62%). Women practiced protective, hand cleansing behaviors most of the time or always after: changing a dirty diaper (95%), changing a wet diaper (85%), or wiping the child's nose (65%), but less commonly after handling the child's toys (26%). Conclusions Few women are aware of CMV and most regularly practice behaviors that may place them at risk when interacting with young children. Women should be informed of practices that can reduce their risk of CMV infection during pregnancy. PMID:22465669

Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus

PubMed Central

Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C.

2017-01-01

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes. PMID:28049284

Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus.

PubMed

Moon, Joon Ho; Kwak, Soo Heon; Jang, Hak C

2017-01-01

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, is characterized by underlying maternal defects in the β-cell response to insulin during pregnancy. Women with a previous history of GDM have a greater than 7-fold higher risk of developing postpartum diabetes compared with women without GDM. Various risk factors for postpartum diabetes have been identified, including maternal age, glucose levels in pregnancy, family history of diabetes, pre-pregnancy and postpartum body mass index, dietary patterns, physical activity, and breastfeeding. Genetic studies revealed that GDM shares common genetic variants with type 2 diabetes. A number of lifestyle interventional trials that aimed to ameliorate modifiable risk factors, including diet, exercise, and breastfeeding, succeeded in reducing the incidence of postpartum diabetes, weight retention, and other obesity-related morbidities. The present review summarizes the findings of previous studies on the incidence and risk factors of postpartum diabetes and discusses recent lifestyle interventional trials that attempted to prevent postpartum diabetes.

Risk forewarning model for rice grain Cd pollution based on Bayes theory.

PubMed

Wu, Bo; Guo, Shuhai; Zhang, Lingyan; Li, Fengmei

2018-03-15

Cadmium (Cd) pollution of rice grain caused by Cd-contaminated soils is a common problem in southwest and central south China. In this study, utilizing the advantages of the Bayes classification statistical method, we established a risk forewarning model for rice grain Cd pollution, and put forward two parameters (the prior probability factor and data variability factor). The sensitivity analysis of the model parameters illustrated that sample size and standard deviation influenced the accuracy and applicable range of the model. The accuracy of the model was improved by the self-renewal of the model through adding the posterior data into the priori data. Furthermore, this method can be used to predict the risk probability of rice grain Cd pollution under similar soil environment, tillage and rice varietal conditions. The Bayes approach thus represents a feasible method for risk forewarning of heavy metals pollution of agricultural products caused by contaminated soils. Copyright © 2017 Elsevier B.V. All rights reserved.

[Decision-making and apathy in early stage of Alzheimer's disease and in mild cognitive impairment].

PubMed

Jacus, Jean-Pierre; Bayard, Sophie; Raffard, Stéphane; Gély-Nargeot, Marie-Christine

2013-06-01

Decision-making and apathy have common neuropsychological processes and neuroanatomical substrates. However, their links in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain unclear. in order to evaluate these links, we compared 3 groups of 20 control subjects to 20 patients with MCI and 20 patients with mild AD. All participants completed the mini mental state examination (MMSE), the Lille apathy rating scale (LARS, a multidimensional scale of apathy), the game of dice task (GDT, assessing decision under risk) and the Iowa gambling task (IGT, assessing decision under ambiguity). 60% of patients in both clinical groups were apathetic versus 5% of control subjects. In both clinical groups the IGT and GDT net scores were comparable (respectively: p = 0.76 and p = 0.84), while the control group had higher scores than MCI and AD's groups (respectively, GDT p < 0.02 and p < 0.05; IGT: p < 0.05 and p < 0.05). Cognitive impairment increased the risk of disadvantageous choices in decision under risk (× 6), and under ambiguity (× 3.5). No global contribution of apathy was found for decision-making performances (all PS > 0.05), but on the LARS, the "intellectual curiosity" (cognitive dimension) was a predictor for the performances on GDT's (OR = 1.73, p = 0.05), while the "action initiation" (behavioral dimension) was a predictor of those on IGT (OR = 1.57, p = 0.05). these results highlight the behavioral and the cognitive sensitivity of the IGT and the GDT, and are analyzed according to Levy and Dubois's model of apathy, and to the three steps of the decision-making process of Gleichgerrcht et al. (2010). However, more researches are necessary to explain the causality links between action initiation and decision under ambiguity.

Thoracic radiology of infections emerging after natural disasters.

PubMed

Ketai, Loren; Currie, Bart J; Alva Lopez, Luis Felipe

2006-11-01

When natural disasters demolish shelter, destroy sources of clean drinking water, and disrupt the availability of medical care, vast numbers of people are placed at increased risk of disease. The infectious diseases that propagate under these conditions are usually common ones. Occasionally, a natural disaster alters the local environment in ways that markedly increase the prevalence of a disease that is endemic to a geographic region, occurring only as isolated cases under normal conditions. Many of these infections may affect the thorax. In this article, we discuss the radiologic findings of 4 infectious diseases, coccidioidomycosis, leptospirosis, melioidosis, and Chagas disease, which may flourish after natural disasters strike areas where they are endemic.

Disability pension due to common mental disorders and subsequent suicidal behaviour: a population-based prospective cohort study.

PubMed

Rahman, Syed Ghulam; Alexanderson, Kristina; Jokinen, Jussi; Mittendorfer-Rutz, Ellenor

2016-04-04

Adverse health outcomes, including suicide, in individuals on disability pension (DP) due to mental diagnoses have been reported. However, scientific knowledge on possible risk factors for suicidal behaviour (suicide attempt and suicide) in this group, such as age, gender, underlying DP diagnoses, comorbidity and DP duration and grade, is surprisingly sparse. This study aimed to investigate associations of different measures (main and secondary diagnoses, duration and grade) of DP due to common mental disorders (CMD) with subsequent suicidal behaviour, considering gender and age differences. Population-based prospective cohort study based on Swedish nationwide registers. A cohort of 46,515 individuals aged 19-64 years on DP due to CMD throughout 2005 was followed-up for 5 years. In relation to different measures of DP, univariate and multivariate HRs and 95% CIs for suicidal behaviour were estimated by Cox regression. All analyses were stratified by gender and age. During 2006-2010, 1036 (2.2%) individuals attempted and 207 (0.5%) completed suicide. Multivariate analyses showed that a main DP diagnosis of 'stress-related mental disorders' was associated with a lower risk of subsequent suicidal behaviour than 'depressive disorders' (HR range 0.4-0.7). Substance abuse or personality disorders as a secondary DP diagnosis predicted suicide attempt in all subgroups (HR range 1.4-2.3) and suicide in women and younger individuals (HR range 2.6-3.3). Full-time DP was associated with a higher risk of suicide attempt compared with part-time DP in women and both age groups (HR range 1.4-1.7). Depressive disorders as the main DP diagnosis and substance abuse or personality disorders as the secondary DP diagnosis were risk markers for subsequent suicidal behaviour in individuals on DP due to CMD. Particular attention should be paid to younger individuals on DP due to anxiety disorders because of the higher suicide risk. 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/

The maternal health clinic: an initiative for cardiovascular risk identification in women with pregnancy-related complications.

PubMed

Cusimano, Maria C; Pudwell, Jessica; Roddy, Michelle; Cho, Chan-Kyung Jane; Smith, Graeme N

2014-05-01

Women who develop certain common pregnancy complications have a greater chance of developing cardiovascular disease (CVD) later in life. However, most health care providers do not provide postpartum cardiovascular risk counselling or follow-up. The Maternal Health Clinic was established to address this gap in care. It targets women at increased risk of CVD to inspire lifestyle changes, encourage long-term follow-up, and initiate primary prevention. Here, we summarize results from the first 17 months of completed clinic visits. Patients experiencing at least one relevant complication in their index pregnancy were referred to the Maternal Health Clinic through standard postpartum order sheets. Patients underwent a complete assessment including screening history, physical examination, fasting bloodwork, and urinalysis. Lifetime and 30-year CVD risk estimates, along with a metabolic syndrome calculation, were determined for each patient. Complications most commonly leading to referral were gestational diabetes or impaired glucose tolerance (32.7%), preeclampsia (29.3%), preterm birth (29.3%), and gestational hypertension (19.6%). The clinic analysis group (n = 92) was compared with a healthy control group from the PreEclampsia New Emerging Team study (n = 118). Patients in the clinic analysis group had significantly increased lifetime and 30-year CVD risk estimates compared with healthy controls (P < .0001). Furthermore, 17.4% of the clinic analysis group had metabolic syndrome, compared with 6.78% of healthy controls (P < .05). This study demonstrates that the Maternal Health Clinic accurately identifies postpartum patients that have underlying cardiovascular risks which make them susceptible to CVD. The clinic may serve as an effective primary prevention strategy. Copyright © 2014 Mosby, Inc. All rights reserved.

Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.

PubMed

Mukanyangezi, M F; Sengpiel, V; Manzi, O; Tobin, G; Rulisa, S; Bienvenu, E; Giglio, D

2018-02-01

Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda. A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains. Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs. The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients. © 2017 British HIV Association.

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

PubMed

Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS 2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity.

PubMed

Chiu, Wei-Ling; Boyle, Jacqueline; Vincent, Amanda; Teede, Helena; Moran, Lisa J

2017-01-01

Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive, metabolic, and psychological features and significantly increased cardiometabolic risks. PCOS is underpinned by inherent insulin resistance and hyperandrogenism. Obesity, more common in PCOS, plays an important role in the pathophysiology, exacerbating hyperinsulinaemia and hyperandrogenism, leading to recommended first-line lifestyle intervention. Significant traditional and non-traditional risk factors are implicated in PCOS in addition to obesity-exacerbated cardiometabolic risks and are explored in this review to promote the understanding of this common metabolic and reproductive condition. © 2016 S. Karger AG, Basel.

Abdominal surgery in neonatal foals.

PubMed

Bryant, James E; Gaughan, Earl M

2005-08-01

Abdominal surgery in foals under 30 days old has become more common with improved neonatal care. Early recognition of a foal at risk and better nursing care have increased the survival rates of foals that require neonatal care. The success of improved neonatal care also has increased the need for accurate diagnosis and treatment of gastrointestinal, umbilical, and bladder disorders in these foals. This chapter focuses on the early and accurate diagnosis of specific disorders that require abdominal exploratory surgery and the specific treatment considerations and prognosis for these disorders.

Symbolic dynamic filtering and language measure for behavior identification of mobile robots.

PubMed

Mallapragada, Goutham; Ray, Asok; Jin, Xin

2012-06-01

This paper presents a procedure for behavior identification of mobile robots, which requires limited or no domain knowledge of the underlying process. While the features of robot behavior are extracted by symbolic dynamic filtering of the observed time series, the behavior patterns are classified based on language measure theory. The behavior identification procedure has been experimentally validated on a networked robotic test bed by comparison with commonly used tools, namely, principal component analysis for feature extraction and Bayesian risk analysis for pattern classification.

Vasoplegic syndrome during Whipple procedure.

PubMed

Anandaswamy, Tejesh C; Rajappa, Geetha C; Krishnamachar, Harish

2017-02-01

Vasoplegic syndrome is an unusual cause of refractory hypotension under general anesthesia. It is commonly described in the setting of cardiac surgery, but rarely seen in noncardiac setting. We describe successful management of vasoplegic syndrome during Whipple procedure with vasopressin infusion. A high index of suspicion and prompt treatment with vasopressin can be lifesaving in patients with risk factors for vasoplegic syndrome who present with severe refractory hypotension and who respond poorly to fluid administration and routine vasopressor infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures

PubMed Central

Stone, Jennifer; Thompson, Deborah J.; dos-Santos-Silva, Isabel; Scott, Christopher; Tamimi, Rulla M.; Lindstrom, Sara; Kraft, Peter; Hazra, Aditi; Li, Jingmei; Eriksson, Louise; Czene, Kamila; Hall, Per; Jensen, Matt; Cunningham, Julie; Olson, Janet E.; Purrington, Kristen; Couch, Fergus J.; Brown, Judith; Leyland, Jean; Warren, Ruth M. L.; Luben, Robert N.; Khaw, Kay-Tee; Smith, Paula; Wareham, Nicholas J.; Jud, Sebastian M.; Heusinger, Katharina; Beckmann, Matthias W.; Douglas, Julie A.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Le Marchand, Loic; Kolonel, Laurence N.; Woolcott, Christy; Maskarinec, Gertraud; Haiman, Christopher; Giles, Graham G.; Baglietto, Laura; Krishnan, Kavitha; Southey, Melissa C.; Apicella, Carmel; Andrulis, Irene L.; Knight, Julia A.; Ursin, Giske; Grenaker Alnaes, Grethe I.; Kristensen, Vessela N.; Borresen-Dale, Anne-Lise; Gram, Inger Torhild; Bolla, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Simard, Jacques; Paroah, Paul; Dunning, Alison M.; Easton, Douglas F.; Fasching, Peter A.; Pankratz, V. Shane; Hopper, John; Vachon, Celine M.

2015-01-01

Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute non-dense area adjusted for study, age and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1) and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all p <10−5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and non-dense areas, and between rs17356907 (NTN4) and adjusted absolute non-dense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiological pathways implicated in how mammographic density predicts breast cancer risk. PMID:25862352

Mortality risks in new-onset childhood epilepsy.

PubMed

Berg, Anne T; Nickels, Katherine; Wirrell, Elaine C; Geerts, Ada T; Callenbach, Petra M C; Arts, Willem F; Rios, Christina; Camfield, Peter R; Camfield, Carol S

2013-07-01

Estimate the causes and risk of death, specifically seizure related, in children followed from onset of epilepsy and to contrast the risk of seizure-related death with other common causes of death in the population. Mortality experiences from 4 pediatric cohorts of newly diagnosed patients were combined. Causes of death were classified as seizure related (including sudden unexpected death [SUDEP]), natural causes, nonnatural causes, and unknown. Of 2239 subjects followed up for >30 000 person-years, 79 died. Ten subjects with lethal neurometabolic conditions were ultimately excluded. The overall death rate (per 100 000 person-years) was 228; 743 in complicated epilepsy (with associated neurodisability or underlying brain condition) and 36 in uncomplicated epilepsy. Thirteen deaths were seizure-related (10 SUDEP, 3 other), accounting for 19% of all deaths. Seizure-related death rates were 43 overall, 122 for complicated epilepsy, and 14 for uncomplicated epilepsy. Death rates from other natural causes were 159, 561, and 9, respectively. Of 48 deaths from other natural causes, 37 were due to pneumonia or other respiratory complications. Most excess death in young people with epilepsy is not seizure-related. Mortality is significantly higher compared with the general population in children with complicated epilepsy but not uncomplicated epilepsy. The SUDEP rate was similar to or higher than sudden infant death syndrome rates. In uncomplicated epilepsy, sudden and seizure-related death rates were similar to or higher than rates for other common causes of death in young people (eg, accidents, suicides, homicides). Relating the risk of death in epilepsy to familiar risks may facilitate discussions of seizure-related mortality with patients and families.

The influence of prenatal exposure to trans-fatty acids for development of childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and a case-control study.

PubMed

Specht, Ina Olmer; Huybrechts, Inge; Frederiksen, Peder; Steliarova-Foucher, Eva; Chajes, Veronique; Heitmann, Berit Lilienthal

2018-01-24

Little is known about the causes of childhood cancer, partly as not many children develop cancer, although childhood cancer is a leading cause of death by disease in the young. The young age of the children suggests that risk factors for childhood cancer may be present during pregnancy. Previous studies have shown that exposure to trans-fat, a type of unsaturated fat common in industrially produced foods (iTFA), has adverse health effects in adults, including the risk of developing cancer. Haematopoietic neoplasms are the most common cancer types among European children under the age of 15 years. This study will bring new knowledge as to whether trans-fat and other fatty acids may also increase the risk of developing haematopoietic neoplasms during childhood. We will investigate if the Danish iTFA legislation ban, which radically reduced the use of iTFA in foodstuffs, influenced the risk of childhood haematopoietic neoplasms in children born either before or after the change in legislation, adjusting for relevant secular trends. Further, in a case-control study, we will examine if levels of fatty acids in dried blood spots from newborns can predict the risk of developing childhood haematopoietic neoplasms. Permission from the Danish Data Protection Agency and the Ethical Committee has been granted. The results from this study will provide important information about fatty acids in the mother's diet as a contributor to development of haematopoietic neoplasms during childhood, which may result in relevant preventive action. Not relevant.

Plasminogen activator inhibitor 1 4G/5G and -844G/A variants in idiopathic recurrent pregnancy loss.

PubMed

Magdoud, Kalthoum; Herbepin, Viviana G; Touraine, Renaud; Almawi, Wassim Y; Mahjoub, Touhami

2013-09-01

Plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis, and the common promoter region variants -675G/A (4G/5G) and -844G/A are associated with increased thrombotic risk. Despite evidence linking altered fibrinolysis with adverse pregnancy events, including idiopathic recurrent pregnancy loss (RPL), the contribution of PAI-1 variants to RPL risk remains controversial. We investigated the association between the PAI-1 -844G/A and 4G/5G (-675G/A) variants with altered risk of RPL. This was a case-control study involving 304 women with confirmed RPL and 371 age- and ethnically matched control women. PAI-1 genotyping was performed by PCR single-specific primer -675 (G/A) and real-time PCR (-844G/A) analysis. Minor allele frequency (MAF) of 4G/5G (P < 0.001), but not -844G/A (P = 0.507), was higher in RPL cases. PAI-1 4G/5G single-nucleotide polymorphism (SNP) was significantly associated with RPL under additive, dominant, and recessive genetic models; no association of -844G/A with RPL was seen irrespective of the genetic model tested. Taking common -844G/5G haplotype as reference (OR = 1.00), multivariate analysis confirmed the association of 4G-containing -844A/4G (P < 0.001) and -844G/4G (P = 0.011) haplotypes with increased RPL risk. 4G/5G, but not -844G/A, PAI-1 variant is associated with an increased risk of RPL. © 2013 John Wiley & Sons Ltd.

Decision-making under risk in children, adolescents, and young adults.

PubMed

Paulsen, David J; Platt, Michael L; Huettel, Scott A; Brannon, Elizabeth M

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk-return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk.

Commonalities between Disaster and Climate Change Risks for Health: A Theoretical Framework.

PubMed

Banwell, Nicola; Rutherford, Shannon; Mackey, Brendan; Street, Roger; Chu, Cordia

2018-03-16

Disasters and climate change have significant implications for human health worldwide. Both climate change and the climate-sensitive hazards that result in disasters, are discussed in terms of direct and indirect impacts on health. A growing body of literature has argued for the need to link disaster risk reduction and climate change adaptation. However, there is limited articulation of the commonalities between these health impacts. Understanding the shared risk pathways is an important starting point for developing joint strategies for adapting to, and reducing, health risks. Therefore, this article discusses the common aspects of direct and indirect health risks of climate change and climate-sensitive disasters. Based on this discussion a theoretical framework is presented for understanding these commonalities. As such, this article hopes to extend the current health impact frameworks and provide a platform for further research exploring opportunities for linked adaptation and risk reduction strategies.

Commonalities between Disaster and Climate Change Risks for Health: A Theoretical Framework

PubMed Central

Banwell, Nicola; Rutherford, Shannon; Mackey, Brendan; Street, Roger; Chu, Cordia

2018-01-01

Disasters and climate change have significant implications for human health worldwide. Both climate change and the climate-sensitive hazards that result in disasters, are discussed in terms of direct and indirect impacts on health. A growing body of literature has argued for the need to link disaster risk reduction and climate change adaptation. However, there is limited articulation of the commonalities between these health impacts. Understanding the shared risk pathways is an important starting point for developing joint strategies for adapting to, and reducing, health risks. Therefore, this article discusses the common aspects of direct and indirect health risks of climate change and climate-sensitive disasters. Based on this discussion a theoretical framework is presented for understanding these commonalities. As such, this article hopes to extend the current health impact frameworks and provide a platform for further research exploring opportunities for linked adaptation and risk reduction strategies. PMID:29547592

Ictal Cardiac Ryhthym Abnormalities.

PubMed

Ali, Rushna

2016-01-01

Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy.

Lipoprotein(a): Biology and Clinical Importance

PubMed Central

McCormick, Sally P A

2004-01-01

Lipoprotein(a) [Lp(a)] is a unique lipoprotein that has emerged as an independent risk factor for developing vascular disease. Plasma Lp(a) levels above the common cut-off level of 300 mg/L place individuals at risk of developing heart disease particularly if combined with other lipid and thrombogenic risk factors. Studies in humans have shown Lp(a) levels to be hugely variable and under strict genetic control, largely by the apolipoprotein(a) [apo(a)] gene. In general, Lp(a) levels have proven difficult to manipulate, although some factors have been identified that can influence levels. Research has shown that Lp(a) has a high affinity for the arterial wall and displays many athero-thrombogenic properties. While a definite function for Lp(a) has not been identified, the last two decades of research have provided much information on the biology and clinical importance of Lp(a). PMID:18516206

Interpretation of genetic testing for lynch syndrome in patients with putative familial colorectal cancer.

PubMed

Rybak, Christina; Hall, Michael J

2011-11-01

Colorectal cancer (CRC) risk assessment involves the evaluation of an individual's personal and family history for characteristics of an inherited susceptibility to develop CRC. Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is the most common cause of hereditary CRC, underlying 2% to 3% of patients with newly diagnosed (incident) CRC. Risk assessment for LS is complex, and the interpretation of the many available tests can be challenging even for the genetics specialist. A move toward universal (reflex) LS screening for mismatch repair in all patients with incident CRC supports the importance of improving the awareness and understanding of LS testing, teaching rational testing approaches, and honing interpretive skills among cancer care providers. This article reviews important clinical features of LS genetic evaluation using 3 pedigree-based case examples from the Fox Chase Cancer Center Gastrointestinal Risk Assessment Clinic.

Perspectives of comparing risks of environmental carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perera, F.; Boffetta, P.

1988-10-19

In 1987, investigators concluded that the risks of man-made industrial carcinogens and pesticides (outside of the workplace) are trivial compared with the risks of naturally occurring carcinogens found mostly in the diet. They used a ranking system based on human exposure and rodent potency (HERP) data to arrive at this conclusion. As a result, they recommend that regulatory agencies, such as the Environmental Protection Agency and the Food and Drug Administration, base their priorities in this area on their HERP system. We analyzed the assumptions and data set upon which the HERPs were based, concluding that such a simplified approachmore » to set public health policy is inappropriate given the underlying uncertainties. However, we note that when comparisons are consistently based on estimates of average daily exposure to common carcinogens, the HERP scores of many man-made pollutants are comparable to those of naturally occurring carcinogens in the diet.158 references.« less

The impact of Alzheimer disease genetics on expert and advanced gerontological nursing practice.

PubMed

Schutte, D L

1998-11-01

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the United States, affecting as many as 4 million people. Extensive research is under way to identify environmental and genetic risk factors for this complex disease. Currently, four genes are associated with an increased risk for AD: the amyloid precursor protein gene on chromosome 21, the Presenilin I gene on chromosome 14, the Presenilin II gene on chromosome 1, and the apolipoprotein E gene on chromosome 19. Expert and advanced practice gerontological nurses are faced with new challenges as a result of these gene discoveries. Gerontological nurses should assess for relevant environmental and genetic risk factors; obtain comprehensive family health histories recorded as pedigrees; integrate genetic information into diagnosis, intervention, and evaluation strategies; initiate and coordinate referrals to genetic specialists; and provide ongoing emotional and decision-making support for patients and families experiencing AD.

Dopamine Reward Prediction Error Responses Reflect Marginal Utility

PubMed Central

Stauffer, William R.; Lak, Armin; Schultz, Wolfram

2014-01-01

Summary Background Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. Results In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions’ shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. Conclusions These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). PMID:25283778

Classification and Reporting of Potentially Proarrhythmic Common Genetic Variation in Long QT Syndrome Genetic Testing.

PubMed

Giudicessi, John R; Roden, Dan M; Wilde, Arthur A M; Ackerman, Michael J

2018-02-06

The acquired and congenital forms of long QT syndrome represent 2 distinct but clinically and genetically intertwined disorders of cardiac repolarization characterized by the shared final common pathway of QT interval prolongation and risk of potentially life-threatening arrhythmias. Over the past 2 decades, our understanding of the spectrum of genetic variation that (1) perturbs the function of cardiac ion channel macromolecular complexes and intracellular calcium-handling proteins, (2) underlies acquired/congenital long QT syndrome susceptibility, and (3) serves as a determinant of QT interval duration in the general population has grown exponentially. In turn, these molecular insights led to the development and increased utilization of clinically impactful genetic testing for congenital long QT syndrome. However, the widespread adoption and potential misinterpretation of the 2015 American College of Medical Genetics and Genomics variant classification and reporting guidelines may have contributed unintentionally to the reduced reporting of common genetic variants, with compelling epidemiological and functional evidence to support a potentially proarrhythmic role in patients with congenital and acquired long QT syndrome. As a result, some genetic testing reports may fail to convey the full extent of a patient's genetic susceptibility for a potentially life-threatening arrhythmia to the ordering healthcare professional. In this white paper, we examine the current classification and reporting (or lack thereof) of potentially proarrhythmic common genetic variants and investigate potential mechanisms to facilitate the reporting of these genetic variants without increasing the risk of diagnostic miscues. © 2018 American Heart Association, Inc.

Refeeding syndrome--awareness, prevention and management.

PubMed

Mehanna, Hisham; Nankivell, Paul C; Moledina, Jamil; Travis, Jane

2009-01-26

Refeeding syndrome is an important, yet commonly overlooked condition affecting patients. It occurs when feeding is commenced after a period of starvation. Head and neck cancer patients are at particular risk owing to prolonged periods of poor nutritional intake. This may be from general effects such as cancer anorexia or from more specific problems of dysphagia associated with this group of patients. Awareness of the condition is crucial in identifying patients at risk and taking measures to prevent its occurrence. The aims of this review are to: 1) Highlight the condition and stress the importance of its consideration when admitting head and neck cancer patients. 2) Discuss the pathophysiology behind refeeding syndrome. 3) Review the literature for the best available evidence and guidelines. 4) Highlight the need for further high quality research. Refeeding syndrome is potentially fatal, yet is preventable. Awareness and identification of at-risk patients is crucial to improving management. Refeeding syndrome is caused by rapid refeeding after a period of under-nutrition, characterised by hypophosphataemia, electrolyte shifts and has metabolic and clinical complications. High risk patients include the chronically under-nourished and those with little intake for greater than 10 days. Patients with dysphagia are at particular risk. Refeeding should commence at 10 kcal/kg per day in patients at risk, and increased slowly. Thiamine, vitamin B complex and multi-vitamin supplements should be started with refeeding. New NICE guidelines state that pre-feeding correction of electrolyte and fluid deficits is unnecessary, but should be done concurrently with re-feeding. More research in this field is needed as the evidence base is lacking.

Refeeding syndrome – awareness, prevention and management

PubMed Central

Mehanna, Hisham; Nankivell, Paul C; Moledina, Jamil; Travis, Jane

2009-01-01

Background Refeeding syndrome is an important, yet commonly overlooked condition affecting patients. It occurs when feeding is commenced after a period of starvation. Head and neck cancer patients are at particular risk owing to prolonged periods of poor nutritional intake. This may be from general effects such as cancer anorexia or from more specific problems of dysphagia associated with this group of patients. Awareness of the condition is crucial in identifying patients at risk and taking measures to prevent its occurrence. Objectives The aims of this review are to: 1) Highlight the condition and stress the importance of its consideration when admitting head and neck cancer patients. 2) Discuss the pathophysiology behind refeeding syndrome. 3) Review the literature for the best available evidence and guidelines. 4) Highlight the need for further high quality research. Conclusion Refeeding syndrome is potentially fatal, yet is preventable. Awareness and identification of at-risk patients is crucial to improving management. Refeeding syndrome is caused by rapid refeeding after a period of under-nutrition, characterised by hypophosphataemia, electrolyte shifts and has metabolic and clinical complications. High risk patients include the chronically under-nourished and those with little intake for greater than 10 days. Patients with dysphagia are at particular risk. Refeeding should commence at 10 kcal/kg per day in patients at risk, and increased slowly. Thiamine, vitamin B complex and multi-vitamin supplements should be started with refeeding. New NICE guidelines state that pre-feeding correction of electrolyte and fluid deficits is unnecessary, but should be done concurrently with re-feeding. More research in this field is needed as the evidence base is lacking. PMID:19284691

Alcohol Mixed with Energy Drink Use and Sexual Risk-Taking: Casual, Intoxicated, and Unprotected Sex

PubMed Central

2012-01-01

Objective This study examined the confluence of several behaviors common to U.S. young adults: caffeinated energy drink use, alcohol use, and sexual risk-taking. The author examined relationships between the use of energy drinks mixed with alcohol (AmEDs) and three sexual risk behaviors: casual sex (i.e., intercourse with a nonexclusive and/or nonromantic partner), intoxicated sex (i.e., intercourse while under the influence of alcohol and/or illicit drugs), and unprotected sex (i.e., intercourse without use of a condom). Method Logistic regression analyses were employed to analyze data from a cross-sectional survey of 648 sexually active undergraduate students at a large public university. Results After controlling for risk-taking norms and frequency of noncaffeinated alcohol use, AmED use was associated with elevated odds of casual sex and intoxicated sex but not unprotected sex. Conclusions Although further studies are needed to test for event-level relationships, AmED use should be considered a possible risk factor for potentially health-compromising sexual behaviors. PMID:24761266

[Interview study on autonomous chemical management system and the contribution of occupational health specialists in companies].

PubMed

Mori, Koji; Takebayashi, Toru

2004-09-01

Under the circumstance that autonomous risk management for chemicals is required in Japan, it is necessary to define fundamental steps for developing chemical management system that are applicable in various types of companies and to understand the effective contribution of chemical or occupational health specialists to the system. For the purposes, we conducted interviews with companies which have an advanced chemical management system in Japan. As the result, each company had a certain policy about detailedness level of collected hazard and exposure information, and also had an efficient risk management system to ensure workers' health in depending on the business type and situations. Moreover, it was commonly observed that the specialists played major roles in developing tools for risk assessment and control, and then business lines led execution of the risk management with their supports. Based on the interviews, we showed a hypothesis of basic steps in introducing autonomous chemical risk management system at the workplaces. It is necessary to verify the hypothesis and to develop a simple system that is applicable to middle or small size companies as the next step.

Compensatory growth following transient intraguild predation risk in predatory mites.

PubMed

Walzer, Andreas; Lepp, Natalia; Schausberger, Peter

2015-05-01

Compensatory or catch-up growth following growth impairment caused by transient environmental stress, due to adverse abiotic factors or food, is widespread in animals. Such growth strategies commonly balance retarded development and reduced growth. They depend on the type of stressor but are unknown for predation risk, a prime selective force shaping life history. Anti-predator behaviours by immature prey typically come at the cost of reduced growth rates with potential negative consequences on age and size at maturity. Here, we investigated the hypothesis that transient intraguild predation (IGP) risk induces compensatory or catch-up growth in the plant-inhabiting predatory mite Phytoseiulus persimilis . Immature P. persimilis were exposed in the larval stage to no, low or high IGP risk, and kept under benign conditions in the next developmental stage, the protonymph. High but not low IGP risk prolonged development of P. persimilis larvae, which was compensated in the protonymphal stage by increased foraging activity and accelerated development, resulting in optimal age and size at maturity. Our study provides the first experimental evidence that prey may balance developmental costs accruing from anti-predator behaviour by compensatory growth.

Compensatory growth following transient intraguild predation risk in predatory mites

PubMed Central

Walzer, Andreas; Lepp, Natalia; Schausberger, Peter

2015-01-01

Compensatory or catch-up growth following growth impairment caused by transient environmental stress, due to adverse abiotic factors or food, is widespread in animals. Such growth strategies commonly balance retarded development and reduced growth. They depend on the type of stressor but are unknown for predation risk, a prime selective force shaping life history. Anti-predator behaviours by immature prey typically come at the cost of reduced growth rates with potential negative consequences on age and size at maturity. Here, we investigated the hypothesis that transient intraguild predation (IGP) risk induces compensatory or catch-up growth in the plant-inhabiting predatory mite Phytoseiulus persimilis. Immature P. persimilis were exposed in the larval stage to no, low or high IGP risk, and kept under benign conditions in the next developmental stage, the protonymph. High but not low IGP risk prolonged development of P. persimilis larvae, which was compensated in the protonymphal stage by increased foraging activity and accelerated development, resulting in optimal age and size at maturity. Our study provides the first experimental evidence that prey may balance developmental costs accruing from anti-predator behaviour by compensatory growth. PMID:26005221

Pediatric foreign bodies and their management.

PubMed

Kay, Marsha; Wyllie, Robert

2005-06-01

Ingestion of foreign bodies is a common pediatric problem, with more than 100,000 cases occurring each year. The vast majority of pediatric ingestions are accidental; increasing incidence of intentional ingestions starts in the adolescent age group. In the United States, the most common pediatric foreign bodies ingested are coins, followed by a variety of other objects, including toys, toy parts, sharp objects, batteries, bones, and food. In adolescents and adults, meat or food impactions are the most common accidental foreign body ingestion. Esophageal pathology underlies most cases of food impaction. Management of foreign body ingestions varies based on the object ingested, its location, and the patient's age and size. Esophageal foreign bodies as a group require early intervention because of their potential to cause respiratory symptoms and complications, esophageal erosions, or even an aortoesophageal fistula. Ingested batteries that lodge in the esophagus require urgent endoscopic removal even in the asymptomatic patient due to the high risk of complications. Sharp foreign bodies increase the foreign body complication rate from less than 1% to 15% to 35%, except for straight pins, which usually follow a relatively benign course unless multiple pins are ingested. Magnets are increasingly ingested, due to their ubiquitous nature and the perception that they do not pose a risk. Ingestion of multiple magnets creates a significant risk of obstruction, perforation, and fistula development. Methods to deal with foreign bodies include the suture technique, the double snare technique, and the combined forceps/snare technique for long, large, and sharp foreign bodies, along with newer equipment, such as retrieval nets and a variety of specialized forceps.

Occupational asthma in the developing and industrialised world: a review.

PubMed

Jeebhay, M F; Quirce, S

2007-02-01

Occupational asthma is the most common occupational lung disease in industrialised countries, and the second most common occupational lung disease reported after pneumoconioses in developing countries. The median proportion of adult cases of asthma attributable to occupational exposure is between 10% and 15%. The population attributable fraction appears to be similar in industrialised and developing countries characterised by rapid industrialisation (13-15%), but lower in less industrialised developing countries (6%). The high-risk occupations and industries associated with the development of occupational asthma vary depending on the dominant industrial sectors in a particular country. High-risk exposure to cleaning agents and pesticide exposure in developing countries appear to be as important as exposure to isocyanates, cereal flour/grain dust, welding fumes, wood dust and, more recently, hairdressing chemicals, commonly reported in industrialised countries. The reported mean annual incidence of occupational asthma in developing countries is less than 2 per 100 000 population, compared to very high rates of up to 18/100 000 in Scandinavian countries. While occupational asthma remains under-recognised, especially in developing countries, it remains poorly diagnosed and managed and inadequately compensated worldwide. Primary and secondary preventive strategies should be directed at controlling workplace exposures, accompanied by intense educational and managerial improvements. Appropriate treatment remains early removal from exposure to ensure that the worker has no further exposure to the causal agent, with preservation of income. However, up to one third of workers with occupational asthma continue to remain exposed to the causative agent or suffer prolonged work disruption, discrimination and risk of unemployment.

Occupational exposure to pesticides and resultant health problems among cotton farmers of Punjab, Pakistan.

PubMed

Khan, Muhammad; Damalas, Christos A

2015-01-01

Occupational exposure to pesticides and resultant health problems were assessed among 318 randomly selected cotton farmers from the two districts of Punjab, Pakistan. Heavy dependence of farmers on pesticides for pest control was reported. A large part (23.3%) of the pesticides belonged to the category highly hazardous, whereas the largest part (54.7%) belonged to the category moderately hazardous. Some of them (8%) were reported to be used on vegetables. Common working practices of high exposure risk were: the confrontation of pesticide spills in the stage of spray solution preparation (76.4%), the use of low-technology and faulty sprayers (67.9%), and spraying under inappropriate weather (46.5%). A large proportion (34%) of the farmers reported multiple intoxication symptoms by pesticide use; the most common were irritation of skin and eyes, headache, and dizziness. Nevertheless, most farmers thought these symptoms were usual; only few reported visiting the doctor. Findings clearly indicated a high level of risk exposure to pesticides among farmers of the study area, calling upon immediate interventions toward increasing awareness about alternative pest control practices with less pesticide use.

Fever in Children: Pearls and Pitfalls

PubMed Central

Barbi, Egidio; Marzuillo, Pierluigi; Neri, Elena; Krauss, Baruch S.

2017-01-01

Fever in children is a common concern for parents and one of the most frequent presenting complaints in emergency department visits, often involving non-pediatric emergency physicians. Although the incidence of serious infections has decreased after the introduction of conjugate vaccines, fever remains a major cause of laboratory investigation and hospital admissions. Furthermore, antipyretics are the most common medications administered to children. We review the epidemiology and measurement of fever, the meaning of fever and associated clinical signs in children of different ages and under special conditions, including fever in children with cognitive impairment, recurrent fevers, and fever of unknown origin. While the majority of febrile children have mild, self-resolving viral illness, a minority may be at risk of life-threatening infections. Clinical assessment differs markedly from adult patients. Hands-off evaluation is paramount for a correct evaluation of breathing, circulation and level of interaction. Laboratory markers and clinical prediction rules provide limited help in identifying children at risk for serious infections; however, clinical examination, prudent utilization of laboratory tests, and post-discharge guidance (“safety netting”) remain the cornerstone of safe management of febrile children. PMID:28862659

Hepatotoxic microcystin removal using pumice embedded monolithic composite cryogel as an alternative water treatment method.

PubMed

Gurbuz, Fatma; Ceylan, Şeyda; Odabaşı, Mehmet; Codd, Geoffrey A

2016-03-01

Microcystins are the most commonly encountered water-borne cyanotoxins which present short- and long-term risks to human health. Guidelines at international and national level, and legislation in some countries, have been introduced for the effective health risk management of these potent hepatotoxic, tumour-promoters. The stable cyclic structure of microcystins and their common production by cyanobacteria in waterbodies at times of high total dissolved organic carbon content presents challenges to drinking water treatment facilities, with conventional, advanced and novel strategies under evaluation. Here, we have studied the removal of microcystins using three different forms of pumice particles (PPs), which are embedded into macroporous cryogel columns. Macroporous composite cryogel columns (MCCs) are a new generation of separation media designed to face this challenging task. Three different MCCs were prepared by adding plain PPs, Cu(2+)-attached PPs and Fe(3+)-attached PPs to reaction media before the cryogelation step. Column studies showed that MCCs could be successfully used as an alternative water treatment method for successful microcystin removal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prediction versus aetiology: common pitfalls and how to avoid them.

PubMed

van Diepen, Merel; Ramspek, Chava L; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2017-04-01

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Essays in financial economics and econometrics

NASA Astrophysics Data System (ADS)

La Spada, Gabriele

Chapter 1 (my job market paper) asks the following question: Do asset managers reach for yield because of competitive pressures in a low rate environment? I propose a tournament model of money market funds (MMFs) to study this issue. I show that funds with different costs of default respond differently to changes in interest rates, and that it is important to distinguish the role of risk-free rates from that of risk premia. An increase in the risk premium leads funds with lower default costs to increase risk-taking, while funds with higher default costs reduce risk-taking. Without changes in the premium, low risk-free rates reduce risk-taking. My empirical analysis shows that these predictions are consistent with the risk-taking of MMFs during the 2006--2008 period. Chapter 2, co-authored with Fabrizio Lillo and published in Studies in Nonlinear Dynamics and Econometrics (2014), studies the effect of round-off error (or discretization) on stationary Gaussian long-memory process. For large lags, the autocovariance is rescaled by a factor smaller than one, and we compute this factor exactly. Hence, the discretized process has the same Hurst exponent as the underlying one. We show that in presence of round-off error, two common estimators of the Hurst exponent, the local Whittle (LW) estimator and the detrended fluctuation analysis (DFA), are severely negatively biased in finite samples. We derive conditions for consistency and asymptotic normality of the LW estimator applied to discretized processes and compute the asymptotic properties of the DFA for generic long-memory processes that encompass discretized processes. Chapter 3, co-authored with Fabrizio Lillo, studies the effect of round-off error on integrated Gaussian processes with possibly correlated increments. We derive the variance and kurtosis of the realized increment process in the limit of both "small" and "large" round-off errors, and its autocovariance for large lags. We propose novel estimators for the variance and lag-one autocorrelation of the underlying, unobserved increment process. We also show that for fractionally integrated processes, the realized increments have the same Hurst exponent as the underlying ones, but the LW estimator applied to the realized series is severely negatively biased in medium-sized samples.

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

PubMed

den Ruijter, H M; Peters, S A E; Groenewegen, K A; Anderson, T J; Britton, A R; Dekker, J M; Engström, G; Eijkemans, M J; Evans, G W; de Graaf, J; Grobbee, D E; Hedblad, B; Hofman, A; Holewijn, S; Ikeda, A; Kavousi, M; Kitagawa, K; Kitamura, A; Koffijberg, H; Ikram, M A; Lonn, E M; Lorenz, M W; Mathiesen, E B; Nijpels, G; Okazaki, S; O'Leary, D H; Polak, J F; Price, J F; Robertson, C; Rembold, C M; Rosvall, M; Rundek, T; Salonen, J T; Sitzer, M; Stehouwer, C D A; Witteman, J C; Moons, K G; Bots, M L

2013-07-01

The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Methylenetetrahydrofolate reductase gene polymorphisms contribute to acute myeloid leukemia and chronic myeloid leukemia susceptibilities: evidence from meta-analyses.

PubMed

He, Hairong; He, Gonghao; Wang, Taotao; Cai, Jiangxia; Wang, Yan; Zheng, Xiaowei; Dong, Yalin; Lu, Jun

2014-10-01

The expression of methylenetetrahydrofolate reductase (MTHFR) is associated with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Most studies have linked the common functional C677T and A1298C polymorphisms of the MTHFR gene and susceptibility to AML and CML, but the results were not consistent. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of MTHFR C677T and A1298C variations with AML and CML were conducted. Eligible articles were identified from the PubMed and EMBASE databases. All statistical analyses were conducted using Review Manager Software. 10 and 10 studies were included in the meta-analysis about the role of C677T polymorphism on the AML and CML risks, respectively; 6 and 4 studies were included about the role of A1298C polymorphism on the AML and CML risks, respectively. Overall, both the C677T and A1298C polymorphisms were significantly associated with CML risk under the recessive model (P=0.04, OR=1.35, 95% CI=1.02-1.79 for C677T and P=0.003, OR=2.17, 95% CI=1.29-3.63 for A1298C). In addition, the risk of CML was higher in 1298CC genotype carriers than in 1298AA genotype carriers (P=0.004, OR=2.17, 95%=1.28-3.69). Conversely, the overall data failed to indicate a significant association of C677T or A1298C polymorphisms with AML risk under any model. The findings provide evidence that C677T and A1298C polymorphisms are risk factors for CML risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Carotid angioplasty and stenting under protection. Techniques, results and limitations.

PubMed

Henry, M; Polydorou, A; Henry, I; Anagnostopoulou, I S; Polydorou, I A; Hugel, M

2006-10-01

A carotid stenosis is responsible for about 30% of strokes occurring. Carotid endarterectomy (CEA) is considered to be the gold standard treatment of a carotid stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative treatment for a carotid artery stenosis, but the risk of neurological complications and brain embolism remains the major drawback to this procedure. Therefore, in order to reduce the risks, we need: 1) good indications, good patient and lesion selection; 2) correct techniques; 3) brain protection devices (cerebral protection devices should be routinely used and are mandatory for any procedure); 4) 3 types of protection devices are available, but filters are the most commonly used (all protection devices have limitations and cannot prevent from all embolic events; however, neurological complications can be reduced by 60%); 5) a good choice of the stent and correct implantation (all stents are not equivalent and have different geometrical effects); 6) pharmacological adjuncts; 7) a good team. Recent studies have shown that CAS has superior short-term outcomes than CEA in high surgical risk patients, but there are enough reported data to conclude that CAS is also not inferior to CEA in low-risk patients. CAS under protection is the standard of care and is maybe becoming the gold standard treatment of a carotid stenosis at least in some subgroups of patients.

Prenatal exposure to ambient temperature variation increases the risk of common cold in children.

PubMed

Lu, Chan; Miao, Yufeng; Zeng, Ji; Jiang, Wei; Shen, Yong-Ming; Deng, Qihong

2018-06-15

Common cold is a frequent upper respiratory tract infection, but the role of ambient temperature in the infection is unclear. We investigated the role of prenatal exposure to diurnal temperature variation (DTV), the difference between the daily maximal and minimal temperatures, in the risk of common cold in children. We conducted a cohort study of 2598 preschool children in Changsha, China. Occurrence of common cold during the past year was surveyed using questionnaire. We then estimated each child's prenatal exposure to DTV during pregnancy. Multivariate logistic regression model was used to examine the association between occurrence of common cold and prenatal exposure to DTV in terms of odds ratios (OR) and 95% confidence interval (CI). About 45% children have common cold (≥3 times) during the past year. We found that common cold in children was associated with maternal DTV exposure during pregnancy, particularly during the first trimester with adjusted OR (95% CI) = 1.27 (1.10-1.46). Male and atopic children were more susceptible to the effect of DTV during pregnancy. The risk of common cold due to DTV is higher in children living in the suburban areas and the bigger houses and in those exposed to environmental tobacco smoke, mold/dampness, new furniture and redecoration. We observed that the risk of common cold in children has been increased in recent years due to increasing DTV. Common cold in children was associated with maternal exposure to temperature variation during pregnancy, suggesting that the risk of common cold may originate in pregnancy. Copyright © 2018 Elsevier Inc. All rights reserved.

Decision-Making Under Risk in Children, Adolescents, and Young Adults

PubMed Central

Paulsen, David J.; Platt, Michael L.; Huettel, Scott A.; Brannon, Elizabeth M.

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk–return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk. PMID:21687443

Skin phenotypes can offer some insight about the association between telomere length and cancer susceptibility.

PubMed

Ribero, S; Mangino, M; Bataille, V

2016-12-01

The role of telomere biology in cancer has been studied for a wide variety of different cancers but the association with telomere length has been controversial. This is because some cancers have been found to be associated with longer telomeres in circulating white cells whilst other cancer types are more common in individuals with shorter telomeres. Hence, there has been some skepticism as to whether telomere length may be helpful in estimating cancer risk. For melanoma, however, results have been fairly consistent showing that longer telomeres are associated with an increased risk. This link was first discovered because of a link between longer telomeres and a high number of naevi. In contrast, for cutaneous squamous cell carcinomas, the relationship is reversed with higher risk in individuals with shorter telomeres. Differences in skin phenotypes with the presence of high number of naevi versus photoageing with solar elastosis and solar keratoses have already been valuable for dermatologists as the former phenotype is associated with melanoma whilst the latter is more common in patients with squamous cell carcinoma of the skin. The hypothesis is that the differences in cutaneous phenotypes already observed by dermatologists for skin cancers may, in fact, be useful as well for cancer prediction in general as it may reflect underlying telomere biology. This manuscript will address the evidence for links between telomere biology, skin phenotypes and cancer risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pacemaker implantation after catheter ablation for atrial fibrillation.

PubMed

Deshmukh, Abhishek J; Yao, Xiaoxi; Schilz, Stephanie; Van Houten, Holly; Sangaralingham, Lindsey R; Asirvatham, Samuel J; Friedman, Paul A; Packer, Douglas L; Noseworthy, Peter A

2016-01-01

Sinus node dysfunction requiring pacemaker implantation is commonly associated with atrial fibrillation (AF), but may not be clinically apparent until restoration of sinus rhythm with ablation or cardioversion. We sought to determine frequency, time course, and predictors for pacemaker implantation after catheter ablation, and to compare the overall rates to a matched cardioversion cohort. We conducted a retrospective analysis using a large US commercial insurance database and identified 12,158 AF patients who underwent catheter ablation between January 1, 2005 and December 31, 2012. Over an average of 2.4 years of follow-up, 5.6 % of the patients underwent pacemaker implantation. Using the Cox proportional hazards models, we found that risk of risks of pacemaker implantation was associated with older age (50-64 and ≥65 versus <50 years), female gender, higher CHADS2 score (≥2 and 1 versus 0), higher Charlson index (≥2 versus 0-1), certain baseline comorbidities (conduction disorder, coronary atherosclerosis, and congestive heart failure), and the year of ablation. There was no significant difference in the risk of pacemaker implantation between ablation patients and propensity score (PS)-matched cardioversion groups (3.5 versus. 4.1 % at 1 year and 8.8 versus 8.3 % at 5 years). Overall, pacemaker implantation occurs in about 1/28 patients within 1 year of catheter ablation. The overall implantation rate decreased between 2005 and 2012. Furthermore, the risk after ablation is similar to cardioversion, suggesting that patients require pacing due to a common underlying electrophysiologic substrate, rather than the ablation itself.

Quantitative approach for incorporating methylmercury risks and omega-3 fatty acid benefits in developing species-specific fish consumption advice.

PubMed

Ginsberg, Gary L; Toal, Brian F

2009-02-01

Despite general agreement about the toxicity of methylmercury (MeHg), fish consumption advice remains controversial. Concerns have been raised that negative messages will steer people away from fish and omega-3 fatty acid (FA) benefits. One approach is to provide advice for individual species that highlights beneficial fish while cautioning against riskier fish. Our goal in this study was to develop a method to quantitatively analyze the net risk/benefit of individual fish species based on their MeHg and omega-3 FA content. We identified dose-response relationships for MeHg and omega-3 FA effects on coronary heart disease (CHD) and neurodevelopment. We used the MeHg and omega-3 FA content of 16 commonly consumed species to calculate the net risk/benefit for each species. Estimated omega-3 FA benefits outweigh MeHg risks for some species (e.g., farmed salmon, herring, trout); however, the opposite was true for others (swordfish, shark). Other species were associated with a small net benefit (e.g., flounder, canned light tuna) or a small net risk (e.g., canned white tuna, halibut). These results were used to place fish into one of four meal frequency categories, with the advice tentative because of limitations in the underlying dose-response information. Separate advice appears warranted for the neurodevelopmental risk group versus the cardiovascular risk group because we found a greater net benefit from fish consumption for the cardiovascular risk group. This research illustrates a framework for risk/benefit analysis that can be used to develop categories of consumption advice ranging from "do not eat" to "unlimited," with the caveat that unlimited may need to be tempered for certain fish (e.g., farm-raised salmon) because of other contaminants and end points (e.g., cancer risk). Uncertainties exist in the underlying dose-response relationships, pointing in particular to the need for more research on the adverse effects of MeHg on cardiovascular end points.

Bladder perforation during sling procedures: diagnosis and management of injury.

PubMed

Israfil-Bayli, F; Bulchandani, S; Parsons, M; Jackson, S; Toozs-Hobson, P

2014-05-01

Midurethral slings are an effective and minimally invasive treatment for stress urinary incontinence. One of the most common intraoperative complications is bladder perforation, complicating between 2 and 10% of all operations, and on average 4.7%. It is usually corrected during surgery, with repositioning of the trocars. The purpose of this video is to demonstrate a method of replacing the trocars under direct vision. This video exhibits a bladder perforation during insertion of a retropubic midurethral sling (Advantage Fit; Boston Scientific) and gives a step-by step guide to the removal and repositioning of the sling under direct visualisation. Repositioning of the trocars under direct vision in cases of bladder perforation may have numerous advantages. It may prevent damage to the urethra, possibly reduce the risk of postoperative infection and may be beneficial for trainees.

Perception of risk for older people living with a mental illness: Balancing uncertainty.

PubMed

Clancy, Leonie; Happell, Brenda; Moxham, Lorna

2015-12-01

Risk is commonly defined as a negative threat which needs to be controlled and mitigated; as a concept, it takes high priority in contemporary mental health services. Health-care organizations and clinicians are now required to use levels of risk as a benchmark for clinical decision-making. However, perceptions of risk change according to the lens through which it is viewed. A qualitative, exploratory research study was undertaken in an aged persons' mental health programme in Victoria, Australia, to explore the notion of risk from the multiple perspectives of service providers and consumers. Data were obtained through in-depth interviews, and analysis was based on the framework of Ritchie and Spencer. Balancing uncertainty emerged as a major theme, and comprised two subthemes: (i) complexity of risk from the perspective of providers of services; and (ii) complexity of safety from the perspectives of recipients of services. These differences emphasize a significant disjuncture between perceptions of risk and the potential for the individual needs and concerns of consumers to be subsumed under broader organizational issues. The uncertainty this tension highlights suggests the need to reconceptualize risk, incorporating the views and experiences of all stakeholders, particularly consumers and carers, to enhance recovery-oriented services and facilitate consumer participation within mental health services. © 2015 Australian College of Mental Health Nurses Inc.

Assessing the seismic risk potential of South America

USGS Publications Warehouse

Jaiswal, Kishor; Petersen, Mark D.; Harmsen, Stephen; Smoczyk, Gregory M.

2016-01-01

We present here a simplified approach to quantifying regional seismic risk. The seismic risk for a given region can be inferred in terms of average annual loss (AAL) that represents long-term value of earthquake losses in any one year caused from a long-term seismic hazard. The AAL are commonly measured in the form of earthquake shaking-induced deaths, direct economic impacts or indirect losses caused due to loss of functionality. In the context of South American subcontinent, the analysis makes use of readily available public data on seismicity, population exposure, and the hazard and vulnerability models for the region. The seismic hazard model was derived using available seismic catalogs, fault databases, and the hazard methodologies that are analogous to the U.S. Geological Survey’s national seismic hazard mapping process. The Prompt Assessment of Global Earthquakes for Response (PAGER) system’s direct empirical vulnerability functions in terms of fatality and economic impact were used for performing exposure and risk analyses. The broad findings presented and the risk maps produced herein are preliminary, yet they do offer important insights into the underlying zones of high and low seismic risks in the South American subcontinent. A more detailed analysis of risk may be warranted by engaging local experts, especially in some of the high risk zones identified through the present investigation.

Comparing probabilistic microbial risk assessments for drinking water against daily rather than annualised infection probability targets.

PubMed

Signor, R S; Ashbolt, N J

2009-12-01

Some national drinking water guidelines provide guidance on how to define 'safe' drinking water. Regarding microbial water quality, a common position is that the chance of an individual becoming infected by some reference waterborne pathogen (e.g. Cryptsporidium) present in the drinking water should < 10(-4) in any year. However the instantaneous levels of risk to a water consumer vary over the course of a year, and waterborne disease outbreaks have been associated with shorter-duration periods of heightened risk. Performing probabilistic microbial risk assessments is becoming commonplace to capture the impacts of temporal variability on overall infection risk levels. A case is presented here for adoption of a shorter-duration reference period (i.e. daily) infection probability target over which to assess, report and benchmark such risks. A daily infection probability benchmark may provide added incentive and guidance for exercising control over short-term adverse risk fluctuation events and their causes. Management planning could involve outlining measures so that the daily target is met under a variety of pre-identified event scenarios. Other benefits of a daily target could include providing a platform for managers to design and assess management initiatives, as well as simplifying the technical components of the risk assessment process.

Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma.

PubMed

Bresalier, Robert S

2018-06-12

Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.

Flood risk and cultural heritage: the case study of Florence (Italy)

NASA Astrophysics Data System (ADS)

Arrighi, Chiara; Castelli, Fabio; Brugioni, Marcello; Franceschini, Serena; Mazzanti, Bernardo

2016-04-01

Cultural heritage plays a key role for communities in terms of both identity and economic value. It is often under serious threat by natural hazards, nevertheless, quantitative assessments of risk are quite uncommon. This work addresses the flood risk assessment to cultural heritage in an exemplary art city, which is Florence, Italy. The risk assessment method here adopted borrows the most common definition of flood risk as the product of hazard, vulnerability and exposure, with some necessary adjustments. The risk estimation is carried out at the building scale for the whole UNESCO site, which coincides with the historical centre of the city. A distinction in macro- and micro-damage categories has been made according to the vulnerability of the objects at risk. Two damage macro-categories are selected namely cultural buildings and contents. Cultural buildings are classified in damage micro-categories as churches/religious complexes, libraries/archives and museums. The damages to the contents are estimated for four micro-categories: paintings, sculptures, books/prints and goldsmith's art. Data from hydraulic simulations for different recurrence scenarios, historical reports of the devastating 1966 flood and the cultural heritage recognition sheets allow estimating and mapping the annual expected number of works of art lost in absence of risk mitigation strategies.

Relative impacts of mitigation, temperature, and precipitation on 21st-century megadrought risk in the American Southwest

PubMed Central

Ault, Toby R.; Mankin, Justin S.; Cook, Benjamin I.; Smerdon, Jason E.

2016-01-01

Megadroughts are comparable in severity to the worst droughts of the 20th century but are of much longer duration. A megadrought in the American Southwest would impose unprecedented stress on the limited water resources of the area, making it critical to evaluate future risks not only under different climate change mitigation scenarios but also for different aspects of regional hydroclimate. We find that changes in the mean hydroclimate state, rather than its variability, determine megadrought risk in the American Southwest. Estimates of megadrought probabilities based on precipitation alone tend to underestimate risk. Furthermore, business-as-usual emissions of greenhouse gases will drive regional warming and drying, regardless of large precipitation uncertainties. We find that regional temperature increases alone push megadrought risk above 70, 90, or 99% by the end of the century, even if precipitation increases moderately, does not change, or decreases, respectively. Although each possibility is supported by some climate model simulations, the latter is the most common outcome for the American Southwest in Coupled Model Intercomparison 5 generation models. An aggressive reduction in global greenhouse gas emissions cuts megadrought risks nearly in half. PMID:27713927

Relative Impacts of Mitigation, Temperature, and Precipitation on 21st-Century Megadrought Risk in the American Southwest

NASA Technical Reports Server (NTRS)

Ault, Toby R.; Mankin, Justin S.; Cook, Benjamin I.; Smerdon, Jason E.

2015-01-01

Megadroughts are comparable in severity to the worst droughts of the 20th century but are of much longer duration. A megadrought in the American Southwest would impose unprecedented stress on the limited water resources of the area, making it critical to evaluate future risks not only under different climate change mitigation scenarios but also for different aspects of regional hydroclimate. We find that changes in the mean hydroclimate state, rather than its variability, determine megadrought risk in the American Southwest. Estimates of megadrought probabilities based on precipitation alone tend to underestimate risk. Furthermore, business-as-usual emissions of greenhouse gases will drive regional warming and drying, regardless of large precipitation uncertainties. We find that regional temperature increases alone push megadrought risk above 70, 90, or 99% by the end of the century, even if precipitation increases moderately, does not change, or decreases, respectively. Although each possibility is supported by some climate model simulations, the latter is the most common outcome for the American Southwest in Coupled Model Intercomparison 5 generation models. An aggressive reduction in global greenhouse gas emissions cuts megadrought risks nearly in half.

Chronic kidney disease risk reduction in a Hispanic population through pharmacist-based disease-state management.

PubMed

Leal, Sandra; Soto, Marisa

2008-04-01

The purpose of this study was to evaluate the ability of a pharmacist-based disease-state management service to improve the care of indigent, predominately Spanish-speaking patients with diabetes mellitus and common comorbid conditions at high risk for the development of chronic kidney disease (CKD). Patients at high risk for developing CKD who have diabetes at a community health center were placed in a pharmacist-based disease state management service for CKD risk reduction. A residency-trained, bilingual, certified diabetes educator, with a PharmD served as the patient's provider using diagnostic, educational, and therapeutic management services under a medical staff approved collaborative practice agreement. Outcomes were assessed by using national standards of care for disease control and prevention screening. The impact on CKD was shown with a mean A1C decrease of 2% and improvement in the proportion of patients at target goals for blood pressure, A1C, and cholesterol levels and receiving aspirin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. A pharmacist-based disease-state management service for CKD risk reduction, care of diabetes, and frequently associated comorbid conditions improved compliance with national standards for diabetes care in a high-risk population.

Contribution of 32 GWAS-Identified Common Variants to Severe Obesity in European Adults Referred for Bariatric Surgery

PubMed Central

Yousseif, Ahmed; Pucci, Andrea; Santini, Ferruccio; Karra, Efthimia; Querci, Giorgia; Pelosini, Caterina; McCarthy, Mark I.; Lindgren, Cecilia M.; Batterham, Rachel L.

2013-01-01

The prevalence of severe obesity, defined as body mass index (BMI) ≥35.0 kg/m2, is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, we sought to determine whether a panel of 32 known common obesity-susceptibility variants contribute to severe obesity in patients (n = 1,003, mean BMI 48.4±8.1 kg/m2) attending bariatric surgery clinics in two European centres. We examined the effects of these 32 common variants on obesity risk and BMI, both as individual markers and in combination as a genetic risk score, in a comparison with normal-weight controls (n = 1,809, BMI 18.0–24.9 kg/m2); an approach which, to our knowledge, has not been previously undertaken in the setting of a bariatric clinic. We found strong associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3×10−8) and SNP rs2815752 near the NEGR1 gene (P = 3.6×10−4), and directionally consistent nominal associations (P<0.05) for 12 other SNPs. The genetic risk score associated with severe obesity (P = 8.3×10−11) but, within the bariatric cohort, this score did not associate with BMI itself (P = 0.264). Our results show significant effects of individual BMI-associated common variants within a relatively small sample size of bariatric patients. Furthermore, the burden of such low-penetrant risk alleles contributes to severe obesity in this population. Our findings support that severe obesity observed in bariatric patients represents an extreme tail of the population BMI variation. Moreover, future genetic studies focused on bariatric patients may provide valuable insights into the pathogenesis of obesity at a population level. PMID:23950990

Fine Mapping on Chromosome 13q32–34 and Brain Expression Analysis Implicates MYO16 in Schizophrenia

PubMed Central

Rodriguez-Murillo, Laura; Xu, Bin; Roos, J Louw; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2014-01-01

We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32–34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32–34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case–control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case–control data sets of European descent highlighted a region across introns 2–6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia. PMID:24141571

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

PubMed

Milne, Roger L; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J; Lissowska, Jolanta; Figueroa, Jonine D; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Hooning, Maartje J; Kriege, Mieke; van den Ouweland, Ans M W; Koppert, Linetta B; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S; Labrèche, France; Fasching, Peter A; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L; Schmidt, Daniel F; Makalic, Enes; Southey, Melissa C; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J; Toland, Amanda E; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D P; Hall, Per; Giles, Graham G; Benítez, Javier; Dunning, Alison M; Chenevix-Trench, Georgia; Easton, Douglas F

2014-11-15

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act. © The Author 2014. Published by Oxford University Press.

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

PubMed Central

Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M.W.; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.P.; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.; Berchuck, Andrew; Eeles, Rosalind A.; Olama, Ali Amin Al; Kote-Jarai, Zsofia; Benlloch, Sara; Antoniou, Antonis; McGuffog, Lesley; Offit, Ken; Lee, Andrew; Dicks, Ed; Luccarini, Craig; Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel; LaBoissière, Sylvie; Robidoux, Frederic; Nielsen, Sune F.; Cunningham, Julie M.; Windebank, Sharon A.; Hilker, Christopher A.; Meyer, Jeffrey; Angelakos, Maggie; Maskiell, Judi; van der Schoot, Ellen; Rutgers, Emiel; Verhoef, Senno; Hogervorst, Frans; Boonyawongviroj, Prat; Siriwanarungsan, Pornthep; Schrauder, Michael; Rübner, Matthias; Oeser, Sonja; Landrith, Silke; Williams, Eileen; Ryder-Mills, Elaine; Sargus, Kara; McInerney, Niall; Colleran, Gabrielle; Rowan, Andrew; Jones, Angela; Sohn, Christof; Schneeweiß, Andeas; Bugert, Peter; Álvarez, Núria; Lacey, James; Wang, Sophia; Ma, Huiyan; Lu, Yani; Deapen, Dennis; Pinder, Rich; Lee, Eunjung; Schumacher, Fred; Horn-Ross, Pam; Reynolds, Peggy; Nelson, David; Ziegler, Hartwig; Wolf, Sonja; Hermann, Volker; Lo, Wing-Yee; Justenhoven, Christina; Baisch, Christian; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Heikkinen, Tuomas; Erkkilä, Irja; Aaltonen, Kirsimari; von Smitten, Karl; Antonenkova, Natalia; Hillemanns, Peter; Christiansen, Hans; Myöhänen, Eija; Kemiläinen, Helena; Thorne, Heather; Niedermayr, Eveline; Bowtell, D; Chenevix-Trench, G; deFazio, A; Gertig, D; Green, A; Webb, P; Green, A.; Parsons, P.; Hayward, N.; Webb, P.; Whiteman, D.; Fung, Annie; Yashiki, June; Peuteman, Gilian; Smeets, Dominiek; Brussel, Thomas Van; Corthouts, Kathleen; Obi, Nadia; Heinz, Judith; Behrens, Sabine; Eilber, Ursula; Celik, Muhabbet; Olchers, Til; Manoukian, Siranoush; Peissel, Bernard; Scuvera, Giulietta; Zaffaroni, Daniela; Bonanni, Bernardo; Feroce, Irene; Maniscalco, Angela; Rossi, Alessandra; Bernard, Loris; Tranchant, Martine; Valois, Marie-France; Turgeon, Annie; Heguy, Lea; Sze Yee, Phuah; Kang, Peter; Nee, Kang In; Mariapun, Shivaani; Sook-Yee, Yoon; Lee, Daphne; Ching, Teh Yew; Taib, Nur Aishah Mohd; Otsukka, Meeri; Mononen, Kari; Selander, Teresa; Weerasooriya, Nayana; staff, OFBCR; Krol-Warmerdam, E.; Molenaar, J.; Blom, J.; Brinton, Louise; Szeszenia-Dabrowska, Neonila; Peplonska, Beata; Zatonski, Witold; Chao, Pei; Stagner, Michael; Bos, Petra; Blom, Jannet; Crepin, Ellen; Nieuwlaat, Anja; Heemskerk, Annette; Higham, Sue; Cross, Simon; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Brock, Ian; Luccarini, Craig; Conroy, Don; Baynes, Caroline; Chua, Kimberley

2014-01-01

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04–1.10, P = 2.9 × 10−6], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03–1.07, P = 1.7 × 10−6) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07–1.12, P = 5.1 × 10−17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05–1.10, P = 1.0 × 10−8); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04–1.07, P = 2.0 × 10−10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act. PMID:24943594

Data-driven risk models could help target pipeline safety inspections

DOT National Transportation Integrated Search

2008-07-01

Federal safety agencies share a common problemthe : need to target resources effectively to reduce risk. One : way this targeting is commonly done is with a risk model : that uses safety data along with expert judgment to identify : and weight ris...

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

PubMed

Ishii, Makoto; Iadecola, Costantino

2016-05-01

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

PubMed

Qiu, Anqi; Shen, Mojun; Buss, Claudia; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Wadhwa, Pathik D; Entringer, Sonja; Styner, Martin; Karnani, Neerja; Heim, Christine M; O'Donnell, Kieran J; Holbrook, Joanna D; Fortier, Marielle V; Meaney, Michael J

2017-05-01

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development. © The Author 2017. Published by Oxford University Press.

Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology.

PubMed

Jackson, Robert; Rosa, Bruce A; Lameiras, Sonia; Cuninghame, Sean; Bernard, Josee; Floriano, Wely B; Lambert, Paul F; Nicolas, Alain; Zehbe, Ingeborg

2016-11-02

Human papillomaviruses (HPVs) are a worldwide burden as they are a widespread group of tumour viruses in humans. Having a tropism for mucosal tissues, high-risk HPVs are detected in nearly all cervical cancers. HPV16 is the most common high-risk type but not all women infected with high-risk HPV develop a malignant tumour. Likely relevant, HPV genomes are polymorphic and some HPV16 single nucleotide polymorphisms (SNPs) are under evolutionary constraint instigating variable oncogenicity and immunogenicity in the infected host. To investigate the tumourigenicity of two common HPV16 variants, we used our recently developed, three-dimensional organotypic model reminiscent of the natural HPV infectious cycle and conducted various "omics" and bioinformatics approaches. Based on epidemiological studies we chose to examine the HPV16 Asian-American (AA) and HPV16 European Prototype (EP) variants. They differ by three non-synonymous SNPs in the transforming and virus-encoded E6 oncogene where AAE6 is classified as a high- and EPE6 as a low-risk variant. Remarkably, the high-risk AAE6 variant genome integrated into the host DNA, while the low-risk EPE6 variant genome remained episomal as evidenced by highly sensitive Capt-HPV sequencing. RNA-seq experiments showed that the truncated form of AAE6, integrated in chromosome 5q32, produced a local gene over-expression and a large variety of viral-human fusion transcripts, including long distance spliced transcripts. In addition, differential enrichment of host cell pathways was observed between both HPV16 E6 variant-containing epithelia. Finally, in the high-risk variant, we detected a molecular signature of host chromosomal instability, a common property of cancer cells. We show how naturally occurring SNPs in the HPV16 E6 oncogene cause significant changes in the outcome of HPV infections and subsequent viral and host transcriptome alterations prone to drive carcinogenesis. Host genome instability is closely linked to viral integration into the host genome of HPV-infected cells, which is a key phenomenon for malignant cellular transformation and the reason for uncontrolled E6 oncogene expression. In particular, the finding of variant-specific integration potential represents a new paradigm in HPV variant biology.

National Kidney Foundation consensus conference on cardiovascular and kidney diseases and diabetes risk: an integrated therapeutic approach to reduce events.

PubMed

Bakris, George; Vassalotti, Joseph; Ritz, Eberhard; Wanner, Christoph; Stergiou, George; Molitch, Mark; Nesto, Richard; Kaysen, George A; Sowers, James R

2010-10-01

Cardiovascular disease (CVD) is the most common cause of death in industrialized nations. Type 2 diabetes is a CVD risk factor that confers risk similar to a previous myocardial infarction in an individual who does not have diabetes. In addition, the most common cause of chronic kidney disease (CKD) is diabetes. Together, diabetes and hypertension account for more than two-thirds of CVD risk, and other risk factors such as dyslipidemia contribute to the remainder of CVD risk. CKD, particularly with presence of significant albuminuria, should be considered an additional cardiovascular risk factor. There is no consensus on how to assess and stratify risk for patients with kidney disease across subspecialties that commonly treat such patients. This paper summarizes the results of a consensus conference utilizing a patient case to discuss the integrated management of hypertension, kidney disease, dyslipidemia, diabetes, and heart failure across disciplines.

Self-control and its relation to joint developmental trajectories of cannabis use and depressive mood symptoms.

PubMed

Otten, Roy; Barker, Edward D; Maughan, Barbara; Arseneault, Louise; Engels, Rutger C M E

2010-12-01

Cannabis use and depressive mood symptoms in adolescence have been found to co-occur. In exploring the nature of this relationship and in the search for mechanisms that explain this link, scholars have postulated the idea for a 'common liability model'. According to this model, the link between cannabis use and depressive symptoms can be explained by an underlying risk factor. One important candidate for this underlying risk factor may be self-control, as a reflection of immature self-regulatory systems in adolescence. In the present study, we will test the extent to which joint development of cannabis use and depressive symptoms can be explained as an expression of self-control. A total of 428 adolescents participated in a five-wave longitudinal design. Main study outcomes were self-reports of self-control (age 12) and cannabis use and depressive symptoms (ages 12-16). We established six trajectories of joint development of cannabis use and depressive symptoms. Conditional probabilities indicated that cannabis use and depressive symptoms were symmetrically related. Levels of self-control were lowest for adolescents following the joint developmental pathway of cannabis use and high depressive symptoms. Low levels of self-control are predictive of joint development of cannabis use and depressive symptoms. Future studies should concentrate on the role of self-control in co-occurrence of other health risk behaviors and on psychological and physiological mechanisms underlying self-control and its relation to co-occurrence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The fetal programming of telomere biology hypothesis: an update

PubMed Central

Entringer, Sonja; Buss, Claudia; Wadhwa, Pathik D.

2018-01-01

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing–related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal–placental–fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’. PMID:29335381

The fetal programming of telomere biology hypothesis: an update.

PubMed

Entringer, Sonja; de Punder, Karin; Buss, Claudia; Wadhwa, Pathik D

2018-03-05

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions.This article is part of the theme issue 'Understanding diversity in telomere dynamics'. © 2018 The Author(s).

The potential of large studies for building genetic risk prediction models

Cancer.gov

NCI scientists have developed a new paradigm to assess hereditary risk prediction in common diseases, such as prostate cancer. This genetic risk prediction concept is based on polygenic analysis—the study of a group of common DNA sequences, known as singl

Healthier central England or North-South divide? Analysis of national survey data on smoking and high-risk drinking.

PubMed

Beard, Emma; Brown, Jamie; West, Robert; Angus, Colin; Kaner, Eileen; Michie, Susan

2017-03-01

This paper compares patterns of smoking and high-risk alcohol use across regions in England, and assesses the impact on these of adjusting for sociodemographic characteristics. Population survey of 53 922 adults in England aged 16+ taking part in the Alcohol and Smoking Toolkit Studies. Participants answered questions regarding their socioeconomic status (SES), gender, age, ethnicity, Government Office Region, smoking status and completed the Alcohol Use Disorders Identification Test (AUDIT). High-risk drinkers were defined as those with a score of 8 or more (7 or more for women) on the AUDIT. In unadjusted analyses, relative to the South West, those in the North of England were more likely to smoke, while those from the East of England, South East and London were less likely. After adjustment for sociodemographics, smoking prevalence was no higher in North East (RR 0.97, p>0.05), North West (RR 0.98, p>0.05) or Yorkshire and the Humber (RR 1.03, p>0.05) but was less common in the East and West Midlands (RR 0.86, p<0.001; RR 0.91, p<0.05), East of England (RR 0.86, p<0.001), South East (RR 0.92, p<0.05) and London (RR 0.85, p<0.001). High-risk drinking was more common in the North but was less common in the Midlands, London and East of England. Adjustment for sociodemographics had little effect. There was a higher prevalence in the North East (RR 1.67, p<0.001), North West (RR 1.42, p<0.001) and Yorkshire and the Humber (RR 1.35, p<0.001); lower prevalence in the East Midlands (RR 0.69, p<0.001), West Midlands (RR 0.77, p<0.001), East of England (RR 0.72, p<0.001) and London (RR 0.71, p<0.001); and a similar prevalence in the South East (RR 1.10, p>0.05) CONCLUSIONS: In adjusted analyses, smoking and high-risk drinking appear less common in 'central England' than in the rest of the country. Regional differences in smoking, but not those in high-risk drinking, appear to be explained to some extent by sociodemographic disparities. 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/.

Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe

PubMed Central

Cortinovis, Cristina; Caloni, Francesca

2015-01-01

Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. PMID:26670251

Common risk factors for postoperative pain following the extraction of wisdom teeth

PubMed Central

2015-01-01

The extraction of third molars is a common task carried out at dental/surgery clinics. Postoperative pain is one of the two most common complications of this surgery, along with dry socket. Knowledge of the frequent risk factors of this complication is useful in determining high-risk patients, planning treatment, and preparing the patients mentally. Since the risk factors for postoperative pain have never been summarized before while the risk factors for dry socket have been highly debated, this report summarizes the literature regarding the common predictors of postextraction pain. Except for surgical difficulty and the surgeon's experience, the influences of other risk factors (age, gender and oral contraceptive use) were rather inconclusive. The case of a female gender or oral contraceptive effect might mainly be associated with estrogen levels (when it comes to dry socket), which can differ considerably from case to case. Improvement in and unification of statistical and diagnostic methods seem necessary. In addition, each risk factor was actually a combination of various independent variables, which should instead be targeted in more comprehensive studies. PMID:25922816

Risk factors for abnormal liver function tests in patients with ileal pouch-anal anastomosis for underlying inflammatory bowel disease.

PubMed

Navaneethan, Udayakumar; Remzi, Feza H; Nutter, Benjamin; Fazio, Victor W; Shen, Bo

2009-10-01

Liver involvement is common in patients with inflammatory bowel disease (IBD). However, the frequency and the significance of liver function test (LFT) abnormalities in patients with ileal pouch-anal anastomosis (IPAA) for underlying IBD have not been studied. The aim of this study was to evaluate the prevalence and to identify risk factors for abnormal LFTs in patients with IPAA and underlying IBD. All patients were identified from our prospectively maintained Pouchitis Database between 2002 and 2008. Abnormal LFTs were classified as the following: (i) any abnormal elevation of transaminases, and/or alkaline phosphatase (ALP), and/or bilirubin; (ii) hepatitis, if there was more than twice the elevation of transaminases; and (iii) cholestatic, if there was more than 1.5 times elevation of ALP. Clinical, endoscopic, and histological variables were assessed using Cox proportional hazard models for evaluating risk for abnormal LFTs. A total of 545 IPAA patients with underlying IBD were identified from the database, of which 373 patients who had LFTs done after their pouch surgery were included. This included 346 patients with ulcerative colitis, 25 with indeterminate colitis, and 2 with Crohn's colitis before surgery. Their mean age was 45.9+/-13.8 years. A total of 65 patients (17.4%) (40 men, 25 women, median age: 47 years) had abnormal LFTs. Of the patients, 52 (13.9%) had abnormal transaminases, whereas 15 (4%) were classified as having hepatitis. Thirty-five (9.4%) patients had an abnormal ALP level, with 18 (4.8%) classified as cholestatic. The most common cause of an abnormal LFT was transient elevation in 32 (49.2%) patients, followed by fatty liver (fatty change on imaging with body mass index (BMI) > or =25 kg/m(2) in the absence of other causes, including alcohol abuse and drug-induced hepatitis) in 10 (15.4%), drug-induced abnormal LFTs in 7 (10.7%), and chronic hepatitis B or C in 6 (9.2%). Primary sclerosing cholangitis (PSC) was responsible for abnormal LFTs in 10 patients (15.4%). Cox proportional hazard model analysis showed that BMI (hazard ratio (HR)=1.07, 95% confidence interval (95% CI): 1.02, 1.12; P=0.003), the presence of PSC (HR=4.49, 95% CI: 1.45, 13.89; P=0.009), autoimmune disorder (HR=2.54, 95% CI: 1.09, 5.93; P=0.031), a family history of IBD (HR=2.32, 95% CI: 1.29, 4.17; P=0.005), and extensive colitis before colectomy (HR=4.59, 95% CI: 2.04, 10.33; P<0.001) predicted any abnormal LFTs. Abnormal LFTs were common in patients with IPAA in this cohort. The presence of co-existing autoimmune disorder, a family history of IBD, extensive colitis before colectomy, the presence of PSC, and a high BMI appear to be a significant risk factors for abnormal LFTs. Whether abnormal LFTs affect health-related quality of life, pouch survival, and selection of pouch-related medical therapy requires further investigation.

Measuring risky adolescent cycling behaviour.

PubMed

Feenstra, Hans; Ruiter, Robert A C; Schepers, Jan; Peters, Gjalt-Jorn; Kok, Gerjo

2011-09-01

Adolescents are at a greater risk of being involved in traffic accidents than most other age groups, even before they start driving cars. This article aims to determine the factor structure of a self-report questionnaire measuring adolescent risky cycling behaviour, the ACBQ (Adolescent Cycling Behaviour Questionnaire). The questionnaire's structure was based on the widely used Driver Behaviour Questionnaire (DBQ). A sample of secondary school students (N = 1749; age range: 13-18 years) filled out the questionnaire. Factor analysis revealed a three-factor structure underlying the questionnaire, which was confirmed on two equally large portions of the entire sample. These three underlying factors were identified as errors, common violations and exceptional violations. The ACBQ is a useful instrument for measuring adolescents' risky cycling behaviour.

Violence and aggression in the emergency department is under-reported and under-appreciated.

PubMed

Richardson, Sandra K; Grainger, Paula C; Ardagh, Michael W; Morrison, Russell

2018-06-08

To examine levels of reporting of violence and aggression within a tertiary level emergency department in New Zealand, and to explore staff attitudes to violence and reporting. A one-month intensive, prospective audit of the emergency department's violence and aggression reporting was undertaken and compared with previously reported data. There was a significant mismatch between the number of events identified during the campaign month and previously reported instances of violence and aggression. The findings identified that failure to report acts of violence was common. Reports of violence and aggression in the emergency department underestimate the true incidence. Failure to report has potential impacts on organisational recognition of risk and the ability to develop appropriate policy responses.

Definitions of climate and climate change under varying external conditions

NASA Astrophysics Data System (ADS)

Werndl, C.

2014-06-01

Commonly, definitions of climate are endorsed where the external conditions are held constant. This paper argues that these definitions risk being empirically void because in reality the external conditions vary. As a consequence, analogous definitions for varying external conditions are explored with help of the recently developed theory of non-autonomous dynamical systems, and the similarities and differences between the cases of constant and varying external conditions are discussed. It is argued that there are analogous definitions for varying external conditions which are preferable to the definitions where the external conditions are held constant. In this context, a novel definition is proposed (namely, climate as the distribution over time under a regime of varying external conditions), which is argued to be promising.

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.

PubMed

Henström, Maria; Diekmann, Lena; Bonfiglio, Ferdinando; Hadizadeh, Fatemeh; Kuech, Eva-Maria; von Köckritz-Blickwede, Maren; Thingholm, Louise B; Zheng, Tenghao; Assadi, Ghazaleh; Dierks, Claudia; Heine, Martin; Philipp, Ute; Distl, Ottmar; Money, Mary E; Belheouane, Meriem; Heinsen, Femke-Anouska; Rafter, Joseph; Nardone, Gerardo; Cuomo, Rosario; Usai-Satta, Paolo; Galeazzi, Francesca; Neri, Matteo; Walter, Susanna; Simrén, Magnus; Karling, Pontus; Ohlsson, Bodil; Schmidt, Peter T; Lindberg, Greger; Dlugosz, Aldona; Agreus, Lars; Andreasson, Anna; Mayer, Emeran; Baines, John F; Engstrand, Lars; Portincasa, Piero; Bellini, Massimo; Stanghellini, Vincenzo; Barbara, Giovanni; Chang, Lin; Camilleri, Michael; Franke, Andre; Naim, Hassan Y; D'Amato, Mauro

2018-02-01

IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase ( SI ) gene variants for their potential relevance in IBS. We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients. 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/.

Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events.

PubMed

Prati, Patrizio; Tosetto, Alberto; Vanuzzo, Diego; Bader, Giovanni; Casaroli, Marco; Canciani, Luigi; Castellani, Sergio; Touboul, Pierre-Jean

2008-09-01

The clinical usefulness of noninvasive measurement of carotid intima media thickness and plaque visualization in the general population is still uncertain. We evaluated the age-specific incidence rates of cerebrovascular events in a cohort of 1348 subjects randomly taken from the census list of San Daniele Township and followed for a mean period of 12.7 years. The association among common carotid intima media thickness, measured at baseline, arterial risk factors, and incidence of ischemic cerebrovascular events was modeled using Poisson regression. The predictive ability of common carotid intima media thickness over arterial risk factors (summarized in the Framingham Stroke Risk Score) was evaluated by receiver operating characteristic curve analysis. During the follow-up, 115 subjects developed nonfatal ischemic stroke, transient ischemic attack, or vascular death, which were the predefined study end points. After adjustment for age and sex, hypertension, diabetes, common carotid intima media thickness above 1 mm, and carotid plaques were all independent risk factors for development of vascular events. Inclusion of carotid findings (presence of common carotid intima media thickness above 1 mm or carotid plaques) resulted in a predictive power higher than Framingham Stroke Risk Score alone only on for those subjects with a Framingham Stroke Risk Score over 20%. Although common carotid intima media thickness and presence of carotid plaques are known to be risk factors for the development of vascular events and to be independent from the conventional risk factors summarized in the Framingham Stroke Risk Score, their contribution to individual risk prediction is limited. Further studies will be required to address the role of carotid ultrasonography in the primary prevention of high-risk subjects.

Biochemical abnormalities in neonatal seizures.

PubMed

Sood, Arvind; Grover, Neelam; Sharma, Roshan

2003-03-01

The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

Respiratory-aspirated 35-mm hairpin successfully retrieved with a Teflon® snare system under fluoroscopic guidance via a split endotracheal tube: a useful technique in cases of failed extraction by bronchoscopy and avoiding the need for a thoracotomy.

PubMed

Gill, S S; Pease, R A; Ashwin, C J; Gill, S S; Tait, N P

2012-09-01

Respiratory foreign body aspiration (FBA) is a common global health problem requiring prompt recognition and early treatment to prevent potentially fatal complications. The majority of FBAs are due to organic objects and treatment is usually via either endoscopic or surgical extraction. FBA of a straight hairpin has been described as a unique entity in the literature, occurring most commonly in females, particularly during adolescence. In the process of inserting hairpins, the pins will typically be between the teeth with the head tilted backwards, while tying their hair with both hands. This position increases the risk of aspiration, particularly if there is any sudden coughing or laughing. To our knowledge, this is the first case report of a 35-mm straight metallic hairpin foreign body that has been successfully retrieved by a radiological snare system under fluoroscopic guidance. This was achieved with the use of a split endotracheal tube, and therefore avoided the need for a thoracotomy in an adolescent female patient.

Diagnosis and medical treatment of otitis externa in the dog and cat.

PubMed

Jacobson, L S

2002-12-01

Otitis externa is no longer viewed as an isolated disease of the ear canal, but is a syndrome that is often a reflection of underlying dermatological disease. Causes are classified as predisposing (increase the risk of otitis); primary (directly induce otitis), secondary (contribute to otitis only in an abnormal ear or in conjunction with predisposing factors) and perpetuating (result from inflammation and pathology in ear, prevent resolution of otitis). Common primary causes include foreign bodies, hypersensitivity (particularly atopy and food allergy), keratinisation disorders (most commonly primary idiopathic seborrhoea and hypothyroidism) and earmites, particularly in cats. A systematic diagnostic procedure is required to identify causes and contributing factors. This should include history, clinical examination, otoscopy and cytology in all cases and culture and sensitivity as well as otitis media assessment and biopsy in severe and recurrent cases. Ancillary tests may be required depending on the underlying cause. Treatment consists of identifying and addressing predisposing and primary factors; cleaning the ear canal; topical therapy; systemic therapy where necessary; client education; follow-up; and preventive and maintenance therapy as required.

Hunting for genes for hypertension: the Millennium Genome Project for Hypertension.

PubMed

Tabara, Yasuharu; Kohara, Katsuhiko; Miki, Tetsuro

2012-06-01

The Millennium Genome Project for Hypertension was started in 2000 to identify genetic variants conferring susceptibility to hypertension, with the aim of furthering the understanding of the pathogenesis of this condition and realizing genome-based personalized medical care. Two different approaches were launched, genome-wide association analysis using single-nucleotide polymorphisms (SNPs) and microsatellite markers, and systematic candidate gene analysis, under the hypothesis that common variants have an important role in the etiology of common diseases. These multilateral approaches identified ATP2B1 as a gene responsible for hypertension in not only Japanese but also Caucasians. The high blood pressure susceptibility conferred by certain alleles of ATP2B1 has been widely replicated in various populations. Ex vivo mRNA expression analysis in umbilical artery smooth muscle cells indicated that reduced expression of this gene associated with the risk allele may be an underlying mechanism relating the ATP2B1 variant to hypertension. However, the effect size of a SNP was too small to clarify the entire picture of the genetic basis of hypertension. Further, dense genome analysis with accurate phenotype data may be required.

Abuse, cancer and sexual dysfunction in women: A potentially vicious cycle.

PubMed

Lees, Brittany F; Stewart, Taylor P; Rash, Joanne K; Baron, Shirley R; Lindau, Stacy Tessler; Kushner, David M

2018-04-13

More than 30% of women have a history of abuse. Women with cancer may be at substantially increased risk for abuse, but this issue is rarely discussed in the course of oncology care. Women with a history of abuse who present for cancer care commonly have a high prevalence of co-morbid illness. Sexual dysfunction, a highly prevalent but under-recognized condition among women of all ages, is also more common among both women with a history of abuse and women with cancer. Although common after cancer, sexual dysfunction, like abuse, can be stigmatizing and often goes undiagnosed and untreated. This review first examines the literature for evidence of a relationship between any history of abuse and cancer among women, addressing two questions: 1) How does abuse promote or create risk for developing cancer? 2) How does cancer increase a woman's susceptibility to abuse? We then examine evidence for a relationship between abuse and female sexual dysfunction, followed by an investigation of the complex relationship between all three factors: abuse, sexual dysfunction and cancer. The literature is limited by a lack of harmonization of measures across studies, retrospective designs, and small and idiosyncratic samples. Despite these limitations, it is imperative that providers integrate the knowledge of this complex relationship into the care of women with cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

A coupled physical and economic model of the response of coastal real estate to climate risk

NASA Astrophysics Data System (ADS)

McNamara, Dylan E.; Keeler, Andrew

2013-06-01

Barring an unprecedented large-scale effort to raise island elevation, barrier-island communities common along the US East Coast are likely to eventually face inundation of the existing built environment on a timescale that depends on uncertain climatic forcing. Between the present and when a combination of sea-level rise and erosion renders these areas uninhabitable, communities must choose levels of defensive expenditures to reduce risks and individual residents must assess whether and when risk levels are unacceptably high to justify investment in housing. We model the dynamics of coastal adaptation as the interplay of underlying climatic risks, collective actions to mitigate those risks, and individual risk assessments based on beliefs in model predictions and processing of past climate events. Efforts linking physical and behavioural models to explore shoreline dynamics have not yet brought together this set of essential factors. We couple a barrier-island model with an agent-based model of real-estate markets to show that, relative to people with low belief in model predictions about climate change, informed property owners invest heavily in defensive expenditures in the near term and then abandon coastal real estate at some critical risk threshold that presages a period of significant price volatility.

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

PubMed Central

Whalley, H C; Papmeyer, M; Sprooten, E; Romaniuk, L; Blackwood, D H; Glahn, D C; Hall, J; Lawrie, S M; Sussmann, Je; McIntosh, A M

2012-01-01

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD. PMID:22760554

Prevalence and risk factors of depression in the elderly nursing home residents in Singapore.

PubMed

Tiong, Wei Wei; Yap, Philip; Huat Koh, Gerald Choon; Phoon Fong, Ngan; Luo, Nan

2013-01-01

Depression is a common health problem in elderly nursing home (NH) residents and is often under-recognized and under-treated. This study aimed to determine the prevalence rates of depression and identify the risk factors associated with depression in the elderly NH population in Singapore. A sample of 375 residents in six NHs in Singapore, aged 55 years and above, was assessed with the Structural Clinical Interview (SCID), based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The association of demographic, functional and health-related characteristics with depression was examined using multivariate logistic regression analyses. Overall point prevalence for depression in the elderly NH residents was found to be 21.1% (95% confidence intervals (CI): 17.1%-25.6%). The prevalence rate for minor depression in the elderly NH residents was 14.4% (95% CI: 11.1%-18.5%) and 6.7% (95% CI: 4.5%-9.8%) for major depression. Significant risk factors that were found to be associated with depression were length of stay for more than 2 years, known history of depression, pain, and no or lack of social contact. The prevalence rates for depression were high among NH residents in Singapore. More attention is needed to care for the psychosocial needs of elderly NH residents in Singapore.

Common variants in FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 show evidence of association with adult obesity in the Greek population.

PubMed

Rouskas, Konstantinos; Kouvatsi, Anastasia; Paletas, Konstantinos; Papazoglou, Dimitrios; Tsapas, Apostolos; Lobbens, Stéphane; Vatin, Vincent; Durand, Emmanuelle; Labrune, Yann; Delplanque, Jérôme; Meyre, David; Froguel, Philippe

2012-02-01

Twenty-four single-nucleotide polymorphisms (SNPs) have been reproducibly associated with obesity. We performed a follow-up study for obesity in the Greek adult population. A total of 510 obese and 469 lean adults were genotyped for 24 SNPs. We tested the association with obesity status using logistic regression and we evaluated the combined genetic risk of 24 SNPs by calculating the area under the receiver-operating characteristic (ROC) curves. We nominally replicated the association with obesity (BMI ≥30 kg/m(2)) of six SNPs in or near the FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 loci (1.28 ≤ odds ratio (OR) ≤ 1.35; 0.004 ≤ P ≤ 0.043). The discrimination ability for obesity was slightly stronger (P = 9.59 × 10(-6)) when the genetic information of the 24 SNPs was added to nongenetic risk factors (area under the curve (AUC) = 0.722) in comparison with nongenetic factors analyzed alone (AUC = 0.685). Our data suggest that SNPs in or near the FTO, MC4R, TMEM18, PRL, AIF1, and PCSK1 loci contribute to obesity risk in the Greek population.

Metabolic syndrome and cardiovascular disease: challenges and opportunities.

PubMed

Cooper-DeHoff, Rhonda M; Pepine, Carl J

2007-12-01

Metabolic syndrome (MetS) has been defined in different ways. However, key components common to most definitions are a constellation of risk factors including abdominal adiposity, impaired fasting glucose, hypertension, and dyslipidemia. A major mediator of MetS appears to be insulin resistance, which relates to the development of the vascular and metabolic dysfunctions that precede overt cardiovascular disease and type 2 diabetes. Evidence suggests that the mechanisms underlying the elevated cardiovascular risk associated with MetS begin with subclinical organ damage. Therapy for MetS targets individual components of the syndrome and includes lifestyle interventions, lipid-modifying therapy, and antihypertensive agents, particularly those that inhibit the renin-angiotensin system. Results of trials of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated reductions in new-onset diabetes and cardiovascular events in a wide range of patients. Clinical trials to investigate further the role of these drugs in the primary prevention of type 2 diabetes in patients with MetS are currently under way. The purpose of this paper is to review the MetS from the perspective of the cardiology workforce with the hope that a better understanding of the links between MetS and cardiovascular disease could lead to improved management of persons at risk.

A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction.

PubMed

Xie, Yi; Xu, Hua; Fang, Fang; Li, Zhiheng; Zhou, Huiting; Pan, Jian; Guo, Wanliang; Zhu, Xueming; Wang, Jian; Wu, Yi

2018-05-22

Neuroblastoma (NB) is the most common extracranial solid tumor in children with contrasting outcomes. Precise risk assessment contributes to prognosis prediction, which is critical for treatment strategy decisions. In this study, we developed a 3-protein predictor model, including the neural stem cell marker Msi1, neural differentiation marker ID1, and proliferation marker proliferating cell nuclear antigen (PCNA), to improve clinical risk assessment of patients with NB. Kaplan-Meier analysis in the microarray data (GSE16476) revealed that low expression of ID1 and high expression of Msi1 and PCNA were associated with poor prognosis in NB patients. Combined application of these 3 markers to constitute a signature further stratified NB patients into different risk subgroups can help obtain more accurate prediction performance. Survival prognostic power of age and Msi1_ID1_PCNA signature by receiver operating characteristics analysis showed that this signature predicted more effectively and sensitively compared with classic risk stratification system, compensating for the deficiency of the prediction function of the age. Furthermore, we validated the expressions of these 3 proteins in neuroblastic tumor spectrum tissues by immunohistochemistry revealed that Msi1 and PCNA exhibited increased expression in NB compared with intermedial ganglioneuroblastoma and benign ganglioneuroma, whereas ID1 levels were reduced in NB. In conclusion, we established a robust risk assessment predictor model based on simple immunohistochemistry for therapeutic decisions of NB patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre.

PubMed

Lim, Jia Wei; Yeap, Frances Sh; Chan, Yiong Huak; Yeoh, Allen Ej; Quah, Thuan Chong; Tan, Poh Lin

2017-01-01

Introduction : One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods : A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results : We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years ( P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion : This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Falls risk assessment outcomes and factors associated with falls for older Indigenous Australians.

PubMed

Hill, Keith D; Flicker, Leon; LoGiudice, Dina; Smith, Kate; Atkinson, David; Hyde, Zoë; Fenner, Stephen; Skeaf, Linda; Malay, Roslyn; Boyle, Eileen

2016-12-01

To describe the prevalence of falls and associated risk factors in older Indigenous Australians, and compare the accuracy of validated falls risk screening and assessment tools in this population in classifying fall status. Cross-sectional study of 289 Indigenous Australians aged ≥45 years from the Kimberley region of Western Australia who had a detailed assessment including self-reported falls in the past year (n=289), the adapted Elderly Falls Screening Tool (EFST; n=255), and the Falls Risk for Older People-Community (FROP-Com) screening tool (3 items, n=74) and FROP-Com falls assessment tool (n=74). 32% of participants had ≥1 fall in the preceding year, and 37.3% were classified high falls risk using the EFST (cut-off ≥2). In contrast, for the 74 participants assessed with the FROP-Com, only 14.9% were rated high risk, 35.8% moderate risk, and 49.3% low risk. The FROP-Com screen and assessment tools had the highest classification accuracy for identifying fallers in the preceding year (area under curve >0.85), with sensitivity/specificity highest for the FROP-Com assessment (cut-off ≥12), sensitivity=0.84 and specificity=0.73. Falls are common in older Indigenous Australians. The FROP-Com falls risk assessment tool appears useful in this population, and this research suggests changes that may improve its utility further. © 2016 Public Health Association of Australia.

The contributions of breast density and common genetic variation to breast cancer risk.

PubMed

Vachon, Celine M; Pankratz, V Shane; Scott, Christopher G; Haeberle, Lothar; Ziv, Elad; Jensen, Matthew R; Brandt, Kathleen R; Whaley, Dana H; Olson, Janet E; Heusinger, Katharina; Hack, Carolin C; Jud, Sebastian M; Beckmann, Matthias W; Schulz-Wendtland, Ruediger; Tice, Jeffrey A; Norman, Aaron D; Cunningham, Julie M; Purrington, Kristen S; Easton, Douglas F; Sellers, Thomas A; Kerlikowske, Karla; Fasching, Peter A; Couch, Fergus J

2015-05-01

We evaluated whether a 76-locus polygenic risk score (PRS) and Breast Imaging Reporting and Data System (BI-RADS) breast density were independent risk factors within three studies (1643 case patients, 2397 control patients) using logistic regression models. We incorporated the PRS odds ratio (OR) into the Breast Cancer Surveillance Consortium (BCSC) risk-prediction model while accounting for its attributable risk and compared five-year absolute risk predictions between models using area under the curve (AUC) statistics. All statistical tests were two-sided. BI-RADS density and PRS were independent risk factors across all three studies (P interaction = .23). Relative to those with scattered fibroglandular densities and average PRS (2(nd) quartile), women with extreme density and highest quartile PRS had 2.7-fold (95% confidence interval [CI] = 1.74 to 4.12) increased risk, while those with low density and PRS had reduced risk (OR = 0.30, 95% CI = 0.18 to 0.51). PRS added independent information (P < .001) to the BCSC model and improved discriminatory accuracy from AUC = 0.66 to AUC = 0.69. Although the BCSC-PRS model was well calibrated in case-control data, independent cohort data are needed to test calibration in the general population. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The impact of attachment and depression symptoms on multiple risk behaviors in post-war adolescents in northern Uganda.

PubMed

Okello, J; Nakimuli-Mpungu, E; Klasen, F; Voss, C; Musisi, S; Broekaert, E; Derluyn, I

2015-07-15

We have previously shown that depression symptoms are associated with multiple risk behaviors and that parental attachments are protective against depression symptoms in post-war adolescents. Accumulating literature indicates that low levels of attachment may sensitize individuals to increased multiple risk behaviors when depression symptoms exist. This investigation examined the interactive effects of attachment and depression symptoms on multiple risk behavior. We conducted hierarchical logistic regression analyses to examine the impact of attachment and depression symptoms on multiple risk behavior in our post-war sample of 551 adolescents in Gulu district. Analyses revealed interactive effects for only maternal attachment-by-depression interaction. Interestingly, high levels of maternal attachment exacerbated the relationship between depression symptoms and multiple risk behaviors while low levels of maternal attachment attenuated this relationship. It is possible that this analysis could be biased by a common underlying factor that influences self-reporting and therefore is correlated with each of self-reported attachment security, depressive symptoms, and multiple risk behaviors. These findings suggest that maternal attachment serves as a protective factor at low levels while serving as an additional risk factor at high levels. Findings support and expand current knowledge about the roles that attachment and depression symptoms play in the development of multiple risk behaviors and suggest a more complex etiology for post-war adolescents. Copyright © 2015 Elsevier B.V. All rights reserved.

Prevention of type 2 Diabetes Mellitus: Potential of pharmacological agents.

PubMed

Samson, Susan L; Garber, Alan J

2016-06-01

People with impaired glucose tolerance or impaired fasting glucose, or "pre-diabetes", are at high risk for progression to type 2 diabetes, as are those with metabolic syndrome or a history of gestational diabetes. Both glucose-lowering and anti-obesity pharmacotherapies have been studied to determine if the onset of type 2 diabetes can be delayed or prevented. Here we review the available data in the field. The most common theme is the reduction in insulin resistance, such as with weight loss, decreasing demands on the beta cell to improve insulin secretion and prolong its function. Overall, therapies which decrease diabetes incidence in high-risk populations delay the onset of diabetes but do not correct the underlying beta cell defect. Copyright © 2016 Elsevier Ltd. All rights reserved.

29 CFR 4001.3 - Trades or businesses under common control; controlled groups.

Code of Federal Regulations, 2012 CFR

2012-07-01

... CORPORATION GENERAL TERMINOLOGY § 4001.3 Trades or businesses under common control; controlled groups. For... control with such person. (2) Persons are under common control if they are members of a “controlled group... 29 Labor 9 2012-07-01 2012-07-01 false Trades or businesses under common control; controlled...

29 CFR 4001.3 - Trades or businesses under common control; controlled groups.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CORPORATION GENERAL TERMINOLOGY § 4001.3 Trades or businesses under common control; controlled groups. For... control with such person. (2) Persons are under common control if they are members of a “controlled group... 29 Labor 9 2010-07-01 2010-07-01 false Trades or businesses under common control; controlled...

29 CFR 4001.3 - Trades or businesses under common control; controlled groups.

Code of Federal Regulations, 2014 CFR

2014-07-01

... CORPORATION GENERAL TERMINOLOGY § 4001.3 Trades or businesses under common control; controlled groups. For... control with such person. (2) Persons are under common control if they are members of a “controlled group... 29 Labor 9 2014-07-01 2014-07-01 false Trades or businesses under common control; controlled...

29 CFR 4001.3 - Trades or businesses under common control; controlled groups.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CORPORATION GENERAL TERMINOLOGY § 4001.3 Trades or businesses under common control; controlled groups. For... control with such person. (2) Persons are under common control if they are members of a “controlled group... 29 Labor 9 2013-07-01 2013-07-01 false Trades or businesses under common control; controlled...

29 CFR 4001.3 - Trades or businesses under common control; controlled groups.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CORPORATION GENERAL TERMINOLOGY § 4001.3 Trades or businesses under common control; controlled groups. For... control with such person. (2) Persons are under common control if they are members of a “controlled group... 29 Labor 9 2011-07-01 2011-07-01 false Trades or businesses under common control; controlled...

Home environment and suspected atopic eczema in Japanese infants: the Osaka Maternal and Child Health Study.

PubMed

Miyake, Yoshihiro; Ohya, Yukihiro; Tanaka, Keiko; Yokoyama, Tetsuji; Sasaki, Satoshi; Fukushima, Wakaba; Ohfuji, Satoko; Saito, Kyoko; Kiyohara, Chikako; Hirota, Yoshio

2007-08-01

Atopic eczema is most commonly diagnosed in children under the age of 5 yr. Environmental factors during pregnancy or in early life may confer risk for childhood atopic eczema. The present prospective study examined the relationship of the perinatal home environment and the risk of suspected atopic eczema among Japanese infants under the age of 1. Study subjects were 865 parent-child pairs. The term 'suspected atopic eczema' was used to define an outcome based on our questionnaire at 2-9 months postpartum. Adjustment was made for maternal age, gestation, family income, maternal and paternal education, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, time of delivery before the second survey, baby's older siblings, baby's sex, and baby's birth weight. A high mite allergen level from maternal bedclothes and mold in the kitchen during pregnancy were significantly associated with an increased risk of suspected atopic eczema. Frequent vacuuming practices during pregnancy and giving the infant a bath or shower at least once a day were significantly inversely related to the risk of suspected atopic eczema. Maternal smoking, maternal use of a synthetic duvet and pillow, carpet use in the living room and maternal bedroom, indoor domestic pets, no ducted heating appliance, and gas use for cooking during pregnancy and household smoking in the same room as the infant, infant's synthetic duvet, carpet use in the infant's room, or vacuuming the infant's room were not related to the risk of suspected atopic eczema. High house dust mite allergen levels and mold in the kitchen during pregnancy may increase the risk of infantile atopic eczema, whereas frequent vacuuming practices during pregnancy and giving the infant a bath or shower at least once a day may protect against infantile atopic eczema.

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

PubMed Central

Li, James J.; Savage, Jeanne E.; Kendler, Kenneth S.; Hickman, Matthew; Mahedy, Liam; Macleod, John; Kaprio, Jaakko; Rose, Richard J.; Dick, Danielle M.

2017-01-01

Objective: Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality. Method: We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality. Results: PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence. Conclusions: These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems. PMID:28499112

The interplay of stressful life events and coping skills on risk for suicidal behavior among youth students in contemporary China: a large scale cross-sectional study.

PubMed

Tang, Fang; Xue, Fuzhong; Qin, Ping

2015-07-31

Stressful life events are common among youth students and may induce psychological problems and even suicidal behaviors in those with poor coping skills. This study aims to assess the influence of stressful life events and coping skills on risk for suicidal behavior and to elucidate the underlying mechanism using a large sample of university students in China. 5972 students, randomly selected from 6 universities, completed the questionnaire survey. Logistic regression analysis was performed to estimate the effect of stressful life events and coping skills on risk for suicidal behavior. Bayesian network was further adopted to probe their probabilistic relationships. Of the 5972 students, 7.64% reported the presence of suicidal behavior (attempt or ideation) within the past one year period. Stressful life events such as strong conflicts with classmates and a failure in study exam constituted strong risk factors for suicidal behavior. The influence of coping skills varied according to the strategies adapted toward problems with a high score of approach coping skills significantly associated with a reduced risk of suicidal behavior. The Bayesian network indicated that the probability of suicidal behavior associated with specific life events was to a large extent conditional on coping skills. For instance, a stressful experience of having strong conflicts with classmates could result in a probability of suicidal behavior of 21.25% and 15.36% respectively, for female and male students with the score of approach coping skills under the average. Stressful life events and deficient coping skills are strong risk factors for suicidal behavior among youth students. The results underscore the importance of prevention efforts to improve coping skills towards stressful life events.

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer.

PubMed

Tighe, D; Sassoon, I; McGurk, M

2017-04-01

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A-C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer-Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34-51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer-Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A-C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer

PubMed Central

Sassoon, I; McGurk, M

2017-01-01

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A–C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer–Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34–51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer–Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A–C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists. PMID:27917662

The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

PubMed

Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

2016-08-01

We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization.

Acute colonic diverticulitis: modern understanding of pathomechanisms, risk factors, disease burden and severity.

PubMed

Søreide, Kjetil; Boermeester, Marja A; Humes, David J; Velmahos, George C

2016-12-01

Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed. Literature search of risk factors, pathophysiology, epidemiology and disease burden/severity reported over the last decade. Acute diverticulitis is a common disease and has a high disease burden. Incidence of hospital admissions is reported around 71 per 100,000 population, with reported increase in several subpopulations over the last decades. The incidence is likely to increase further with the aging populations. Risk factors for left-sided acute diverticulitis include dietary, anthropometric and lifestyle factors. Disease mechanisms are still poorly understood, but a distinction between inflammation and infection is emerging. The integrative and complex role of the gut microbiota has become an interesting factor for both understanding the disease as well as a potential target for intervention using probiotics. Mild, self-limiting events are increasingly reported from studies of successful non-antibiotic management in a considerable number of cases. Risk markers of progression to or presence of severe, complicated disease are needed for better disease stratification. Current risk stratification by clinical, imaging or endoscopic means is imperfect and needs validation. Long-term results from minimal-invasive and comparative surgical trials may better help inform clinicians and patients. Over- and under-treatment as well as over- and under-diagnosis of severity is likely to continue in clinical practice due to lack of reliable, robust and universal severity and classification systems. Better understanding of pathophysiology is needed.

Dopamine reward prediction error responses reflect marginal utility.

PubMed

Stauffer, William R; Lak, Armin; Schultz, Wolfram

2014-11-03

Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions' shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Ventricular ectopy in patients with left ventricular dysfunction: should it be treated?

PubMed

Chen, Taibo; Koene, Ryan; Benditt, David G; Lü, Fei

2013-01-01

Ventricular premature complexes (VPCs) are commonly encountered in patients with congestive heart failure (CHF). Frequent ventricular ectopy can be associated with deterioration of cardiac function and may lead to VPC-induced cardiomyopathy. VPC-induced inter- and/or intraventricular dyssynchrony has been postulated as the main mechanism underlying VPC-induced left ventricular dysfunction. For risk stratification, VPCs in the setting of CHF can not be regarded to be a benign arrhythmia as in an apparently healthy subject. However, any potential survival benefits to be derived from suppression of VPCs or nonsustained ventricular tachycardia in CHF may be offset by the negative inotropic and proarrhythmic effects of antiarrhythmic drugs and may be masked by the risk of death that is already high in this subgroup of patients. β-Blockers are currently considered to be the first-line therapy, with amiodarone as a back-up. Catheter ablation, although invasive and not without procedural risk, avoids the common adverse effects of currently available antiarrhythmic medications. From a standpoint of preventing or reversing left ventricular dysfunction, frequent VPCs should be treated earlier regardless of their site of origin or the presence of associated symptoms, such as palpitations. Catheter ablation may be the preferable approach in selected patients, particularly when β-blocker therapy has been ineffective or not tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

Dispositional Affect Moderates the Stress-Buffering Effect of Social Support on Risk for Developing the Common Cold.

PubMed

Janicki Deverts, Denise; Cohen, Sheldon; Doyle, William J

2017-10-01

The aim was to examine whether trait positive and negative affect (PA, NA) moderate the stress-buffering effect of perceived social support on risk for developing a cold subsequent to being exposed to a virus that causes mild upper respiratory illness. Analyses were based on archival data from 694 healthy adults (M age  = 31.0 years, SD = 10.7 years; 49.0% female; 64.6% Caucasian). Perceived social support and perceived stress were assessed by self-report questionnaire and trait affect by aggregating responses to daily mood items administered by telephone interview across several days. Subsequently, participants were exposed to a virus that causes the common cold and monitored for 5 days for clinical illness (infection + objective signs of illness). Two 3-way interactions emerged-Support × Stress × PA and Support × Stress × NA. The nature of these effects was such that among persons with high trait PA or low trait NA, greater social support attenuated the risk of developing a cold when under high but not low perceived stress; this stress-buffering effect did not emerge among persons with low trait PA or high trait NA. Dispositional affect might be used to identify individuals who may be most responsive to social support and support-based interventions. © 2016 Wiley Periodicals, Inc.

Discriminatory power of common genetic variants in personalized breast cancer diagnosis

NASA Astrophysics Data System (ADS)

Wu, Yirong; Abbey, Craig K.; Liu, Jie; Ong, Irene; Peissig, Peggy; Onitilo, Adedayo A.; Fan, Jun; Yuan, Ming; Burnside, Elizabeth S.

2016-03-01

Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine.

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs.

PubMed

Varnell, Charles D; Fukuda, Tsuyoshi; Kirby, Cassie L; Martin, Lisa J; Warshaw, Barry L; Patel, Hiren P; Chand, Deepa H; Barletta, Gina-Marie; Van Why, Scott K; VanDeVoorde, Rene G; Weaver, Donald J; Wilson, Amy; Verghese, Priya S; Vinks, Alexander A; Greenbaum, Larry A; Goebel, Jens; Hooper, David K

2017-11-01

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Validation of Demographics, Etiology, and Risk Factors for Chronic Pancreatitis in the USA: A Report of the North American Pancreas Study (NAPS) Group.

PubMed

Conwell, Darwin L; Banks, Peter A; Sandhu, Bimaljit S; Sherman, Stuart; Al-Kaade, Samer; Gardner, Timothy B; Anderson, Michelle A; Wilcox, C Mel; Lewis, Michele D; Muniraj, Thiruvengadam; Forsmark, Christopher E; Cote, Gregory A; Guda, Nalini M; Tian, Ye; Romagnuolo, Joseph; Wisniewski, Stephen R; Brand, Randall; Gelrud, Andres; Slivka, Adam; Whitcomb, David C; Yadav, Dhiraj

2017-08-01

Our aim was to validate recent epidemiologic trends and describe the distribution of TIGAR-O risk factors in chronic pancreatitis (CP) patients. The NAPS-2 Continuation and Validation (NAPS2-CV) study prospectively enrolled 521 CP patients from 13 US centers from 2008 to 2012. CP was defined by definitive changes in imaging, endoscopy, or histology. Data were analyzed after stratification by demographic factors, physician-defined etiology, participating center, and TIGAR-O risk factors. Demographics and physician-defined etiology in the NAPS2-CV study were similar to the original NAPS2 study. Mean age was 53 years (IQR 43, 62) with 55% males and 87% white. Overall, alcohol was the single most common etiology (46%) followed by idiopathic etiology (24%). Alcohol etiology was significantly more common in males, middle-aged (35-65 years), and non-whites. Females and elderly (≥65 years) were more likely to have idiopathic etiology, while younger patients (<35 years) to have genetic etiology. Variability in etiology was noted by participating centers (e.g., alcohol etiology ranged from 27 to 67% among centers enrolling ≥25 patients). Smoking was the most commonly identified (59%) risk factor followed by alcohol (53%), idiopathic (30%), obstructive (19%), and hyperlipidemia (13%). The presence of multiple TIGAR-O risk factors was common, with 1, 2, ≥3 risk factors observed in 27.6, 47.6, and 23.6% of the cohort, respectively. Our data validate the current epidemiologic trends in CP. Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor. Identification of multiple risk factors suggests CP to be a complex disease.

Outcomes of patients with severe influenza infection admitted to intensive care units: a retrospective study in a medical centre.

PubMed

Chao, Chien-Ming; Lai, Chih-Cheng; Chan, Khee-Siang; Cheng, Kuo-Chen; Chou, Willy; Yuan, Kuo-Shu; Chen, Chin-Ming

2017-10-01

This study assessed clinical manifestations and prognostic factors of critically ill patients with severe influenza admitted to the intensive care unit (ICU) in Taiwan's recent outbreak. Patients admitted to ICU for severe influenza between January 1, 2015, and March 31, 2016, were identified and their medical records were retrospectively reviewed. The primary endpoints were outcomes and predictors of in-hospital mortality. There were 125 patients with an average Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 20.8. Hypertension (62.4 %) and diabetes mellitus (40.8 %) were the two most common underlying diseases. Ninety-eight (78.4 %) patients had at least one organ failure: the lungs were the most common (71.2 %), followed by the heart (53.6 %). Two of the most common symptoms of patients at ICU admission were fever (68.0 %) and cough (78.4 %). Thirty-three patients (26.4 %) died; most (40.9 %) were middle-aged (50-65 years old). A Cox regression analysis showed that multiple organ failure (MOF) [hazard ratio (HR)=3.618; 95 % CI=1.058-13.662] was significantly associated with higher risk of death. In contrast, a fluid-negative balance within 7 days of admission (HR=0.362; 95 % CI=0.140-0.934) was significantly associated with a lower risk of death. The mortality rate of severe influenza patients admitted to the ICU was high, especially in middle-aged adults. The risk of mortality was associated with ≥2 organ failures. A negative fluid balance predicts survival.

Diarrhoea in the enterally fed patient

PubMed Central

Bowling, T E

2010-01-01

Diarrhoea complicating enteral feeding is very common in all clinical settings. The major risk factor is the use of concomitant antibiotics. The underlying mechanisms for the diarrhoea mainly relate to alterations in the colonic flora and physiological responses to the mode of feed delivery although a clear understanding of what is actually happening in vivo remains elusive. Management of diarrhoea includes rationalising medications, excluding relevant comorbidity and using antidiarrhoeal medications. Altering the method and site of feed delivery—for example, continuous to bolus, gastric to postpyloric—can also be tried in the more difficult cases. PMID:28839565

Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS.

PubMed

Teede, H J; Hutchison, S; Zoungas, S; Meyer, C

2006-08-01

Polycystic ovary syndrome is the most common endocrinopathy of reproductive aged women affecting 6-10% of the population. Traditionally considered a reproductive disorder manifesting as chronic anovulation, infertility, and hyperandrogenism, management has primarily focused on short-term reproductive outcomes. Recently, however, significant metabolic aspects in conjunction with longer-term health sequealae of PCOS have been recognized. The metabolic features are primarily related to underlying insulin resistance (IR), which is now understood to play an important role in both the pathogenesis and long-term sequelae of PCOS.

Electrolyte imbalance and sleep problems during anti-retroviral therapy: an under-recognized problem.

PubMed

Manzar, Md Dilshad; Sony, Peter; Salahuddin, Mohammed; Kumalo, Abera; Geneto, Mathewos; Pandi-Perumal, Seithikurippu R; Moscovitch, Adam; BaHammam, Ahmed S

2017-01-01

Human immunodeficiency virus (HIV) infection, and the anti-retroviral therapy (ART) associated complications necessitate that the medical care system keeps evolving for proper management of this group of patients. Electrolyte imbalance and sleep problems are common in patients on ART. Both of these conditions are associated with increased morbidity (such as acute kidney injury, chronic kidney disease, low CD4 count, non-adherence and depression) and mortality. Therefore, screening for both sleep problems and electrolytes imbalance may help to decrease the risk of complications in patients on ART.

Electrolyte imbalance and sleep problems during anti-retroviral therapy: an under-recognized problem

PubMed Central

Manzar, Md Dilshad; Sony, Peter; Salahuddin, Mohammed; Kumalo, Abera; Geneto, Mathewos; Pandi-Perumal, Seithikurippu R; Moscovitch, Adam; BaHammam, Ahmed S

2017-01-01

Human immunodeficiency virus (HIV) infection, and the anti-retroviral therapy (ART) associated complications necessitate that the medical care system keeps evolving for proper management of this group of patients. Electrolyte imbalance and sleep problems are common in patients on ART. Both of these conditions are associated with increased morbidity (such as acute kidney injury, chronic kidney disease, low CD4 count, non-adherence and depression) and mortality. Therefore, screening for both sleep problems and electrolytes imbalance may help to decrease the risk of complications in patients on ART. PMID:28966741

Cardiovascular magnetic resonance in systemic hypertension

PubMed Central

2012-01-01

Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053

Prevalence and early determinants of common mental disorders in the 1982 birth cohort, Pelotas, Southern Brazil

PubMed Central

Anselmi, Luciana; Barros, Fernando C; Minten, Gicele C; Gigante, Denise P; Horta, Bernardo L; Victora, Cesar G

2009-01-01

OBJECTIVE To estimate the prevalence of common mental disorders and assess its association with risk factors in a cohort of young adults. METHODS Cross-sectional study nested in a 1982 birth cohort study conducted in Pelotas, Southern Brazil. In 2004-5, 4,297 subjects were interviewed during home visits. Common mental disorders were assessed using the Self-Report Questionnaire. Risk factors included socioeconomic, demographic, perinatal, and environmental variables. The analysis was stratified by gender and crude and adjusted prevalence ratios were estimated by Poisson regression. RESULTS The overall prevalence of common mental disorders was 28.0%; 32.8% and 23.5% in women and men, respectively. Men and women who were poor in 2004-5, regardless of their poor status in 1982, had nearly 1.5-fold increased risk for common mental disorders (p≤0.001) when compared to those who have never been poor. Among women, being poor during childhood (p≤0.001) and black/mixed skin color (p=0.002) increased the risk for mental disorders. Low birth weight and duration of breastfeeding were not associated to the risk of these disorders. CONCLUSIONS Higher prevalence of common mental disorders among low-income groups and race-ethnic minorities suggests that social inequalities present at birth have a major impact on mental health, especially common mental disorders. PMID:19142342

Intelligence Involves Risk-Awareness and Intellectual Disability Involves Risk-Unawareness: Implications of a Theory of Common Sense

ERIC Educational Resources Information Center

Greenspan, Stephen; Switzky, Harvey N.; Woods, George W.

2011-01-01

Survival in the everyday world (in both social and practical functioning) depends on one's ability to recognise and avoid going down the worst possible path, especially when doing so places one at risk of death, injury, or social disaster. Most people possess "common sense" (the ability to recognise obvious risk) but some people lack that ability…

Common pitfalls in statistical analysis: Absolute risk reduction, relative risk reduction, and number needed to treat

PubMed Central

Ranganathan, Priya; Pramesh, C. S.; Aggarwal, Rakesh

2016-01-01

In the previous article in this series on common pitfalls in statistical analysis, we looked at the difference between risk and odds. Risk, which refers to the probability of occurrence of an event or outcome, can be defined in absolute or relative terms. Understanding what these measures represent is essential for the accurate interpretation of study results. PMID:26952180

Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features.

PubMed

Merkel, Emily A; Gerami, Pedram

2017-06-01

In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes. To better understand non-UV-mediated pathogenesis in melanoma, we conducted a joint literature review of clinical, histological, and molecular features in acral and mucosal melanoma. We also reviewed the current literature regarding aberrations in KIT, PDGFRA, TERT, and other commonly involved genes. By comparing common features of these two subtypes, we suggest potential mechanisms underlying acral and/or mucosal melanoma and offer direction for future investigations.

Evaluation and management of lower back pain in young athletes

PubMed Central

Kinsella, Elizabeth

2017-01-01

Lower back pain in young athletes is a common problem. The prevalence of back pain from different causes in adolescent age group is between 20% and 30%. However, the incidence of low back pain in young athletes varies widely in different sports. Overuse injuries are the most common cause of low back pain in young athletes. In case of overuse injuries, the cause and effect relationship between back pain and specific condition is often difficult to establish. In adolescent athletes, the most common underlying identified cause of low back pain is lumbar spondylolysis. During adolescent growth spurt, the severity of the pain generally correlates with adolescent growth spurt. Participation in sports starting at an early age and for a longer duration tends to increase the risk for back pain. Numerous conditions cause low back pain in athletes. These include acute trauma, chronic overuse or repetitive trauma, and referred pain. Our focus in here will be on selected conditions that cause recurrent or chronic low back pain. PMID:28795014

Foot osteoarthritis: latest evidence and developments

PubMed Central

Roddy, Edward; Menz, Hylton B.

2018-01-01

Foot osteoarthritis (OA) is a common problem in older adults yet is under-researched compared to knee or hand OA. Most existing studies focus on the first metatarsophalangeal joint, with evidence relating to midfoot OA being particularly sparse. Symptomatic radiographic foot OA affects 17% of adults aged 50 years and over. The first metatarsophalangeal joint is most commonly affected, followed by the second cuneometatarsal and talonavicular joints. Epidemiological studies suggest the existence of distinct first metatarsophalangeal joint and polyarticular phenotypes, which have differing clinical and risk factor profiles. There are few randomized controlled trials in foot OA. Existing trials provide some evidence of the effectiveness for pain relief of physical therapy, rocker-sole shoes, foot orthoses and surgical interventions in first metatarsophalangeal joint OA and prefabricated orthoses in midfoot OA. Prospective epidemiological studies and randomized trials are needed to establish the incidence, progression and prognosis of foot OA and determine the effectiveness of both commonly used and more novel interventions. PMID:29619094

A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.

PubMed

Ismail, Hanafy M; Barton, Victoria E; Panchana, Matthew; Charoensutthivarakul, Sitthivut; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

2016-05-23

In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.

Commonalities and distinctions among mechanisms of addiction to alcohol and other drugs

PubMed Central

Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.

2015-01-01

Alcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. In this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in pre-clinical studies using rodent models of drug self-administration. While there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. For alcohol, versus other drugs of abuse, we discuss and compare advances in: 1) neurocircuitry important for the different stages of drug dependence; 2) transcriptomics and genetical genomics; and 3) enduring effects. We note in particular the contributions of behavioral genetics and animal models: discussions of progress specifically relevant to treatment development can be found in the accompanying review (Karoly et al, this issue). PMID:26431116

Effects of wastewater disinfection on waterborne bacteria and viruses

USGS Publications Warehouse

Blatchley, E. R.; Gong, W.-L.; Alleman, J.E.; Rose, J.B.; Huffman, D.E.; Otaki, M.; Lisle, J.T.

2007-01-01

Wastewater disinfection is practiced with the goal of reducing risks of human exposure to pathogenic microorganisms. In most circumstances, the efficacy of a wastewater disinfection process is regulated and monitored based on measurements of the responses of indicator bacteria. However, inactivation of indicator bacteria does not guarantee an acceptable degree of inactivation among other waterborne microorganisms (e.g., microbial pathogens). Undisinfected effluent samples from several municipal wastewater treatment facilities were collected for analysis. Facilities were selected to provide a broad spectrum of effluent quality, particularly as related to nitrogenous compounds. Samples were subjected to bench-scale chlorination and dechlorination and UV irradiation under conditions that allowed compliance with relevant discharge regulations and such that disinfectant exposures could be accurately quantified. Disinfected samples were subjected to a battery of assays to assess the immediate and long-term effects of wastewater disinfection on waterborne bacteria and viruses. In general, (viable) bacterial populations showed an immediate decline as a result of disinfectant exposure; however, incubation of disinfected samples under conditions that were designed to mimic the conditions in a receiving stream resulted in substantial recovery of the total bacterial community. The bacterial groups that are commonly used as indicators do not provide an accurate representation of the response of the bacterial community to disinfectant exposure and subsequent recovery in the environment. UV irradiation and chlorination/dechlorination both accomplished measurable inactivation of indigenous phage; however, the extent of inactivation was fairly modest under the conditions of disinfection used in this study. UV irradiation was consistently more effective as a virucide than chlorination/dechlorination under the conditions of application, based on measurements of virus (phage) diversity and concentration. Taken together, and when considered in conjunction with previously published research, the results of these experiments illustrate several important limitations of common disinfection processes as applied in the treatment of municipal wastewaters. In general, it is not clear that conventional disinfection processes, as commonly implemented, are effective for control of the risks of disease transmission, particularly those associated with viral pathogens. Microbial quality in receiving streams may not be substantially improved by the application of these disinfection processes; under some circumstances, an argument can be made that disinfection may actually yield a decrease in effluent and receiving water quality. Decisions regarding the need for effluent disinfection must account for site-specific characteristics, but it is not clear that disinfection of municipal wastewater effluents is necessary or beneficial for all facilities. When direct human contact or ingestion of municipal wastewater effluents is likely, disinfection may be necessary. Under these circumstances, UV irradiation appears to be superior to chlorination in terms of microbial quality and chemistry and toxicology. This advantage is particularly evident in effluents that contain appreciable quantities of ammonia-nitrogen or organic nitrogen.

Neural response to reward anticipation under risk is nonlinear in probabilities.

PubMed

Hsu, Ming; Krajbich, Ian; Zhao, Chen; Camerer, Colin F

2009-02-18

A widely observed phenomenon in decision making under risk is the apparent overweighting of unlikely events and the underweighting of nearly certain events. This violates standard assumptions in expected utility theory, which requires that expected utility be linear (objective) in probabilities. Models such as prospect theory have relaxed this assumption and introduced the notion of a "probability weighting function," which captures the key properties found in experimental data. This study reports functional magnetic resonance imaging (fMRI) data that neural response to expected reward is nonlinear in probabilities. Specifically, we found that activity in the striatum during valuation of monetary gambles are nonlinear in probabilities in the pattern predicted by prospect theory, suggesting that probability distortion is reflected at the level of the reward encoding process. The degree of nonlinearity reflected in individual subjects' decisions is also correlated with striatal activity across subjects. Our results shed light on the neural mechanisms of reward processing, and have implications for future neuroscientific studies of decision making involving extreme tails of the distribution, where probability weighting provides an explanation for commonly observed behavioral anomalies.

Communication strategies for enhancing understanding of the behavioral implications of genetic and biomarker tests for disease risk: the role of coherence.

PubMed

Cameron, Linda D; Marteau, Theresa M; Brown, Paul M; Klein, William M P; Sherman, Kerry A

2012-06-01

Individuals frequently have difficulty understanding how behavior can reduce genetically-conferred risk for diseases such as colon cancer. With increasing opportunities to purchase genetic tests, communication strategies are needed for presenting information in ways that optimize comprehension and adaptive behavior. Using the Common-Sense Model, we tested the efficacy of a strategy for providing information about the relationships (links) among the physiological processes underlying disease risk and protective action on understanding, protective action motivations, and willingness to purchase tests. We tested the generalizability of the strategy's effects across varying risk levels, for genetic tests versus tests of a non-genetic biomarker, and when using graphic and numeric risk formats. In an internet-based experiment, 749 adults from four countries responded to messages about a hypothetical test for colon cancer risk. Messages varied by Risk-Action Link Information (provision or no provision of information describing how a low-fat diet reduces risk given positive results, indicating presence of a gene fault), Risk Increment (20%, 50%, or 80% risk given positive results), Risk Format (numeric or graphic presentation of risk increments), and Test Type (genetic or enzyme). Providing risk-action link information enhanced beliefs of coherence (understanding how a low-fat diet reduces risk) and response efficacy (low-fat diets effectively reduce risk) and lowered appraisals of anticipated risk of colon cancer given positive results. These effects held across risk increments, risk formats, and test types. For genetic tests, provision of risk-action link information reduced the amount individuals were willing to pay for testing. Brief messages explaining how action can reduce genetic and biomarker-detected risks can promote beliefs motivating protective action. By enhancing understanding of behavioral control, they may reduce the perceived value of genetic risk information.

Toxoplasma gondii in sheep and goats: seroprevalence and potential risk factors under dairy husbandry practices.

PubMed

Tzanidakis, Nikolaos; Maksimov, Pavlo; Conraths, Franz J; Kiossis, Evaggelos; Brozos, Christos; Sotiraki, Smaragda; Schares, Gereon

2012-12-21

Sheep and goats are highly susceptible for infections with Toxoplasma gondii and may play a major role in the transmission of toxoplasmosis to humans. The aim of this study was to obtain up-to-date data on T. gondii infection in small ruminants and to identify putative risk factors in sheep and goats reared under dairy husbandry systems most commonly applied in Greece. To this end, ELISA tests were established for the examination of sheep and goat sera based on the use of TgSAG1, a major surface antigen of T. gondii tachyzoites. Serum samples from 2-4 years old small ruminants, 1501 from sheep and 541 from goats were examined. These samples had been collected on 69 farms in a mountainous and in a costal environment of Northern Greece from September 2008 to January 2009. In addition to farms containing only sheep (n=28) and farms containing only goats (n=9) also mixed farms with both animal species (n=32) were sampled. A standardized questionnaire was used to obtain information on putative risk factors. Sheep showed a higher seroprevalence (48.6% [729/1501]) for T. gondii than goats (30.7% [166/541]). Univariate multi-level modelling assuming random effects by the factor "farm" revealed that goats were statistically significantly less often seropositive than sheep (OR 0.475 [95% CI: 0.318-0.707]). No statistically significant regional differences in seroprevalence were observed. Risk factor analysis using univariate multi-level modelling revealed that sheep and goats that were kept under intensive (OR 4.30 [95% CI: 1.39-13.27]) or semi-intensive (OR 5.35 [95% CI: 2.33-12.28]) conditions had significantly higher odds of being seropositive. Further significant risk factors were "feeding concentrate" (OR 3.88 [95% CI: 1.81-8.29]) and providing "water from the public supply" (OR 1.67 [95% CI: 4.56-12.39]) to small ruminants. Copyright © 2012 Elsevier B.V. All rights reserved.

Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model.

PubMed

Engerström, Lars; Nolin, Thomas; Mårdh, Caroline; Sjöberg, Folke; Karlström, Göran; Fredrikson, Mats; Walther, Sten M

2017-12-01

The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 model's performance. Retrospective analysis of prospectively collected data. Sixty-three ICUs in the Swedish Intensive Care Registry. Patients admitted during 2011-2014 (n = 107,310). None. Model performance was analyzed using the area under the receiver operating curve, scaled Brier's score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

Common vole (Microtus arvalis) ecology and management: implications for risk assessment of plant protection products.

PubMed

Jacob, Jens; Manson, Phil; Barfknecht, Ralf; Fredricks, Timothy

2014-06-01

Common voles (Microtus arvalis) are common small mammals in some European landscapes. They can be a major rodent pest in European agriculture and they are also a representative generic focal small herbivorous mammal species used in risk assessment for plant protection products. In this paper, common vole population dynamics, habitat and food preferences, pest potential and use of the common vole as a model small wild mammal species in the risk assessment process are reviewed. Common voles are a component of agroecosystems in many parts of Europe, inhabiting agricultural areas (secondary habitats) when the carrying capacity of primary grassland habitats is exceeded. Colonisation of secondary habitats occurs during multiannual outbreaks, when population sizes can exceed 1000 individuals ha(-1) . In such cases, in-crop common vole population control management has been practised to avoid significant crop damage. The species' status as a crop pest, high fecundity, resilience to disturbance and intermittent colonisation of crop habitats are important characteristics that should be reflected in risk assessment. Based on the information provided in the scientific literature, it seems justified to modify elements of the current risk assessment scheme for plant protection products, including the use of realistic food intake rates, reduced assessment factors or the use of alternativee focal rodent species in particular European regions. Some of these adjustments are already being applied in some EU member states. Therefore, it seems reasonable consistently to apply such pragmatic and realistic approaches in risk assessments for plant protection products across the EU. © 2013 Society of Chemical Industry.

Management of Retinal Vein Occlusion, Who Is Responsible?

PubMed

Aghamirsalim, Mohamadreza; Sorbi, Reza; Naderian, Mohammadreza; Cugati, Sudha; Shahsuvaryan, Marianne Levon; Ghazizadeh Hashemi, Maryam

2016-11-01

Retinal vein occlusion (RVO) is a common retinal vascular occlusive disorder and is associated with a variety of systemic risk factors. The aim of this study was to investigate whether the underlying diseases were evaluated and managed appropriately by ophthalmologists. We performed a study of 1344 patients with retinal vein occlusion (RVO). Patients were evaluated with a questionnaire including ten closed questions to determine whether ophthalmologists evaluated and informed their patients about the underlying systemic diseases. None of the patients' homocysteine levels were measured. Only a small percentage of the patients were asked about the history of thrombotic diseases or family history of thrombotic diseases. We believe that most ophthalmologists are still not entirely convinced of their responsibility of managing the underlying predisposing factors of RVO. Ophthalmologists should either manage or engage other healthcare providers in the management of RVO to guarantee the patient the best care.

Hypoglycemia in Older People - A Less Well Recognized Risk Factor for Frailty

PubMed Central

Abdelhafiz, Ahmed H; Rodríguez-Mañas, Leocadio; Morley, John E.; Sinclair, Alan J

2015-01-01

Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognized and under reported by patients and health care professionals. Hypoglycemia in this age group is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients’ general health. This negative impact of hypoglycemia is likely to eventually lead to frailty, disability and poor outcomes. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail older people with diabetes may be worthwhile. PMID:25821643

Surveying hospital network structure in New York State: how are they structured?

PubMed

Nauenberg, E; Brewer, C S

2000-01-01

We determine the most common network structures in New York state. The taxonomy employed uses three structural dimensions: integration, complexity, and risk-sharing between organizations. Based on a survey conducted in 1996, the most common type of network (26.4 percent) had medium levels of integration, medium or high levels of complexity, and some risk-sharing. Also common were networks with low levels of integration, low levels of complexity, and no risk-sharing (22.1 percent).

New technologies provide insights into genetic basis of psychiatric disorders and explain their co-morbidity.

PubMed

Rudan, Igor

2010-06-01

The completion of Human Genome Project and the "HapMap" project was followed by translational activities from companies within the private sector. This led to the introduction of genome-wide scans based on hundreds of thousands of single nucleotide polymorphysms (SNP). These scans were based on common genetic variants in human populations. This new and powerful technology was then applied to the existing DNA-based datasets with information on psychiatric disorders. As a result, an unprecedented amount of novel scientific insights related to the underlying biology and genetics of psychiatric disorders was obtained. The dominant design of these studies, so called "genome-wide association studies" (GWAS), used statistical methods which minimized the risk of false positive reports and provided much greater power to detect genotype-phenotype associations. All findings were entirely data-driven rather than hypothesis-driven, which often made it difficult for researchers to understand or interpret the findings. Interestingly, this work in genetics is indicating how non-specific some genes are for psychiatric disorders, having associations in common for schizophrenia, bipolar disorder and autism. This suggests that the earlier stages of psychiatric disorders may be multi-valent and that early detection, coupled with a clearer understanding of the environmental factors, may allow prevention. At the present time, the rich "harvest" from GWAS still has very limited power to predict the variation in psychiatric disease status at individual level, typically explaining less than 5% of the total risk variance. The most recent studies of common genetic variation implicated the role of major histocompatibility complex in schizophrenia and other disorders. They also provided molecular evidence for a substantial polygenic component to the risk of psychiatric diseases, involving thousands of common alleles of very small effect. The studies of structural genetic variation, such as copy number variants (CNV), coupled with the efforts targeting rare genetic variation (using the emerging whole-genome "deep" sequencing technologies) will become the area of the greatest interest in the field of genetic epidemiology. This will be complemented by the studies of epigenetic phoenomena, changes of expression at a large scale and understanding gene-gene interactions in complex networks using systems biology approaches. A deeper understanding of the underlying biology of psychiatric disorders is essential to improve diagnoses and therapies of these diseases. New technologies - genome-wide association studies, imaging and the optical manipulation of neural circuits - are promising to provide novel insights and lead to new treatments.

Myocardial Bridge and Acute Plaque Rupture.

PubMed

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

A biopsychosocial model of violence when sleepwalking: review and reconceptualisation

PubMed Central

Bari, Andrea

2017-01-01

Summary Violence towards others during sleepwalking is relatively uncommon, but can result in serious injury or even death. Much of the research in this field has focused on the forensic consequences of violence during sleepwalking without sufficient attention to an understanding of the risk factors for violence during sleepwalking and the development of prevention and interventions based on these risk factors. This paper reviews the characteristics of impulsive violence in general and reconceptualises violence during sleepwalking as an extension of this prior vulnerability. We propose a biopsychosocial model of the risk for violence during sleepwalking that is supported through a review of empirical literature both within sleepwalking and violent behaviour more generally. Biological, psychological and social risk factors are hypothesised to mediate the relationship between sleepwalking and violence. Implications for prevention and treatment of this potentially fatal problem are discussed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28446961

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

PubMed

Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb; Pomerantz, Mark; Li, Fugen; Long, Henry W; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Zheng, Wei; Pettaway, Curtis A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; John, Esther M; Murphy, Adam B; Signorello, Lisa B; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anslem J M; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Witte, John S; Casey, Graham; Kaggwa, Sam; Cook, Michael B; Stram, Daniel O; Blot, William J; Eeles, Rosalind A; Easton, Douglas; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel M; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Teerlink, Craig; Brenner, Hermann; Dieffenbach, Aida K; Arndt, Volker; Park, Jong Y; Sellers, Thomas A; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A; Teixeira, Manuel R; Pandha, Hardev; Michael, Agnieszka; Paulo, Paula; Maia, Sofia; Kierzek, Andrzej; Conti, David V; Albanes, Demetrius; Berg, Christine; Berndt, Sonja I; Campa, Daniele; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Gaziano, J Michael; Giovannucci, Edward; Hoover, Robert; Hunter, David J; Johansson, Mattias; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Navarro, Carmen; Overvad, Kim; Riboli, Elio; Siddiq, Afshan; Stevens, Victoria L; Trichopoulos, Dimitrios; Vineis, Paolo; Yeager, Meredith; Trynka, Gosia; Raychaudhuri, Soumya; Schumacher, Frederick R; Price, Alkes L; Freedman, Matthew L; Haiman, Christopher A; Pasaniuc, Bogdan

2016-04-07

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

A sticky situation: myocardial infarction in a young woman with immune thrombocytopenia on eltrombopag and a history of mediastinal radiation.

PubMed

Teichman, Jennifer; Taher, Ahmed; Hashi, Abdulaziz; Bagai, Akshay; Sholzberg, Michelle

2018-01-01

More recent immune thrombocytopenia (ITP) treatment strategies enhance platelet production with the use of thrombopoietin receptor agonists (TPO-RA) such as eltrombopag. Patients receiving TPO-RA agents may be at an increased risk of thromboembolism, however the pathophysiology and common underlying risk factors are not well understood. We present the case of a young asplenic woman on eltrombopag for chronic ITP with acute myocardial infarction involving the right coronary artery. Past medical history was significant for remote mediastinal radiation for lymphoma and splenectomy for ITP. She had no other risk factors for coronary artery disease. She underwent coronary catheterization and balloon angioplasty to the culprit lesion, although stenting was deferred due to concerns with dual antiplatelet therapy. She was discharged from hospital on single antiplatelet therapy with acetylsalicylic acid. We believe that the patient's ITP, recent eltrombopag use, surgical asplenia and history of mediastinal radiation synergistically contributed to her myocardial infarction. The risks of bleeding and thromboembolism must be carefully weighed in patients receiving TPO-RA therapy.

Assessing Breast Cancer Risk with an Artificial Neural Network

PubMed

Sepandi, Mojtaba; Taghdir, Maryam; Rezaianzadeh, Abbas; Rahimikazerooni, Salar

2018-04-25

Objectives: Radiologists face uncertainty in making decisions based on their judgment of breast cancer risk. Artificial intelligence and machine learning techniques have been widely applied in detection/recognition of cancer. This study aimed to establish a model to aid radiologists in breast cancer risk estimation. This incorporated imaging methods and fine needle aspiration biopsy (FNAB) for cyto-pathological diagnosis. Methods: An artificial neural network (ANN) technique was used on a retrospectively collected dataset including mammographic results, risk factors, and clinical findings to accurately predict the probability of breast cancer in individual patients. Area under the receiver-operating characteristic curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive values were used to evaluate discriminative performance. Result: The network incorporating the selected features performed best (AUC = 0.955). Sensitivity and specificity of the ANN were respectively calculated as 0.82 and 0.90. In addition, negative and positive predictive values were respectively computed as 0.90 and 0.80. Conclusion: ANN has potential applications as a decision-support tool to help underperforming practitioners to improve the positive predictive value of biopsy recommendations. Creative Commons Attribution License

Recruitment into diabetes prevention programs: what is the impact of errors in self-reported measures of obesity?

PubMed

Hernan, Andrea; Philpot, Benjamin; Janus, Edward D; Dunbar, James A

2012-07-08

Error in self-reported measures of obesity has been frequently described, but the effect of self-reported error on recruitment into diabetes prevention programs is not well established. The aim of this study was to examine the effect of using self-reported obesity data from the Finnish diabetes risk score (FINDRISC) on recruitment into the Greater Green Triangle Diabetes Prevention Project (GGT DPP). The GGT DPP was a structured group-based lifestyle modification program delivered in primary health care settings in South-Eastern Australia. Between 2004-05, 850 FINDRISC forms were collected during recruitment for the GGT DPP. Eligible individuals, at moderate to high risk of developing diabetes, were invited to undertake baseline tests, including anthropometric measurements performed by specially trained nurses. In addition to errors in calculating total risk scores, accuracy of self-reported data (height, weight, waist circumference (WC) and Body Mass Index (BMI)) from FINDRISCs was compared with baseline data, with impact on participation eligibility presented. Overall, calculation errors impacted on eligibility in 18 cases (2.1%). Of n = 279 GGT DPP participants with measured data, errors (total score calculation, BMI or WC) in self-report were found in n = 90 (32.3%). These errors were equally likely to result in under- or over-reported risk. Under-reporting was more common in those reporting lower risk scores (Spearman-rho = -0.226, p-value < 0.001). However, underestimation resulted in only 6% of individuals at high risk of diabetes being incorrectly categorised as moderate or low risk of diabetes. Overall FINDRISC was found to be an effective tool to screen and recruit participants at moderate to high risk of diabetes, accurately categorising levels of overweight and obesity using self-report data. The results could be generalisable to other diabetes prevention programs using screening tools which include self-reported levels of obesity.

Legal and ethical aspects of deliberate G-induced loss of consciousness experiments.

PubMed

Euretig, J G

1991-07-01

Informed consent is both a legal and accepted ethical prerequisite to nontherapeutic human experimentation. The informed consent obtained from the subject in G-LOC experimentation is in the same form as the risk disclosures used in high-G acceleration experiments. However, in high acceleration protocols G-LOC is a potential risk while in G-LOC experiments it is the result. The case law embodies three modern evidentiary standards (the "professional," "material fact," and "possible risks" tests) employed by common law courts when deciding whether the risk disclosures are sufficient to elicit the informed consent of the subject. Each standard is applied against the disclosures in the G-LOC protocol to determine if the elements of the requirement are met. The risk disclosures are wanting in specific identification under the three tests. The deficiency is the failure to inform the subject that G-LOC may result in a pathologic state of unconsciousness about which little is known. Without complete disclosure of this lacking state of medical knowledge, it is questionable whether informed consent can be given. If subjected to judicial scrutiny, the disclosures stated in the G-LOC protocol used in government sponsored research will probably be found deficient.

Misrepresentation of health risks by mass media.

PubMed

Bomlitz, Larisa J; Brezis, Mayer

2008-06-01

Mass media are a leading source of health information for general public. We wished to examine the relationship between the intensity of media coverage for selected health topics and their actual risk to public health. Mass media reports in the United States on emerging and chronic health hazards (severe acute respiratory syndrome (SARS), bioterrorism, West Nile Fever, AIDS, smoking and physical inactivity) were counted for the year 2003, using LexisNexis database. The number of media reports for each health risk was correlated with the corresponding death rate as reported by the Centers for Disease Control and Prevention. The number of media reports inversely correlated with the actual number of deaths for the health risks evaluated. SARS and bioterrorism killed less than a dozen people in 2003, but together generated over 100 000 media reports, far more than those covering smoking and physical inactivity, which killed nearly a million Americans. Emerging health hazards are over-reported in mass media by comparison to common threats to public health. Since premature mortality in industrialized societies is most often due to well-known risks such as smoking and physical inactivity, their under-representation on public agendas may cause suboptimal prioritization of public health resources.

Hazard identification by methods of animal-based toxicology.

PubMed

Barlow, S M; Greig, J B; Bridges, J W; Carere, A; Carpy, A J M; Galli, C L; Kleiner, J; Knudsen, I; Koëter, H B W M; Levy, L S; Madsen, C; Mayer, S; Narbonne, J-F; Pfannkuch, F; Prodanchuk, M G; Smith, M R; Steinberg, P

2002-01-01

This paper is one of several prepared under the project "Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet" (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy. They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.

Biomarkers for Wilms Tumor: a Systematic Review

PubMed Central

Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

2016-01-01

Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655