Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

PubMed

Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

2018-06-02

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

21 CFR 812.66 - Significant risk device determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Significant risk device determinations. 812.66... risk device determinations. If an IRB determines that an investigation, presented for approval under § 812.2(b)(1)(ii), involves a significant risk device, it shall so notify the investigator and, where...

Identifying risk event in Indonesian fresh meat supply chain

NASA Astrophysics Data System (ADS)

Wahyuni, H. C.; Vanany, I.; Ciptomulyono, U.

2018-04-01

The aim of this paper is to identify risk issues in Indonesian fresh meat supply chain from the farm until to the “plate”. The critical points for food safety in physical fresh meat product flow are also identified. The paper employed one case study in the Indonesian fresh meat company by conducting observations and in-depth three stages of interviews. At the first interview, the players, process, and activities in the fresh meat industry were identified. In the second interview, critical points for food safety were recognized. The risk events in each player and process were identified in the last interview. The research will be conducted in three stages, but this article focuses on risk identification process (first stage) only. The second stage is measuring risk and the third stage focuses on determining the value of risk priority. The results showed that there were four players in the fresh meat supply chain: livestock (source), slaughter (make), distributor and retail (deliver). Each player has different activities and identified 16 risk events in the fresh meat supply chain. Some of the strategies that can be used to reduce the occurrence of such risks include improving the ability of laborers on food safety systems, improving cutting equipment and distribution processes

Identifying medical students at risk of underperformance from significant stressors.

PubMed

Wilkinson, Tim J; McKenzie, Jan M; Ali, Anthony N; Rudland, Joy; Carter, Frances A; Bell, Caroline J

2016-02-02

Stress is associated with poorer academic performance but identifying vulnerable students is less clear. A series of earthquakes and disrupted learning environments created an opportunity to explore the relationships among stress, student factors, support and academic performance within a medical course. The outcomes were deviations from expected performances on end of year written and clinical examinations. The predictors were questionnaire-based measures of connectedness/support, impact of the earthquakes, safety, depression, anxiety, stress, resilience and personality. The response rate was 77%. Poorer than expected performance on all examinations was associated with greater disruptions to living arrangements and fewer years in the country; on the written examination with not having a place to study; and on the clinical examination with relationship status, not having the support of others, less extroversion, and feeling less safe. There was a suggestion of a beneficial association with some markers of stress. We show that academic performance is assisted by students having a secure physical and emotional base. The students who are most vulnerable are those with fewer social networks, and those who are recent immigrants.

Incidence of neonatal hypoglycemia in babies identified as at risk.

PubMed

Harris, Deborah L; Weston, Philip J; Harding, Jane E

2012-11-01

Routine blood glucose screening is recommended for babies at risk of neonatal hypoglycemia. However, the incidence of hypoglycemia in those screened is not well described. We sought to determine the incidence of hypoglycemia in babies identified as being at risk, and also to determine differences in incidence between at risk groups. Infants (n = 514) were recruited who were born in a tertiary hospital, ≥35 weeks gestation and identified as at risk of hypoglycemia (small, large, infant of a diabetic, late-preterm, and other). Blood glucose screening used a standard protocol and a glucose oxidase method of glucose measurement in the first 48 hours after birth. One-half of the babies (260/514, 51%) became hypoglycemic (<2.6 mM), 97 (19%) had severe hypoglycemia (≤2.0 mM), and 98 (19%) had more than 1 episode. The mean duration of an episode was 1.4 hours. Most episodes (315/390, 81%) occurred in the first 24 hours. The median number of blood glucose measurements for each baby was 9 (range 1-22). The incidence and timing of hypoglycemia was similar in all at risk groups, but babies with a total of 3 risk factors were more likely to have severe hypoglycemia. Hypoglycemia is common amongst babies recommended for routine blood glucose screening. We found no evidence that screening protocols should differ in different at risk groups, but multiple risk factors may increase severity. The significance of these hypoglycemic episodes for long-term outcome remains undetermined. Copyright © 2012 Mosby, Inc. All rights reserved.

Genome-wide association study identifies multiple loci associated with bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

2014-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

In Search of Black Swans: Identifying Students at Risk of Failing Licensing Examinations.

PubMed

Barber, Cassandra; Hammond, Robert; Gula, Lorne; Tithecott, Gary; Chahine, Saad

2018-03-01

To determine which admissions variables and curricular outcomes are predictive of being at risk of failing the Medical Council of Canada Qualifying Examination Part 1 (MCCQE1), how quickly student risk of failure can be predicted, and to what extent predictive modeling is possible and accurate in estimating future student risk. Data from five graduating cohorts (2011-2015), Schulich School of Medicine & Dentistry, Western University, were collected and analyzed using hierarchical generalized linear models (HGLMs). Area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of predictive models and determine whether they could be used to predict future risk, using the 2016 graduating cohort. Four predictive models were developed to predict student risk of failure at admissions, year 1, year 2, and pre-MCCQE1. The HGLM analyses identified gender, MCAT verbal reasoning score, two preclerkship course mean grades, and the year 4 summative objective structured clinical examination score as significant predictors of student risk. The predictive accuracy of the models varied. The pre-MCCQE1 model was the most accurate at predicting a student's risk of failing (AUC 0.66-0.93), while the admissions model was not predictive (AUC 0.25-0.47). Key variables predictive of students at risk were found. The predictive models developed suggest, while it is not possible to identify student risk at admission, we can begin to identify and monitor students within the first year. Using such models, programs may be able to identify and monitor students at risk quantitatively and develop tailored intervention strategies.

Predicting the unpredictable? Identifying high-risk versus low-risk parents with intellectual disabilities.

PubMed

McGaw, Sue; Scully, Tamara; Pritchard, Colin

2010-09-01

This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates 'high-risk' from 'low-risk' parenting; and (iii) the impact of partner relationships on parental competency and risk status. Secondary data analysis was conducted on data gathered from 101 parents with IDs and 172 of their children, all of whom had been referred to a specialist parenting service over a 5 year period. Cross-tabulations were applied to the data to examine causal processes and to improve general understanding of the risks associated with families. Contrary to popular expectations IQ levels of the main parent, relationship status, parental age, employment, amenities, valued support and parents' perception of need were not identified as contributory factors distinguishing 'high-risk' from 'low-risk' parents. Instead, 'high-risk' parenting associated more with parental reports of childhood trauma (emotional abuse and physical neglect in particular), parents' having additional special needs in addition to their IDs or parents who were raising a child with special needs. Other 'high-risk' factors identified related to the male partners of mothers with IDs, many of whom did not have IDs and/or whose histories included anti-social behaviors or criminality. The study identified some high-risk variables among parents with IDs that can distinguish them from low-risk parents with IDs. These findings generate challenges for agencies who attempt to capture the needs of parents with IDs and who endeavour to provide services to families deemed to be "at risk." These outcomes will be of special interest to the courts, especially when parents with IDs are involved in care proceedings. Copyright © 2010. Published by Elsevier Ltd.

Identifying and managing the risks of medical ionizing radiation in endourology.

PubMed

Yecies, Todd; Averch, Timothy D; Semins, Michelle J

2018-02-01

The risks of exposure to medical ionizing radiation is of increasing concern both among medical professionals and the general public. Patients with nephrolithiasis are exposed to high levels of ionizing radiation through both diagnostic and therapeutic modalities. Endourologists who perform a high-volume of fluoroscopy guided procedures are also exposed to significant quantities of ionizing radiation. The combination of judicious use of radiation-based imaging modalities, application of new imaging techniques such as ultra-low dose computed tomography (CT) scan, and modifying use of current technology such as increasing ultrasound and pulsed fluoroscopy utilization offers the possibility of significantly reducing radiation exposure. We present a review of the literature regarding the risks of medical ionizing radiation to patients and surgeons as it pertains to the field of endourology and interventions that can be performed to limit this exposure. A review of the current state of the literature was performed using MEDLINE and PubMed. Interventions designed to limit patient and surgeon radiation exposure were identified and analyzed. Summaries of the data were compiled and synthesized in the body of the text. While no level 1 evidence exists demonstrating the risk of secondary malignancy with radiation exposure, the preponderance of evidence suggests a dose and age dependent increase in malignancy risk from ionizing radiation. Patients with nephrolithiasis were exposed to an average effective dose of 37mSv over a 2 year period. Multiple evidence-based interventions to limit patient and surgeon radiation exposure and associated risk were identified. Current evidence suggest an age and dose dependent risk of secondary malignancy from ionizing radiation. Urologists must act in accordance with ALARA principles to safely manage nephrolithiasis while minimizing radiation exposure.

Identifying children at risk for type 2 diabetes in underserved communities.

PubMed

Vivian, Eva M; Carrel, Aaron L; Becker, Tara

2011-01-01

The purpose of this study was to identify and assess health behaviors among ethnic minority children at high risk for type 2 diabetes. Diabetes screenings were conducted at community centers, churches, and local neighborhood health fairs in Madison, Wisconsin. During these events, diabetes risk assessment surveys were given to parents of children between the ages of 10 to 19 years. Parents who identified their children as having 2 or more risk factors for type 2 diabetes were invited to have their child screened for type 2 diabetes. A total of 86 children between the ages of 10 to 19 years (mean age = 13; 58% male) were screened for diabetes. Fifty-one percent of the children were overweight or obese with 38% having >3 risk factors for type 2 diabetes. While there was no significant difference in the nutritional habits reported between normal, overweight, or obese children, fewer overweight and obese children reported exercising at least 30 minutes 5 to 7 days a week compared to children with a normal weight (P = .033). Prevention of diabetes is a powerful public health intervention. Targeted diabetes screening in disadvantaged, underserved communities is an effective way to identify families with children at risk for type 2 diabetes. In addition, information obtained from these screenings can assist researchers and clinicians in designing accessible and affordable health promotion interventions that are culturally relevant to the youth and families within the community.

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE PAGES

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.; ...

2015-10-21

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Framework for Identifying Cybersecurity Risks in Manufacturing

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

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

A partner-related risk behavior index to identify people at elevated risk for sexually transmitted infections.

PubMed

Crosby, Richard; Shrier, Lydia A

2013-04-01

The purpose of this study was to develop and test a sexual-partner-related risk behavior index to identify high-risk individuals most likely to have a sexually transmitted infection (STI). Patients from five STI and adolescent medical clinics in three US cities were recruited (N = 928; M age = 29.2 years). Data were collected using audio-computer-assisted self-interviewing. Of seven sexual-partner-related variables, those that were significantly associated with the outcomes were combined into a partner-related risk behavior index. The dependent variables were laboratory-confirmed infection with Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. Nearly one-fifth of the sample (169/928; 18.4%) tested positive for an STI. Three of the seven items were significantly associated with having one or more STIs: sex with a newly released prisoner, sex with a person known or suspected of having an STI, and sexual concurrency. In combined form, this three-item index was significantly associated with STI prevalence (p < .001). In the presence of three covariates (gender, race, and age), those classified as being at-risk by the index were 1.8 times more likely than those not classified as such to test positive for an STI (p < .001). Among individuals at risk for STIs, a three-item index predicted testing positive for one or more of three STIs. This index could be used to prioritize and guide intensified clinic-based counseling for high-risk patients of STI and other clinics.

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression.

PubMed

Tin, Adrienne; Nadkarni, Girish; Evans, Anne M; Winkler, Cheryl A; Bottinger, Erwin; Rebholz, Casey M; Sarnak, Mark J; Inker, Lesley A; Levey, Andrew S; Lipkowitz, Michael S; Appel, Lawrence J; Arking, Dan E; Coresh, Josef; Grams, Morgan E

2018-05-18

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles-genetic variants associated with CKD risk commonly present in persons of African descent-may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) ( n =588; Bonferroni significance threshold P <6.5×10 -5 ) and replicated findings in 678 black participants with CKD in Bio Me , an electronic medical record-linked biobank. We tested the metabolite association with CKD progression in AASK, Bio Me , and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK ( P =4.7×10 -5 ) and replicated in Bio Me ( P =5.7×10 -3 ) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and Bio Me participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; Bio Me , 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression. Copyright © 2018 by the American Society of Nephrology.

A Practical Method for Identifying Significant Change Scores

ERIC Educational Resources Information Center

Cascio, Wayne F.; Kurtines, William M.

1977-01-01

A test of significance for identifying individuals who are most influenced by an experimental treatment as measured by pre-post test change score is presented. The technique requires true difference scores, the reliability of obtained differences, and their standard error of measurement. (Author/JKS)

Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

PubMed

Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

2017-03-01

To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely

Screening for Albuminuria Identifies Individuals at Increased Renal Risk

PubMed Central

van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

2009-01-01

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

Identifying Children At Risk for Being Bullies in the US

PubMed Central

Shetgiri, Rashmi; Lin, Hua; Flores, Glenn

2012-01-01

Objective To identify risk factors associated with the highest and lowest prevalence of bullying perpetration among US children. Methods Using the 2001–2002 Health Behavior in School-Aged Children, a nationally-representative survey of US children in 6th–10th grades, bivariate analyses were conducted to identify factors associated with any (≥ once or twice), moderate (≥ two-three times/month), and frequent (≥ weekly) bullying. Stepwise multivariable analyses identified risk factors associated with bullying. Recursive partitioning analysis (RPA) identified risk factors which, in combination, identify students with the highest and lowest bullying prevalence. Results The prevalence of any bullying in the 13,710 students was 37.3%, moderate bullying was 12.6%, and frequent bullying was 6.6%. Characteristics associated with bullying were similar in the multivariable analyses and RPA clusters. In RPA, the highest prevalence of any bullying (67%) accrued in children with a combination of fighting and weapon-carrying. Students who carry weapons, smoke, and drink alcohol more than 5–6 days weekly were at highest risk for moderate bullying (61%). Those who carry weapons, smoke, drink > once daily, have above-average academic performance, moderate/high family affluence, and feel irritable or bad-tempered daily were at highest risk for frequent bullying (68%). Conclusions Risk clusters for any, moderate, and frequent bullying differ. Children who fight and carry weapons are at highest risk of any bullying. Weapon-carrying, smoking, and alcohol use are included in the highest risk clusters for moderate and frequent bullying. Risk-group categories may be useful to providers in identifying children at highest risks for bullying and in targeting interventions. PMID:22989731

Fetal alcohol-spectrum disorders: identifying at-risk mothers

PubMed Central

Montag, Annika C

2016-01-01

Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

Identifying high-risk areas for sporadic measles outbreaks: lessons from South Africa.

PubMed

Sartorius, Benn; Cohen, C; Chirwa, T; Ntshoe, G; Puren, A; Hofman, K

2013-03-01

To develop a model for identifying areas at high risk for sporadic measles outbreaks based on an analysis of factors associated with a national outbreak in South Africa between 2009 and 2011. Data on cases occurring before and during the national outbreak were obtained from the South African measles surveillance programme, and data on measles immunization and population size, from the District Health Information System. A Bayesian hierarchical Poisson model was used to investigate the association between the risk of measles in infants in a district and first-dose vaccination coverage, population density, background prevalence of human immunodeficiency virus (HIV) infection and expected failure of seroconversion. Model projections were used to identify emerging high-risk areas in 2012. A clear spatial pattern of high-risk areas was noted, with many interconnected (i.e. neighbouring) areas. An increased risk of measles outbreak was significantly associated with both the preceding build-up of a susceptible population and population density. The risk was also elevated when more than 20% of infants in a populous area had missed a first vaccine dose. The model was able to identify areas at high risk of experiencing a measles outbreak in 2012 and where additional preventive measures could be undertaken. The South African measles outbreak was associated with the build-up of a susceptible population (owing to poor vaccine coverage), high prevalence of HIV infection and high population density. The predictive model developed could be applied to other settings susceptible to sporadic outbreaks of measles and other vaccine-preventable diseases.

Identifying the necessary and sufficient number of risk factors for predicting academic failure.

PubMed

Lucio, Robert; Hunt, Elizabeth; Bornovalova, Marina

2012-03-01

Identifying the point at which individuals become at risk for academic failure (grade point average [GPA] < 2.0) involves an understanding of which and how many factors contribute to poor outcomes. School-related factors appear to be among the many factors that significantly impact academic success or failure. This study focused on 12 school-related factors. Using a thorough 5-step process, we identified which unique risk factors place one at risk for academic failure. Academic engagement, academic expectations, academic self-efficacy, homework completion, school relevance, school safety, teacher relationships (positive relationship), grade retention, school mobility, and school misbehaviors (negative relationship) were uniquely related to GPA even after controlling for all relevant covariates. Next, a receiver operating characteristic curve was used to determine a cutoff point for determining how many risk factors predict academic failure (GPA < 2.0). Results yielded a cutoff point of 2 risk factors for predicting academic failure, which provides a way for early identification of individuals who are at risk. Further implications of these findings are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Identifying Occupations at Risk for Laryngeal Disorders Requiring Specialty Voice Care.

PubMed

Mori, Matthew C; Francis, David O; Song, Phillip C

2017-10-01

Objective To identify occupational groups' use of specialty voice clinic evaluation. Study Design Retrospective cohort study. Setting Tertiary subspecialty clinic. Subjects and Methods We analyzed data collected on patients presenting to the Massachusetts Eye and Ear Infirmary Voice and Speech Laboratory over a 20-year period (1993-2013). The relative risk (RR) and 99% confidence interval (CI) of presentation were calculated for each occupational category in the greater Boston population using year-matched data from the Bureau of Labor Statistics (BLS). Results The records of 12,120 new patients were reviewed. Using year- and occupation-matched BLS data from 2005 to 2013, 2726 patients were included in the cohort analysis. Several occupations had significantly higher risk of presentation. These included arts and entertainment (RR 4.98, CI 4.18-5.95), law (RR 3.24, CI 2.48-4.23), education (RR 3.08, CI 2.70-3.52), and social services (RR 2.07, CI 1.57-2.73). In contrast, many occupations had significantly reduced risk of presentation for laryngological disorders, for example, maintenance (RR 0.25, CI 0.15-0.42), food preparation (RR 0.35, CI 0.26-0.48), and administrative support (RR 0.49, CI 0.41-0.57). Conclusion Certain occupations are associated with higher use of laryngological services presumably because of their vocational voice needs. In addition to confirming findings from other studies, we identified several new occupation groups with increased or decreased risk for laryngologic disorders. Understanding what factors predispose to requiring specialty voice evaluation may help in targeting preventative efforts.

Body mass index cut-points to identify cardiometabolic risk in black South Africans.

PubMed

Kruger, H Salome; Schutte, Aletta E; Walsh, Corinna M; Kruger, Annamarie; Rennie, Kirsten L

2017-02-01

To determine optimal body mass index (BMI) cut-points for the identification of cardiometabolic risk in black South African adults. We performed a cross-sectional study of a weighted sample of healthy black South Africans aged 25-65 years (721 men, 1386 women) from the North West and Free State Provinces. Demographic, lifestyle and anthropometric measures were taken, and blood pressure, fasting serum triglycerides, high-density lipoprotein (HDL) cholesterol and blood glucose were measured. We defined elevated cardiometabolic risk as having three or more risk factors according to international metabolic syndrome criteria. Receiver operating characteristic curves were applied to identify an optimal BMI cut-point for men and women. BMI had good diagnostic performance to identify clustering of three or more risk factors, as well as individual risk factors: low HDL-cholesterol, elevated fasting glucose and triglycerides, with areas under the curve >.6, but not for high blood pressure. Optimal BMI cut-points averaged 22 kg/m 2 for men and 28 kg/m 2 for women, respectively, with better sensitivity in men (44.0-71.9 %), and in women (60.6-69.8 %), compared to a BMI of 30 kg/m 2 (17-19.1, 53-61.4 %, respectively). Men and women with a BMI >22 and >28 kg/m 2 , respectively, had significantly increased probability of elevated cardiometabolic risk after adjustment for age, alcohol use and smoking. In black South African men, a BMI cut-point of 22 kg/m 2 identifies those at cardiometabolic risk, whereas a BMI of 30 kg/m 2 underestimates risk. In women, a cut-point of 28 kg/m 2 , approaching the WHO obesity cut-point, identifies those at risk.

What’s the risk? Identifying potential human pathogens within grey-headed flying foxes faeces

PubMed Central

Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

2018-01-01

Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

41 CFR 102-80.50 - Are Federal agencies responsible for identifying/estimating risks and for appropriate risk...

Code of Federal Regulations, 2010 CFR

2010-07-01

... identify and estimate safety and environmental management risks and appropriate risk reduction strategies... responsible for identifying/estimating risks and for appropriate risk reduction strategies? 102-80.50 Section... Environmental Management Risks and Risk Reduction Strategies § 102-80.50 Are Federal agencies responsible for...

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

PubMed

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

Automated identification and predictive tools to help identify high-risk heart failure patients: pilot evaluation.

PubMed

Evans, R Scott; Benuzillo, Jose; Horne, Benjamin D; Lloyd, James F; Bradshaw, Alejandra; Budge, Deborah; Rasmusson, Kismet D; Roberts, Colleen; Buckway, Jason; Geer, Norma; Garrett, Teresa; Lappé, Donald L

2016-09-01

Develop and evaluate an automated identification and predictive risk report for hospitalized heart failure (HF) patients. Dictated free-text reports from the previous 24 h were analyzed each day with natural language processing (NLP), to help improve the early identification of hospitalized patients with HF. A second application that uses an Intermountain Healthcare-developed predictive score to determine each HF patient's risk for 30-day hospital readmission and 30-day mortality was also developed. That information was included in an identification and predictive risk report, which was evaluated at a 354-bed hospital that treats high-risk HF patients. The addition of NLP-identified HF patients increased the identification score's sensitivity from 82.6% to 95.3% and its specificity from 82.7% to 97.5%, and the model's positive predictive value is 97.45%. Daily multidisciplinary discharge planning meetings are now based on the information provided by the HF identification and predictive report, and clinician's review of potential HF admissions takes less time compared to the previously used manual methodology (10 vs 40 min). An evaluation of the use of the HF predictive report identified a significant reduction in 30-day mortality and a significant increase in patient discharges to home care instead of to a specialized nursing facility. Using clinical decision support to help identify HF patients and automatically calculating their 30-day all-cause readmission and 30-day mortality risks, coupled with a multidisciplinary care process pathway, was found to be an effective process to improve HF patient identification, significantly reduce 30-day mortality, and significantly increase patient discharges to home care. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identifying risk factors for victimization among male prisoners in Taiwan.

PubMed

Kuo, Shih-Ya; Cuvelier, Steven J; Huang, Yung-Shun

2014-02-01

This study identified risk factors for prison victimization in Taiwan with an application of Western literature and assessed the extent of its applicability in an Eastern context. The sample was drawn from four male prisons located in Northern, Central, Southern, and Eastern Taiwan; a total of 1,181 valid surveys were collected. The results generally support the major findings of the extant Western studies. Crowding, however, was not significantly associated with the risk of victimization in any of the statistical models, which might be related to the different experiences and living conditions in the free community between Taiwanese and American inmates. This study generated clear policy implications, which may reduce prison victimization and engender a greater sense of well-being in the prison environment.

Panel 2: anticipatory risk assessment: identifying, assessing, and mitigating exposure risks before they occur.

PubMed

Guidotti, Tee L; Pacha, Laura

2011-07-01

Health threats place the military mission and deployed service members at risk. A commander's focus is on preventing acute health risks, such as diarrhea, because these quickly compromise the mission. However, in recent conflicts chronic and long-term illness risks have emerged as concerns. Department of Defense and Joint Chiefs of Staff mandates require documentation of exposures and environmental conditions to reconstruct exposures and evaluate future health risks. Current processes for identifying and assessing hazards, including identification and assessment before deployment and in time to take action to prevent or reduce exposures, when followed, are generally adequate for known hazards. Identifying and addressing novel, unexpected risks remain challenges. Armed conflicts are associated with rapidly changing conditions, making ongoing hazard identification and assessment difficult. Therefore, surveillance of the environment for hazards and surveillance of personnel for morbidity must be practiced at all times. Communication of risk information to decision makers is critical but problematic. Preventive Medicine (PM) personnel should take responsibility for communicating this information to non-PM military medical people and to military commanders. Communication of risks identified and lessons learned between PM personnel of different military units is extremely important when one military unit replaces another in a deployed environment.

Using latent class analysis to identify academic and behavioral risk status in elementary students.

PubMed

King, Kathleen R; Lembke, Erica S; Reinke, Wendy M

2016-03-01

Identifying classes of children on the basis of academic and behavior risk may have important implications for the allocation of intervention resources within Response to Intervention (RTI) and Multi-Tiered System of Support (MTSS) models. Latent class analysis (LCA) was conducted with a sample of 517 third grade students. Fall screening scores in the areas of reading, mathematics, and behavior were used as indicators of success on an end of year statewide achievement test. Results identified 3 subclasses of children, including a class with minimal academic and behavioral concerns (Tier 1; 32% of the sample), a class at-risk for academic problems and somewhat at-risk for behavior problems (Tier 2; 37% of the sample), and a class with significant academic and behavior problems (Tier 3; 31%). Each class was predictive of end of year performance on the statewide achievement test, with the Tier 1 class performing significantly higher on the test than the Tier 2 class, which in turn scored significantly higher than the Tier 3 class. The results of this study indicated that distinct classes of children can be determined through brief screening measures and are predictive of later academic success. Further implications are discussed for prevention and intervention for students at risk for academic failure and behavior problems. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The more from East-Asian, the better: risk prediction of colorectal cancer risk by GWAS-identified SNPs among Japanese.

PubMed

Abe, Makiko; Ito, Hidemi; Oze, Isao; Nomura, Masatoshi; Ogawa, Yoshihiro; Matsuo, Keitaro

2017-12-01

Little is known about the difference of genetic predisposition for CRC between ethnicities; however, many genetic traits common to colorectal cancer have been identified. This study investigated whether more SNPs identified in GWAS in East Asian population could improve the risk prediction of Japanese and explored possible application of genetic risk groups as an instrument of the risk communication. 558 Patients histologically verified colorectal cancer and 1116 first-visit outpatients were included for derivation study, and 547 cases and 547 controls were for replication study. Among each population, we evaluated prediction models for the risk of CRC that combined the genetic risk group based on SNPs from GWASs in European-population and a similarly developed model adding SNPs from GWASs in East Asian-population. We examined whether adding East Asian-specific SNPs would improve the discrimination. Six SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) from 23 SNPs by European-based GWAS and five SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) among ten SNPs by Asian-based GWAS were selected in CRC risk prediction model. Compared with a 6-SNP-based model, an 11-SNP model including Asian GWAS-SNPs showed improved discrimination capacity in Receiver operator characteristic analysis. A model with 11 SNPs resulted in statistically significant improvement in both derivation (P = 0.0039) and replication studies (P = 0.0018) compared with six SNP model. We estimated cumulative risk of CRC by using genetic risk group based on 11 SNPs and found that the cumulative risk at age 80 is approximately 13% in the high-risk group while 6% in the low-risk group. We constructed a more efficient CRC risk prediction model with 11 SNPs including newly identified East Asian-based GWAS SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279). Risk grouping based on 11 SNPs depicted lifetime difference of CRC risk. This might be useful for

Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify increased cardio-metabolic risk in young, healthy South Asians.

PubMed

Flowers, Elena; Molina, César; Mathur, Ashish; Reaven, Gerald M

2015-01-01

Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of "high risk" individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. More concentrations of all cardio-metabolic risk factors were significantly higher in "high risk" groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in "high risk" groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.

Root Source Analysis/ValuStream[Trade Mark] - A Methodology for Identifying and Managing Risks

NASA Technical Reports Server (NTRS)

Brown, Richard Lee

2008-01-01

Root Source Analysis (RoSA) is a systems engineering methodology that has been developed at NASA over the past five years. It is designed to reduce costs, schedule, and technical risks by systematically examining critical assumptions and the state of the knowledge needed to bring to fruition the products that satisfy mission-driven requirements, as defined for each element of the Work (or Product) Breakdown Structure (WBS or PBS). This methodology is sometimes referred to as the ValuStream method, as inherent in the process is the linking and prioritizing of uncertainties arising from knowledge shortfalls directly to the customer's mission driven requirements. RoSA and ValuStream are synonymous terms. RoSA is not simply an alternate or improved method for identifying risks. It represents a paradigm shift. The emphasis is placed on identifying very specific knowledge shortfalls and assumptions that are the root sources of the risk (the why), rather than on assessing the WBS product(s) themselves (the what). In so doing RoSA looks forward to anticipate, identify, and prioritize knowledge shortfalls and assumptions that are likely to create significant uncertainties/ risks (as compared to Root Cause Analysis, which is most often used to look back to discover what was not known, or was assumed, that caused the failure). Experience indicates that RoSA, with its primary focus on assumptions and the state of the underlying knowledge needed to define, design, build, verify, and operate the products, can identify critical risks that historically have been missed by the usual approaches (i.e., design review process and classical risk identification methods). Further, the methodology answers four critical questions for decision makers and risk managers: 1. What s been included? 2. What's been left out? 3. How has it been validated? 4. Has the real source of the uncertainty/ risk been identified, i.e., is the perceived problem the real problem? Users of the RoSA methodology

Combining Knowledge and Data Driven Insights for Identifying Risk Factors using Electronic Health Records

PubMed Central

Sun, Jimeng; Hu, Jianying; Luo, Dijun; Markatou, Marianthi; Wang, Fei; Edabollahi, Shahram; Steinhubl, Steven E.; Daar, Zahra; Stewart, Walter F.

2012-01-01

Background: The ability to identify the risk factors related to an adverse condition, e.g., heart failures (HF) diagnosis, is very important for improving care quality and reducing cost. Existing approaches for risk factor identification are either knowledge driven (from guidelines or literatures) or data driven (from observational data). No existing method provides a model to effectively combine expert knowledge with data driven insight for risk factor identification. Methods: We present a systematic approach to enhance known knowledge-based risk factors with additional potential risk factors derived from data. The core of our approach is a sparse regression model with regularization terms that correspond to both knowledge and data driven risk factors. Results: The approach is validated using a large dataset containing 4,644 heart failure cases and 45,981 controls. The outpatient electronic health records (EHRs) for these patients include diagnosis, medication, lab results from 2003–2010. We demonstrate that the proposed method can identify complementary risk factors that are not in the existing known factors and can better predict the onset of HF. We quantitatively compare different sets of risk factors in the context of predicting onset of HF using the performance metric, the Area Under the ROC Curve (AUC). The combined risk factors between knowledge and data significantly outperform knowledge-based risk factors alone. Furthermore, those additional risk factors are confirmed to be clinically meaningful by a cardiologist. Conclusion: We present a systematic framework for combining knowledge and data driven insights for risk factor identification. We demonstrate the power of this framework in the context of predicting onset of HF, where our approach can successfully identify intuitive and predictive risk factors beyond a set of known HF risk factors. PMID:23304365

Identifying children at risk for being bullies in the United States.

PubMed

Shetgiri, Rashmi; Lin, Hua; Flores, Glenn

2012-01-01

To identify risk factors associated with the greatest and lowest prevalence of bullying perpetration among U.S. children. Using the 2001-2002 Health Behavior in School-Aged Children, a nationally representative survey of U.S. children in 6th-10th grades, bivariate analyses were conducted to identify factors associated with any (once or twice or more), moderate (two to three times/month or more), and frequent (weekly or more) bullying. Stepwise multivariable analyses identified risk factors associated with bullying. Recursive partitioning analysis (RPA) identified risk factors which, in combination, identify students with the highest and lowest bullying prevalence. The prevalence of any bullying in the 13,710 students was 37.3%, moderate bullying was 12.6%, and frequent bullying was 6.6%. Characteristics associated with bullying were similar in the multivariable analyses and RPA clusters. In RPA, the highest prevalence of any bullying (67%) accrued in children with a combination of fighting and weapon-carrying. Students who carry weapons, smoke, and drink alcohol more than 5 to 6 days/week were at greatest risk for moderate bullying (61%). Those who carry weapons, smoke, have more than one alcoholic drink per day, have above-average academic performance, moderate/high family affluence, and feel irritable or bad-tempered daily were at greatest risk for frequent bullying (68%). Risk clusters for any, moderate, and frequent bullying differ. Children who fight and carry weapons are at greatest risk of any bullying. Weapon-carrying, smoking, and alcohol use are included in the greatest risk clusters for moderate and frequent bullying. Risk-group categories may be useful to providers in identifying children at the greatest risk for bullying and in targeting interventions. Copyright © 2012 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms.

PubMed

Tashjian, Robert Z; Granger, Erin K; Farnham, James M; Cannon-Albright, Lisa A; Teerlink, Craig C

2016-02-01

The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Limited data exist identifying specific genes associated with rotator cuff tearing. The purpose of this study was to identify specific genes or genetic variants associated with rotator cuff tearing by a genome-wide association study with an independent set of rotator cuff tear cases. A set of 311 full-thickness rotator cuff tear cases genotyped on the Illumina 5M single-nucleotide polymorphism (SNP) platform were used in a genome-wide association study with 2641 genetically matched white population controls available from the Illumina iControls database. Tests of association were performed with GEMMA software at 257,558 SNPs that compose the intersection of Illumina SNP platforms and that passed general quality control metrics. SNPs were considered significant if P < 1.94 × 10(-7) (Bonferroni correction: 0.05/257,558). Tests of association revealed 2 significantly associated SNPs, one occurring in SAP30BP (rs820218; P = 3.8E-9) on chromosome 17q25 and another occurring in SASH1 (rs12527089; P = 1.9E-7) on chromosome 6q24. This study represents the first attempt to identify genetic factors influencing rotator cuff tearing by a genome-wide association study using a dense/complete set of SNPs. Two SNPs were significantly associated with rotator cuff tearing, residing in SAP30BP on chromosome 17 and SASH1 on chromosome 6. Both genes are associated with the cellular process of apoptosis. Identification of potential genes or genetic variants associated with rotator cuff tearing may help in identifying individuals at risk for the development of rotator cuff tearing. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Risk-Significant Adverse Condition Awareness Strengthens Assurance of Fault Management Systems

NASA Technical Reports Server (NTRS)

Fitz, Rhonda

2017-01-01

As spaceflight systems increase in complexity, Fault Management (FM) systems are ranked high in risk-based assessment of software criticality, emphasizing the importance of establishing highly competent domain expertise to provide assurance. Adverse conditions (ACs) and specific vulnerabilities encountered by safety- and mission-critical software systems have been identified through efforts to reduce the risk posture of software-intensive NASA missions. Acknowledgement of potential off-nominal conditions and analysis to determine software system resiliency are important aspects of hazard analysis and FM. A key component of assuring FM is an assessment of how well software addresses susceptibility to failure through consideration of ACs. Focus on significant risk predicted through experienced analysis conducted at the NASA Independent Verification & Validation (IV&V) Program enables the scoping of effective assurance strategies with regard to overall asset protection of complex spaceflight as well as ground systems. Research efforts sponsored by NASAs Office of Safety and Mission Assurance (OSMA) defined terminology, categorized data fields, and designed a baseline repository that centralizes and compiles a comprehensive listing of ACs and correlated data relevant across many NASA missions. This prototype tool helps projects improve analysis by tracking ACs and allowing queries based on project, mission type, domain/component, causal fault, and other key characteristics. Vulnerability in off-nominal situations, architectural design weaknesses, and unexpected or undesirable system behaviors in reaction to faults are curtailed with the awareness of ACs and risk-significant scenarios modeled for analysts through this database. Integration within the Enterprise Architecture at NASA IV&V enables interfacing with other tools and datasets, technical support, and accessibility across the Agency. This paper discusses the development of an improved workflow process utilizing

Risk-Significant Adverse Condition Awareness Strengthens Assurance of Fault Management Systems

NASA Technical Reports Server (NTRS)

Fitz, Rhonda

2017-01-01

As spaceflight systems increase in complexity, Fault Management (FM) systems are ranked high in risk-based assessment of software criticality, emphasizing the importance of establishing highly competent domain expertise to provide assurance. Adverse conditions (ACs) and specific vulnerabilities encountered by safety- and mission-critical software systems have been identified through efforts to reduce the risk posture of software-intensive NASA missions. Acknowledgement of potential off-nominal conditions and analysis to determine software system resiliency are important aspects of hazard analysis and FM. A key component of assuring FM is an assessment of how well software addresses susceptibility to failure through consideration of ACs. Focus on significant risk predicted through experienced analysis conducted at the NASA Independent Verification Validation (IVV) Program enables the scoping of effective assurance strategies with regard to overall asset protection of complex spaceflight as well as ground systems. Research efforts sponsored by NASA's Office of Safety and Mission Assurance defined terminology, categorized data fields, and designed a baseline repository that centralizes and compiles a comprehensive listing of ACs and correlated data relevant across many NASA missions. This prototype tool helps projects improve analysis by tracking ACs and allowing queries based on project, mission type, domaincomponent, causal fault, and other key characteristics. Vulnerability in off-nominal situations, architectural design weaknesses, and unexpected or undesirable system behaviors in reaction to faults are curtailed with the awareness of ACs and risk-significant scenarios modeled for analysts through this database. Integration within the Enterprise Architecture at NASA IVV enables interfacing with other tools and datasets, technical support, and accessibility across the Agency. This paper discusses the development of an improved workflow process utilizing this

Predicting the Unpredictable? Identifying High-Risk versus Low-Risk Parents with Intellectual Disabilities

ERIC Educational Resources Information Center

McGaw, Sue; Scully, Tamara; Pritchard, Colin

2010-01-01

Objectives: This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates "high-risk"…

Computer-based malnutrition risk calculation may enhance the ability to identify pediatric patients at malnutrition-related risk for unfavorable outcome.

PubMed

Karagiozoglou-Lampoudi, Thomais; Daskalou, Efstratia; Lampoudis, Dimitrios; Apostolou, Aggeliki; Agakidis, Charalampos

2015-05-01

The study aimed to test the hypothesis that computer-based calculation of malnutrition risk may enhance the ability to identify pediatric patients at malnutrition-related risk for an unfavorable outcome. The Pediatric Digital Scaled MAlnutrition Risk screening Tool (PeDiSMART), incorporating the World Health Organization (WHO) growth reference data and malnutrition-related parameters, was used. This was a prospective cohort study of 500 pediatric patients aged 1 month to 17 years. Upon admission, the PeDiSMART score was calculated and anthropometry was performed. Pediatric Yorkhill Malnutrition Score (PYMS), Screening Tool Risk on Nutritional Status and Growth (STRONGkids), and Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) malnutrition screening tools were also applied. PeDiSMART's association with the clinical outcome measures (weight loss/nutrition support and hospitalization duration) was assessed and compared with the other screening tools. The PeDiSMART score was inversely correlated with anthropometry and bioelectrical impedance phase angle (BIA PhA). The score's grading scale was based on BIA Pha quartiles. Weight loss/nutrition support during hospitalization was significantly independently associated with the malnutrition risk group allocation on admission, after controlling for anthropometric parameters and age. Receiver operating characteristic curve analysis showed a sensitivity of 87% and a specificity of 75% and a significant area under the curve, which differed significantly from that of STRONGkids and STAMP. In the subgroups of patients with PeDiSMART-based risk allocation different from that based on the other tools, PeDiSMART allocation was more closely related to outcome measures. PeDiSMART, applicable to the full age range of patients hospitalized in pediatric departments, graded according to BIA PhA, and embeddable in medical electronic records, enhances efficacy and reproducibility in identifying pediatric patients at

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders.

PubMed

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-06-04

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as "relatively low", contrasting with 21.4% rated as "relatively high". Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders.

High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance.

PubMed

Hudson, Melissa M; Mulrooney, Daniel A; Bowers, Daniel C; Sklar, Charles A; Green, Daniel M; Donaldson, Sarah S; Oeffinger, Kevin C; Neglia, Joseph P; Meadows, Anna T; Robison, Leslie L

2009-05-10

Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

Identifying nursing home residents at risk for falling.

PubMed

Kiely, D K; Kiel, D P; Burrows, A B; Lipsitz, L A

1998-05-01

To develop a fall risk model that can be used to identify prospectively nursing home residents at risk for falling. The secondary objective was to determine whether the nursing home environment independently influenced the development of falls. A prospective study involving 1 year of follow-up. Two hundred seventy-two nursing homes in the state of Washington. A total of 18,855 residents who had a baseline assessment in 1991 and a follow-up assessment within the subsequent year. Baseline Minimum Data Set items that could be potential risk factors for falling were considered as independent variables. The dependent variable was whether the resident fell as reported at the follow-up assessment. We estimated the extrinsic risk attributable to particular nursing home environments by calculating the annual fall rate in each nursing home and grouping them into tertiles of fall risk according to these rates. Factors associated independently with falling were fall history, wandering behavior, use of a cane or walker, deterioration of activities of daily living performance, age greater than 87 years, unsteady gait, transfer independence, wheelchair independence, and male gender. Nursing home residents with a fall history were more than three times as likely to fall during the follow-up period than residents without a fall history. Residents in homes with the highest tertile of fall rates were more than twice as likely to fall compared with residents of homes in the lowest tertile, independent of resident-specific risk factors. Fall history was identified as the strongest risk factor associated with subsequent falls and accounted for the vast majority of the predictive strength of the model. We recommend that fall history be used as an initial screener for determining eligibility for fall intervention efforts. Studies are needed to determine the facility characteristics that contribute to fall risk, independent of resident-specific risk factors.

Hazardous drinking and military community functioning: identifying mediating risk factors.

PubMed

Foran, Heather M; Heyman, Richard E; Slep, Amy M Smith

2011-08-01

Hazardous drinking is a serious societal concern in military populations. Efforts to reduce hazardous drinking among military personnel have been limited in effectiveness. There is a need for a deeper understanding of how community-based prevention models apply to hazardous drinking in the military. Community-wide prevention efforts may be most effective in targeting community functioning (e.g., support from formal agencies, community cohesion) that impacts hazardous drinking via other proximal risk factors. The goal of the current study is to inform community-wide prevention efforts by testing a model of community functioning and mediating risk factors of hazardous drinking among active duty U.S. Air Force personnel. A large, representative survey sample of U.S. Air Force active duty members (N = 52,780) was collected at 82 bases worldwide. Hazardous drinking was assessed with the widely used Alcohol Use Disorders Identification Test (Saunders, Aasland, Babor, de la Fuente, & Grant, 1993). A variety of individual, family, and community measures were also assessed. Structural equation modeling was used to test a hypothesized model of community functioning, mediating risk factors and hazardous drinking. Depressive symptoms, perceived financial stress, and satisfaction with the U.S. Air Force were identified as significant mediators of the link between community functioning and hazardous drinking for men and women. Relationship satisfaction was also identified as a mediator for men. These results provide a framework for further community prevention research and suggest that prevention efforts geared at increasing aspects of community functioning (e.g., the U.S. Air Force Community Capacity model) may indirectly lead to reductions in hazardous drinking through other proximal risk factors.

Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

PubMed Central

Leidy, Nancy K; Kim, Katherine; Bacci, Elizabeth D; Yawn, Barbara P; Mannino, David M; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K; Meldrum, Catherine A; Make, Barry J; Bowler, Russ P; Steenrod, Anna W; Murray, Lindsey T; Walsh, John W; Martinez, Fernando

2015-01-01

Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. Results: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. Conclusions: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. PMID:26028486

Comparison of 3 Methods for Identifying Dietary Patterns Associated With Risk of Disease

PubMed Central

DiBello, Julia R.; Kraft, Peter; McGarvey, Stephen T.; Goldberg, Robert; Campos, Hannia

2008-01-01

Reduced rank regression and partial least-squares regression (PLS) are proposed alternatives to principal component analysis (PCA). Using all 3 methods, the authors derived dietary patterns in Costa Rican data collected on 3,574 cases and controls in 1994–2004 and related the resulting patterns to risk of first incident myocardial infarction. Four dietary patterns associated with myocardial infarction were identified. Factor 1, characterized by high intakes of lean chicken, vegetables, fruit, and polyunsaturated oil, was generated by all 3 dietary pattern methods and was associated with a significantly decreased adjusted risk of myocardial infarction (28%–46%, depending on the method used). PCA and PLS also each yielded a pattern associated with a significantly decreased risk of myocardial infarction (31% and 23%, respectively); this pattern was characterized by moderate intake of alcohol and polyunsaturated oil and low intake of high-fat dairy products. The fourth factor derived from PCA was significantly associated with a 38% increased risk of myocardial infarction and was characterized by high intakes of coffee and palm oil. Contrary to previous studies, the authors found PCA and PLS to produce more patterns associated with cardiovascular disease than reduced rank regression. The most effective method for deriving dietary patterns related to disease may vary depending on the study goals. PMID:18945692

PTEN IDENTIFIED AS IMPORTANT RISK FACTOR OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

PubMed Central

Hosgood, H Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing

2009-01-01

Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures. PMID:19625176

Risk of abnormal triple screen for Down syndrome is significantly higher in patients with female fetuses.

PubMed

Spong, C Y; Ghidini, A; Stanley-Christian, H; Meck, J M; Seydel, F D; Pezzullo, J C

1999-04-01

Previous studies have shown that mid-trimester maternal serum alpha-fetoprotein (AFP) levels are significantly higher and human chorionic gonadotrophin (hCG) levels significantly lower in women with male compared with female fetuses. We have evaluated whether triple-screen criteria are more likely to identify women with female fetuses as at risk for Down syndrome. From the Georgetown University genetics database we obtained the absolute values and corresponding multiples of the median (MoM) for AFP, hCG and unconjugated oestriol (uE3) in singleton gestations for the period database November 1992 July 1996. A Down syndrome risk of 1/270 or greater at mid-trimester was considered as high risk. A total of 977 patients with triple screen and outcome information were identified, including 502 female and 475 male fetuses. Patients with female fetuses were significantly more likely to have lower serum AFP (p=0.003) and a positive triple screen for Down syndrome (72 (14 per cent) versus 45 (9 per cent), p<0.02) than those with male fetuses. The gestational age at triple screen, maternal serum hCG and uE3, race and diabetes were not significantly different between the two groups. Since Down syndrome is less common in female than male fetuses, and the rates of female and male Down syndrome fetuses detected by triple screen and subsequent amniocentesis are not significantly different, the excess of positive mid-trimester maternal serum triple screen in women with female fetuses is likely due to false-positive results.

Identifying Factors Associated with Risk Assessment Competencies of Public Health Emergency Responders

PubMed Central

Hao, Jiejing; Ren, Jiaojiao; Wu, Qunhong; Hao, Yanhua; Sun, Hong; Ning, Ning; Ding, Ding

2017-01-01

This study aimed to better understand the current situation of risk assessment and identify the factors associated with competence of emergency responders in public health risk assessment. The participants were selected by a multi-stage, stratified cluster sampling method in Heilongjiang Centers for Disease Control and Prevention (CDC). The questionnaires that measured their perceptions on risk assessment competences were administered through the face-to-face survey. A final sample of 1889 staff was obtained. Of this sample, 78.6% of respondents rated their own risk assessment competences as “relatively low”, contrasting with 21.4% rated as “relatively high”. Most of the respondents (62.7%) did not participate in any risk assessment work. Only 13.7% and 42.7% of respondents reported participating in risk assessment training and were familiar with risk assessment tools. There existed statistical significance between risk assessment-related characteristics of respondents and their self-rated competences scores. Financial support from the government and administrative attention were regarded as the important factors contributing to risk assessment competences of CDC responders. Higher attention should be given to risk assessment training and enhancing the availability of surveillance data. Continuous efforts should be made to remove the financial and technical obstacles to improve the competences of risk assessment for public health emergency responders. PMID:28587226

Gene-based rare allele analysis identified a risk gene of Alzheimer's disease.

PubMed

Kim, Jong Hun; Song, Pamela; Lim, Hyunsun; Lee, Jae-Hyung; Lee, Jun Hong; Park, Sun Ah

2014-01-01

Alzheimer's disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10(-6) (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

PubMed

Tobias, J H; Hutchinson, A P; Hunt, L P; McCloskey, E V; Stone, M D; Martin, J C; Thompson, P W; Palferman, T G; Bhalla, A K

2007-01-01

Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the

Identifying areas of deforestation risk for REDD+ using a species modeling tool

PubMed Central

Riveros, Juan Carlos; Forrest, Jessica L

2014-01-01

Background To implement the REDD+ mechanism (Reducing Emissions for Deforestation and Forest Degradation, countries need to prioritize areas to combat future deforestation CO2 emissions, identify the drivers of deforestation around which to develop mitigation actions, and quantify and value carbon for financial mechanisms. Each comes with its own methodological challenges, and existing approaches and tools to do so can be costly to implement or require considerable technical knowledge and skill. Here, we present an approach utilizing a machine learning technique known as Maximum Entropy Modeling (Maxent) to identify areas at high deforestation risk in the study area in Madre de Dios, Peru under a business-as-usual scenario in which historic deforestation rates continue. We link deforestation risk area to carbon density values to estimate future carbon emissions. We quantified area deforested and carbon emissions between 2000 and 2009 as the basis of the scenario. Results We observed over 80,000 ha of forest cover lost from 2000-2009 (0.21% annual loss), representing over 39 million Mg CO2. The rate increased rapidly following the enhancement of the Inter Oceanic Highway in 2005. Accessibility and distance to previous deforestation were strong predictors of deforestation risk, while land use designation was less important. The model performed consistently well (AUC > 0.9), significantly better than random when we compared predicted deforestation risk to observed. If past deforestation rates continue, we estimate that 132,865 ha of forest could be lost by the year 2020, representing over 55 million Mg CO2. Conclusions Maxent provided a reliable method for identifying areas at high risk of deforestation and the major explanatory variables that could draw attention for mitigation action planning under REDD+. The tool is accessible, replicable and easy to use; all necessary for producing good risk estimates and adapt models after potential landscape change. We

Identifying areas of deforestation risk for REDD+ using a species modeling tool.

PubMed

Aguilar-Amuchastegui, Naikoa; Riveros, Juan Carlos; Forrest, Jessica L

2014-01-01

To implement the REDD+ mechanism (Reducing Emissions for Deforestation and Forest Degradation, countries need to prioritize areas to combat future deforestation CO2 emissions, identify the drivers of deforestation around which to develop mitigation actions, and quantify and value carbon for financial mechanisms. Each comes with its own methodological challenges, and existing approaches and tools to do so can be costly to implement or require considerable technical knowledge and skill. Here, we present an approach utilizing a machine learning technique known as Maximum Entropy Modeling (Maxent) to identify areas at high deforestation risk in the study area in Madre de Dios, Peru under a business-as-usual scenario in which historic deforestation rates continue. We link deforestation risk area to carbon density values to estimate future carbon emissions. We quantified area deforested and carbon emissions between 2000 and 2009 as the basis of the scenario. We observed over 80,000 ha of forest cover lost from 2000-2009 (0.21% annual loss), representing over 39 million Mg CO2. The rate increased rapidly following the enhancement of the Inter Oceanic Highway in 2005. Accessibility and distance to previous deforestation were strong predictors of deforestation risk, while land use designation was less important. The model performed consistently well (AUC > 0.9), significantly better than random when we compared predicted deforestation risk to observed. If past deforestation rates continue, we estimate that 132,865 ha of forest could be lost by the year 2020, representing over 55 million Mg CO2. Maxent provided a reliable method for identifying areas at high risk of deforestation and the major explanatory variables that could draw attention for mitigation action planning under REDD+. The tool is accessible, replicable and easy to use; all necessary for producing good risk estimates and adapt models after potential landscape change. We propose this approach for developing

Identifying Causal Risk Factors for Violence among Discharged Patients

PubMed Central

Coid, Jeremy W.; Kallis, Constantinos; Doyle, Mike; Shaw, Jenny; Ullrich, Simone

2015-01-01

Background Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. Methods We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. Results In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85–12.65, P<0.001), instability (OR 5.41, 95% CI 3.44–8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21–16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08–0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. Conclusions Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors

Identifying mortality risks in patients with opioid use disorder using brief screening assessment: Secondary mental health clinical records analysis.

PubMed

Bogdanowicz, Karolina Magda; Stewart, Robert; Chang, Chin-Kuo; Downs, Johnny; Khondoker, Mizanur; Shetty, Hitesh; Strang, John; Hayes, Richard Derek

2016-07-01

Risk assessments are widely used, but their ability to predict outcomes in opioid use disorder (OUD) treatment remains unclear. Therefore, the aim was to investigate if addiction-specific brief risk screening is effective in identifying high mortality risk groups and if subsequent clinical actions following risk assessment impacts on mortality levels. Opioid use disorder (OUD) patients were identified in the South London and Maudsley Case Register. Deaths were identified through database linkage to the national mortality dataset. Cox and competing-risk regression were used to model associations between brief risk assessment domains and all-cause and overdose mortality in 4488 OUD patients, with up-to 6-year follow-up time where 227 deaths were registered. Data were stratified by admission to general mental health services. All-cause mortality was significantly associated with unsafe injecting (HR 1.53, 95% CI 1.10-2.11) and clinically appraised likelihood of accidental overdose (HR 1.48, 95% CI 1.00-2.19). Overdose-mortality was significantly associated with unsafe injecting (SHR 2.52, 95% CI 1.11-5.70) and clinically appraised suicidality (SHR 2.89, 95% CI 1.38-6.03). Suicidality was associated with a twofold increase in mortality risk among OUD patients who were not admitted to mental health services within 2 months of their risk assessment (HR 2.03, 95% CI 1.67-3.24). Diagnosis-specific brief risk screening can identify OUD patient subgroups at increased risk of all-cause and overdose mortality. OUD patients, where suicidality is evident, who are not admitted into services are particularly vulnerable. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients

PubMed Central

Kim, Su-A; Kim, Jang Young; Park, Jeong Bae

2016-01-01

Abstract There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings. PMID:27310982

GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

PubMed

Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2013-04-24

Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aβ₄₂ are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10⁻⁹ for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10⁻⁸ and p = 3.22 × 10⁻⁹ for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10⁻⁸ for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10⁻⁴, 0.039, 4.86 × 10⁻⁵, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. Copyright © 2013 Elsevier Inc. All rights reserved.

Significant oral cancer risk associated with low socioeconomic status.

PubMed

Warnakulasuriya, Saman

2009-01-01

Searches were made for studies in Medline, Medline In-Process and other Non-indexed Citations Embase, CINAHL, PsychINFO, CAB Abstracts 1973-date, EBM Reviews, ACP Journal Club, Cochrane Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Management Information Consortium database and Pubmed. Un-published data were also received from the International Head and Neck Cancer Epidemiology Consortium. Studies were identified independently by two reviewers and were included if their subject was oral and/ or oropharyngeal cancer; they used case-control methodology; gave data regarding socioeconomic status (SES; eg, educational attainment, occupational social classification or income) for both cases and controls; and the odds ratio (OR) for any SES measure was presented or could be calculated. Corresponding authors were contacted where there was an indication that data on oral and/ or oropharyngeal cancers could potentially be obtained from the wider cancer definition or grouping presented in the article, or if SES data were collected but had not been presented in the article. Methodological assessment of selected studies was undertaken. Countries where the study was undertaken were classified according to level of development and income as defined by the World Bank. Where available the adjusted OR (or crude OR) with corresponding 95% confidence intervals (CI) were extracted, or were calculated for low compared with high SES categories. Meta-analyses were performed on the following subgroups: SES measure, age, sex, global region, development level, time-period and lifestyle factor adjustments. Sensitivity analyses were conducted based on study methodological issues. Publication bias was assessed using a funnel plot. Forty-one studies met the inclusion criteria and yielded 15,344 cases and 33,852 controls. Compared with individuals who were in high SES strata, the pooled OR for the risk of developing

Can we identify patients at risk of life-threatening allergic reactions to food?

PubMed

Turner, P J; Baumert, J L; Beyer, K; Boyle, R J; Chan, C-H; Clark, A T; Crevel, R W R; DunnGalvin, A; Fernández-Rivas, M; Gowland, M H; Grabenhenrich, L; Hardy, S; Houben, G F; O'B Hourihane, J; Muraro, A; Poulsen, L K; Pyrz, K; Remington, B C; Schnadt, S; van Ree, R; Venter, C; Worm, M; Mills, E N C; Roberts, G; Ballmer-Weber, B K

2016-09-01

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia.

PubMed

Park, S Lani; Fesinmeyer, Megan D; Timofeeva, Maria; Caberto, Christian P; Kocarnik, Jonathan M; Han, Younghun; Love, Shelly-Ann; Young, Alicia; Dumitrescu, Logan; Lin, Yi; Goodloe, Robert; Wilkens, Lynne R; Hindorff, Lucia; Fowke, Jay H; Carty, Cara; Buyske, Steven; Schumacher, Frederick R; Butler, Anne; Dilks, Holli; Deelman, Ewa; Cote, Michele L; Chen, Wei; Pande, Mala; Christiani, David C; Field, John K; Bickebller, Heike; Risch, Angela; Heinrich, Joachim; Brennan, Paul; Wang, Yufei; Eisen, Timothy; Houlston, Richard S; Thun, Michael; Albanes, Demetrius; Caporaso, Neil; Peters, Ulrike; North, Kari E; Heiss, Gerardo; Crawford, Dana C; Bush, William S; Haiman, Christopher A; Landi, Maria Teresa; Hung, Rayjean J; Kooperberg, Charles; Amos, Christopher I; Le Marchand, Loïc; Cheng, Iona

2014-04-01

Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non-lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10(-5) was used to assign statistical significance. The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10(-6)). This association was strongest for women with adenocarcinoma (P = 1.2×10(-4)) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10(-5)), respectively. Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.

Suicide Risk Screening in Healthcare Settings: Identifying Males and Females at Risk

PubMed Central

King, Cheryl A.; Horwitz, Adam; Czyz, Ewa; Lindsay, Rebecca

2017-01-01

Suicide is the 10th leading cause of death in the United States, accounting for more than 42,000 deaths in 2014. Although this tragedy cuts across groups defined by age, sex, race/ethnicity, and geographic location, it is striking that nearly four times as many males as females die by suicide in the U.S. We describe the current regulations and recommendations for suicide risk screening in healthcare systems and also describe the aspirational goal of “Zero Suicide,” put forth by the National Action Alliance for Suicide Prevention. We then provide information about suicide risk screening tools and steps to take when a patient screens positive for suicide risk. Given the substantially higher suicide rate among males than females, we argue that it is important to consider how we could optimize suicide risk screening strategies to identify males and females at risk. Further research is needed to accomplish this. It is recommended that we consider multi-factorial suicide risk screens that incorporate risk factors known to be particularly important for males as well computerized, adaptive screens that are tailored for the specific risk considerations of the individual patient, male or female. These strategies are not mutually exclusive. Finally, universal suicide risk screening in healthcare settings, especially primary care, specialty medical care, and emergency department settings, is recommended. PMID:28251427

Risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance.

PubMed

Pasqualetti, P; Casale, R

1997-01-01

The acturial probability of malignant transformation was analyzed in a series of 263 patients with monoclonal gammopathy of undetermined significance (MGUS) over a 15-year period and followed from 5 to 20 years. At a median follow-up of 11.5 years, 157 patients (59.7%) had died of causes unrelated to MGUS, 47 (17.9%) were still alive and presented no increase in monoclonal component, 11 (4.1%) presented an increase in monoclonal component without evidence of malignant immunoproliferative disease, and 48 (18.3%) had developed a malignant transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia, three of malignant lymphoma, two of amyloidosis, one of chronic lymphocytic leukemia, and one of plasma cell leukemia. The cumulative incidence of malignant transformation was 18.3%; and the actuarial risk of malignant transformation was 6.1, 15.4, and 31.3% at 5, 10 and 20 years, respectively. The multivariate regression analysis according to Cox's proportional hazard model selected among 22 different variables established at initial diagnosis of MGUS only age as the factor significantly (P < 0.011) and negatively (b = -1.104) related to the risk of developing a malignant immunoproliferative disease. Therefore, patients with MGUS present an increased risk of developing a malignant lymphoproliferative or plasma cell proliferative disease, and MGUS could be considered a pre-neoplastic condition. Since no clinical or laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up periodically and over an indefinite period.

Informed Consent in Implantable BCI Research: Identifying Risks and Exploring Meaning.

PubMed

Klein, Eran

2016-10-01

Implantable brain-computer interface (BCI) technology is an expanding area of engineering research now moving into clinical application. Ensuring meaningful informed consent in implantable BCI research is an ethical imperative. The emerging and rapidly evolving nature of implantable BCI research makes identification of risks, a critical component of informed consent, a challenge. In this paper, 6 core risk domains relevant to implantable BCI research are identified-short and long term safety, cognitive and communicative impairment, inappropriate expectations, involuntariness, affective impairment, and privacy and security. Work in deep brain stimulation provides a useful starting point for understanding this core set of risks in implantable BCI. Three further risk domains-risks pertaining to identity, agency, and stigma-are identified. These risks are not typically part of formalized consent processes. It is important as informed consent practices are further developed for implantable BCI research that attention be paid not just to disclosing core research risks but exploring the meaning of BCI research with potential participants.

PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease.

PubMed

Noyce, Alastair J; R'Bibo, Lea; Peress, Luisa; Bestwick, Jonathan P; Adams-Carr, Kerala L; Mencacci, Niccolo E; Hawkes, Christopher H; Masters, Joseph M; Wood, Nicholas; Hardy, John; Giovannoni, Gavin; Lees, Andrew J; Schrag, Anette

2017-02-01

A number of early features can precede the diagnosis of Parkinson's disease (PD). To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population. Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD ("intermediate markers"), including smell loss, rapid eye movement-sleep behavior disorder, and finger-tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed. A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow-up (all P values < 0.001). Incident PD diagnoses during follow-up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores. The online PREDICT-PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder

Efficiently Identifying Significant Associations in Genome-wide Association Studies

PubMed Central

Eskin, Eleazar

2013-01-01

Abstract Over the past several years, genome-wide association studies (GWAS) have implicated hundreds of genes in common disease. More recently, the GWAS approach has been utilized to identify regions of the genome that harbor variation affecting gene expression or expression quantitative trait loci (eQTLs). Unlike GWAS applied to clinical traits, where only a handful of phenotypes are analyzed per study, in eQTL studies, tens of thousands of gene expression levels are measured, and the GWAS approach is applied to each gene expression level. This leads to computing billions of statistical tests and requires substantial computational resources, particularly when applying novel statistical methods such as mixed models. We introduce a novel two-stage testing procedure that identifies all of the significant associations more efficiently than testing all the single nucleotide polymorphisms (SNPs). In the first stage, a small number of informative SNPs, or proxies, across the genome are tested. Based on their observed associations, our approach locates the regions that may contain significant SNPs and only tests additional SNPs from those regions. We show through simulations and analysis of real GWAS datasets that the proposed two-stage procedure increases the computational speed by a factor of 10. Additionally, efficient implementation of our software increases the computational speed relative to the state-of-the-art testing approaches by a factor of 75. PMID:24033261

Using Participatory Risk Mapping (PRM) to Identify and Understand People's Perceptions of Crop Loss to Animals in Uganda

PubMed Central

Webber, Amanda D.; Hill, Catherine M.

2014-01-01

Considering how people perceive risks to their livelihoods from local wildlife is central to (i) understanding the impact of crop damage by animals on local people and (ii) recognising how this influences their interactions with, and attitudes towards, wildlife. Participatory risk mapping (PRM) is a simple, analytical tool that can be used to identify and classify risk within communities. Here we use it to explore local people's perceptions of crop damage by wildlife and the animal species involved. Interviews (n = 93, n = 76) and seven focus groups were conducted in four villages around Budongo Forest Reserve, Uganda during 2004 and 2005. Farms (N = 129) were simultaneously monitored for crop loss. Farmers identified damage by wildlife as the most significant risk to their crops; risk maps highlighted its anomalous status compared to other anticipated challenges to agricultural production. PRM was further used to explore farmers' perceptions of animal species causing crop damage and the results of this analysis compared with measured crop losses. Baboons (Papio anubis) were considered the most problematic species locally but measurements of loss indicate this perceived severity was disproportionately high. In contrast goats (Capra hircus) were considered only a moderate risk, yet risk of damage by this species was significant. Surprisingly, for wild pigs (Potamochoerus sp), perceptions of severity were not as high as damage incurred might have predicted, although perceived incidence was greater than recorded frequency of damage events. PRM can assist researchers and practitioners to identify and explore perceptions of the risk of crop damage by wildlife. As this study highlights, simply quantifying crop loss does not determine issues that are important to local people nor the complex relationships between perceived risk factors. Furthermore, as PRM is easily transferable it may contribute to the identification and development of standardised approaches

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

PubMed

Sung, Yun J; Winkler, Thomas W; de Las Fuentes, Lisa; Bentley, Amy R; Brown, Michael R; Kraja, Aldi T; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K; Li, Changwei; Feitosa, Mary F; Kilpeläinen, Tuomas O; Richard, Melissa A; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M; Tayo, Bamidele O; Warren, Helen R; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E; Hartwig, Fernando Pires; Horimoto, Andrea R V R; Hsu, Fang-Chi; Jackson, Anne U; Kähönen, Mika; Kasturiratne, Anuradhani; Kühnel, Brigitte; Leander, Karin; Lee, Wen-Jane; Lin, Keng-Hung; 'an Luan, Jian; McKenzie, Colin A; Meian, He; Nelson, Christopher P; Rauramaa, Rainer; Schupf, Nicole; Scott, Robert A; Sheu, Wayne H H; Stančáková, Alena; Takeuchi, Fumihiko; van der Most, Peter J; Varga, Tibor V; Wang, Heming; Wang, Yajuan; Ware, Erin B; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Alfred, Tamuno; Amin, Najaf; Arking, Dan; Aung, Tin; Barr, R Graham; Bielak, Lawrence F; Boerwinkle, Eric; Bottinger, Erwin P; Braund, Peter S; Brody, Jennifer A; Broeckel, Ulrich; Cabrera, Claudia P; Cade, Brian; Caizheng, Yu; Campbell, Archie; Canouil, Mickaël; Chakravarti, Aravinda; Chauhan, Ganesh; Christensen, Kaare; Cocca, Massimiliano; Collins, Francis S; Connell, John M; de Mutsert, Renée; de Silva, H Janaka; Debette, Stephanie; Dörr, Marcus; Duan, Qing; Eaton, Charles B; Ehret, Georg; Evangelou, Evangelos; Faul, Jessica D; Fisher, Virginia A; Forouhi, Nita G; Franco, Oscar H; Friedlander, Yechiel; Gao, He; Gigante, Bruna; Graff, Misa; Gu, C Charles; Gu, Dongfeng; Gupta, Preeti; Hagenaars, Saskia P; Harris, Tamara B; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hofman, Albert; Howard, Barbara V; Hunt, Steven; Irvin, Marguerite R; Jia, Yucheng; Joehanes, Roby; Justice, Anne E; Katsuya, Tomohiro; Kaufman, Joel; Kerrison, Nicola D; Khor, Chiea Chuen; Koh, Woon-Puay; Koistinen, Heikki A; Komulainen, Pirjo; Kooperberg, Charles; Krieger, Jose E; Kubo, Michiaki; Kuusisto, Johanna; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lehne, Benjamin; Lewis, Cora E; Li, Yize; Lim, Sing Hui; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Jingmin; Liu, Kiang; Liu, Yeheng; Loh, Marie; Lohman, Kurt K; Long, Jirong; Louie, Tin; Mägi, Reedik; Mahajan, Anubha; Meitinger, Thomas; Metspalu, Andres; Milani, Lili; Momozawa, Yukihide; Morris, Andrew P; Mosley, Thomas H; Munson, Peter; Murray, Alison D; Nalls, Mike A; Nasri, Ubaydah; Norris, Jill M; North, Kari; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R; Palmer, Nicholette D; Pankow, James S; Pedersen, Nancy L; Peters, Annette; Peyser, Patricia A; Polasek, Ozren; Raitakari, Olli T; Renström, Frida; Rice, Treva K; Ridker, Paul M; Robino, Antonietta; Robinson, Jennifer G; Rose, Lynda M; Rudan, Igor; Sabanayagam, Charumathi; Salako, Babatunde L; Sandow, Kevin; Schmidt, Carsten O; Schreiner, Pamela J; Scott, William R; Seshadri, Sudha; Sever, Peter; Sitlani, Colleen M; Smith, Jennifer A; Snieder, Harold; Starr, John M; Strauch, Konstantin; Tang, Hua; Taylor, Kent D; Teo, Yik Ying; Tham, Yih Chung; Uitterlinden, André G; Waldenberger, Melanie; Wang, Lihua; Wang, Ya X; Wei, Wen Bin; Williams, Christine; Wilson, Gregory; Wojczynski, Mary K; Yao, Jie; Yuan, Jian-Min; Zonderman, Alan B; Becker, Diane M; Boehnke, Michael; Bowden, Donald W; Chambers, John C; Chen, Yii-Der Ida; de Faire, Ulf; Deary, Ian J; Esko, Tõnu; Farrall, Martin; Forrester, Terrence; Franks, Paul W; Freedman, Barry I; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo Lessa; Hung, Yi-Jen; Jonas, Jost B; Kato, Norihiro; Kooner, Jaspal S; Laakso, Markku; Lehtimäki, Terho; Liang, Kae-Woei; Magnusson, Patrik K E; Newman, Anne B; Oldehinkel, Albertine J; Pereira, Alexandre C; Redline, Susan; Rettig, Rainer; Samani, Nilesh J; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E; Wareham, Nicholas J; Watkins, Hugh; Weir, David R; Wickremasinghe, Ananda R; Wu, Tangchun; Zheng, Wei; Kamatani, Yoichiro; Laurie, Cathy C; Bouchard, Claude; Cooper, Richard S; Evans, Michele K; Gudnason, Vilmundur; Kardia, Sharon L R; Kritchevsky, Stephen B; Levy, Daniel; O'Connell, Jeff R; Psaty, Bruce M; van Dam, Rob M; Sims, Mario; Arnett, Donna K; Mook-Kanamori, Dennis O; Kelly, Tanika N; Fox, Ervin R; Hayward, Caroline; Fornage, Myriam; Rotimi, Charles N; Province, Michael A; van Duijn, Cornelia M; Tai, E Shyong; Wong, Tien Yin; Loos, Ruth J F; Reiner, Alex P; Rotter, Jerome I; Zhu, Xiaofeng; Bierut, Laura J; Gauderman, W James; Caulfield, Mark J; Elliott, Paul; Rice, Kenneth; Munroe, Patricia B; Morrison, Alanna C; Cupples, L Adrienne; Rao, Dabeeru C; Chasman, Daniel I

2018-03-01

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10 -8 ) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10 -8 ). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2). Copyright © 2018 American Society of Human Genetics. All rights reserved.

Identifying patients with AAA with the highest risk following endovascular repair.

PubMed

Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

2012-08-01

It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

[Identifying clinical risk factors in recurrent idiopathic deep venous thrombosis].

PubMed

Del Río Solá, M Lourdes; González Fajardo, José Antonio; Vaquero Puerta, Carlos

2016-03-18

Oral anticoagulant therapy for more than 6 months in patients with an episode of idiopathic thromboembolic disease is controversial. The objective was to determine predictive clinical signs that identify patients at increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic deep vein thrombosis (DVT). A prospective study which included 306 consecutive patients with a first episode of idiopathic DVT from June 2012 to June 2014. Predictor variables of recurrent thromboembolic disease and episodes of recurrence during follow-up of the patients (28.42 months) were collected. We performed a multivariate analysis to analyze possible predictors (P<.20) and an analysis of Kaplan-Meier to establish mean recurrence-free survival. We identified 91 episodes of residual vein thrombosis on follow-up of the patients (37.5% men and 20.3% women) (OR 1.84; 95% CI 1.25-2.71). In the Cox regression analysis stratified by gender, variables showed significant presence of hyperechoic thrombus (P=.001) in males, and persistence of residual thrombus in women (P=.046). The mean recurrence-free survival was shorter in both groups. The presence of echogenic thrombus in men and the existence of residual DVT in women were 2 clinical signs associated with increased risk of thromboembolic recurrence after stopping anticoagulant therapy for 6 months after an episode of idiopathic DVT in our study. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Identifying Home Care Clinicians’ Information Needs for Managing Fall Risks

PubMed Central

Alhuwail, Dari

2016-01-01

Summary Objectives To help manage the risk of falls in home care, this study aimed to (i) identify home care clinicians’ information needs and how they manage missing or inaccurate data, (ii) identify problems that impact effectiveness and efficiency associated with retaining, exchanging, or processing information about fall risks in existing workflows and currently adopted health information technology (IT) solutions, and (iii) offer informatics-based recommendations to improve fall risk management interventions. Methods A case study was carried out in a single not-for-profit suburban Medicare-certified home health agency with three branches. Qualitative data were collected over a six month period through observations, semi-structured interviews, and focus groups. The Framework method was used for analysis. Maximum variation sampling was adopted to recruit a diverse sample of clinicians. Results Overall, the information needs for fall risk management were categorized into physiological, care delivery, educational, social, environmental, and administrative domains. Examples include a brief fall-related patient history, weight-bearing status, medications that affect balance, availability of caregivers at home, and the influence of patients’ cultures on fall management interventions. The unavailability and inaccuracy of critical information related to fall risks can delay necessary therapeutic services aimed at reducing patients’ risk for falling and thereby jeopardizing their safety. Currently adopted IT solutions did not adequately accommodate data related to fall risk management. Conclusion The results highlight the essential information for fall risk management in home care. Home care workflows and health IT solutions must effectively and efficiently retain, exchange, and process information necessary for fall risk management. Interoperability and integration of the various health IT solutions to make data sharing accessible to all clinicians is critical

Creating a Chinese suicide dictionary for identifying suicide risk on social media.

PubMed

Lv, Meizhen; Li, Ang; Liu, Tianli; Zhu, Tingshao

2015-01-01

Introduction. Suicide has become a serious worldwide epidemic. Early detection of individual suicide risk in population is important for reducing suicide rates. Traditional methods are ineffective in identifying suicide risk in time, suggesting a need for novel techniques. This paper proposes to detect suicide risk on social media using a Chinese suicide dictionary. Methods. To build the Chinese suicide dictionary, eight researchers were recruited to select initial words from 4,653 posts published on Sina Weibo (the largest social media service provider in China) and two Chinese sentiment dictionaries (HowNet and NTUSD). Then, another three researchers were recruited to filter out irrelevant words. Finally, remaining words were further expanded using a corpus-based method. After building the Chinese suicide dictionary, we tested its performance in identifying suicide risk on Weibo. First, we made a comparison of the performance in both detecting suicidal expression in Weibo posts and evaluating individual levels of suicide risk between the dictionary-based identifications and the expert ratings. Second, to differentiate between individuals with high and non-high scores on self-rating measure of suicide risk (Suicidal Possibility Scale, SPS), we built Support Vector Machines (SVM) models on the Chinese suicide dictionary and the Simplified Chinese Linguistic Inquiry and Word Count (SCLIWC) program, respectively. After that, we made a comparison of the classification performance between two types of SVM models. Results and Discussion. Dictionary-based identifications were significantly correlated with expert ratings in terms of both detecting suicidal expression (r = 0.507) and evaluating individual suicide risk (r = 0.455). For the differentiation between individuals with high and non-high scores on SPS, the Chinese suicide dictionary (t1: F 1 = 0.48; t2: F 1 = 0.56) produced a more accurate identification than SCLIWC (t1: F 1 = 0.41; t2: F 1 = 0.48) on different

Creating a Chinese suicide dictionary for identifying suicide risk on social media

PubMed Central

Liu, Tianli

2015-01-01

Introduction. Suicide has become a serious worldwide epidemic. Early detection of individual suicide risk in population is important for reducing suicide rates. Traditional methods are ineffective in identifying suicide risk in time, suggesting a need for novel techniques. This paper proposes to detect suicide risk on social media using a Chinese suicide dictionary. Methods. To build the Chinese suicide dictionary, eight researchers were recruited to select initial words from 4,653 posts published on Sina Weibo (the largest social media service provider in China) and two Chinese sentiment dictionaries (HowNet and NTUSD). Then, another three researchers were recruited to filter out irrelevant words. Finally, remaining words were further expanded using a corpus-based method. After building the Chinese suicide dictionary, we tested its performance in identifying suicide risk on Weibo. First, we made a comparison of the performance in both detecting suicidal expression in Weibo posts and evaluating individual levels of suicide risk between the dictionary-based identifications and the expert ratings. Second, to differentiate between individuals with high and non-high scores on self-rating measure of suicide risk (Suicidal Possibility Scale, SPS), we built Support Vector Machines (SVM) models on the Chinese suicide dictionary and the Simplified Chinese Linguistic Inquiry and Word Count (SCLIWC) program, respectively. After that, we made a comparison of the classification performance between two types of SVM models. Results and Discussion. Dictionary-based identifications were significantly correlated with expert ratings in terms of both detecting suicidal expression (r = 0.507) and evaluating individual suicide risk (r = 0.455). For the differentiation between individuals with high and non-high scores on SPS, the Chinese suicide dictionary (t1: F1 = 0.48; t2: F1 = 0.56) produced a more accurate identification than SCLIWC (t1: F1 = 0.41; t2: F1 = 0.48) on different

Using an autologistic regression model to identify spatial risk factors and spatial risk patterns of hand, foot and mouth disease (HFMD) in Mainland China

PubMed Central

2014-01-01

Background There have been large-scale outbreaks of hand, foot and mouth disease (HFMD) in Mainland China over the last decade. These events varied greatly across the country. It is necessary to identify the spatial risk factors and spatial distribution patterns of HFMD for public health control and prevention. Climate risk factors associated with HFMD occurrence have been recognized. However, few studies discussed the socio-economic determinants of HFMD risk at a space scale. Methods HFMD records in Mainland China in May 2008 were collected. Both climate and socio-economic factors were selected as potential risk exposures of HFMD. Odds ratio (OR) was used to identify the spatial risk factors. A spatial autologistic regression model was employed to get OR values of each exposures and model the spatial distribution patterns of HFMD risk. Results Results showed that both climate and socio-economic variables were spatial risk factors for HFMD transmission in Mainland China. The statistically significant risk factors are monthly average precipitation (OR = 1.4354), monthly average temperature (OR = 1.379), monthly average wind speed (OR = 1.186), the number of industrial enterprises above designated size (OR = 17.699), the population density (OR = 1.953), and the proportion of student population (OR = 1.286). The spatial autologistic regression model has a good goodness of fit (ROC = 0.817) and prediction accuracy (Correct ratio = 78.45%) of HFMD occurrence. The autologistic regression model also reduces the contribution of the residual term in the ordinary logistic regression model significantly, from 17.25 to 1.25 for the odds ratio. Based on the prediction results of the spatial model, we obtained a map of the probability of HFMD occurrence that shows the spatial distribution pattern and local epidemic risk over Mainland China. Conclusions The autologistic regression model was used to identify spatial risk factors and model spatial risk patterns of HFMD. HFMD

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

PubMed Central

Ferreira, Manuel A. R.; Matheson, Melanie C.; Tang, Clara S.; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K.; Duffy, David L.; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D.; Eriksson, Nicholas; Madden, Pamela A.; Abramson, Michael J.; Holt, Patrick G.; Heath, Andrew C.; Hunter, Michael; Musk, Bill; Robertson, Colin F.; Le Souëf, Peter; Montgomery, Grant W.; Henderson, A. John; Tung, Joyce Y.; Dharmage, Shyamali C.; Brown, Matthew A.; James, Alan; Thompson, Philip J.; Pennell, Craig; Martin, Nicholas G.; Evans, David M.; Hinds, David A.; Hopper, John L.

2014-01-01

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. PMID:24388013

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

PubMed

Ferreira, Manuel A R; Matheson, Melanie C; Tang, Clara S; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K; Duffy, David L; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D; Eriksson, Nicholas; Madden, Pamela A; Abramson, Michael J; Holt, Patrick G; Heath, Andrew C; Hunter, Michael; Musk, Bill; Robertson, Colin F; Le Souëf, Peter; Montgomery, Grant W; Henderson, A John; Tung, Joyce Y; Dharmage, Shyamali C; Brown, Matthew A; James, Alan; Thompson, Philip J; Pennell, Craig; Martin, Nicholas G; Evans, David M; Hinds, David A; Hopper, John L

2014-06-01

To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)). By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

PubMed

Fox, A S; Bonacci, J; McLean, S G; Saunders, N

2017-05-01

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor.

PubMed

Quek, Richard; Farid, Mohamad; Kanjanapan, Yada; Lim, Cindy; Tan, Iain Beehuat; Kesavan, Sittampalam; Lim, Tony Kiat Hon; Oon, Lynette Lin-Ean; Goh, Brian Kp; Chan, Weng Hoong; Teo, Melissa; Chung, Alexander Yf; Ong, Hock Soo; Wong, Wai Keong; Tan, Patrick; Yip, Desmond

2017-06-01

Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy. In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included. Risk classification was based on the modified National Institute of Health (NIH) criteria. In this cohort, 74% (n = 105) of patients harbored a KIT mutation; 61% (n = 86) were found in exon 11 of which nearly 70% were KIT exon 11 deletions (n = 60). A total of 18% (n = 25) of cases were classified as having intermediate-risk disease. Univariate analysis confirmed tumor size, mitotic index, nongastric origin, presence of tumor rupture and modified NIH criteria were adversely prognostic for relapse-free survival (RFS). Among KIT/PDGFRA mutants, KIT exon 11 deletions had a significantly worse prognosis (hazard ratio 2.31; 95% confidence interval, 1.30-4.10; P = 0.003). Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients. The presence of KIT exon 11 deletion mutation in patients with intermediate-risk GIST is associated with an inferior clinical outcome with RFS similar to high-risk patients. © 2016 John Wiley & Sons Australia, Ltd.

Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

PubMed

Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

2015-06-01

Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have

Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia[S

PubMed Central

Medeiros, Ana Margarida; Alves, Ana Catarina; Aguiar, Pedro; Bourbon, Mafalda

2014-01-01

The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem≥ia. An apoB/apoA1 ratio ≥0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ≥0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients. PMID:24627126

Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.

PubMed

Levey, Allan; Lah, James; Goldstein, Felicia; Steenland, Kyle; Bliwise, Donald

2006-07-01

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small

Evaluation and applications of the clinically significant change method with the Violence Risk Scale-Sexual Offender version: implications for risk-change communication.

PubMed

Olver, Mark E; Beggs Christofferson, Sarah M; Wong, Stephen C P

2015-02-01

We examined the use of the clinically significant change (CSC) method with the Violence Risk Scale-Sexual Offender version (VRS-SO), and its implications for risk communication, in a combined sample of 945 treated sexual offenders from three international settings, followed up for a minimum 5 years post-release. The reliable change (RC) index was used to identify thresholds of clinically meaningful change and to create four CSC groups (already okay, recovered, improved, unchanged) based on VRS-SO dynamic scores and amount of change made. Outcome analyses demonstrated important CSC-group differences in 5-year rates of sexual and violent recidivism. However, when baseline risk was controlled via Cox regression survival analysis, the pattern and magnitude of CSC-group differences in sexual and violent recidivism changed to suggest that observed variation in recidivism base rates could be at least partly explained by pre-existing group differences in risk level. Implications for communication of risk-change information and applications to clinical practice are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Germline genetic variants in somatically significantly mutated genes in tumors are associated with renal cell carcinoma risk and outcome.

PubMed

Shu, Xiang; Gu, Jianchun; Huang, Maosheng; Tannir, Nizar M; Matin, Surena F; Karam, Jose A; Wood, Christopher G; Wu, Xifeng; Ye, Yuanqing

2018-05-28

Genome-wide association studies (GWAS) have identified 13 susceptibility loci for renal cell carcinoma (RCC). Additional genetic loci of risk remain to be explored. Moreover, the role of germline genetic variants in predicting RCC recurrence and overall survival (OS) is less understood. In this study, we focused on 127 significantly mutated genes from The Cancer Genome Atlas (TCGA) Pan-Cancer Analysis across 12 major cancer sites to identify potential genetic variants predictive of RCC risk and clinical outcomes. In a three-phase design with a total of 2657 RCC cases and 5315 healthy controls, two single nucleotide polymorphisms (SNPs) that map to PIK3CG (rs6466135:A, ORmeta = 0.85, 95% CI = 0.77-0.94, Pmeta = 1.4 × 10-3) and ATM (rs611646:T, ORmeta = 1.17, 95% CI = 1.05-1.31, Pmeta = 3.5 × 10-3) were significantly associated with RCC risk. With respect to RCC recurrence and OS, two separate datasets with a total of 661 stages I-III RCC patients (discovery: 367; validation: 294) were analyzed. The most significant association was observed for rs10932384:C (ERBB4) with both outcomes (recurrence: HRmeta = 0.52, 95% CI = 0.39-0.68, Pmeta = 3.81 × 10-6; OS: HRmeta = 0.50, 95% CI = 0.37-0.67, Pmeta = 6.00 × 10-6). In addition, six SNPs were significantly associated with either RCC recurrence or OS but not both (Pmeta < 0.01). Rs10932384:C was significantly correlated with mutation frequency of ERBB4 in clear cell RCC (ccRCC) patients (P = 0.003, Fisher's exact test). Cis-eQTL was observed for several SNPs in blood/transformed fibroblasts but not in RCC tumor tissues. In summary, we identified promising genetic predictors of recurrence and OS among RCC patients with localized disease.

Metabolic syndrome is a significant and independent risk factor for increased arterial stiffness in Japanese subjects.

PubMed

Satoh, Hiroki; Kishi, Reiko; Tsutsui, Hiroyuki

2009-12-01

Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular disease; however, the impact of MetS on arterial stiffness has not been fully established in the general Japanese population. We analyzed the relationship between MetS and the severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 2744 male and 358 female subjects aged 38-62 years, adjusted for conventional risk factors and C-reactive protein. The prevalence rates of MetS identified by Japanese criteria were 22.7% (n=624) and 7.8% (n=28) in male and female subjects, respectively. The subjects with MetS had significantly greater mean values of baPWV than those without MetS among both male and female subjects (1444+/-209 vs. 1294+/-165 cm/s in male subjects, P<0.001; 1379+/-151 vs. 1220+/-171 cm/s in female subjects, P<0.001). After adjustment for atherosclerotic variables such as age, smoking habits, total cholesterol and C-reactive protein, the odds ratio (OR) of MetS for increased baPWV was 3.65 in male subjects (95% confidence interval (CI): 2.99-4.47, P<0.001) and 8.02 in female subjects (95% CI: 3.18-20.25 P<0.001). In conclusion, MetS was identified as a significant and independent risk factor for increased arterial stiffness in both the male and female general population in Japan.

How Many Significant Figures are Useful for Public Risk Estimates?

NASA Astrophysics Data System (ADS)

Wilde, Paul D.; Duffy, Jim

2013-09-01

This paper considers the level of uncertainty in the calculation of public risks from launch or reentry and provides guidance on the number of significant digits that can be used with confidence when reporting the analysis results to decision-makers. The focus of this paper is the uncertainty in collective risk calculations that are used for launches of new and mature ELVs. This paper examines the computational models that are used to estimate total collective risk to the public for a launch, including the model input data and the model results, and characterizes the uncertainties due to both bias and variability. There have been two recent efforts to assess the uncertainty in state-of-the-art risk analysis models used in the US and their input data. One assessment focused on launch area risk from an Atlas V at Vandenberg Air Force Base (VAFB) and the other focused on downrange risk to Eurasia from a Falcon 9 launched from Cape Canaveral Air Force Station (CCAFS). The results of these studies quantified the uncertainties related to both the probability and the consequence of the launch debris hazards. This paper summarizes the results of both of these relatively comprehensive launch risk uncertainty analyses, which addressed both aleatory and epistemic uncertainties. The epistemic uncertainties of most concern were associated with probability of failure and the debris list. Other major sources of uncertainty evaluated were: the casualty area for people in shelters that are impacted by debris, impact distribution size, yield from exploding propellant and propellant tanks, probability of injury from a blast wave for people in shelters or outside, and population density. This paper also summarizes a relatively comprehensive over-flight risk uncertainty analysis performed by the FAA for the second stage of flight for a Falcon 9 from CCAFS. This paper is applicable to baseline collective risk analyses, such as those used to make a commercial license determination, and

Development of a claims-based risk score to identify obese individuals.

PubMed

Clark, Jeanne M; Chang, Hsien-Yen; Bolen, Shari D; Shore, Andrew D; Goodwin, Suzanne M; Weiner, Jonathan P

2010-08-01

Obesity is underdiagnosed, hampering system-based health promotion and research. Our objective was to develop and validate a claims-based risk model to identify obese persons using medical diagnosis and prescription records. We conducted a cross-sectional analysis of de-identified claims data from enrollees of 3 Blue Cross Blue Shield plans who completed a health risk assessment capturing height and weight. The final sample of 71,057 enrollees was randomly split into 2 subsamples for development and validation of the obesity risk model. Using the Johns Hopkins Adjusted Clinical Groups case-mix/predictive risk methodology, we categorized study members' diagnosis (ICD) codes. Logistic regression was used to determine which claims-based risk markers were associated with a body mass index (BMI) > or = 35 kg/m(2). The sensitivities of the scores > or =90(th) percentile to detect obesity were 26% to 33%, while the specificities were >90%. The areas under the receiver operator curve ranged from 0.67 to 0.73. In contrast, a diagnosis of obesity or an obesity medication alone had very poor sensitivity (10% and 1%, respectively); the obesity risk model identified an additional 22% of obese members. Varying the percentile cut-point from the 70(th) to the 99(th) percentile resulted in positive predictive values ranging from 15.5 to 59.2. An obesity risk score was highly specific for detecting a BMI > or = 35 kg/m(2) and substantially increased the detection of obese members beyond a provider-coded obesity diagnosis or medication claim. This model could be used for obesity care management and health promotion or for obesity-related research.

Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia.

PubMed

Loth, Leo; Gilbert, Marius; Wu, Jianmei; Czarnecki, Christina; Hidayat, Muhammad; Xiao, Xiangming

2011-10-01

Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors "elevation", "human population density" and "rice cropping" were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition "commercial poultry population", and two indicators of market locations and transport; "human settlements" and "road length", were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. Copyright © 2011 Elsevier B.V. All rights reserved.

Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia

PubMed Central

Leo, Loth; Marius, Gilbert; Jianmei, Wu; Christina, Czarnecki; Muhammad, Hidayat; Xiangming, Xiao

2016-01-01

Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors “elevation”, “human population density” and “rice cropping” were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition “commercial poultry population”, and two indicators of market locations and transport; “human settlements” and “road length”, were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. PMID:21813198

The MAT-sf: identifying risk for major mobility disability.

PubMed

Rejeski, W Jack; Rushing, Julia; Guralnik, Jack M; Ip, Edward H; King, Abby C; Manini, Todd M; Marsh, Anthony P; McDermott, Mary M; Fielding, Roger A; Newman, Anne B; Tudor-Locke, Catrine; Gill, Thomas M

2015-05-01

The assessment of mobility is essential to both aging research and clinical geriatric practice. A newly developed self-report measure of mobility, the mobility assessment tool-short form (MAT-sf), uses video animations as an innovative method to improve measurement accuracy/precision. The primary aim of the current study was to evaluate whether MAT-sf scores can be used to identify risk for major mobility disability (MMD). This article is based on data collected from the Lifestyle Interventions and Independence for Elders study and involved 1,574 older adults between the ages of 70-89. The MAT-sf was administered at baseline; MMD, operationalized as failure to complete the 400-m walk ≤ 15 minutes, was evaluated at 6-month intervals across a period of 42 months. The outcome of interest was the first occurrence of MMD or incident MMD. After controlling for age, sex, clinic site, and treatment arm, baseline MAT-sf scores were found to be effective in identifying risk for MMD (p < .0001). Partitioning the MAT-sf into four groups revealed that persons with scores <40, 40-49, 50-59, and 60+ had failure rates across 42 months of follow-up of 66%, 52%, 35%, and 22%, respectively. The MAT-sf is a quick and efficient way of identifying older adults at risk for MMD. It could be used to clinically identify older adults that are in need of intervention for MMD and provides a simple means for monitoring the status of patients' mobility, an important dimension of functional health. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identifying children at risk for language impairment: screening of communication at 18 months.

PubMed

Bruce, B; Kornfält, R; Radeborg, K; Hansson, K; Nettelbladt, U

2003-09-01

To investigate the possibility of identifying children at risk for language impairment based on a new screening instrument to assess communication and language skills at 18 mo of age. At 18 mo, 58 children were assessed with a screening instrument for communication and language consisting of a professional assessment and a parents' questionnaire. Students of speech and language pathology, well trained in child language assessment, carried out the professional assessment, which was based on observations of play behaviour, interaction and expressive and receptive language skills. Of the 58 children, 43 attended a follow-up assessment of language skills at 54 mo of age. Nine children were considered to be at risk for language impairment at 18 mo and 10 children were evaluated as being at risk at 54 mo. A significant positive correlation was found between the professional evaluations at 18 mo and the language tests at 54 mo. Verbal comprehension and pretend play correlated significantly with the results on the language tests. A professional screening of communication and language at 18 mo of age is worthwhile for predicting problems in language development. The results further show that language comprehension and pretend play rather than expressive skills should be emphasized.

77 FR 546 - Adjustment of Nationwide Significant Risk Threshold

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

...In accordance with Appendix D to Title 49 Code of Federal Regulations (CFR) Part 222, Use of Locomotive Horns at Highway-Rail Grade Crossings, FRA is updating the Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper threshold of permissible risk for calculating quiet zones established in relationship to the NSRT. This is the fifth update to the NSRT, which has fallen from 14,007 to 13,722.

75 FR 82136 - Adjustment of Nationwide Significant Risk Threshold

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

...In accordance with Appendix D to Title 49 Code of Federal Regulations (CFR) Part 222, Use of Locomotive Horns at Highway-Rail Grade Crossings, FRA is updating the Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper threshold of permissible risk for calculating quiet zones established in relationship to the NSRT. This is the fourth update to the NSRT, which has fallen from 18,775 to 14,007.

78 FR 70623 - Adjustment of Nationwide Significant Risk Threshold

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

...In accordance with appendix D to title 49 Code of Federal Regulations (CFR) part 222, Use of Locomotive Horns at Public Highway- Rail Grade Crossings, FRA is updating the Nationwide Significant Risk Threshold (NSRT). This action is needed to ensure that the public has the proper threshold of permissible risk for calculating quiet zones established in relationship to the NSRT. This is the sixth update to the NSRT, which is increasing from 13,722 to 14,347.

A Modified Delphi to Identify the Significant Works Pertaining to the Understanding of Reading Comprehension and Content Analysis of the Identified Works

ERIC Educational Resources Information Center

Zunker, Norma D.; Pearce, Daniel L.

2012-01-01

The first part of this study explored the significant works pertaining to the understanding of reading comprehension using a Modified Delphi Method. A panel of reading comprehension experts identified 19 works they considered to be significant to the understanding of reading comprehension. The panel of experts identified the reasons they…

Identifying environmental risk factors and mapping the risk of human West Nile virus in South Dakota.

NASA Astrophysics Data System (ADS)

Hess, A.; Davis, J. K.; Wimberly, M. C.

2017-12-01

Human West Nile virus (WNV) first arrived in the USA in 1999 and has since then spread across the country. Today, the highest incidence rates are found in the state of South Dakota. The disease occurrence depends on the complex interaction between the mosquito vector, the bird host and the dead-end human host. Understanding the spatial domain of this interaction and being able to identify disease transmission hotspots is crucial for effective disease prevention and mosquito control. In this study we use geospatial environmental information to understand what drives the spatial distribution of cases of human West Nile virus in South Dakota and to map relative infection risk across the state. To map the risk of human West Nile virus in South Dakota, we used geocoded human case data from the years 2004-2016. Satellite data from the Landsat ETM+ and MODIS for the years 2003 to 2016 were used to characterize environmental patterns. From these datasets we calculated indices, such as the normalized differenced vegetation index (NDVI) and the normalized differenced water index (NDWI). In addition, datasets such as the National Land Data Assimilation System (NLDAS), National Land Cover Dataset (NLCD), National Wetland inventory (NWI), National Elevation Dataset (NED) and Soil Survey Geographic Database (SSURGO) were utilized. Environmental variables were summarized for a buffer zone around the case and control points. We used a boosted regression tree model to identify the most important variables describing the risk of WNV infection. We generated a risk map by applying this model across the entire state. We found that the highest relative risk is present in the James River valley in northeastern South Dakota. Factors that were identified as influencing the transmission risk include inter-annual variability of vegetation cover, water availability and temperature. Land covers such as grasslands, low developed areas and wetlands were also found to be good predictors for human

Identifying At-Risk Students in General Chemistry via Cluster Analysis of Affective Characteristics

ERIC Educational Resources Information Center

Chan, Julia Y. K.; Bauer, Christopher F.

2014-01-01

The purpose of this study is to identify academically at-risk students in first-semester general chemistry using affective characteristics via cluster analysis. Through the clustering of six preselected affective variables, three distinct affective groups were identified: low (at-risk), medium, and high. Students in the low affective group…

Risk factors associated with bovine trichomoniasis in beef cattle identified by a questionnaire.

PubMed

Jin, Yinzhu; Schumaker, Brant; Logan, Jim; Yao, Chaoqun

2014-06-01

Bovine trichomoniasis is a venereal disease that causes substantial economic losses to the cattle industry worldwide. It has been endemic in the USA since its discovery in the 1930s. The reasons for this long-lasting endemism are poorly understood. The main objective of this study was to identify herd-level risk factors for trichomoniasis in Wyoming beef cattle. A questionnaire was sent to all Wyoming beef cattle producers. The overall response proportion was 23.4 %. Questionnaires were returned from producers throughout the state in different geographical regions and with various herd sizes. In total, 863 questionnaires were analysed for correlation between the disease endemism and 25 variables. Tritrichomonas foetus infections were found to be significantly (P<0.05) associated with neighbouring a positive herd(s), grazing on public allotments and commingling with other herds. In addition, a delay in fixing broken fences approached statistical significance (P = 0.078). This study provides producers with valuable information and useful suggestions on how to effectively control and reduce the risks of bovine trichomoniasis. © 2014 The Authors.

The triglyceride to high-density lipoprotein ratio identifies children who may be at risk of developing cardiometabolic disease.

PubMed

Bailey, Daniel P; Savory, Louise A; Denton, Sarah J; Davies, Ben R; Kerr, Catherine J

2014-08-01

It is important to develop simple, reliable methods to identify high-risk individuals who may benefit from intervention. This study investigated the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and cardiometabolic risk, cardiorespiratory fitness and physical activity in children. Anthropometric, biochemical parameters, cardiorespiratory fitness and accelerometry determined physical activity were assessed in 155 children (80 girls) from 10 to 14 years of age from Bedfordshire, UK. Participants were grouped into high and low TG/HDL ratio groups, according to published thresholds. MANCOVA and logistic regression were used in the analysis. Cardiometabolic risk factor levels were significantly higher in participants with a high TG/HDL ratio (p < 0.05). The odds of having high waist circumference (OR = 13.99; 95% CI 2.93, 69.25), elevated systolic blood pressure (5.27; 1.39, 20.01), high non-HDL cholesterol (19.47; 4.42, 85.81) and ≥2 cardiometabolic risk factors (15.32; 3.10, 75.79) were higher in participants with a high TG/HDL ratio. The TG/HDL ratio values were significantly lower in those with high cardiorespiratory fitness (p = 0.01), but there was no association with physical activity. These findings support the use of the TG/HDL ratio to identify children with cardiometabolic risk factors who may be at risk of developing cardiometabolic disease. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

A measurement model of perinatal stressors: identifying risk for postnatal emotional distress in mothers of high-risk infants.

PubMed

DeMier, R L; Hynan, M T; Hatfield, R F; Varner, M W; Harris, H B; Manniello, R L

2000-01-01

A measurement model of perinatal stressors was first evaluated for reliability and then used to identify risk factors for postnatal emotional distress in high-risk mothers. In Study 1, six measures (gestational age of the baby, birthweight, length of the baby's hospitalization, a postnatal complications rating for the infant, and Apgar scores at 1 and 5 min) were obtained from chart reviews of preterm births at two different hospitals. Confirmatory factor analyses revealed that the six measures could be accounted for by three factors: (a) Infant Maturity, (b) Apgar Ratings, and (c) Complications. In Study 2, a modified measurement model indicated that Infant Maturity and Complications were significant predictors of postnatal emotional distress in an additional sample of mothers. This measurement model may also be useful in predicting (a) other measures of psychological distress in parents, and (b) measures of cognitive and motor development in infants.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

PubMed

Lim, Woo Hyeon; Park, Chang Min; Yoon, Soon Ho; Lim, Hyun-Ju; Hwang, Eui Jin; Lee, Jong Hyuk; Goo, Jin Mo

2018-03-01

To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

Risk assessment of soils identified on firefighter turnout gear.

PubMed

Easter, Elizabeth; Lander, Deborah; Huston, Tabitha

2016-09-01

The purpose of this research was to identify the composition of soils on firefighter turnout gear and to determine the dermal exposure risks associated with the soils. Nine used Nomex hoods from the Philadelphia fire department were analyzed for the presence of trace metals and seven sets of used turnout gear were analyzed for semi-volatile organics. Turnout gear samples were removed from areas of the gear known to have high levels of dermal absorption including the collar, armpit, wrist, and crotch areas, from either the outer shell or thermal liner layers. The following compounds were detected: polycyclic aromatic hydrocarbons (PAHs), phthalate plasticizers, and polybrominated diphenyl ether flame retardants (PBDEs). A screening risk assessment was conducted by converting the measured concentrations to an estimated dermally absorbed dose based on estimates for the permeation coefficient (Kp) and an assumed firefighting exposure scenario. Benzo(a) pyrene had the highest dermal exposure risk based on carcinogenic effects and PBDE-99 had the highest dermal exposure risk based on non-carcinogenic effects. For the metals, arsenic had the highest dermal exposure risk for the use hoods.

Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study.

PubMed

Murray, Anna; Bennett, Claire E; Perry, John R B; Weedon, Michael N; Jacobs, Patricia A; Morris, Danielle H; Orr, Nicholas; Schoemaker, Minouk J; Jones, Michael; Ashworth, Alan; Swerdlow, Anthony J

2011-01-01

Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and early menopause (EM) are highly heritable, suggesting a genetic aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40-60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated genetic variants in a cohort of approximately 2000 women with menopause≤45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4-7.1, P=4.0×10(-7)). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common genetic variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.

Modeling Success: Using Preenrollment Data to Identify Academically At-Risk Students

ERIC Educational Resources Information Center

Gansemer-Topf, Ann M.; Compton, Jonathan; Wohlgemuth, Darin; Forbes, Greg; Ralston, Ekaterina

2015-01-01

Improving student success and degree completion is one of the core principles of strategic enrollment management. To address this principle, institutional data were used to develop a statistical model to identify academically at-risk students. The model employs multiple linear regression techniques to predict students at risk of earning below a…

The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

PubMed

Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

2015-01-01

To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

Active Learning with Rationales for Identifying Operationally Significant Anomalies in Aviation

NASA Technical Reports Server (NTRS)

Sharma, Manali; Das, Kamalika; Bilgic, Mustafa; Matthews, Bryan; Nielsen, David Lynn; Oza, Nikunj C.

2016-01-01

A major focus of the commercial aviation community is discovery of unknown safety events in flight operations data. Data-driven unsupervised anomaly detection methods are better at capturing unknown safety events compared to rule-based methods which only look for known violations. However, not all statistical anomalies that are discovered by these unsupervised anomaly detection methods are operationally significant (e.g., represent a safety concern). Subject Matter Experts (SMEs) have to spend significant time reviewing these statistical anomalies individually to identify a few operationally significant ones. In this paper we propose an active learning algorithm that incorporates SME feedback in the form of rationales to build a classifier that can distinguish between uninteresting and operationally significant anomalies. Experimental evaluation on real aviation data shows that our approach improves detection of operationally significant events by as much as 75% compared to the state-of-the-art. The learnt classifier also generalizes well to additional validation data sets.

Identifying Patients With Vesicovaginal Fistula at High Risk of Urinary Incontinence After Surgery

PubMed Central

Bengtson, Angela M.; Kopp, Dawn; Tang, Jennifer H.; Chipungu, Ennet; Moyo, Margaret; Wilkinson, Jeffrey

2016-01-01

Objective To develop a risk score to identify women with vesicovaginal fistula at high risk of residual urinary incontinence after surgical repair. Methods We conducted a prospective cohort study among 401 women undergoing their first vesicovaginal fistula repair at a referral fistula repair center in Lilongwe, Malawi, between September 2011 and December 2014, who returned for follow-up within 120 days of surgery. We used logistic regression to develop a risk score to identify women with high likelihood of residual urinary incontinence, defined as incontinence grade 2-5 within 120 days of vesicovaginal fistula repair, based on preoperative clinical and demographic characteristics (age, number of years with fistula, HIV status, body mass index, previous repair surgery at an outside facility, revised Goh Classification, Goh vesicovaginal fistula size, circumferential fistula, vaginal scaring, bladder size, and urethral length). The sensitivity, specificity, positive and negative predictive values of the risk score at each cut-point were assessed. Results Overall, 11 (3%) women had unsuccessful fistula closure. Of those with successful fistula closure (n=372), 85 (23%) experienced residual incontinence. A risk score cut-point of 20 had sensitivity 82% (95% CI 72%, 89%) and specificity 63% (95% CI 57%, 69%) to potentially identify women with residual incontinence. In our population, the positive predictive value for a risk score cut-point of _20 or higher was 43% (95% CI 36%, 51%) and the negative predictive value was 91% (95% CI 86%, 94%). Forty-eight percent of our study population had a risk score ≥20 and therefore, would have been identified for further intervention. Conclusions A risk score 20 or higher was associated with an increased likelihood of residual incontinence, with satisfactory sensitivity and specificity. If validated in alternative settings, the risk score could be used to refer women with high likelihood of postoperative incontinence to more

"It drives us to do it": pregnant adolescents identify drivers for sexual risk-taking.

PubMed

King Jones, Tammy C

2010-01-01

Sexual risk-taking behaviors have a negative effect on the heath and future of American adolescents. To gain insight into these behaviors and preventative efforts, this study explored the experiences and perceptions of 15 pregnant adolescents using a qualitative feminist approach and in-depth interviews. As participants discussed sex education, each identified influences on sexual decision-making that often overpowered the information received. Content analysis and constant comparison of this data led to the overarching theme "Drivers for Sexual Risk-taking." Drivers were categorized as internal and external and each demonstrated a significant influence on adolescent sexual decision-making. Results of this study can inform the development of educational efforts, reform of social policy, and the focus of future research.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.

PubMed

Amin Al Olama, Ali; Dadaev, Tokhir; Hazelett, Dennis J; Li, Qiuyan; Leongamornlert, Daniel; Saunders, Edward J; Stephens, Sarah; Cieza-Borrella, Clara; Whitmore, Ian; Benlloch Garcia, Sara; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L; 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; Wokołorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Govindasami, Koveela; Guy, Michelle; Lophatonanon, Artitaya; Muir, Kenneth; Viñuela, Ana; Brown, Andrew A; Freedman, Mathew; Conti, David V; Easton, Douglas; Coetzee, Gerhard A; Eeles, Rosalind A; Kote-Jarai, Zsofia

2015-10-01

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. © The Author 2015. Published by Oxford University Press.

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

PubMed

Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

2015-01-01

To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

PubMed Central

Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

2015-01-01

Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.

PubMed

Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K; Eyre, Steve; Bowes, John; Pappas, Dimitrios A; Kremer, Joel M; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P; Karlson, Elizabeth W; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K; Worthington, Jane; Greenberg, Jeffrey D; Plenge, Robert M; Bae, Sang-Cheol

2015-03-01

A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples. We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. 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.

Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-08-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Final 3. DATES COVERED (From - To) 15May2012 - 31Aug2016 Identifying Military and Combat-Specific Risk Factors for Child Adjustment...deployment and has a child between the age of 3 and 7 and comparison groups of civilain single parent families (N=200) and civilian dual parent

Identifying Risk Factors Associated with Inappropriate Use of Acid Suppressive Therapy at a Community Hospital

PubMed Central

Bodukam, Vijay; Saigal, Kirit; Bahl, Jaya; Wang, Yvette; Hanlon, Alexandra; Lu, Yinghui; Davis, Michael

2016-01-01

Purpose. By examining the prescribing patterns and inappropriate use of acid suppressive therapy (AST) during hospitalization and at discharge we sought to identify the risk factors associated with such practices. Methods. In this retrospective observational study, inpatient records were reviewed from January 2011 to December 2013. Treatment with AST was considered appropriate if the patient had a known specific indication or met criteria for stress ulcer prophylaxis. Results. In 2011, out of 58 patients who were on AST on admission, 32 were newly started on it and 23 (72%) were inappropriate cases. In 2012, out of 97 patients on AST, 61 were newly started on it and 51 (84%) were inappropriate cases. In 2013, 99 patients were on AST, of which 48 were newly started on it and 36 (75%) were inappropriate cases. 19% of the patients inappropriately started on AST were discharged on it in three years. Younger age, female sex, and 1 or more handoffs between services were significantly associated with increased risk of inappropriate AST. Conclusion. Our findings reflect inappropriate prescription of AST which leads to increase in costs of care and unnecessarily puts the patient at risk for potential adverse events. The results of this study emphasize the importance of examining the patient's need for AST at each level of care especially when the identified risk factors are present. PMID:27818680

Identifying patients at high risk for obstructive sleep apnoea syndrome in Nigeria: A multicentre observational study.

PubMed

Desalu, Olufemi O; Onyedum, Cajetan C; Adeoti, Adekunle O; Fadare, Joseph O; Sanya, Emmanuel O; Fawale, Michael B; Bello, Hamzat A

2017-06-01

Obstructive sleep apnoea is associated with significant health consequences. A significant proportion of hospitalized patients at risk for obstructive sleep apnoea were never identified and referred for polysomnography for diagnosis. The objective of this study was to determine the factors associated with high risk for obstructive sleep apnoea and use it to identify patients at risk for the condition in tertiary hospitals in Nigeria. This was a multicentre observational study of adult patients hospitalized in three selected hospitals from 15th January to 17th March 2015. Berlin questionnaire and Epworth sleepiness scale were used to assess for obstructive sleep apnoea risk and excessive daytime sleepiness respectively. Additional questions on traditional risk factors for obstructive sleep apnoea were also obtained. Nine hundred and twenty-six patients were recruited into the study. Respondents' mean age was 44.3 years ± 15.2years, 486 (52.5%) were females and 556 (60.0%) had one or more medical co-morbidity and none of the patients had a previous diagnosis of obstructive sleep apnoea. Factors that were independently associated with high risk for obstructive sleep apnoea include systemic hypertension(aOR-10.33;95%: CI 6.42-16.61), obesity(aOR-7.87;95% CI: 4.33-14.29); excessive daytime sleepiness (aOR-3.77;95% CI :2.28-6.22), tobacco smoking (aOR-2.99;95% CI: 1.76-5.07), snoring in a first-degree relative (aOR-1.83;95% CI: 1.19-2.81); and the use of sedative (aOR-1.82;95% CI: 1.06-3.15). This study shows that patients with systemic hypertension, obesity, excessive daytime sleepiness, history of smoking, snoring in a first-degree relative and use of sedatives are at high risk of obstructive sleep apnoea. None of the patients at high risk had a previous diagnosis of sleep apnoea by a physician, highlighting the diagnostic challenges of this condition. The results of this study will assist health care professionals in early identification of individuals at risk of

Identifying at-risk profiles and protective factors for problem gambling: A longitudinal study across adolescence and early adulthood.

PubMed

Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E

2018-05-01

Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Grades and Graduation: A Longitudinal Risk Perspective to Identify Student Dropouts

ERIC Educational Resources Information Center

Bowers, Alex J.

2010-01-01

Studies of student risk of school dropout have shown that present predictors of at-risk status do not accurately identify a large percentage of students who eventually drop out. Through the analysis of the entire Grade 1-12 longitudinal cohort-based grading histories of the class of 2006 for two school districts in the United States, the author…

[Predicting individual risk of high healthcare cost to identify complex chronic patients].

PubMed

Coderch, Jordi; Sánchez-Pérez, Inma; Ibern, Pere; Carreras, Marc; Pérez-Berruezo, Xavier; Inoriza, José M

2014-01-01

To develop a predictive model for the risk of high consumption of healthcare resources, and assess the ability of the model to identify complex chronic patients. A cross-sectional study was performed within a healthcare management organization by using individual data from 2 consecutive years (88,795 people). The dependent variable consisted of healthcare costs above the 95th percentile (P95), including all services provided by the organization and pharmaceutical consumption outside of the institution. The predictive variables were age, sex, morbidity-based on clinical risk groups (CRG)-and selected data from previous utilization (use of hospitalization, use of high-cost drugs in ambulatory care, pharmaceutical expenditure). A univariate descriptive analysis was performed. We constructed a logistic regression model with a 95% confidence level and analyzed sensitivity, specificity, positive predictive values (PPV), and the area under the ROC curve (AUC). Individuals incurring costs >P95 accumulated 44% of total healthcare costs and were concentrated in ACRG3 (aggregated CRG level 3) categories related to multiple chronic diseases. All variables were statistically significant except for sex. The model had a sensitivity of 48.4% (CI: 46.9%-49.8%), specificity of 97.2% (CI: 97.0%-97.3%), PPV of 46.5% (CI: 45.0%-47.9%), and an AUC of 0.897 (CI: 0.892 to 0.902). High consumption of healthcare resources is associated with complex chronic morbidity. A model based on age, morbidity, and prior utilization is able to predict high-cost risk and identify a target population requiring proactive care. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Identifying fine sediment sources to alleviate flood risk caused by fine sediments through catchment connectivity analysis

NASA Astrophysics Data System (ADS)

Twohig, Sarah; Pattison, Ian; Sander, Graham

2017-04-01

Fine sediment poses a significant threat to UK river systems in terms of vegetation, aquatic habitats and morphology. Deposition of fine sediment onto the river bed reduces channel capacity resulting in decreased volume to contain high flow events. Once the in channel problem has been identified managers are under pressure to sustainably mitigate flood risk. With climate change and land use adaptations increasing future pressures on river catchments it is important to consider the connectivity of fine sediment throughout the river catchment and its influence on channel capacity, particularly in systems experiencing long term aggradation. Fine sediment erosion is a continuing concern in the River Eye, Leicestershire. The predominately rural catchment has a history of flooding within the town of Melton Mowbray. Fine sediment from agricultural fields has been identified as a major contributor of sediment delivery into the channel. Current mitigation measures are not sustainable or successful in preventing the continuum of sediment throughout the catchment. Identifying the potential sources and connections of fine sediment would provide insight into targeted catchment management. 'Sensitive Catchment Integrated Modelling Analysis Platforms' (SCIMAP) is a tool often used by UK catchment managers to identify potential sources and routes of sediment within a catchment. SCIMAP is a risk based model that combines hydrological (rainfall) and geomorphic controls (slope, land cover) to identify the risk of fine sediment being transported from source into the channel. A desktop version of SCIMAP was run for the River Eye at a catchment scale using 5m terrain, rainfall and land cover data. A series of SCIMAP model runs were conducted changing individual parameters to determine the sensitivity of the model. Climate Change prediction data for the catchment was used to identify potential areas of future connectivity and erosion risk for catchment managers. The results have been

Screening for violence risk factors identifies young adults at risk for return emergency department visit for injury.

PubMed

Hankin, Abigail; Wei, Stanley; Foreman, Juron; Houry, Debra

2014-08-01

Homicide is the second leading cause of death among youth aged 15-24. Prior cross-sectional studies, in non-healthcare settings, have reported exposure to community violence, peer behavior, and delinquency as risk factors for violent injury. However, longitudinal cohort studies have not been performed to evaluate the temporal or predictive relationship between these risk factors and emergency department (ED) visits for injuries among at-risk youth. The objective was to assess whether self-reported exposure to violence risk factors in young adults can be used to predict future ED visits for injuries over a 1-year period. This prospective cohort study was performed in the ED of a Southeastern US Level I trauma center. Eligible participants were patients aged 18-24, presenting for any chief complaint. We excluded patients if they were critically ill, incarcerated, or could not read English. Initial recruitment occurred over a 6-month period, by a research assistant in the ED for 3-5 days per week, with shifts scheduled such that they included weekends and weekdays, over the hours from 8AM-8PM. At the time of initial contact in the ED, patients were asked to complete a written questionnaire, consisting of previously validated instruments measuring the following risk factors: a) aggression, b) perceived likelihood of violence, c) recent violent behavior, d) peer behavior, e) community exposure to violence, and f) positive future outlook. At 12 months following the initial ED visit, the participants' medical records were reviewed to identify any subsequent ED visits for injury-related complaints. We analyzed data with chi-square and logistic regression analyses. Three hundred thirty-two patients were approached, of whom 300 patients consented. Participants' average age was 21.1 years, with 60.1% female, 86.0% African American. After controlling for participant gender, ethnicity, or injury complaint at time of first visit, return visits for injuries were significantly

Identifying Military and Combat Specific Risk Factors for Child Adjustment: Comparing High and Low Risk Military Families and Civilian Families

DTIC Science & Technology

2016-06-01

Award Number: W81XWH-12-2-0034 TITLE: Identifying Military and Combat-Specific Risk Factors for Child Adjustment: Comparing High and Low Risk...2. REPORT TYPE Annual 3. DATES COVERED (From - To) 15 May - 2013 - 14 May 2014. Identifying Military and Combat-Specific Risk Factors for Child ...parents (N=200) whose spouse/partner is currently in a “low perceived risk” deployment and has a child between the age of 3 and 7 and comparison

Identifying Adolescents at Highly Elevated Risk for Suicidal Behavior in the Emergency Department

PubMed Central

Berona, Johnny; Czyz, Ewa; Horwitz, Adam G.; Gipson, Polly Y.

2015-01-01

Abstract Objective: The feasibility and concurrent validity of adolescent suicide risk screening in medical emergency departments (EDs) has been documented. The objectives of this short-term prospective study of adolescents who screened positive for suicide risk in the ED were: 1) to examine adolescents' rate of suicidal behavior during the 2 months following their ED visits and compare it with reported rates for psychiatric samples; and 2) to identify possible predictors of acute risk for suicidal behavior in this at-risk sample. Method: Participants were 81 adolescents, ages 14–19 years, seeking services for psychiatric and nonpsychiatric chief complaints, who screened positive for suicide risk because of recent suicidal ideation, a suicide attempt, and/or depression plus alcohol or substance misuse. A comprehensive assessment of suicidal behavior, using the Columbia-Suicide Severity Rating Scale, was conducted at baseline and 2 month follow-up. Results: Six adolescents (7.4%) reported a suicide attempt and 15 (18.5%) engaged in some type of suicidal behavior (actual, aborted, or interrupted suicide attempt; preparatory behavior) during the 2 months following their ED visit. These rates suggest that this screen identified a high-risk sample. Furthermore, adolescents who screened positive for suicidal ideation and/or attempt plus depression and alcohol/substance misuse were most likely to engage in future suicidal behavior (38.9%). Conclusions: In this study, use of a higher screen threshold (multiple suicide risk factors) showed promise for identifying highly elevated acute risk for suicidal behavior. PMID:25746114

Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

PubMed Central

Tonomura, Noriko; Elvers, Ingegerd; Thomas, Rachael; Megquier, Kate; Turner-Maier, Jason; Howald, Cedric; Sarver, Aaron L.; Swofford, Ross; Frantz, Aric M.; Ito, Daisuke; Mauceli, Evan; Arendt, Maja; Noh, Hyun Ji; Koltookian, Michele; Biagi, Tara; Fryc, Sarah; Williams, Christina; Avery, Anne C.; Kim, Jong-Hyuk; Barber, Lisa; Burgess, Kristine; Lander, Eric S.; Karlsson, Elinor K.; Azuma, Chieko

2015-01-01

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers. PMID:25642983

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

PubMed

Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P

2015-10-01

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

[Facilitating the diagnosis of depression and burnout by identifying demographic and work-related risk and protective factors among nurses].

PubMed

Ádám, Szilvia; Nistor, Anikó; Nistor, Katalin; Cserháti, Zoltán; Mészáros, Veronika

2015-08-09

Depression and burnout are frequent comorbidities among nurses. Despite similar symptoms, their management differ. Therefore, their timely diagnosis is essential. To identify demographic and work-related risk and protective factors of burnout and depression, and facilitate their diagnosis. A cross-sectional study among 1,713 nurses was carried out. Depression and burnout were assessed by the shortened Beck Depression Questionnaire and Maclach Burnout Inventory, respectively. Risk and protective factors were explored using t-tests and analysis of variance. The prevalence of depression and moderate-to-high burnout was 35.1% and 34-74%, respectively. Having a partner/child and longer employment in the outpatient setting protected from burnout. Lack of a partner and male sex emerged as risk factors of depression and depersonalisation, respectively. High prevalence of depression and burnout among nurses poses a significant public health issue. Familiarity with the disease-specific risk and protective factors identified in this research may facilitate timely diagnosis and effective disease management.

Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting

PubMed Central

Litwin, Alain H.; Smith, Bryce D.; Koppelman, Elisa A.; McKee, M. Diane; Christiansen, Cindy L.; Gifford, Allen L.; Weinbaum, Cindy M.; Southern, William N.

2012-01-01

Objectives. We evaluated an intervention designed to identify patients at risk for hepatitis C virus (HCV) through a risk screener used by primary care providers. Methods. A clinical reminder sticker prompted physicians at 3 urban clinics to screen patients for 12 risk factors and order HCV testing if any risks were present. Risk factor data were collected from the sticker; demographic and testing data were extracted from electronic medical records. We used the t test, χ2 test, and rank-sum test to compare patients who had and had not been screened and developed an analytic model to identify the incremental value of each element of the screener. Results. Among screened patients, 27.8% (n = 902) were identified as having at least 1 risk factor. Of screened patients with risk factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements (injection drug use, intranasal drug use, elevated alanine aminotransferase, transfusions before 1992, ≥ 20 lifetime sex partners, maternal HCV, existing liver disease) accounted for all HCV infections identified. Conclusions. A brief risk screener with a paper-based clinical reminder was effective in increasing HCV testing in a primary care setting. PMID:22994166

Preseason shoulder strength measurements in professional baseball pitchers: identifying players at risk for injury.

PubMed

Byram, Ian R; Bushnell, Brandon D; Dugger, Keith; Charron, Kevin; Harrell, Frank E; Noonan, Thomas J

2010-07-01

The ability to identify pitchers at risk for injury could be valuable to a professional baseball organization. To our knowledge, there have been no prior studies examining the predictive value of preseason strength measurements. Preseason weakness of shoulder external rotators is associated with increased risk of in-season throwing-related injury in professional baseball pitchers. Cohort study (prognosis); Level of evidence, 2. Preseason shoulder strength was measured for all pitchers in a professional baseball organization over a 5-year period (2001-2005). Prone internal rotation (IR), prone external rotation (PER), seated external rotation (SER), and supraspinatus (SS) strength were tested during spring training before each season. The players were then prospectively followed throughout the season for incidence of throwing-related injury. Injuries were categorized on an ordinal scale, with no injury, injury treated conservatively, and injury resulting in surgery delineated 0, 1, and 2, respectively. Subset analyses of shoulder injuries and of players with prior surgery were also performed. The association between strength measurements and injury was analyzed using Spearman rank correlation. A statistically significant association was observed for PER strength (P = .003), SER strength (P = .048), and SS strength (P = .006) with throwing-related injury requiring surgical intervention. Supraspinatus strength was also significantly associated with incidence of any shoulder injury (P = .031). There was an association between the ratio of PER/IR strength and incidence of shoulder injury (P = .037) and some evidence for an association with overall incidence of throwing-related injury (P = .051). No associations were noted in the subgroup of players with prior surgery. Preseason weakness of external rotation and SS strength is associated with in-season throwing-related injury resulting in surgical intervention in professional baseball pitchers. Thus, preseason strength

A random urine test can identify patients at risk of mesalamine non-adherence: a prospective study.

PubMed

Gifford, Anne E; Berg, Anders H; Lahiff, Conor; Cheifetz, Adam S; Horowitz, Gary; Moss, Alan C

2013-02-01

Mesalamine non-adherence is common among patients with ulcerative colitis (UC), and can be difficult to identify in practice. We sought to determine whether a random urine test for salicylates could be used as a marker of 5-aminosalicylic acid (5-ASA) ingestion and identify patients at risk of non-adherence. Our aim is to determine whether measurement of salicylates in a random urine sample correlates with 5-ASA levels, and predicts an individual's risk of mesalamine non-adherence. Prospective observational study. Urinary salicylates (by colorimetry) and 5-ASA (by liquid chromatography and tandem-mass spectrometry) were measured in a random urine sample at baseline in patients and controls. Mesalamine adherence was quantified by patient self-reports at enrollment and pharmacy refills of mesalamine over 6 months. A total of 93 patients with UC taking mesalamine maintenance therapy were prospectively enrolled from the clinic. Random urine salicylate levels (by colorimetry) were highly correlated with urine 5-ASA metabolite levels (by mass spectrometry; R2=0.9). A random urine salicylate level above 15 mg/dl distinguished patients who had recently taken mesalamine from controls (area under the curve value 0.9, sensitivity 95%, specificity 77%). A significant proportion of patients (27%) who self-identified as "high adherers" by an adherence questionnaire (Morisky Medication Adherence Scale-8) had random levels of urine salicylate below this threshold. These patients were at higher risk of objectively measured non-adherence to mesalamine over the subsequent 6 months (RR: 2.7, 95% CI: 1.1-7.0). A random urine salicylate level measured in the clinic can identify patients who have not recently taken mesalamine, and who are at higher risk of longitudinal non-adherence. This test could be used to screen patients who may warrant interventions to improve adherence and prevent disease relapse.

Risk factors of falls in inpatients and their practical use in identifying high-risk persons at admission: Fukushima Medical University Hospital cohort study.

PubMed

Hayakawa, Takehito; Hashimoto, Shigeatsu; Kanda, Hideyuki; Hirano, Noriko; Kurihara, Yumi; Kawashima, Takako; Fukushima, Tetsuhito

2014-01-01

To clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission. Prospective cohort study. Fukushima Medical University Hospital, Japan, from August 2008 and September 2009. 9957 adult consecutive inpatients admitted to our hospital. Information was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records. The proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women. To prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered.

Risk factors of falls in inpatients and their practical use in identifying high-risk persons at admission: Fukushima Medical University Hospital cohort study

PubMed Central

Hayakawa, Takehito; Hashimoto, Shigeatsu; Kanda, Hideyuki; Hirano, Noriko; Kurihara, Yumi; Kawashima, Takako; Fukushima, Tetsuhito

2014-01-01

Objectives To clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission. Design Prospective cohort study. Setting Fukushima Medical University Hospital, Japan, from August 2008 and September 2009. Participants 9957 adult consecutive inpatients admitted to our hospital. Methods Information was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records. Results The proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women. Conclusions To prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered. PMID:25232563

Association analysis identifies 65 new breast cancer risk loci.

PubMed

Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; Ghoussaini, Maya; Carroll, Jason S; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Aronson, Kristan J; Arun, Banu; Auer, Paul L; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D; Castelao, Jose E; Chan, Tsun L; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L; Collée, Margriet; Conroy, Don M; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Doheny, Kimberly F; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M; García-Sáenz, José A; Gaudet, Mia M; Georgoulias, Vassilios; Giles, Graham G; Glendon, Gord; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Grenaker Alnæs, Grethe I; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela N; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P; Ma, Edmond S K; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Noh, Dong-Young; Nordestgaard, Børge G; Norman, Aaron; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V Shane; Park, Sue K; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F

2017-11-02

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Impact of Patient Reminders on Papanicolaou Test Completion for High-Risk Patients Identified by a Clinical Decision Support System.

PubMed

MacLaughlin, Kathy L; Kessler, Maya E; Komandur Elayavilli, Ravikumar; Hickey, Branden C; Scheitel, Marianne R; Wagholikar, Kavishwar B; Liu, Hongfang; Kremers, Walter K; Chaudhry, Rajeev

2018-05-01

A clinical decision support system (CDSS) for cervical cancer screening identifies patients due for routine cervical cancer screening. Yet, high-risk patients who require more frequent screening or earlier follow-up to address past abnormal results are not identified. We aimed to assess the effect of a complex CDSS, incorporating national guidelines for high-risk patient screening and abnormal result management, its implementation to identify patients overdue for testing, and the outcome of sending a targeted recommendation for follow-up. At three primary care clinics affiliated with an academic medical center, a reminder recommending an appointment for Papanicolaou (Pap) testing or Pap and human papillomavirus cotesting was sent to high-risk women aged 18 through 65 years (intervention group) identified by CDSS as overdue for testing. Historical control patients, who did not receive a reminder, were identified by CDSS 1 year before the date when reminders were sent to the intervention group. Test completion rates were compared between the intervention and control groups through a generalized estimating equation extension. Across the three sites, the average completion rate of recommended follow-up testing was significantly higher in the intervention group at 23.7% (61/257) than the completion rate at 3.3% (17/516) in the control group (p < 0.001). A CDSS with enhanced capabilities to identify high-risk women due for cervical cancer testing beyond routine screening intervals, with subsequent patient notification, has the potential to decrease cervical precancer and cancer by improving adherence to guideline-compliant follow-up and needed treatment.

Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system.

PubMed

Toivo, T M; Mikkola, J A V; Laine, K; Airaksinen, M

2016-01-01

Drug-drug interactions (DDIs) are a significant cause for adverse drug events (ADEs). DDIs are often predictable and preventable, but their prevention and management require systematic service development. Most DDI studies focus on interaction rates in hospitalized patients. Less is known of DDIs in outpatients, particularly how community pharmacists could contribute to DDI management by applying their surveillance systems for identifying high-risk medications. The study was related to the implementation of the first online DDI surveillance system in Finnish community pharmacies. The goal was to demonstrate how community pharmacies can utilize their prospective surveillance system 1) for identifying high risk medications causing potential DDIs in outpatients, 2) for collaborative service development with local physicians, and 3) for academic risk management research purposes. All DDI alerts given by the online surveillance system were collected during a one-month period in 16 out of 17 University Pharmacy outlets in Finland, covering approximately 10% of the national outpatient prescription volume. The surveillance system was based on the FASS database, which categorizes DDIs into four classes (A-D) according to their clinical significance. Potential drug-drug DDIs were analyzed for 276,891 dispensed community pharmacy prescriptions. Potential DDIs were associated with 10.8%, or 31,110 of these prescriptions. Clinically significant interaction alerts categorized as FASS classes D (most severe, should be avoided) and C (clinically significant but controllable) were associated with 0.5% and 7.0% of the prescriptions, respectively. Methotrexate and warfarin had the highest risk of causing potentially serious (class D) interactions. These interaction alerts were most frequently between methotrexate and NSAIDs and warfarin and NSAIDs. In general, NSAIDs were the most commonly interacting drugs in this study. This study demonstrates that community pharmacies can actively

Model of areas for identifying risks influencing the compliance of technological processes and products

NASA Astrophysics Data System (ADS)

Misztal, A.; Belu, N.

2016-08-01

Operation of every company is associated with the risk of interfering with proper performance of its fundamental processes. This risk is associated with various internal areas of the company, as well as the environment in which it operates. From the point of view of ensuring compliance of the course of specific technological processes and, consequently, product conformity with requirements, it is important to identify these threats and eliminate or reduce the risk of their occurrence. The purpose of this article is to present a model of areas of identifying risk affecting the compliance of processes and products, which is based on multiregional targeted monitoring of typical places of interference and risk management methods. The model is based on the verification of risk analyses carried out in small and medium-sized manufacturing companies in various industries..

The accuracy of physical examination in identifying significant pathologies in penetrating thoracic trauma.

PubMed

Kong, V Y; Sartorius, B; Clarke, D L

2015-12-01

Accurate physical examination (PE) remains a key component in the assessment of penetrating thoracic trauma (PTT), despite the increasing availability of advanced radiological imaging. Evidence regarding the accuracy of PE in identifying significant pathology following PTT is limited. A retrospective review of 405 patients was undertaken over a twelve-month period to determine the accuracy of PE in identifying significant pathology (SP) subsequently confirmed on chest radiographs (CXRs) in patients who sustained stab injuries to the thorax. Ninety-seven per cent (372/405) of patients were males, and the mean age was 24 years. The weapons involved were knives in 98 % (398/405), screwdrivers in 1 % (3/405) and unknown in the remaining 1 %. Fifty-nine per cent (238/405) of all injuries were on the left side. There were 306 (76 %) SPs identified on CXR. Ninety-nine (24 %) CXRs were entirely normal. Based on PE alone, 223 (55 %) patients were thought to have SPs present, 182 (45 %) patients were thought to have no SPs. The overall sensitivity of PE in identifying SPs was 68 % (63-73, 95 % CI), with a specificity of 86 % (77-92, 95 % CI). The PPV of PE was 94 % (90-97, 95 % CI) and the NPV was 47 % (39-54, 95 % CI). The sensitivity of PE for identifying a pneumothorax was 59 % (51-66, 95 % CI), with a specificity of 96 % (89-99, 95 % CI) and the sensitivity of PE for identifying a haemothorax was 79 % (72-86, 95 % CI), with a specificity of 96 % (89-99, 95 % CI). PE is inaccurate in identifying SPs in PTT. The increased reliance on advanced radiological imaging and the subsequent reduced emphasis on PE may have contributed to rapid deskilling amongst surgical residents. The importance of PE must be repeatedly re-emphasised.

Identifying protective and risk factors for injurious falls in patients hospitalized for acute care: a retrospective case-control study.

PubMed

Aryee, Emmanuel; James, Spencer L; Hunt, Guenola M; Ryder, Hilary F

2017-11-07

Admitted patients who fall and injure themselves during an acute hospitalization incur increased costs, morbidity, and mortality, but little research has been conducted on identifying inpatients at high risk to injure themselves in a fall. Falls risk assessment tools have been unsuccessful due to their low positive predictive value when applied broadly to entire hospital populations. We aimed to identify variables associated with the risk of or protection against injurious fall in the inpatient setting. We also aimed to test the variables in the ABCs mnemonic (Age > 85, Bones-orthopedic conditions, anti-Coagulation and recent surgery) for correlation with injurious fall. We performed a retrospective case-control study at an academic tertiary care center comparing admitted patients with injurious fall to admitted patients without fall. We collected data on the demographics, medical and fall history, outcomes, and discharge disposition of injured fallers and control patients. We performed multivariate analysis of potential risk factors for injurious fall with logistic regression to calculate adjusted odds ratios. We identified 117 injured fallers and 320 controls. There were no differences in age, anti-coagulation use or fragility fractures between cases and controls. In multivariate analysis, recent surgery (OR 0.46, p = 0.003) was protective; joint replacement (OR 5.58, P = 0.002), psychotropic agents (OR 2.23, p = 0.001), the male sex (OR 2.08, p = 0.003) and history of fall (OR 2.08, p = 0.02) were significantly associated with injurious fall. In this study, the variables in the ABCs parameters were among the variables not useful for identifying inpatients at risk of injuring themselves in a fall, while other non-ABCs variables demonstrated a significant association with injurious fall. Recent surgery was a protective factor, and practices around the care of surgical patients could be extrapolated to reduce the in-hospital fall rates.

Clinical significance of nutritional risk screening tool for hospitalised children with acute burn injuries: a cross-sectional study.

PubMed

Bang, Y K; Park, M K; Ju, Y S; Cho, K Y

2018-06-01

We assessed the nutritional risks among children hospitalised with acute burn injuries and their associated clinical outcomes using three nutritional risk screening (NRS) tools: Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONG KIDS ), Pediatric Yorkhill Malnutrition Score (PYMS) and Screening Tool for the Assessment for Malnutrition in Pediatrics (STAMP). This prospective cross-sectional study was conducted from October 2015 to November 2016, in a regional burn centre. Patients were screened by two independent observers, using the three NRS tools. A total of 100 children aged 3 months to 16.5 years were included. STRONG KIDS identified 16% of patients as having high risk, with being identified 45% by PYMS and 44% by STAMP. After adjustment for confounding factors in multivariate regression analysis, patients in the high-risk group had significantly longer median (SD) lengths of stay [medium versus high risk: STRONG KIDS , 9.5 (6.6) versus 15.0 (24.2) days; PYMS, 8.5 (4.4) versus 13.0 (16.1) days; STAMP, 9.0 (5.7) versus 11.0 (17.4) days] and greater median (SD) weight loss [medium versus high risk: STRONG KIDS , 0.15 (0.8) versus -0.35 (0.8) kg; STAMP, 0.5 (0.7) versus 0 (0.1) kg] than patients in the medium-risk group (P < 0.05). The strengths of agreement in the nutritional risk classification between the two observers were good (κ for STRONG KIDS = 0.61; PYMS = 0.79; STAMP = 0.75) (P < 0.01). The STRONG KIDS , PYMS and STAMP tools could be useful and practical for determining which hospitalised children with acute burn injuries will need additional nutritional intervention. © 2017 The British Dietetic Association Ltd.

Exploring demands from the perspective of employees identified as being at risk of burnout

PubMed Central

Gauche, Cecile; de Beer, Leon T.; Brink, Lizelle

2017-01-01

ABSTRACT Purpose: Burnout has become an occupational health concern. However, little is known about the experiences of individuals identified as being at risk of burnout. This study aimed to address this gap by exploring employees’ experiences of well-being who were identified as burnout risks. Method: Interviews were conducted with 26 employees who agreed to participate in the study. A phenomenological approach was taken, with a case study design as the research strategy. Results: Three major themes were identified: job demands, life demands, and health concerns. It was evident that participants were experiencing demanding conditions in both their work and personal lives, indicating burnout to be a multi-domain phenomenon. Conclusions: Professionals and managers should take note of these results to assist and support employees who are identified as being at risk of burnout. PMID:28784048

Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.

PubMed

Claus, Elizabeth B; Cornish, Alex J; Broderick, Peter; Schildkraut, Joellen M; Dobbins, Sara E; Holroyd, Amy; Calvocoressi, Lisa; Lu, Lingeng; Hansen, Helen M; Smirnov, Ivan; Walsh, Kyle M; Schramm, Johannes; Hoffmann, Per; Nöthen, Markus M; Jöckel, Karl-Heinz; Swerdlow, Anthony; Larsen, Signe Benzon; Johansen, Christoffer; Simon, Matthias; Bondy, Melissa; Wrensch, Margaret; Houlston, Richard; Wiemels, Joseph L

2018-05-12

Meningioma are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. To identify a susceptibility locus for meningioma, we conducted a meta-analysis of two GWAS, imputed using a merged reference panel of 1,000 Genomes and UK10K data, with validation in two independent sample series totaling 2,138 cases and 12,081 controls. We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

Identifying rare variants for genetic risk through a combined pedigree and phenotype approach: application to suicide and asthma.

PubMed

Darlington, T M; Pimentel, R; Smith, K; Bakian, A V; Jerominski, L; Cardon, J; Camp, N J; Callor, W B; Grey, T; Singleton, M; Yandell, M; Renshaw, P F; Yurgelun-Todd, D A; Gray, D; Coon, H

2014-10-21

Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12,000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion. A number of medical conditions co-occur with suicide, including asthma, and this study was undertaken to identify genetic risk common to asthma and suicide. This study tests the hypothesis that a particular comorbid condition may identify a more homogeneous genetic subgroup, facilitating the identification of specific genetic risk factors in that group. From pedigrees at increased risk for suicide, we identified three pedigrees also at significantly increased familial risk for asthma. Five suicide decedents from each of these pedigrees, plus an additional three decedents not from these pedigrees with diagnosed asthma, and 10 decedents with close relatives with asthma were genotyped. Results were compared with 183 publicly available unaffected control exomes from 1000 Genomes and CEPH (Centre d'etude du polymorphisme humain) samples genotyped on the same platform. A further 432 suicide decedents were also genotyped as non-asthma suicide controls. Genotyping was done using the Infinium HumanExome BeadChip. For analysis, we used the pedigree extension of Variant Annotation, Analysis and Search Tool (pVAAST) to calculate the disease burden of each gene. The Phenotype Driven Variant Ontological Re-ranking tool (Phevor) then re-ranked our pVAAST results in context of the phenotype. Using asthma as a seed phenotype, Phevor traversed biomedical ontologies and identified genes with similar biological properties to those known to

Identifying rare variants for genetic risk through a combined pedigree and phenotype approach: application to suicide and asthma

PubMed Central

Darlington, T M; Pimentel, R; Smith, K; Bakian, A V; Jerominski, L; Cardon, J; Camp, N J; Callor, W B; Grey, T; Singleton, M; Yandell, M; Renshaw, P F; Yurgelun-Todd, D A; Gray, D; Coon, H

2014-01-01

Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12 000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion. A number of medical conditions co-occur with suicide, including asthma, and this study was undertaken to identify genetic risk common to asthma and suicide. This study tests the hypothesis that a particular comorbid condition may identify a more homogeneous genetic subgroup, facilitating the identification of specific genetic risk factors in that group. From pedigrees at increased risk for suicide, we identified three pedigrees also at significantly increased familial risk for asthma. Five suicide decedents from each of these pedigrees, plus an additional three decedents not from these pedigrees with diagnosed asthma, and 10 decedents with close relatives with asthma were genotyped. Results were compared with 183 publicly available unaffected control exomes from 1000 Genomes and CEPH (Centre d'etude du polymorphisme humain) samples genotyped on the same platform. A further 432 suicide decedents were also genotyped as non-asthma suicide controls. Genotyping was done using the Infinium HumanExome BeadChip. For analysis, we used the pedigree extension of Variant Annotation, Analysis and Search Tool (pVAAST) to calculate the disease burden of each gene. The Phenotype Driven Variant Ontological Re-ranking tool (Phevor) then re-ranked our pVAAST results in context of the phenotype. Using asthma as a seed phenotype, Phevor traversed biomedical ontologies and identified genes with similar biological properties to those known to

Network-based integration of GWAS and gene expression identifies a HOX-centric network associated with serous ovarian cancer risk

PubMed Central

Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K.; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K.; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston-Campbell, Lara E.; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Monteiro, Alvaro N. A.; Freedman, Matthew L.; Gayther, Simon A.; Pharoah, Paul D. P.

2015-01-01

Background Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by co-expression may also be enriched for additional EOC risk associations. Methods We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. PMID:26209509

Association analysis identifies 65 new breast cancer risk loci

PubMed Central

Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Chen, Xiao Qing; Fachal, Laura; McCue, Karen; McCart Reed, Amy E.; Ghoussaini, Maya; Carroll, Jason; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; Cheng, Ting-Yuan David; Chia, Kee Seng; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung-Won; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Marchand, Loic Le; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Lee, Chuen Neng; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S.K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Mohd Taib, Nur Aishah; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong-Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I.A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofieva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J. Th.; Saloustros, Emmanouil; Sandler, Dale P.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J.; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A.; Tengström, Maria; Teo, Soo H.; Terry, Mary Beth; Tessier, Daniel C.; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J.; Van Den Berg, David; van den Ouweland, Ans M.W.; van der Kolk, Lizet; van der Luijt, Rob B.; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H.; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R.; Yip, Cheng Har; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R.; Antoniou, Antonis C.; Droit, Arnaud; Andrulis, Irene L.; Amos, Christopher I.; Couch, Fergus J.; Pharoah, Paul D.P.; Chang-Claude, Jenny; Hall, Per; Hunter, David J.; Milne, Roger L.; García-Closas, Montserrat; Schmidt, Marjanka K.; Chanock, Stephen J.; Dunning, Alison M.; Edwards, Stacey L.; Bader, Gary D.; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F.

2017-01-01

Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci associated with overall breast cancer at p<5x10-8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention. PMID:29059683

Standardised survey method for identifying catchment risks to water quality.

PubMed

Baker, D L; Ferguson, C M; Chier, P; Warnecke, M; Watkinson, A

2016-06-01

This paper describes the development and application of a systematic methodology to identify and quantify risks in drinking water and recreational catchments. The methodology assesses microbial and chemical contaminants from both diffuse and point sources within a catchment using Escherichia coli, protozoan pathogens and chemicals (including fuel and pesticides) as index contaminants. Hazard source information is gathered by a defined sanitary survey process involving use of a software tool which groups hazards into six types: sewage infrastructure, on-site sewage systems, industrial, stormwater, agriculture and recreational sites. The survey estimates the likelihood of the site affecting catchment water quality, and the potential consequences, enabling the calculation of risk for individual sites. These risks are integrated to calculate a cumulative risk for each sub-catchment and the whole catchment. The cumulative risks process accounts for the proportion of potential input sources surveyed and for transfer of contaminants from upstream to downstream sub-catchments. The output risk matrices show the relative risk sources for each of the index contaminants, highlighting those with the greatest impact on water quality at a sub-catchment and catchment level. Verification of the sanitary survey assessments and prioritisation is achieved by comparison with water quality data and microbial source tracking.

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.

Identifying emotional and behavioral risk among gifted and nongifted children: A multi-gate, multi-informant approach.

PubMed

Eklund, Katie; Tanner, Nick; Stoll, Katie; Anway, Leslie

2015-06-01

The purpose of the current investigation was to compare 1,206 gifted and nongifted elementary students on the identification of emotional and behavioral risk (EBR) as rated by teachers and parents using a multigate, multi-informant approach to assessment. The Parent and Teacher Behavioral Assessment System for Children, Second Edition (BASC-2) and the Behavioral and Emotional Screening System were used to assess behavioral functioning as rated by teachers and parents. There were significant differences between the number of gifted and nongifted children demonstrating emotional and behavioral risk, with parents and teachers identifying a higher number of boys and nongifted children as at risk. Among children demonstrating EBR, gifted children demonstrated elevated internalizing behaviors as rated by parents. Gifted students demonstrated higher academic performance regardless of risk level, suggesting higher cognitive abilities may be one of several protective factors that serve to attenuate the development of other social, emotional, or behavioral concerns. Implications for practice and future research needs are discussed. (c) 2015 APA, all rights reserved).

Identifying significant environmental features using feature recognition.

DOT National Transportation Integrated Search

2015-10-01

The Department of Environmental Analysis at the Kentucky Transportation Cabinet has expressed an interest in feature-recognition capability because it may help analysts identify environmentally sensitive features in the landscape, : including those r...

Agreement between calcaneal quantitative ultrasound and osteoporosis self-assessment tool for Asians in identifying individuals at risk of osteoporosis

PubMed Central

Chin, Kok-Yong; Low, Nie Yen; Kamaruddin, Alia Annessa Ain; Dewiputri, Wan Ilma; Soelaiman, Ima-Nirwana

2017-01-01

Background Calcaneal quantitative ultrasound (QUS) is a useful tool in osteoporosis screening. However, QUS device may not be available at all primary health care settings. Osteoporosis self-assessment tool for Asians (OSTA) is a simple algorithm for osteoporosis screening that does not require any sophisticated instruments. This study explored the possibility of replacing QUS with OSTA by determining their agreement in identifying individuals at risk of osteoporosis. Methods A cross-sectional study was conducted to recruit Malaysian men and women aged ≥50 years. Their bone health status was measured using a calcaneal QUS device and OSTA. The association between OSTA and QUS was determined using Spearman’s correlation and their agreement was assessed using Cohen Kappa and receiver-operating curve. Results All QUS indices correlated significantly with OSTA (p<0.05). The agreement between QUS and OSTA was minimal but statistically significant (p<0.05). The performance of OSTA in identifying subjects at risk of osteoporosis according to QUS was poor-to-fair in women (p<0.05), but not statistically significant for men (p>0.05). Changing the cut-off values improved the performance of OSTA in women but not in men. Conclusion The agreement between QUS and OSTA is minimal in categorizing individuals at risk of osteoporosis. Therefore, they cannot be used interchangeably in osteoporosis screening. PMID:29070951

Malpractice risk and cost are significantly reduced after tort reform.

PubMed

Stewart, Ronald M; Geoghegan, Kathy; Myers, John G; Sirinek, Kenneth R; Corneille, Michael G; Mueller, Deborah; Dent, Daniel L; Wolf, Steven E; Pruitt, Basil A

2011-04-01

Rising medical malpractice premiums have reached a crisis point in many areas of the United States. In 2003 the Texas legislature passed a comprehensive package of tort reform laws that included a cap at $250,000 on noneconomic damages in most medical malpractice cases. We hypothesized that tort reform laws significantly reduce the risk of malpractice lawsuit in an academic medical center. We compared malpractice prevalence, incidence, and liability costs before and after comprehensive state tort reform measures were implemented. Two prospectively maintained institutional databases were used to calculate and characterize malpractice risk: a surgical operation database and a risk management and malpractice database. Risk groups were divided into pretort reform (1992 to 2004) and post-tort reform groups (2004 to the present). Operative procedures were included for elective, urgent, and emergency general surgery procedures. During the study period, 98,513 general surgical procedures were performed. A total of 28 lawsuits (25 pre-reform, 3 postreform) were filed, naming general surgery faculty or residents. The prevalence of lawsuits filed/100,000 procedures performed is as follows: before reform, 40 lawsuits/100,000 procedures, and after reform, 8 lawsuits/100,000 procedures (p < 0.01, relative risk 0.21 [95% CI 0.063 to 0.62]). Virtually all of the liability and defense cost was in the pretort reform period: $595,000/year versus $515/year in the postreform group (p < 0.01). Implementation of comprehensive tort reform in Texas was associated with a significant decrease in the prevalence and cost of surgical malpractice lawsuits at one academic medical center. Copyright © 2011. Published by Elsevier Inc.

Identifying Voxels at Risk for Progression in Glioblastoma Based on Dosimetry, Physiologic and Metabolic MRI.

PubMed

Anwar, Mekhail; Molinaro, Annette M; Morin, Olivier; Chang, Susan M; Haas-Kogan, Daphne A; Nelson, Sarah J; Lupo, Janine M

2017-09-01

Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease. In this study, we hypothesize that parameters from physiologic and metabolic magnetic resonance imaging (MRI) at diagnosis could predict the likelihood of voxel progression at radiographic recurrence in glioblastoma by identifying voxel characteristics that indicate subclinical disease. Integrating dosimetry can reveal its effect on voxel outcome, enabling risk-adapted voxel dosing. As a system example, 24 patients with glioblastoma treated with radiotherapy, temozolomide and an anti-angiogenic agent were analyzed. Pretreatment median apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), vessel leakage (percentage recovery), choline-to-NAA index (CNI) and dose of voxels in the T2 nonenhancing lesion (NEL), T1 post-contrast enhancing lesion (CEL) or normal-appearing volume (NAV) of brain, were calculated for voxels that progressed [NAV→NEL, CEL (N = 8,765)] and compared against those that remained stable [NAV→NAV (N = 98,665)]. Voxels that progressed (NAV→NEL) had significantly different (P < 0.01) ADC (860), FA (0.36) and CNI (0.67) versus stable voxels (804, 0.43 and 0.05, respectively), indicating increased cell turnover, edema and decreased directionality, consistent with subclinical disease. NAV→CEL voxels were more abnormal (1,014, 0.28, 2.67, respectively) and leakier (percentage recovery = 70). A predictive model

Type 2 diabetes mellitus disease risk genes identified by genome wide copy number variation scan in normal populations.

PubMed

Prabhanjan, Manasa; Suresh, Raviraj V; Murthy, Megha N; Ramachandra, Nallur B

2016-03-01

To identify the role of copy number variations (CNVs) on disease risk genes and its effect on disease phenotypes in type 2 diabetes mellitus (T2DM) in 12 random populations using high throughput arrays. CNV analysis was carried out on a total of 1715 individuals from 12 populations, from ArrayExpress Archive of the European Bioinformatics Institute along with our subjects using Affymetrix Genome Wide SNP 6.0 array. CNV effect on T2DM genes were analyzed using several bioinformatics tools and a molecular protein interaction network was constructed to identify the disease mechanism altered by the CNVs. Analysis showed 34.4% of the total population to be under CNV burden for T2DM, with 83 disease causal and associated genes being under CNV influence. Hotspots were identified on chromosomes 22, 12, 6, 19 and 11.Overlap studies with case cohorts revealed significant disease risk genes such as EGFR, E2F1, PPP1R3A, HLA and TSPAN8. CNVs play a significant role in predisposing T2DM in normal cohorts and contribute to the phenotypic effects. Thus, CNVs should be considered as one of the major contributors in predisposition of the disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C.

PubMed

Kurosaki, Masayuki; Hiramatsu, Naoki; Sakamoto, Minoru; Suzuki, Yoshiyuki; Iwasaki, Manabu; Tamori, Akihiro; Matsuura, Kentaro; Kakinuma, Sei; Sugauchi, Fuminaka; Sakamoto, Naoya; Nakagawa, Mina; Izumi, Namiki

2012-03-01

Assessment of the risk of hepatocellular carcinoma (HCC) development is essential for formulating personalized surveillance or antiviral treatment plan for chronic hepatitis C. We aimed to build a simple model for the identification of patients at high risk of developing HCC. Chronic hepatitis C patients followed for at least 5 years (n=1003) were analyzed by data mining to build a predictive model for HCC development. The model was externally validated using a cohort of 1072 patients (472 with sustained virological response (SVR) and 600 with nonSVR to PEG-interferon plus ribavirin therapy). On the basis of factors such as age, platelet, albumin, and aspartate aminotransferase, the HCC risk prediction model identified subgroups with high-, intermediate-, and low-risk of HCC with a 5-year HCC development rate of 20.9%, 6.3-7.3%, and 0-1.5%, respectively. The reproducibility of the model was confirmed through external validation (r(2)=0.981). The 10-year HCC development rate was also significantly higher in the high-and intermediate-risk group than in the low-risk group (24.5% vs. 4.8%; p<0.0001). In the high-and intermediate-risk group, the incidence of HCC development was significantly reduced in patients with SVR compared to those with nonSVR (5-year rate, 9.5% vs. 4.5%; p=0.040). The HCC risk prediction model uses simple and readily available factors and identifies patients at a high risk of HCC development. The model allows physicians to identify patients requiring HCC surveillance and those who benefit from IFN therapy to prevent HCC. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Identifying and assessing highly hazardous drugs within quality risk management programs.

PubMed

Sussman, Robert G; Schatz, Anthony R; Kimmel, Tracy A; Ader, Allan; Naumann, Bruce D; Weideman, Patricia A

2016-08-01

Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

A simple risk score identifies individuals at high risk of developing Type 2 diabetes: a prospective cohort study.

PubMed

Rahman, Mushtaqur; Simmons, Rebecca K; Harding, Anne-Helen; Wareham, Nicholas J; Griffin, Simon J

2008-06-01

Randomized trials have demonstrated that Type 2 diabetes is preventable among high-risk individuals. To date, such individuals have been identified through population screening using the oral glucose tolerance test. To assess whether a risk score comprising only routinely collected non-biochemical parameters was effective in identifying those at risk of developing Type 2 diabetes. Population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40-79 recruited from UK general practices attended a health check between 1993 and 1998 (n = 25 639) and were followed for a mean of 5 years for diabetes incidence. The Cambridge Diabetes Risk Score was computed for 24 495 individuals with baseline data on age, sex, prescription of steroids and anti-hypertensive medication, family history of diabetes, body mass index and smoking status. We examined the incidence of diabetes across quintiles of the risk score and plotted a receiver operating characteristic (ROC) curve to assess discrimination. There were 323 new cases of diabetes, a cumulative incidence of 2.76/1000 person-years. Those in the top quintile of risk were 22 times more likely to develop diabetes than those in the bottom quintile (odds ratio 22.3; 95% CI: 11.0-45.4). In all, 54% of all clinically incident cases occurred in individuals in the top quintile of risk (risk score > 0.37). The area under the ROC was 74.5%. The risk score is a simple, effective tool for the identification of those at risk of developing Type 2 diabetes. Such methods may be more feasible than mass population screening with biochemical tests in defining target populations for prevention programmes.

A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.

PubMed

Lee, Alice W; Bomkamp, Ashley; Bandera, Elisa V; Jensen, Allan; Ramus, Susan J; Goodman, Marc T; Rossing, Mary Anne; Modugno, Francesmary; Moysich, Kirsten B; Chang-Claude, Jenny; Rudolph, Anja; Gentry-Maharaj, Aleksandra; Terry, Kathryn L; Gayther, Simon A; Cramer, Daniel W; Doherty, Jennifer A; Schildkraut, Joellen M; Kjaer, Susanne K; Ness, Roberta B; Menon, Usha; Berchuck, Andrew; Mukherjee, Bhramar; Roman, Lynda; Pharoah, Paul D; Chenevix-Trench, Georgia; Olson, Sara; Hogdall, Estrid; Wu, Anna H; Pike, Malcolm C; Stram, Daniel O; Pearce, Celeste Leigh

2016-12-15

Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non-users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (p int  = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users of 10+ years (OR = 1.85, 95% CI 1.28-2.66, p int  = 0.034). Non-users showed essentially no association (OR = 1.08, 95% CI 0.96-1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (p int  = 0.021 and p int  = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci. © 2016 UICC.

Using a personality inventory to identify risk of distress and burnout among early stage medical students.

PubMed

Bughi, Stephanie A; Lie, Desiree A; Zia, Stephanie K; Rosenthal, Jane

2017-01-01

Distress and burnout are common among medical students and negatively impact students' physical, mental, and emotional health. Personality inventories such as the Myers-Briggs Type Indicator (MBTI), used in medical education, may have a role in identifying burnout risk early. The authors conducted a cross-sectional survey study among 185 1st year medical students with the MBTI, the general well-being schedule (GWB), and Maslach Burnout Inventory-Student Survey (MBI-SS). Descriptive statistics and one-way MANOVAs were used to identify the prevalence and differences in MBTI preferences and distress/burnout risk. Response rate was 185/185 (100%). Distress (GWB) was reported by 84/185 (45.4%). High scores on exhaustion were reported by 118/182 (64.8%), cynicism by 76/182 (41.8%), and decreased professional efficacy by 38/182 (20.9%) for the three dimensions of the MBI-SS. Only 21/182 (11.5%) of respondents had high scores on all three dimensions of burnout. Students with MBTI preferences for extraversion reported greater positive well-being (P < 0.05), self-control (P < 0.05), professional efficacy (P < 0.01), and lower levels of depression (P < 0.01) compared with those with introversion preference. Distress and burnout are prevalent early in medical training. The significant difference between extraversion and introversion in relation to distress and burnout deserves further study. Use of a personality inventory may help identify students at risk of burnout and allow appropriate early stress management.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

PubMed

Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Veer, Laura J Van't; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

2013-04-01

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk

PubMed Central

Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Silva, Isabel dos Santos; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Van’t Veer, Laura J; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

2013-01-01

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

In-depth Investigation of Genetic Region Identifies Mechanism that Contributes to Cancer Risk

Cancer.gov

Investigators in the Laboratory of Translational Genomics have identified a genetic variant in a multi-cancer risk locus at chromosome 5p15.33 that explains, at least in part, the molecular mechanism through which this variant influences cancer risk.

Using decision tree analysis to identify risk factors for relapse to smoking

PubMed Central

Piper, Megan E.; Loh, Wei-Yin; Smith, Stevens S.; Japuntich, Sandra J.; Baker, Timothy B.

2010-01-01

This research used classification tree analysis and logistic regression models to identify risk factors related to short- and long-term abstinence. Baseline and cessation outcome data from two smoking cessation trials, conducted from 2001 to 2002, in two Midwestern urban areas, were analyzed. There were 928 participants (53.1% women, 81.8% white) with complete data. Both analyses suggest that relapse risk is produced by interactions of risk factors and that early and late cessation outcomes reflect different vulnerability factors. The results illustrate the dynamic nature of relapse risk and suggest the importance of efficient modeling of interactions in relapse prediction. PMID:20397871

42 CFR 137.22 - May the Secretary consider uncorrected significant and material audit exceptions identified...

Code of Federal Regulations, 2010 CFR

2010-10-01

... and material audit exceptions identified regarding centralized financial and administrative functions... Tribes for Participation in Self-Governance Planning Phase § 137.22 May the Secretary consider uncorrected significant and material audit exceptions identified regarding centralized financial and...

Identifying Children at High Risk for a Child Maltreatment Report

ERIC Educational Resources Information Center

Dubowitz, Howard; Kim, Jeongeun; Black, Maureen M.; Weisbart, Cindy; Semiatin, Joshua; Magder, Laurence S.

2011-01-01

Objective: To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method: The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for…

Worsening renal function in patients hospitalized with acute heart failure: risk factors and prognostic significances.

PubMed

Verdiani, Valerio; Lastrucci, Vieri; Nozzoli, Carlo

2010-10-11

Objectives. To determine the prevalence, the clinical predictors, and the prognostic significances of Worsening Renal Function (WRF) in hospitalized patients with Acute Heart Failure (AHF). Methods. 394 consecutively hospitalized patients with AHF were evaluated. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dL from baseline to discharge. Results. Nearly 11% of patients developed WRF. The independent predictors of WRF analyzed with a multivariable logistic regression were history of chronic kidney disease (P = .047), age >75 years (P = .049), and admission heart rates ≥100 bpm (P = .004). Mortality or rehospitalization rates at 1 month, 6 months, and 1year were not significantly different between patients with WRF and those without WRF. Conclusion. Different clinical predictors at hospital admission can be used to identify patients at increased risk for developing WRF. Patients with WRF compared with those without WRF experienced no significant differences in hospital length of stay, mortality, or rehospitalization rates.

Worsening Renal Function in Patients Hospitalized with Acute Heart Failure: Risk Factors and Prognostic Significances

PubMed Central

Verdiani, Valerio; Lastrucci, Vieri; Nozzoli, Carlo

2011-01-01

Objectives. To determine the prevalence, the clinical predictors, and the prognostic significances of Worsening Renal Function (WRF) in hospitalized patients with Acute Heart Failure (AHF). Methods. 394 consecutively hospitalized patients with AHF were evaluated. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dL from baseline to discharge. Results. Nearly 11% of patients developed WRF. The independent predictors of WRF analyzed with a multivariable logistic regression were history of chronic kidney disease (P = .047), age >75 years (P = .049), and admission heart rates ≥100 bpm (P = .004). Mortality or rehospitalization rates at 1 month, 6 months, and 1year were not significantly different between patients with WRF and those without WRF. Conclusion. Different clinical predictors at hospital admission can be used to identify patients at increased risk for developing WRF. Patients with WRF compared with those without WRF experienced no significant differences in hospital length of stay, mortality, or rehospitalization rates. PMID:21188211

[Clinical significance of HPV L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women].

PubMed

Wang, Jiajian; Tian, Qifang; Zhang, Su; Lyu, Liping; Dong, Jie; Lyu, Weiguo

2015-04-01

To explore the clinical significance of human papillomavirus L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women. From November 2012 to June 2013, 386 high-risk HPV positive (detected by hybrid capture II) cases were enrolled as eligible women from Huzhou Maternity & Child Care Hospital and Women's Hospital, School of Medicine, Zhejiang University. All eligible women underwent liquid-based cytology (ThinPrep) followed by colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1 capsid protein detection by immunocytochemistry. Expression of HPV L1 capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1 capsid protein detection in cervical exfoliated cells in cervical lesions screening was accessed. Total 386 enrolled eligible women were finally diagnosed histologically as follwed: 162 normal cervix, 94 low-grade squamous intraepithelial lesion (LSIL), 128 high-grade squamous intraepithelial lesion (HSIL) and 2 squamous cervical cancer (SCC). The positive expression rate of HPV L1 in HSIL+ (HSIL or worse) group was significantly lower than that in LSIL- (LSIL or better) group (19.2% vs 66.4%, P=0.000). While identifying HSIL+ in HPV positive cases and compared with cytology, HPV L1 detection resulted in significant higher sensitivity (80.77% vs 50.77%, P=0.000) and negative predictive value (NPV; 87.18% vs 76.47%, P=0.004), significant lower specificity (66.41% vs 81.25%, P=0.000), and comparable positive predictive value (PPV; 54.97% vs 57.89%, P=0.619). To identify HSIL+ in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1 detection were 87.50%, 61.54%, 41.18%, and 94.12% respectively, while 80.00%, 86.36%, 80.00% and 86.36% respectively in HPV-positive/atypical squamous cell of undetermined significance (ASCUS) women. HPV L1 capsid detection in cervical exfoliated cells have a role in cervical lesions

Genomewide association study of cocaine dependence and related traits: FAM53B identified as a risk gene

PubMed Central

Gelernter, Joel; Sherva, Richard; Koesterer, Ryan; Almasy, Laura; Zhao, Hongyu; Kranzler, Henry R.; Farrer, Lindsay

2013-01-01

We report a GWAS for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively), to identify pathways, genes, and alleles important in CD risk. The discovery GWAS dataset (n=5,697 subjects) was genotyped using the Illumina OmniQuad microarray (890,000 analyzed SNPs). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4,063 subjects. Then, the most significant GWAS SNPs were genotyped in 2,549 independent subjects. We observed one genomewide-significant (GWS) result: rs7086629 at the FAM53B (“family with sequence similarity 53, member B”) locus. This was supported in both AAs and EAs; p-value (meta-analysis of all samples) =4.28×10−8. The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 1) SNP rs150954431 was associated with p=1.19×10−9 in the EA discovery sample. SNP rs2456778, which maps to CDK1 (“cyclin-dependent kinase 1”), was associated with cocaine-induced paranoia in AAs in the discovery sample only (p=4.68×10−8). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies. PMID:23958962

Mapping eQTLs in the Norfolk Island Genetic Isolate Identifies Candidate Genes for CVD Risk Traits

PubMed Central

Benton, Miles C.; Lea, Rod A.; Macartney-Coxson, Donia; Carless, Melanie A.; Göring, Harald H.; Bellis, Claire; Hanna, Michelle; Eccles, David; Chambers, Geoffrey K.; Curran, Joanne E.; Harper, Jacquie L.; Blangero, John; Griffiths, Lyn R.

2013-01-01

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10−7) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations. PMID:24314549

Identifying and reducing risk factors related to trainee-client sexual misconduct.

PubMed

Hamilton, J C; Spruill, J

1999-06-01

Sexual misconduct involving therapists-in-training and their clients is addressed. Personal and situational factors that may constitute risk factors for the development of inappropriate sexual activity between trainees and their clients are identified. Although there may be certain characteristics that put particular students at risk for such involvement, the authors believe this risk is more strongly related to systemic, programmatic, and pedagogic characteristics of the environments in which students train. Examples include, respectively, the decline of concern over transference and countertransference, failure to include education about client-therapist sexual attraction and the consequences of sexual misconduct in graduate psychology curricula, and the reluctance of supervisors to deal straightforwardly with trainees' sexual feelings. Suggestions for reducing risks for client-therapist sexual misconduct are directed toward these situational factors.

Hospital Readmission and Social Risk Factors Identified from Physician Notes.

PubMed

Navathe, Amol S; Zhong, Feiran; Lei, Victor J; Chang, Frank Y; Sordo, Margarita; Topaz, Maxim; Navathe, Shamkant B; Rocha, Roberto A; Zhou, Li

2018-04-01

To evaluate the prevalence of seven social factors using physician notes as compared to claims and structured electronic health records (EHRs) data and the resulting association with 30-day readmissions. A multihospital academic health system in southeastern Massachusetts. An observational study of 49,319 patients with cardiovascular disease admitted from January 1, 2011, to December 31, 2013, using multivariable logistic regression to adjust for patient characteristics. All-payer claims, EHR data, and physician notes extracted from a centralized clinical registry. All seven social characteristics were identified at the highest rates in physician notes. For example, we identified 14,872 patient admissions with poor social support in physician notes, increasing the prevalence from 0.4 percent using ICD-9 codes and structured EHR data to 16.0 percent. Compared to an 18.6 percent baseline readmission rate, risk-adjusted analysis showed higher readmission risk for patients with housing instability (readmission rate 24.5 percent; p < .001), depression (20.6 percent; p < .001), drug abuse (20.2 percent; p = .01), and poor social support (20.0 percent; p = .01). The seven social risk factors studied are substantially more prevalent than represented in administrative data. Automated methods for analyzing physician notes may enable better identification of patients with social needs. © Health Research and Educational Trust.

Utility of the HARP Diabetes Risk Calculator in Identifying Patients with Type 2 Diabetes at Risk of Unplanned Hospital Presentations.

PubMed

McGrath, Rachel T; Dryden, Justin C; Newlyn, Neroli; Pamplona, Elline; O'Dea, Judy; Hocking, Samantha L; Glastras, Sarah J; Fulcher, Gregory R

2018-03-31

Prevention of hospitalisation is an important aspect of type 2 diabetes (T2D) management. We retrospectively determined the utility of the Hospital Admission Risk Programme (HARP) Diabetes Risk Calculator (HARP tool) in identifying patients with T2D more likely to have unplanned hospital presentations. The HARP tool includes a clinical assessment score (Part A) and a psychosocial and self-management impact score (Part B), and categorises patients into low, medium, high or urgent risk of acute hospitalisation. It was completed for T2D patients attending Royal North Shore Hospital, Sydney in 2013. Within the cohort of 278 patients (age 65.3 ± 10.5 years; 62.9% male; diabetes duration 10.7 ± 6.6 years), 67.3% were classified as low risk, 32.7% as medium risk and none as high or urgent risk. Following adjustment for confounders, a medium HARP score was associated with a 3.1-fold increased risk of unplanned hospital presentations in the subsequent 12 months (95% CI: 1.35 to 7.31; p = 0.008). Part A scores were significantly higher for patients that presented to hospital compared to those that did not (14.2 ± 6.8 vs. 11.4 ± 5.5; p = 0.034), whereas there was no difference in Part B scores (p = 0.860). In patients with low and medium HARP scores, clinical features were more predictive of hospital presentations than certain psychosocial or self-management factors in the cohort. Further studies are required to characterise unplanned hospitalisation in patients with higher HARP scores, or whether additional psychosocial assessments could improve the tool's predictability. This article is protected by copyright. All rights reserved.

Locoregional Tumor Extension and Preoperative Smoking are Significant Risk Factors for Early Recurrence After Esophagectomy for Cancer.

PubMed

Mantziari, Styliani; Allemann, Pierre; Winiker, Michael; Demartines, Nicolas; Schäfer, Markus

2018-07-01

Tumor recurrence during the first year after oncological esophagectomy has been reported in up to 17-66% of patients. However, little is known as to the risk factors potentially associated with this adverse outcome. The aim of this retrospective observational study was to identify clinically relevant parameters associated with early recurrence. All patients with squamous cell cancer or adenocarcinoma of the esophagus or gastroesophageal junction, operated with curative intent in our center from 2000 to 2014, were screened for this study. Univariate analysis was conducted to identify variables potentially associated with early recurrence, and clinically relevant parameters with P < 0.1 were included in multiple logistic regression. Survival analyses were conducted with the Kaplan-Meier method. Significance threshold was set at P < 0.05. Among the 164 included patients, 46 (28%) presented early recurrence. Eight patients (17.4%) had locoregional and 38 patients (82.6%) metastatic recurrence. Advanced T and N stages, lymph node capsular effraction, a high positive-to-resected lymph node ratio, positive resection margins, poor response to neoadjuvant treatment, preoperative active smoking, malnutrition and dysphagia were associated with early recurrence on a univariate level. In multivariable analysis, preoperative smoking (OR 2.76, 95% CI 1.28-6.17), pT stage (OR 1.72, 95% CI 1.18-2.58) and an increased positive-to-resected lymph node ratio (OR 6.72, 95% CI 1.08-48.51) remained independently associated with ER. Our study identified both patient- and tumor-related parameters as risk factors for early recurrence after oncological esophagectomy. Of particular interest, active smoking was significantly associated with this adverse outcome, highlighting the importance of preoperative smoking cessation.

Quantifying family dissemination and identifying barriers to communication of risk information in Australian BRCA families.

PubMed

Healey, Emma; Taylor, Natalie; Greening, Sian; Wakefield, Claire E; Warwick, Linda; Williams, Rachel; Tucker, Kathy

2017-12-01

PurposeRecommendations for BRCA1 and BRCA2 mutation carriers to disseminate information to at-risk relatives pose significant challenges. This study aimed to quantify family dissemination, to explain the differences between fully informed families (all relatives informed verbally or in writing) and partially informed families (at least one relative uninformed), and to identify dissemination barriers.MethodsBRCA1 and BRCA2 mutation carriers identified from four Australian hospitals (n=671) were invited to participate in the study. Distress was measured at consent using the Kessler psychological distress scale (K10). A structured telephone interview was used to assess the informed status of relatives, geographical location of relatives, and dissemination barriers. Family dissemination was quantified, and fully versus partially informed family differences were examined. Dissemination barriers were thematically coded and counted.ResultsA total of 165 families participated. Information had been disseminated to 81.1% of relatives. At least one relative had not been informed in 52.7% of families, 4.3% were first-degree relatives, 27.0% were second-degree relatives, and 62.0% were cousins. Partially informed families were significantly larger than fully informed families, had fewer relatives living in close proximity, and exhibited higher levels of distress. The most commonly recorded barrier to dissemination was loss of contact.ConclusionLarger, geographically diverse families have greater difficulty disseminating BRCA mutation risk information to all relatives. Understanding these challenges can inform future initiatives for communication, follow-up and support.

The application of visceral adiposity index in identifying type 2 diabetes risks based on a prospective cohort in China.

PubMed

Chen, Chen; Xu, Yan; Guo, Zhi-rong; Yang, Jie; Wu, Ming; Hu, Xiao-shu

2014-07-08

Visceral adiposity index (VAI), a novel sex-specific index for visceral fat measurement, has been proposed recently. We evaluate the efficacy of VAI in identifying diabetes risk in Chinese people, and compare the predictive ability between VAI and other body fatness indices, i.e., waist circumference (WC), body mass index (BMI) and waist- to- height ratio (WHtR). Participants (n=3,461) were recruited from an ongoing cohort study in Jiangsu Province, China. Hazard ratio (HR) and corresponding 95% confidence interval (CI) between diabetes risk and different body fatness indices were evaluated by Cox proportional hazard regression model. Receiver operating characteristic (ROC) curve and area under curve (AUC) were applied to compare the ability of identifying diabetes risk between VAI, WC, WHtR and BMI. A total number of 160 new diabetic cases occurred during the follow-up, with an incidence of 4.6%. Significant positive associations were observed for VAI with blood pressure, fasting plasma glucose, triglyceride, WC, BMI and WHtR. Moreover, increased VAI was observed to be associated with higher diabetes risk with a positive dose-response trend (p for trend<0.001). As compared to individuals with the lowest VAI, those who had the highest VAI were at 2.55-fold risk of diabetes (95% CI: 1.58-4.11). The largest AUC was observed for VAI, following by WC, WHtR and BMI. VAI is positively associated with the risk of diabetes. Compared to other indices for body fatness measurements, VAI is a better and convenience surrogate marker for visceral adipose measurement and could be used in identifying the risk of diabetes in large-scale epidemiologic studies.

Anterior cruciate ligament injury: Identifying information sources and risk factor awareness among the general population.

PubMed

Nagano, Yasuharu; Yako-Suketomo, Hiroko; Natsui, Hiroaki

2018-01-01

Raising awareness on a disorder is important for its prevention and for promoting public health. However, for sports injuries like the anterior cruciate ligament (ACL) injury no studies have investigated the awareness on risk factors for injury and possible preventative measures in the general population. The sources of information among the population are also unclear. The purpose of the present study was to identify these aspects of public awareness about the ACL injury. A questionnaire was randomly distributed among the general population registered with a web based questionnaire supplier, to recruit 900 participants who were aware about the ACL injury. The questionnaire consisted of two parts: Question 1 asked them about their sources of information regarding the ACL injury; Question 2 asked them about the risk factors for ACL injury. Multivariate logistic regression was used to determine the information sources that provide a good understanding of the risk factors. The leading source of information for ACL injury was television (57.0%). However, the results of logistic regression analysis revealed that television was not an effective medium to create awareness about the risk factors, among the general population. Instead "Lecture by a coach", "Classroom session on Health", and "Newspaper" were significantly more effective in creating a good awareness of the risk factors (p < 0.001).

Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.

PubMed

Orlando, Giulia; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Aaltonen, Lauri A; Houlston, Richard S

2016-06-01

To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10 -8 , odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r 2 = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD. © The Author 2016. Published by Oxford University Press.

Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease

PubMed Central

Orlando, Giulia; Law, Philip J.; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Timothy S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Aaltonen, Lauri A.; Houlston, Richard S.

2016-01-01

To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10−8, odds ratio = 1.10, 95% confidence interval = 1.06–1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D′ = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD. PMID:27005424

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

PubMed

O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2015-10-01

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. © 2015 Society for Endocrinology.

Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients: CoCoNet study.

PubMed

Kim, Su-A; Kim, Jang Young; Park, Jeong Bae

2016-06-01

There has been a rising interest in interarm blood pressure difference (IAD), due to its relationship with peripheral arterial disease and its possible relationship with cardiovascular disease. This study aimed to characterize hypertensive patients with a significant IAD in relation to cardiovascular risk. A total of 3699 patients (mean age, 61 ± 11 years) were prospectively enrolled in the study. Blood pressure (BP) was measured simultaneously in both arms 3 times using an automated cuff-oscillometric device. IAD was defined as the absolute difference in averaged BPs between the left and right arm, and an IAD ≥ 10 mm Hg was considered to be significant. The Framingham risk score was used to calculate the 10-year cardiovascular risk. The mean systolic IAD (sIAD) was 4.3 ± 4.1 mm Hg, and 285 (7.7%) patients showed significant sIAD. Patients with significant sIAD showed larger body mass index (P < 0.001), greater systolic BP (P = 0.050), more coronary artery disease (relative risk = 1.356, P = 0.034), and more cerebrovascular disease (relative risk = 1.521, P = 0.072). The mean 10-year cardiovascular risk was 9.3 ± 7.7%. By multiple regression, sIAD was significantly but weakly correlated with the 10-year cardiovascular risk (β = 0.135, P = 0.008). Patients with significant sIAD showed a higher prevalence of coronary artery disease, as well as an increase in 10-year cardiovascular risk. Therefore, accurate measurements of sIAD may serve as a simple and cost-effective tool for predicting cardiovascular risk in clinical settings.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Precursor Analysis for Flight- and Ground-Based Anomaly Risk Significance Determination

NASA Technical Reports Server (NTRS)

Groen, Frank

2010-01-01

This slide presentation reviews the precursor analysis for flight and ground based anomaly risk significance. It includes information on accident precursor analysis, real models vs. models, and probabilistic analysis.

Identifying Falls Risk Screenings Not Documented with Administrative Codes Using Natural Language Processing

PubMed Central

Zhu, Vivienne J; Walker, Tina D; Warren, Robert W; Jenny, Peggy B; Meystre, Stephane; Lenert, Leslie A

2017-01-01

Quality reporting that relies on coded administrative data alone may not completely and accurately depict providers’ performance. To assess this concern with a test case, we developed and evaluated a natural language processing (NLP) approach to identify falls risk screenings documented in clinical notes of patients without coded falls risk screening data. Extracting information from 1,558 clinical notes (mainly progress notes) from 144 eligible patients, we generated a lexicon of 38 keywords relevant to falls risk screening, 26 terms for pre-negation, and 35 terms for post-negation. The NLP algorithm identified 62 (out of the 144) patients who falls risk screening documented only in clinical notes and not coded. Manual review confirmed 59 patients as true positives and 77 patients as true negatives. Our NLP approach scored 0.92 for precision, 0.95 for recall, and 0.93 for F-measure. These results support the concept of utilizing NLP to enhance healthcare quality reporting. PMID:29854264

Identifying high-risk roadways for infrastructure investment using naturalistic driving data.

DOT National Transportation Integrated Search

2015-08-01

The state-of-the-practice for most municipal traffic agencies seeking to identify high-risk road segments : has been to use prior crash history. While historic traffic crash data is recognized to be valuable in : improving roadway safety, it relies o...

Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors.

PubMed

Rudolph, Anja; Milne, Roger L; Truong, Thérèse; Knight, Julia A; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Munday, Hannah R; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Olson, Janet; Vachon, Celine M; Hallberg, Emily; Castelao, J Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G; Nielsen, Sune F; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G; Broeks, Annegien; Rutgers, Emiel J; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Arias Perez, José Ignacio; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W; Ekici, Arif B; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J; Lissowska, Jolanta; Sherman, Mark E; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G; Brenner, Hermann; Fasching, Peter A; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E; Easton, Doug F; Schmidt, Marjanka K; Guénel, Pascal; Hall, Per; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chang-Claude, Jenny

2015-03-15

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. © 2014 UICC.

Ability of the plasma concentration ratio of triglyceride/high-density lipoprotein cholesterol to identify increased cardio-metabolic risk in an east Asian population.

PubMed

Sung, Ki-Chul; Reaven, Gerald; Kim, Sun

2014-07-01

The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) has identified increased cardio-metabolic risk and outcome in European populations. The goal of this study was to see if this ratio would also have clinical utility in identifying cardio-metabolic risk in an East Asian population. Measurements of various cardio-metabolic risk factors, including coronary calcium scores, were available on 12,166 apparently healthy Korean adults. Approximately 25% of men and women with the highest TG/HDL-C ratios were classified as being at high cardio-metabolic risk, and their risk factor profiles compared to the remainder of the population, as well as to individuals with the metabolic syndrome (MetS). High cardio-metabolic risk (upper 25%) was defined as a TG/HDL-C ratio ≥3.5 (men) or ≥2.0 (women), and all cardio-metabolic risk factors measured, including coronary calcium scores, were significantly more adverse when compared to individuals beneath these cut-points. Although cardio-metabolic risk profiles appeared reasonably comparable in subjects identified by either a high TG/HDL-C or a diagnosis of MetS, use of the TG/HDL-C increased the numbers at high risk. Evidence that determination of the plasma TG/HDL-C concentration ratio provides a simple way to identify individual at increased cardio-metabolic risk has been extended to an East Asian population. The ability of an elevated TG/HDL-C ratio to accomplish this goal is comparable to that achieved using the more complicated MetS criteria. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection.

PubMed

Williams, Kirsten Marie; Agwu, Allison L; Dabb, Alix A; Higman, Meghan A; Loeb, David M; Valsamakis, Alexandra; Chen, Allen R

2009-11-01

Adenoviral infections cause morbidity and mortality in blood and marrow transplantation and pediatric oncology patients. Cidofovir is active against adenovirus, but must be used judiciously because of its nephrotoxicity and unclear indications. Therefore, before introducing cidofovir use during an adenoviral outbreak, we developed a clinical algorithm to distinguish low risk patients from those who merited cidofovir therapy because of significant adenoviral disease and high risk for death. This study was conducted to determine whether the algorithm accurately predicted severe adenovirus disease and whether selective cidofovir treatment was beneficial. A retrospective analysis of a pediatric oncology/blood and marrow transplantation cohort prealgorithm and postalgorithm implementation was performed. Twenty patients with adenovirus infection were identified (14 high risk and 6 low risk). All low-risk patients cleared their infections without treatment. Before algorithm implementation, all untreated high-risk patients died, 4 out of 5 (80%), from adenoviral infection. In contrast, cidofovir reduced adenovirus-related mortality in the high-risk group postalgorithm implementation (9 patients treated, 1 patient died; RR 0.14, P<0.05) and all treated high-risk patients cleared their virus. The clinical algorithm accurately identified patients at high risk for severe fatal adenoviral disease who would benefit from selective use of cidofovir.

Performance of Risk-Based and Birth-Cohort Strategies for Identifying Hepatitis C Virus Infection Among People Entering Prison, Wisconsin, 2014.

PubMed

Stockman, Lauren J; Greer, James; Holzmacher, Ryan; Dittmann, Beth; Hoftiezer, Scott A; Alsum, Lori E; Prieve, Audrey; Westergaard, Ryan P; Guilfoyle, Sheila M; Vergeront, James M

2016-01-01

The prevalence of hepatitis C virus (HCV) infection among young adults is rising in Wisconsin. We examined the prevalence of HCV infection among male and female inmates entering two Wisconsin prisons and evaluated existing and alternate risk-based strategies for identifying HCV infection at intake. We added HCV testing to the intake procedures for all 1,239 adults prison entrants at the Wisconsin Department of Corrections (WDOC) from November 3, 2014, to January 31, 2015. We identified risk factors associated with HCV infection during the routine intake examination and calculated the sensitivity and specificity of risk-based testing strategies for identifying HCV infection. The prevalence of HCV antibody among prison entrants was 12.5% (95% confidence interval [CI] 10.7, 14.4) overall and was almost two times higher at the women's facility (21.3%, 95% CI 15.4, 27.2) than at the men's facility (11.0%, 95% CI 0.0, 12.9) (p<0.001). The sensitivity and specificity of the WDOC risk-based criteria were 88% (95% CI 83, 93) and 80% (95% CI 78, 83), respectively. Adding a new criterion, the 1945-1965 birth cohort, to the risk-based criteria improved the sensitivity to 92% (95% CI 88, 96) and lowered the specificity to 71% (95% CI 68, 74). Compared with entrants without these risk factors, HCV antibody prevalence was significantly higher among prison entrants who had the following risk factors: injection drug use (prevalence ratio [PR] = 9.9, 95% CI 7.4, 13.2), liver disease (PR=9.7, 95% CI 7.8, 12.0), and elevated levels of alanine transaminase (PR=3.6, 95% CI 2.7, 4.9). The WDOC risk criteria for HCV testing identified 88% of HCV infections among prison entrants. Including the 1945-1965 birth cohort as a criterion along with the other WDOC risk criteria increased the sensitivity of targeted testing to 92%. These findings may be informative to jurisdictions where universal HCV testing is not feasible because of resource limitations.

Identifying, Assessing, and Mitigating Risk of Single-Point Inspections on the Space Shuttle Reusable Solid Rocket Motor

NASA Technical Reports Server (NTRS)

Greenhalgh, Phillip O.

2004-01-01

In the production of each Space Shuttle Reusable Solid Rocket Motor (RSRM), over 100,000 inspections are performed. ATK Thiokol Inc. reviewed these inspections to ensure a robust inspection system is maintained. The principal effort within this endeavor was the systematic identification and evaluation of inspections considered to be single-point. Single-point inspections are those accomplished on components, materials, and tooling by only one person, involving no other check. The purpose was to more accurately characterize risk and ultimately address and/or mitigate risk associated with single-point inspections. After the initial review of all inspections and identification/assessment of single-point inspections, review teams applied risk prioritization methodology similar to that used in a Process Failure Modes Effects Analysis to derive a Risk Prioritization Number for each single-point inspection. After the prioritization of risk, all single-point inspection points determined to have significant risk were provided either with risk-mitigating actions or rationale for acceptance. This effort gave confidence to the RSRM program that the correct inspections are being accomplished, that there is appropriate justification for those that remain as single-point inspections, and that risk mitigation was applied to further reduce risk of higher risk single-point inspections. This paper examines the process, results, and lessons learned in identifying, assessing, and mitigating risk associated with single-point inspections accomplished in the production of the Space Shuttle RSRM.

Identifying Students at Risk: An Examination of Computer-Adaptive Measures and Latent Class Growth Analysis

ERIC Educational Resources Information Center

Keller-Margulis, Milena; McQuillin, Samuel D.; Castañeda, Juan Javier; Ochs, Sarah; Jones, John H.

2018-01-01

Multitiered systems of support depend on screening technology to identify students at risk. The purpose of this study was to examine the use of a computer-adaptive test and latent class growth analysis (LCGA) to identify students at risk in reading with focus on the use of this methodology to characterize student performance in screening.…

[Nutritional risk screening and its clinical significance in 706 children hospitalized in the surgical department].

PubMed

Peng, Lu-Ting; Li, Rong; Zhao, Wei-Hua; Chen, Yin-Hua; Li, Xiao-Mei; Chen, Meng-Ying; Cao, Jia; Li, Xiao-Nan

2013-10-01

To investigate nutritional risk and its relationship with clinical outcome in children hospitalized in the surgical department, and to provide a scientific basis for clinical nutrition management. Nutritional risk screening was performed on 706 children hospitalized in the surgical department using the Screening Tool for Risk on Nutritional Status and Growth. The data on nutritional support during hospitalization, incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses were recorded. Of the 706 cases, 11.5% had high nutritional risk, 46.0% had moderate nutritional risk, and 42.5% had low nutritional risk. Congenital hypertrophic pyloric stenosis, intestinal obstruction and congenital heart disease were the three most common types of high nutritional risk. The incidence of high nutritional risk was significantly higher in infants than in other age groups (P<0.01). Fifty-two (64.2%) of the eighty-one children with high nutritional risk received parenteral nutrition. Children with high nutritional risk were significantly more likely to have weight loss than children with low nutritional risk (P<0.05). Children with high nutritional risk had significantly increased incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses compared with those with moderate or low nutritional risk (P<0.01). Moderate or high nutritional risk is seen in children hospitalized in the surgical department. Nutritional risk score is correlated with clinical outcome. Nutritional support for these children is not yet properly provided. Nutritional risk screening and standard nutritional support should be widely applied among hospitalized children.

Diagnostic performance of Body Mass Index, Waist Circumference and the Waist-to-Height Ratio for identifying cardiometabolic risk in Scottish pre-adolescents.

PubMed

Buchan, Duncan S; McLellan, Gillian; Donnelly, Samantha; Arthur, Rosie

2017-06-01

Limited studies have examined the diagnostic performance of body mass index (BMI), waist circumference (WC) or waist-to-height ratio (WHtR) for identifying cardiometabolic risk (increased clustered glucose, triglycerides, mean arterial pressure and inv-HDL-cholesterol) in pre-adolescent youth. To compare the utility of BMI, WC and WHtR as predictors of cardiometabolic risk (CMR) in Scottish pre-adolescent children. A cross-sectional analysis of 223 Scottish children (55.2% boys, mean age =8.4 years) was undertaken. BMI, WC and WHtR were used as exposure variables within multivariate logistic regression analysis and ROC analysis to examine the utility of these anthropometrical indices in identifying those at cardiometabolic risk. Individuals with an elevated WHtR, WC and BMI were 3.51 (95% CI = 1.71-7.23; p < .001); 2.34 (95% CI = 1.35-4.06; p = .002) and 2.59 (95% CI = 1.42-4.73; p = .002) times more likely to be at cardiometabolic risk, respectively. The areas under the curves [AUC] to identify children with cardiometabolic risk were significant and similar among anthropometric indices (AUC's = 0.60-0.65). When stratified by BMI, both WC and WHtR demonstrated a fair-to-good ability for identifying those at cardiometabolic risk (AUC = 0.75-0.81). Findings suggest that the combination of BMI with either WC or WHtR may provide an added benefit in the assessment of cardiometabolic risk amongst pre-adolescents.

A Radio-genomics Approach for Identifying High Risk Estrogen Receptor-positive Breast Cancers on DCE-MRI: Preliminary Results in Predicting OncotypeDX Risk Scores

PubMed Central

Wan, Tao; Bloch, B. Nicolas; Plecha, Donna; Thompson, CheryI L.; Gilmore, Hannah; Jaffe, Carl; Harris, Lyndsay; Madabhushi, Anant

2016-01-01

To identify computer extracted imaging features for estrogen receptor (ER)-positive breast cancers on dynamic contrast en-hanced (DCE)-MRI that are correlated with the low and high OncotypeDX risk categories. We collected 96 ER-positivebreast lesions with low (<18, N = 55) and high (>30, N = 41) OncotypeDX recurrence scores. Each lesion was quantitatively charac-terize via 6 shape features, 3 pharmacokinetics, 4 enhancement kinetics, 4 intensity kinetics, 148 textural kinetics, 5 dynamic histogram of oriented gradient (DHoG), and 6 dynamic local binary pattern (DLBP) features. The extracted features were evaluated by a linear discriminant analysis (LDA) classifier in terms of their ability to distinguish low and high OncotypeDX risk categories. Classification performance was evaluated by area under the receiver operator characteristic curve (Az). The DHoG and DLBP achieved Az values of 0.84 and 0.80, respectively. The 6 top features identified via feature selection were subsequently combined with the LDA classifier to yield an Az of 0.87. The correlation analysis showed that DHoG (ρ = 0.85, P < 0.001) and DLBP (ρ = 0.83, P < 0.01) were significantly associated with the low and high risk classifications from the OncotypeDX assay. Our results indicated that computer extracted texture features of DCE-MRI were highly correlated with the high and low OncotypeDX risk categories for ER-positive cancers. PMID:26887643

A newly identified group of adolescents at "invisible" risk for psychopathology and suicidal behavior: findings from the SEYLE study.

PubMed

Carli, Vladimir; Hoven, Christina W; Wasserman, Camilla; Chiesa, Flaminia; Guffanti, Guia; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Brunner, Romuald; Corcoran, Paul; Cosman, Doina; Haring, Christian; Iosue, Miriam; Kaess, Michael; Kahn, Jean Pierre; Keeley, Helen; Postuvan, Vita; Saiz, Pilar; Varnik, Airi; Wasserman, Danuta

2014-02-01

This study explored the prevalence of risk behaviors (excessive alcohol use, illegal drug use, heavy smoking, reduced sleep, overweight, underweight, sedentary behavior, high use of Internet/TV/videogames for reasons not related to school or work, and truancy), and their association with psychopathology and self-destructive behaviors, in a sample of 12,395 adolescents recruited in randomly selected schools across 11 European countries. Latent class analysis identified three groups of adolescents: a low-risk group (57.8%) including pupils with low or very low frequency of risk behaviors; a high-risk group (13.2%) including pupils who scored high on all risk behaviors, and a third group ("invisible" risk, 29%) including pupils who were positive for high use of Internet/TV/videogames for reasons not related to school or work, sedentary behavior and reduced sleep. Pupils in the "invisible" risk group, compared with the high-risk group, had a similar prevalence of suicidal thoughts (42.2% vs. 44%), anxiety (8% vs. 9.2%), subthreshold depression (33.2% vs. 34%) and depression (13.4% vs. 14.7%). The prevalence of suicide attempts was 5.9% in the "invisible" group, 10.1% in the high-risk group and 1.7% in the low-risk group. The prevalence of all risk behaviors increased with age and most of them were significantly more frequent among boys. Girls were significantly more likely to experience internalizing (emotional) psychiatric symptoms. The "invisible" group may represent an important new intervention target group for potentially reducing psychopathology and other untoward outcomes in adolescence, including suicidal behavior. Copyright © 2014 World Psychiatric Association.

Genome-wide significant association between a sequence variant at 15q15.2 and lung cancer risk

PubMed Central

Rafnar, Thorunn; Sulem, Patrick; Besenbacher, Soren; Gudbjartsson, Daniel F.; Zanon, Carlo; Gudmundsson, Julius; Stacey, Simon N.; Kostic, Jelena P.; Thorgeirsson, Thorgeir E.; Thorleifsson, Gudmar; Bjarnason, Hjordis; Skuladottir, Halla; Gudbjartsson, Tomas; Isaksson, Helgi J.; Isla, Dolores; Murillo, Laura; García-Prats, Maria D.; Panadero, Angeles; Aben, Katja K.H.; Vermeulen, Sita H.; van der Heijden, Henricus F.M.; Feser, William; Miller, York E.; Bunn, Paul A.; Kong, Augustine; Wolf, Holly J.; Franklin, Wilbur A.; Mayordomo, Jose I; Kiemeney, Lambertus A.; Jonsson, Steinn; Thorsteinsdottir, Unnur; Stefansson, Kari

2010-01-01

Genome-wide association studies (GWAS) have identified three genomic regions, at 15q24-25.1, 5p15.33 and 6p21.33, which associate with risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P<10−5) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, three correlated variants on 15q15.2 (rs504417, rs11853991 and rs748404) showed a significant association with lung cancer whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31 and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain and the USA and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR=1.15, P=1.1×10−9). Another variant at the same locus, rs12050604, showed association with lung cancer (OR=1.09, 3.6×10−6) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, non-synonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D), showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that one or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2. PMID:21303977

The Readmission Risk Flag: Using the Electronic Health Record to Automatically Identify Patients at Risk for 30-day Readmission

PubMed Central

Baillie, Charles A.; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C. William; Behta, Maryam; Umscheid, Craig A.

2015-01-01

Background Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. Objective To develop and implement an automated prediction model integrated into our health system’s EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Design Retrospective and prospective cohort. Setting Healthcare system consisting of three hospitals. Patients All adult patients admitted from August 2009 to September 2012. Interventions An automated readmission risk flag integrated into the EHR. Measures Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Results Using retrospective data, a single risk factor, ≥2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a c-statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%) and c-statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. Conclusions An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. PMID:24227707

The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission.

PubMed

Baillie, Charles A; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C William; Behta, Maryam; Umscheid, Craig A

2013-12-01

Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Retrospective and prospective cohort. Healthcare system consisting of 3 hospitals. All adult patients admitted from August 2009 to September 2012. An automated readmission risk flag integrated into the EHR. Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Using retrospective data, a single risk factor, ≥ 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. © 2013 Society of Hospital Medicine.

A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

PubMed

Clark, Renee M; Besterfield-Sacre, Mary E

2009-03-01

We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

Identifying high-risk small business industries for occupational safety and health interventions.

PubMed

Okun, A; Lentz, T J; Schulte, P; Stayner, L

2001-03-01

Approximately one-third (32%) of U.S. workers are employed in small business industries (those with 80% of workers in establishments with fewer than 100 employees), and approximately 53 million persons in private industry work in small business establishments. This study was performed to identify small business industries at high risk for occupational injuries, illnesses, and fatalities. Small business industries were identified from among all three- and four-digit Standard Industrial Classification (SIC) codes and ranked using Bureau of Labor Statistics (BLS) data by rates and numbers of occupational injuries, illnesses, and fatalities. Both incidence rates and number of injury, illness, and fatality cases were evaluated. The 253 small business industries identified accounted for 1,568 work-related fatalities (34% of all private industry). Transportation incidents and violent acts were the leading causes of these fatalities. Detailed injury and illness data were available for 105 small business industries, that accounted for 1,476,400 work-related injuries, and 55,850 occupational illnesses. Many of the small business industries had morbidity and mortality rates exceeding the average rates for all private industry. The highest risk small business industries, based on a combined morbidity and mortality index, included logging, cut stone and stone products, truck terminals, and roofing, siding, and sheet metal work. Identification of high-risk small business industries indicates priorities for those interested in developing targeted prevention programs.

GWAS-identified schizophrenia risk SNPs at TSPAN18 are highly diverged between Europeans and East Asians.

PubMed

Liu, Jiewei; Li, Ming; Su, Bing

2016-12-01

Genome-wide association studies (GWASs) have identified multiple schizophrenia (SCZ) risk variants for samples of European and East Asian descent, but most of the identified susceptibility variants are population-specific to either Europeans or East Asians. This strong genetic heterogeneity suggests that differential population histories may play a role in SCZ susceptibility. Here, we explored this possibility by examining the allele frequency divergence of 136 previously reported genome-wide SCZ risk SNPs between European and East Asian populations. Our results showed that two SNPs (rs11038167 and rs11038172) at TSPAN18, reported as genome-wide significant SCZ risk variants in Han Chinese, were entirely monomorphic in Europeans, indicating a deep between-population divergence at this gene locus. To explore the evolutionary history of TSPAN18 in East Asians, we conducted population genetic analyses including multiple neutrality tests, the haplotype-based iHS and EHH tests, as well as haplotype bifurcation map and network constructions. We found that the protective allele of rs11038172 (G allele) had a long extended haplotype with much slower decay compared to the A allele. The star-like shape of the G-allele-carrying haplotypes indicates a recent enrichment in East Asians. Together, the evidences suggest that the protective allele of rs11038172 has experienced recent Darwinian positive selection in East Asians. These findings provide new insights that may help explain the strong genetic heterogeneity in SCZ risk and previous inconsistent association results for SCZ among both Europeans and East Asians. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Using a single binge drinking question to identify Russian women at risk for an alcohol-exposed pregnancy.

PubMed

Balachova, Tatiana; Sobell, Linda Carter; Agrawal, Sangeeta; Isurina, Galina; Tsvetkova, Larissa; Volkova, Elena; Bohora, Som

2015-07-01

Low rates of contraception and at-risk drinking place many Russian women at risk of an alcohol-exposed pregnancy (AEP). The only realistic way to determine when women are at risk of AEP is by self-reports. A U.S. study found that a single binge-drinking question (SBD) effectively identified nearly all women whose drinking placed them at risk of AEP. The present study replicated the U.S. Participants were 689 non-pregnant Russian women of childbearing age who were at AEP risk. Their answers to SBD, "During the previous three months, how often did you have four or more drinks on one occasion", were compared with their reports of binge drinking on a 90-day Timeline Followback (TLFB) calendar. The SBD identified 99% of at-risk Russian women as binge drinkers, replicating U.S. Only 8% of the women were identified at-risk using a second AEP criterion of ≥8 drinks on average per week. Although Russian women did not report heavy weekly drinking and two-thirds did not meet AUDIT criteria for problem drinking, when they did drink, 40% of the time it was binge drinking. Almost all Russian women who were at risk of an AEP were identified by a single binge-drinking question. Results from this study suggest that Russian health care practitioners can use SBD to successfully screen women for AEP risk. SBD identified 99% of Russian women who were at AEP risk. Consequently, it is recommended that SBD be incorporated into routine health care screenings at OB/GYN clinic visits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer.

PubMed

Washington, Samuel L; Bonham, Michael; Whitson, Jared M; Cowan, Janet E; Carroll, Peter R

2012-07-01

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS-guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole-gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade. To evaluate the ability of transrectal ultrasonography (TRUS)-guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer. Patients with early stage, low-risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified. Re-review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV). Pathology findings were then compared with biopsy results. A total of 51 men with early stage, low-risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading. Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies. Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5-0.6) of specimens and the highest grade in 37% (95 CI 0.3-0.5). No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease.

PubMed

Kuo, Ho-Chang; Wong, Henry Sung-Ching; Chang, Wei-Pin; Chen, Ben-Kuen; Wu, Mei-Shin; Yang, Kuender D; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei-Chiao

2017-10-01

Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively). This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG. © 2017 The Authors.

Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin

PubMed Central

Forrest, Elizabeth Ann; Reiling, Janske; Lipka, Geraldine; Fawcett, Jonathan

2017-01-01

AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland. METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system. In addition, intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures. RESULTS Of 296 liver transplants performed, 285 (96.3%) were from brain dead donors. Biliary strictures developed in 45 (15.2%) recipients. Anastomotic stricture formation (n = 25, 48.1%) was the commonest complication, with 14 (58.3%) of these occurred within 6-mo of transplant. A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17 (37.8%) patients with biliary strictures. Biliary reconstruction was initially or ultimately required in 22 (48.9%) patients. In recipients developing biliary strictures, bilirubin was significantly increased within the first post-operative week (Day 7 total bilirubin 74 μmol/L vs 49 μmol/L, P = 0.012). In both univariate and multivariate regression analysis, Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation. In addition, hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors. CONCLUSION In addition to known risk factors, bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation. PMID:29312864

Risk Prioritization Tool to Identify the Public Health Risks of Wildlife Trade: The Case of Rodents from Latin America.

PubMed

Bueno, I; Smith, K M; Sampedro, F; Machalaba, C C; Karesh, W B; Travis, D A

2016-06-01

Wildlife trade (both formal and informal) is a potential driver of disease introduction and emergence. Legislative proposals aim to prevent these risks by banning wildlife imports, and creating 'white lists' of species that are cleared for importation. These approaches pose economic harm to the pet industry, and place substantial burden on importers and/or federal agencies to provide proof of low risk for importation of individual species. As a feasibility study, a risk prioritization tool was developed to rank the pathogens found in rodent species imported from Latin America into the United States with the highest risk of zoonotic consequence in the United States. Four formally traded species and 16 zoonotic pathogens were identified. Risk scores were based on the likelihood of pathogen release and human exposure, and the severity of the disease (consequences). Based on the methodology applied, three pathogens (Mycobacterium microti, Giardia spp. and Francisella tularensis) in one species (Cavia porcellus) were ranked as highest concern. The goal of this study was to present a methodological approach by which preliminary management resources can be allocated to the identified high-concern pathogen-species combinations when warranted. This tool can be expanded to other taxa and geographic locations to inform policy surrounding the wildlife trade. © 2015 Blackwell Verlag GmbH.

Head multidetector computed tomography: emergency medicine physicians overestimate the pretest probability and legal risk of significant findings.

PubMed

Baskerville, Jerry Ray; Herrick, John

2012-02-01

This study focuses on clinically assigned prospective estimated pretest probability and pretest perception of legal risk as independent variables in the ordering of multidetector computed tomographic (MDCT) head scans. Our primary aim is to measure the association between pretest probability of a significant finding and pretest perception of legal risk. Secondarily, we measure the percentage of MDCT scans that physicians would not order if there was no legal risk. This study is a prospective, cross-sectional, descriptive analysis of patients 18 years and older for whom emergency medicine physicians ordered a head MDCT. We collected a sample of 138 patients subjected to head MDCT scans. The prevalence of a significant finding in our population was 6%, yet the pretest probability expectation of a significant finding was 33%. The legal risk presumed was even more dramatic at 54%. These data support the hypothesis that physicians presume the legal risk to be significantly higher than the risk of a significant finding. A total of 21% or 15% patients (95% confidence interval, ±5.9%) would not have been subjected to MDCT if there was no legal risk. Physicians overestimated the probability that the computed tomographic scan would yield a significant result and indicated an even greater perceived medicolegal risk if the scan was not obtained. Physician test-ordering behavior is complex, and our study queries pertinent aspects of MDCT testing. The magnification of legal risk vs the pretest probability of a significant finding is demonstrated. Physicians significantly overestimated pretest probability of a significant finding on head MDCT scans and presumed legal risk. Copyright © 2012 Elsevier Inc. All rights reserved.

Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

PubMed

Eltabbakh, G H; Lipman, J N; Mount, S L; Morgan, A

2000-10-01

The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P < 0.05 was considered significant. One hundred twenty-six patients with ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS

Work Ability Index as tool to identify workers at risk of premature work exit.

PubMed

Roelen, Corné A M; Heymans, Martijn W; Twisk, Jos W R; van der Klink, Jac J L; Groothoff, Johan W; van Rhenen, Willem

2014-12-01

To investigate the Work Ability Index (WAI) as tool for identifying workers at risk of premature work exit in terms of disability pension, unemployment, or early retirement. Prospective cohort study of 11,537 male construction workers (mean age 45.5 years), who completed the WAI at baseline and reported their work status (employed, unemployed, disability pension, or retired) after mean 2.3 years of follow-up. Associations between WAI scores and work status were investigated by multinomial logistic regression analysis. The ability of the WAI to discriminate between workers at high and low risk of premature work exit was analyzed by the area (AUC) under the receiver operating characteristic curve. 9,530 (83 %) construction workers had complete data for analysis. At follow-up, 336 (4 %) workers reported disability pension, 125 (1 %) unemployment, and 255 (3 %) retirement. WAI scores were prospectively associated with the risk of disability pension at follow-up, but not with the risk of unemployment and early retirement. The WAI showed fair discrimination to identify workers at risk of disability pension [AUC = 0.74; 95 % confidence interval (CI) 0.70-0.77]. The discriminative ability decreased with age from AUC = 0.78 in workers aged 30-39 years to AUC = 0.69 in workers ≥50 years of age. Discrimination failed for unemployment (AUC = 0.51; 95 % CI 0.47-0.55) and early retirement (AUC = 0.58; 95 % CI 0.53-0.61). The WAI can be used to identify construction workers <50 years of age at increased risk of disability pension and invite them for preventive interventions.

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

PubMed

Do, Ron; Stitziel, Nathan O; Won, Hong-Hee; Jørgensen, Anders Berg; Duga, Stefano; Angelica Merlini, Pier; Kiezun, Adam; Farrall, Martin; Goel, Anuj; Zuk, Or; Guella, Illaria; Asselta, Rosanna; Lange, Leslie A; Peloso, Gina M; Auer, Paul L; Girelli, Domenico; Martinelli, Nicola; Farlow, Deborah N; DePristo, Mark A; Roberts, Robert; Stewart, Alexander F R; Saleheen, Danish; Danesh, John; Epstein, Stephen E; Sivapalaratnam, Suthesh; Hovingh, G Kees; Kastelein, John J; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; Shah, Svati H; Kraus, William E; Davies, Robert; Nikpay, Majid; Johansen, Christopher T; Wang, Jian; Hegele, Robert A; Hechter, Eliana; Marz, Winfried; Kleber, Marcus E; Huang, Jie; Johnson, Andrew D; Li, Mingyao; Burke, Greg L; Gross, Myron; Liu, Yongmei; Assimes, Themistocles L; Heiss, Gerardo; Lange, Ethan M; Folsom, Aaron R; Taylor, Herman A; Olivieri, Oliviero; Hamsten, Anders; Clarke, Robert; Reilly, Dermot F; Yin, Wu; Rivas, Manuel A; Donnelly, Peter; Rossouw, Jacques E; Psaty, Bruce M; Herrington, David M; Wilson, James G; Rich, Stephen S; Bamshad, Michael J; Tracy, Russell P; Cupples, L Adrienne; Rader, Daniel J; Reilly, Muredach P; Spertus, John A; Cresci, Sharon; Hartiala, Jaana; Tang, W H Wilson; Hazen, Stanley L; Allayee, Hooman; Reiner, Alex P; Carlson, Christopher S; Kooperberg, Charles; Jackson, Rebecca D; Boerwinkle, Eric; Lander, Eric S; Schwartz, Stephen M; Siscovick, David S; McPherson, Ruth; Tybjaerg-Hansen, Anne; Abecasis, Goncalo R; Watkins, Hugh; Nickerson, Deborah A; Ardissino, Diego; Sunyaev, Shamil R; O'Donnell, Christopher J; Altshuler, David; Gabriel, Stacey; Kathiresan, Sekar

2015-02-05

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

Developing a Model for Identifying Students at Risk of Failure in a First Year Accounting Unit

ERIC Educational Resources Information Center

Smith, Malcolm; Therry, Len; Whale, Jacqui

2012-01-01

This paper reports on the process involved in attempting to build a predictive model capable of identifying students at risk of failure in a first year accounting unit in an Australian university. Identifying attributes that contribute to students being at risk can lead to the development of appropriate intervention strategies and support…

Developing an online tool for identifying at-risk populations to wildfire smoke hazards.

PubMed

Vaidyanathan, Ambarish; Yip, Fuyuen; Garbe, Paul

2018-04-01

Wildfire episodes pose a significant public health threat in the United States. Adverse health impacts associated with wildfires occur near the burn area as well as in places far downwind due to wildfire smoke exposures. Health effects associated with exposure to particulate matter arising from wildfires can range from mild eye and respiratory tract irritation to more serious outcomes such as asthma exacerbation, bronchitis, and decreased lung function. Real-time operational forecasts of wildfire smoke concentrations are available but they are not readily integrated with information on vulnerable populations necessary to identify at-risk communities during wildfire smoke episodes. Efforts are currently underway at the Centers for Disease Control and Prevention (CDC) to develop an online tool that utilizes short-term predictions and forecasts of smoke concentrations and integrates them with measures of population-level vulnerability for identifying at-risk populations to wildfire smoke hazards. The tool will be operationalized on a national scale, seeking input and assistance from several academic, federal, state, local, Tribal, and Territorial partners. The final product will then be incorporated into CDC's National Environmental Public Health Tracking Network (http://ephtracking.cdc.gov), providing users with access to a suite of mapping and display functionalities. A real-time vulnerability assessment tool incorporating standardized health and exposure datasets, and prevention guidelines related to wildfire smoke hazards is currently unavailable for public health practitioners and emergency responders. This tool could strengthen existing situational awareness competencies, and expedite future response and recovery efforts during wildfire episodes. Published by Elsevier B.V.

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

PubMed

Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

2016-01-01

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

CURB-65 Score is Equal to NEWS for Identifying Mortality Risk of Pneumonia Patients: An Observational Study.

PubMed

Brabrand, Mikkel; Henriksen, Daniel Pilsgaard

2018-06-01

The CURB-65 score is widely implemented as a prediction tool for identifying patients with community-acquired pneumonia (cap) at increased risk of 30-day mortality. However, since most ingredients of CURB-65 are used as general prediction tools, it is likely that other prediction tools, e.g. the British National Early Warning Score (NEWS), could be as good as CURB-65 at predicting the fate of CAP patients. To determine whether NEWS is better than CURB-65 at predicting 30-day mortality of CAP patients. This was a single-centre, 6-month observational study using patients' vital signs and demographic information registered upon admission, survival status extracted from the Danish Civil Registration System after discharge and blood test results extracted from a local database. The study was conducted in the medical admission unit (MAU) at the Hospital of South West Jutland, a regional teaching hospital in Denmark. The participants consisted of 570 CAP patients, 291 female and 279 male, median age 74 (20-102) years. The CURB-65 score had a discriminatory power of 0.728 (0.667-0.789) and NEWS 0.710 (0.645-0.775), both with good calibration and no statistical significant difference. CURB-65 was not demonstrated to be significantly statistically better than NEWS at identifying CAP patients at risk of 30-day mortality.

Obstetric care providers are able to assess psychosocial risks, identify and refer high-risk pregnant women: validation of a short assessment tool - the KINDEX Greek version.

PubMed

Spyridou, Andria; Schauer, Maggie; Ruf-Leuschner, Martina

2015-02-21

Prenatal assessment for psychosocial risk factors and prevention and intervention is scarce and, in most cases, nonexistent in obstetrical care. In this study we aimed to evaluate if the KINDEX, a short instrument developed in Germany, is a useful tool in the hands of non-trained medical staff, in order to identify and refer women in psychosocial risk to the adequate mental health and social services. We also examined the criterion-related concurrent validity of the tool through a validation interview carried out by an expert clinical psychologist. Our final objective was to achieve the cultural adaptation of the KINDEX Greek Version and to offer a valid tool for the psychosocial risk assessment to the obstetric care providers. Two obstetricians and five midwives carried out 93 KINDEX interviews (duration 20 minutes) with pregnant women to assess psychosocial risk factors present during pregnancy. Afterwards they referred women who they identified having two or more psychosocial risk factors to the mental health attention unit of the hospital. During the validation procedure an expert clinical psychologist carried out diagnostic interviews with a randomized subsample of 50 pregnant women based on established diagnostic instruments for stress and psychopathology, like the PSS-14, ESI, PDS, HSCL-25. Significant correlations between the results obtained through the assessment using the KINDEX and the risk areas of stress, psychopathology and trauma load assessed in the validation interview demonstrate the criterion-related concurrent validity of the KINDEX. The referral accuracy of the medical staff is confirmed through comparisons between pregnant women who have and have not been referred to the mental health attention unit. Prenatal screenings for psychosocial risks like the KINDEX are feasible in public health settings in Greece. In addition, validity was confirmed in high correlations between the KINDEX results and the results of the validation interviews. The

Clinically Significant Pocket Hematoma Increases Long-Term Risk of Device Infection: BRUISE CONTROL INFECTION Study.

PubMed

Essebag, Vidal; Verma, Atul; Healey, Jeff S; Krahn, Andrew D; Kalfon, Eli; Coutu, Benoit; Ayala-Paredes, Felix; Tang, Anthony S; Sapp, John; Sturmer, Marcio; Keren, Arieh; Wells, George A; Birnie, David H

2016-03-22

The BRUISE CONTROL trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial) demonstrated that a strategy of continued warfarin during cardiac implantable electronic device surgery was safe and reduced the incidence of clinically significant pocket hematoma (CSH). CSH was defined as a post-procedure hematoma requiring further surgery and/or resulting in prolongation of hospitalization of at least 24 h, and/or requiring interruption of anticoagulation. Previous studies have inconsistently associated hematoma with the subsequent development of device infection; reasons include the retrospective nature of many studies, lack of endpoint adjudication, and differing subjective definitions of hematoma. The BRUISE CONTROL INFECTION (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial Extended Follow-Up for Infection) prospectively examined the association between CSH and subsequent device infection. The study included 659 patients with a primary outcome of device-related infection requiring hospitalization, defined as 1 or more of the following: pocket infection; endocarditis; and bloodstream infection. Outcomes were verified by a blinded adjudication committee. Multivariable analysis was performed to identify predictors of infection. The overall 1-year device-related infection rate was 2.4% (16 of 659). Infection occurred in 11% of patients (7 of 66) with previous CSH and in 1.5% (9 of 593) without CSH. CSH was the only independent predictor and was associated with a >7-fold increased risk of infection (hazard ratio: 7.7; 95% confidence interval: 2.9 to 20.5; p < 0.0001). Empiric antibiotics upon development of hematoma did not reduce long-term infection risk. CSH is associated with a significantly increased risk of infection requiring hospitalization within 1 year following cardiac implantable electronic device surgery. Strategies aimed at reducing hematomas may decrease the long-term risk of infection. (Bridge or Continue

Identifying areas at risk of low birth weight using spatial epidemiology: A small area surveillance study.

PubMed

Insaf, Tabassum Z; Talbot, Thomas

2016-07-01

To assess the geographic distribution of Low Birth Weight (LBW) in New York State among singleton births using a spatial regression approach in order to identify priority areas for public health actions. LBW was defined as birth weight less than 2500g. Geocoded data from 562,586 birth certificates in New York State (years 2008-2012) were merged with 2010 census data at the tract level. To provide stable estimates and maintain confidentiality, data were aggregated to yield 1268 areas of analysis. LBW prevalence among singleton births was related with area-level behavioral, socioeconomic and demographic characteristics using a Poisson mixed effects spatial error regression model. Observed low birth weight showed statistically significant auto-correlation in our study area (Moran's I 0.16 p value 0.0005). After over-dispersion correction and accounting for fixed effects for selected social determinants, spatial autocorrelation was fully accounted for (Moran's I-0.007 p value 0.241). The proportion of LBW was higher in areas with larger Hispanic or Black populations and high smoking prevalence. Smoothed maps with predicted prevalence were developed to identify areas at high risk of LBW. Spatial patterns of residual variation were analyzed to identify unique risk factors. Neighborhood racial composition contributes to disparities in LBW prevalence beyond differences in behavioral and socioeconomic factors. Small-area analyses of LBW can identify areas for targeted interventions and display unique local patterns that should be accounted for in prevention strategies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Nursing Home Pneumonia Risk Index: A Simple, Valid MDS-Based Method of Identifying 6-Month Risk for Pneumonia and Mortality.

PubMed

Sloane, Philip D; Zimmerman, Sheryl; Ward, Kimberly; Reed, David; Preisser, John S; Weber, David J

2017-09-01

Pneumonia is the leading infectious cause of hospitalization and death for nursing home (NH) residents; however, diagnosis is often delayed because classic signs of infection are not present. We sought to identify NH residents at high risk for pneumonia, to identify persons to target for more intensive surveillance and preventive measures. Based on a literature review, we identified key risk factors for pneumonia and compiled them for use as prediction tool, limiting risk factors to those available on the Minimum Data Set (MDS). Next, we tested the tool's ability to predict 6-month pneumonia incidence and mortality rates in a sample of 674 residents from 7 NHs, evaluating it both as a continuous and a dichotomous variable, and applying both logistic regression and survival analysis to calculate estimates. NH Pneumonia Risk Index scores ranged from -1 to 6, with a mean of 2.1, a median of 2, and a mode of 2. For the outcome of pneumonia, a 1-point increase in the index was associated with a risk odds ratio of 1.26 (P = .038) or a hazard ratio of 1.24 (P = .037); using it as a dichotomous variable (≤2 vs ≥3), the corresponding figures were a risk odds ratio of 1.78 (P = .045) and a hazard ratio of 1.82 (P = .025). For the outcome of mortality, a 1-point increase in the NH Pneumonia Risk Index was associated with a risk odds ratio of 1.58 (P = .002) and a hazard ratio of 1.45 (P = .013); using the index as a dichotomous variable, the corresponding figures were a risk odds ratio of 3.71 (P < .001) and a hazard ratio of 3.29 (P = .001). The NH Pneumonia Risk Index can be used by NH staff to identify residents for whom to apply especially intensive preventive measures and surveillance. Because of its strong association with mortality, the index may also be valuable in care planning and discussion of advance directives. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Identifying depression severity risk factors in persons with traumatic spinal cord injury.

PubMed

Williams, Ryan T; Wilson, Catherine S; Heinemann, Allen W; Lazowski, Linda E; Fann, Jesse R; Bombardier, Charles H

2014-02-01

Examine the relationship between demographic characteristics, health-, and injury-related characteristics, and substance misuse across multiple levels of depression severity. 204 persons with traumatic spinal cord injury (SCI) volunteered as part of screening efforts for a randomized controlled trial of venlafaxine extended release for major depressive disorder (MDD). Instruments included the Patient Health Questionnaire-9 (PHQ-9) depression scale, the Alcohol Use Disorders Identification Test (AUDIT), and the Substance Abuse in Vocational Rehabilitation-Screener (SAVR-S), which contains 3 subscales: drug misuse, alcohol misuse, and a subtle items scale. Each of the SAVR-S subscales contributes to an overall substance use disorder (SUD) outcome. Three proportional odds models were specified, varying the substance misuse measure included in each model. 44% individuals had no depression symptoms, 31% had mild symptoms, 16% had moderate symptoms, 6% had moderately severe symptoms, and 3% had severe depression symptoms. Alcohol misuse, as indicated by the AUDIT and the SAVR-S drug misuse subscale scores were significant predictors of depression symptom severity. The SAVR-S substance use disorder (SUD) screening outcome was the most predictive variable. Level of education was only significantly predictive of depression severity in the model using the AUDIT alcohol misuse indicator. Likely SUD as measured by the SAVR-S was most predictive of depression symptom severity in this sample of persons with traumatic SCI. Drug and alcohol screening are important for identifying individuals at risk for depression, but screening for both may be optimal. Further research is needed on risk and protective factors for depression, including psychosocial characteristics. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms.

PubMed

Fan, Jin; Sun, Wen; Lin, Min; Yu, Ke; Wang, Jian; Duan, Dan; Zheng, Bo; Yang, Zhenghui; Wang, Qingsong

2016-03-29

Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case- control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16-1.57; Ptrend = 1.18 × 10-4). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02-1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24-2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P < 0.01). Our data suggests that the deletion genotypes of CNV-67048 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese.

A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study

PubMed Central

Carli, Vladimir; Hoven, Christina W; Wasserman, Camilla; Chiesa, Flaminia; Guffanti, Guia; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Brunner, Romuald; Corcoran, Paul; Cosman, Doina; Haring, Christian; Iosue, Miriam; Kaess, Michael; Kahn, Jean Pierre; Keeley, Helen; Postuvan, Vita; Saiz, Pilar; Varnik, Airi; Wasserman, Danuta

2014-01-01

This study explored the prevalence of risk behaviors (excessive alcohol use, illegal drug use, heavy smoking, reduced sleep, overweight, underweight, sedentary behavior, high use of Internet/TV/videogames for reasons not related to school or work, and truancy), and their association with psychopathology and self-destructive behaviors, in a sample of 12,395 adolescents recruited in randomly selected schools across 11 European countries. Latent class analysis identified three groups of adolescents: a low-risk group (57.8%) including pupils with low or very low frequency of risk behaviors; a high-risk group (13.2%) including pupils who scored high on all risk behaviors, and a third group (“invisible” risk, 29%) including pupils who were positive for high use of Internet/TV/videogames for reasons not related to school or work, sedentary behavior and reduced sleep. Pupils in the “invisible” risk group, compared with the high-risk group, had a similar prevalence of suicidal thoughts (42.2% vs. 44%), anxiety (8% vs. 9.2%), subthreshold depression (33.2% vs. 34%) and depression (13.4% vs. 14.7%). The prevalence of suicide attempts was 5.9% in the “invisible” group, 10.1% in the high-risk group and 1.7% in the low-risk group. The prevalence of all risk behaviors increased with age and most of them were significantly more frequent among boys. Girls were significantly more likely to experience internalizing (emotional) psychiatric symptoms. The “invisible” group may represent an important new intervention target group for potentially reducing psychopathology and other untoward outcomes in adolescence, including suicidal behavior. PMID:24497256

Using the Care Dependency Scale for identifying patients at risk for pressure ulcer.

PubMed

Dijkstra, Ate; Kazimier, Hetty; Halfens, Ruud J G

2015-11-01

The aim of this study was to evaluate risk screening for pressure ulcer by using the Care Dependency Scale (CDS) for patients receiving home care or admitted to a residential or nursing home in the Netherlands. Pressure ulcer is a serious and persistent problem for patients throughout the Western world. Pressure ulcer is among the most common adverse events in nursing practice and when a pressure ulcer occurs it has many consequences for patients and healthcare professionals. Cross-sectional design. The convenience sample consisted of 13,633 study participants, of whom 2639 received home care from 15 organisations, 4077 were patients from 67 residential homes and 6917 were admitted in 105 nursing homes. Data were taken from the Dutch National Prevalence Survey of Care Problems that was carried out in April 2012 in Dutch healthcare settings. For the three settings, cut-off points above 80% sensitivity were established, while in the residential home sample an almost 60% combined specificity score was identified. The CDS items 'Body posture' (home care), 'Getting dressed and undressed' (residential homes) and 'Mobility' (nursing homes) were the most significant variables which affect PU. The CDS is able to distinguish between patients at risk for pressure ulcer development and those not at risk in both home care and residential care settings. In nursing homes, the usefulness of the CDS for pressure ulcer detection is limited. © 2015 John Wiley & Sons Ltd.

Determining significant endpoints for ecological risk analyses. 1997 annual progress report

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

Hinton, T.G.; Congdon, J.; Rowe, C.

1997-11-01

'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses thatmore » reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'« less

TAGCNA: A Method to Identify Significant Consensus Events of Copy Number Alterations in Cancer

PubMed Central

Yuan, Xiguo; Zhang, Junying; Yang, Liying; Zhang, Shengli; Chen, Baodi; Geng, Yaojun; Wang, Yue

2012-01-01

Somatic copy number alteration (CNA) is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs) from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4) and tumor suppressor genes (e.g. CDKN2A, CDKN2B), and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/. PMID:22815924

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

PubMed

Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah E; Collins, Ann L; Crowley, James J; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K E; Sanchez, Nick; Stahl, Eli A; Williams, Stephanie; Wray, Naomi R; Xia, Kai; Bettella, Francesco; Borglum, Anders D; Bulik-Sullivan, Brendan K; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L; Holmans, Peter; Hougaard, David M; Kendler, Kenneth S; Lin, Kuang; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; O'Neill, Francis A; Owen, Michael J; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L; Riley, Brien P; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T; Levinson, Douglas F; Gejman, Pablo V; Kendler, Kenneth S; Laurent, Claudine; Mowry, Bryan J; O'Donovan, Michael C; Owen, Michael J; Pulver, Ann E; Riley, Brien P; Schwab, Sibylle G; Wildenauer, Dieter B; Dudbridge, Frank; Holmans, Peter; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A; Nestadt, Gerald; Norton, Nadine; O'Neill, Francis A; Papadimitriou, George N; Ribble, Robert; Sanders, Alan R; Silverman, Jeremy M; Walsh, Dermot; Williams, Nigel M; Wormley, Brandon; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M; Lin, Kuang; Linszen, Don H; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M; Ophoff, Roel A; Powell, John; Rujescu, Dan; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden P; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Spencer, Chris C A; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T; Liddle, Jennifer; Potter, Simon C; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G; Blackwell, Jenefer M; Brown, Matthew A; Corvin, Aiden P; McCarthy, Mark I; Spencer, Chris C A; Bramon, Elvira; Corvin, Aiden P; O'Donovan, Michael C; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A; Sklar, Pamela; Hultman, Christina M; Sullivan, Patrick F

2013-10-01

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

The contribution of recently identified adult BMI risk loci to paediatric obesity in a Singaporean Chinese childhood dataset.

PubMed

Dorajoo, R; Ong, R T-H; Sim, X; Wang, L; Liu, W; Tai, E S; Liu, J; Saw, S-M

2017-12-01

Recent genome-wide association studies have identified 103 adult obesity risk loci; however, it is unclear if these findings are relevant to East-Asian childhood body mass index (BMI) levels. We evaluated for paediatric obesity associations at these risk loci utilizing genome-wide data from Chinese childhood subjects in the Singapore Cohort study Of the Risk factors for Myopia study (N = 1006). A weighted gene-risk score of all adult obesity risk loci in the Singapore Cohort study Of the Risk factors for Myopia study showed strong associations with BMI at age 9 (p-value = 3.40 × 10 -12 ) and 4-year average BMI (age 9 to 12, p-value = 6.67 × 10 -8 ). Directionally consistent nominal associations for 15 index single nucleotide polymorphisms (SNPs) (p-value < 0.05) were observed. Pathway analysis with genes from these 15 replicating loci revealed over-representation for the G-protein-coupled receptor (GPCR)-mediated integration of entero-endocrine signalling pathway exemplified by L-cell (adjusted p-value = 0.018). Evaluations of birth weight to modify the effects of BMI risk SNPs in paediatric obesity did not reveal significant interactions, and these SNPs were generally not associated with birth weight. At least some common adult BMI risk variants predispose to paediatric obesity risk in East-Asians. © 2016 World Obesity Federation.

Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

PubMed Central

van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry TC; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Bo, Roberto Del; Comi, Giacomo P; D’Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc’h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

2017-01-01

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk. PMID:27455348

HIV risks among gay- and non-gay-identified migrant money boys in Shanghai, China.

PubMed

Wong, F Y; Huang, Z J; He, N; Smith, B D; Ding, Y; Fu, C; Young, D

2008-02-01

Men having sex with men (MSM) now account for 7% of all HIV/AIDS cases in China and there is growing awareness that internal rural-to-urban migration might shift the HIV epidemic within China by broadening social and sexual mixing. About 70% of HIV/AIDS infections are among rural residents, of whom 80% are males and 60% aged 16-29. This young, male, rural-to-urban migrant population has been identified as the 'tipping point' for the AIDS epidemic in China. A subgroup of these migrants is the 'money boy' population, i.e. those who engage in same-sex transactional sex for economic survival. However, the literature addressing money boys is very limited. The present study aims to elucidate factors for preventing substance abuse and HIV among two types of money boys 'gay-identified' and 'non-gay-identified' living in the Shanghai metropolitan area. This work is conceptually underpinned by Chng et al.'s (2003) tripartite model, which postulates that risk behaviors (e.g. substance abuse) engaged in by transient or non-native individuals are often shaped and regulated by factors in the home environment, migration experience and current environment. Results reveal gay and non-gay money boys were not significantly different in age, income, marriage status and education. Both groups shared similar patterns of substance use. Both groups had high self-reported depressive symptoms and low HIV knowledge. However, sexual orientation differentially predicted HIV testing, with gay money boys more likely to be tested for HIV. Non-gay money boys showed fewer sexual risks. HIV prevention targeting MSM (including money boys) within rapidly changing China is discussed, as are methodologies and outreach strategies most effective for particular subgroups of MSM.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Lupus nephritis and Raynaud's phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies.

PubMed

Choojitarom, Kittiwan; Verasertniyom, Orawan; Totemchokchyakarn, Kitti; Nantiruj, Kanokrat; Sumethkul, Vasant; Janwityanujit, Suchela

2008-03-01

This study is aimed to determine the predictors of nongravid vascular thrombosis in systemic lupus erythematosus (SLE) patients with positive antiphospholipid antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of vascular thrombosis. Association between thrombosis and risk factors was examined by contingency table. The odds ratio (OR) of significant predictors was determined by logistic regression. Three percent of patients were LA(+), 6% were aCL(+), 31% were B2(+), 3% were aCL(+)LA(+), 35.8% were aCL(+)B2(+), 7.5% were LA(+)B2(+), and 13.4% were positive for all tests. As for clinical manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 19.4% had Raynaud's phenomenon (RP). Thrombosis occurred in 26 patients. The prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more frequently in patients with LA(+) (12 of 18) than the others (14 of 49; p = 0.01). Two-by-two table showed that oral contraceptive and LN were significantly associated with increased risk of thrombosis, while lymphopenia and antimalarials were significantly associated with decreased risk of thrombosis. Multivariate analysis confirmed that LN and RP were associated with increased risk of thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and 0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis, while lymphopenia and antimalarials are protective. These findings help to identify patients who may benefit from prophylactic therapy.

Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment

EPA Science Inventory

For presentation at the 45th Annual Symposium of the Society of Toxicology of Canada. The meeting will be held on 4-5 December 2013 at the Ottawa Convention Centre. Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment. Rory Conolly, Offi...

Clinicopathological factors increased the risk of malignancy in thyroid nodules with atypical or follicular lesions of undetermined significance (AUS/FLUS) risk factor of malignancy in thyroid nodule with AUS/FLUS

PubMed Central

Hong, In Ki; Kim, Jun Ho; Cho, Young Up; Park, Shin-Young

2016-01-01

Purpose Ultrasound-guided fine needle aspiration (US-FNA) in thyroid nodules is presently most commonly used to identify whether these nodules are benign or malignant. However, atypical or follicular lesions of undetermined significance (AUS/FLUS), as categorized in the Bethesda System for reporting the results of FNA, cannot be classified as benign or malignant. Therefore, several clinical factors should be considered to assess the risk of malignancy in patients with AUS/FLUS. The purpose of the present study was to determine which clinical factor increased the risk of malignancy in patients with AUS/FLUS. Methods A retrospective study was done on 129 patients with fine needle aspiration categorized as AUS/FLUS from January 2011 through April 2015. Univariate and multivariate analyses were performed to assess the independent effect of risk factors such as age, sex, size of nodule, atypical descriptors, and ultrasonography criteria for malignancy. Results We identified that the presence of spiculated margin (odds ratio [OR], 5.655; 95% confidence interval [CI], 2.114-15.131; P = 0.001), nuclear grooving (OR, 3.697; 95% CI, 1.409-9.701; P = 0.008), irregular nuclei (OR, 3.903; 95% CI, 1.442-10.560; P = 0.001) were shown to be significantly related to malignancy on univariate and multivariate analyses. Conclusion We recommend that surgical resection of thyroid nodules be considered in patients with AUS/FLUS showing the histologic findings such as nuclear grooving, irregular nuclei along with spiculated margin of ultrasonographic finding. PMID:27073790

Previously identified patellar tendinopathy risk factors differ between elite and sub-elite volleyball players.

PubMed

Janssen, I; Steele, J R; Munro, B J; Brown, N A T

2015-06-01

Patellar tendinopathy is the most common knee injury incurred in volleyball, with its prevalence in elite athletes more than three times that of their sub-elite counterparts. The purpose of this study was to determine whether patellar tendinopathy risk factors differed between elite and sub-elite male volleyball players. Nine elite and nine sub-elite male volleyball players performed a lateral stop-jump block movement. Maximum vertical jump, training history, muscle extensibility and strength, three-dimensional landing kinematics (250 Hz), along with lower limb neuromuscular activation patterns (1500 Hz), and patellar tendon loading were collected during each trial. Multivariate analyses of variance (P < 0.05) assessed for between-group differences in risk factors or patellar tendon loading. Significant interaction effects were further evaluated using post-hoc univariate analysis of variance tests. Landing kinematics, neuromuscular activation patterns, patellar tendon loading, and most of the previously identified risk factors did not differ between the elite and sub-elite players. However, elite players participated in a higher training volume and had less quadriceps extensibility than sub-elite players. Therefore, high training volume is likely the primary contributor to the injury discrepancy between elite and sub-elite volleyball players. Interventions designed to reduce landing frequency and improve quadriceps extensibility are recommended to reduce patellar tendinopathy prevalence in volleyball players. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause.

PubMed

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-08-01

We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193) and a retrospective validation (n = 567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high (≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95% CI 93.9-100.0%) in the validation cohort and 100.0% (95% CI 97.8-100.0%) in bacterial meningitis patients. The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

RISK SCORE FOR IDENTIFYING ADULTS WITH CSF PLEOCYTOSIS AND NEGATIVE CSF GRAM STAIN AT LOW RISK FOR AN URGENT TREATABLE CAUSE

PubMed Central

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H.; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-01-01

Background We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Methods Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n=193) and a retrospective validation (n=567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high ( ≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. Findings A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95%CI 93.9-100.0%) in the validation cohort and 100.0% (95%CI 97.8-100.0%) in bacterial meningitis patients. Interpretation The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. PMID:23619080

Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer.

PubMed

Tice, Jeffrey A; Miglioretti, Diana L; Li, Chin-Shang; Vachon, Celine M; Gard, Charlotte C; Kerlikowske, Karla

2015-10-01

Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. © 2015 by American Society of Clinical Oncology.

Breast Density and Benign Breast Disease: Risk Assessment to Identify Women at High Risk of Breast Cancer

PubMed Central

Tice, Jeffrey A.; Miglioretti, Diana L.; Li, Chin-Shang; Vachon, Celine M.; Gard, Charlotte C.; Kerlikowske, Karla

2015-01-01

Purpose Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. Methods We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. Results We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P < .001). Conclusion The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. PMID:26282663

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

PubMed

Bime, Christian; Pouladi, Nima; Sammani, Saad; Batai, Ken; Casanova, Nancy; Zhou, Tong; Kempf, Carrie L; Sun, Xiaoguang; Camp, Sara M; Wang, Ting; Kittles, Rick A; Lussier, Yves A; Jones, Tiffanie K; Reilly, John P; Meyer, Nuala J; Christie, Jason D; Karnes, Jason H; Gonzalez-Garay, Manuel; Christiani, David C; Yates, Charles R; Wurfel, Mark M; Meduri, Gianfranco U; Garcia, Joe G N

2018-06-01

Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. To identify genetic susceptibility targets for ARDS. A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg -/- mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation. These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

Identifying beliefs underlying pre-drivers' intentions to take risks: An application of the Theory of Planned Behaviour.

PubMed

Rowe, Richard; Andrews, Elizabeth; Harris, Peter R; Armitage, Christopher J; McKenna, Frank P; Norman, Paul

2016-04-01

Novice motorists are at high crash risk during the first few months of driving. Risky behaviours such as speeding and driving while distracted are well-documented contributors to crash risk during this period. To reduce this public health burden, effective road safety interventions need to target the pre-driving period. We use the Theory of Planned Behaviour (TPB) to identify the pre-driver beliefs underlying intentions to drive over the speed limit (N=77), and while over the legal alcohol limit (N=72), talking on a hand-held mobile phone (N=77) and feeling very tired (N=68). The TPB explained between 41% and 69% of the variance in intentions to perform these behaviours. Attitudes were strong predictors of intentions for all behaviours. Subjective norms and perceived behavioural control were significant, though weaker, independent predictors of speeding and mobile phone use. Behavioural beliefs underlying these attitudes could be separated into those reflecting perceived disadvantages (e.g., speeding increases my risk of crash) and advantages (e.g., speeding gives me a thrill). Interventions that can make these beliefs safer in pre-drivers may reduce crash risk once independent driving has begun. Copyright © 2015 Elsevier Ltd. All rights reserved.

Screening and prioritisation of chemical risks from metal mining operations, identifying exposure media of concern.

PubMed

Pan, Jilang; Oates, Christopher J; Ihlenfeld, Christian; Plant, Jane A; Voulvoulis, Nikolaos

2010-04-01

Metals have been central to the development of human civilisation from the Bronze Age to modern times, although in the past, metal mining and smelting have been the cause of serious environmental pollution with the potential to harm human health. Despite problems from artisanal mining in some developing countries, modern mining to Western standards now uses the best available mining technology combined with environmental monitoring, mitigation and remediation measures to limit emissions to the environment. This paper develops risk screening and prioritisation methods previously used for contaminated land on military and civilian sites and engineering systems for the analysis and prioritisation of chemical risks from modern metal mining operations. It uses hierarchical holographic modelling and multi-criteria decision making to analyse and prioritise the risks from potentially hazardous inorganic chemical substances released by mining operations. A case study of an active platinum group metals mine in South Africa is used to demonstrate the potential of the method. This risk-based methodology for identifying, filtering and ranking mining-related environmental and human health risks can be used to identify exposure media of greatest concern to inform risk management. It also provides a practical decision-making tool for mine acquisition and helps to communicate risk to all members of mining operation teams.

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

PubMed

Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

2017-01-01

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients.

Identifying Risk Factors for Elder Falls in Geriatric Rehabilitation in Israel.

PubMed

Ben Natan, Merav; Heyman, Neomi; Ben Israel, Joshua

2016-01-01

To identify risk factors for elder falls in a geriatric rehabilitation center in Israel. Retrospective chart review study. Four hundred and twelve medical records of inpatients in geriatric rehabilitation were retrospectively analyzed to compare between elders who sustained falls and those who did not. Of elders hospitalized during this year, 14% sustained falls. Fallers included a high proportion of males, with little comorbidity, not obese, and cardiovascular patients. Falls occurred frequently during patients' first week at the facility, mostly during the daytime. The falls occurred frequently in patients' rooms, and a common scenario was a fall during transition. The research findings single out patients who are allegedly at a lower risk of falls than more complex patients. Caregivers in geriatric rehabilitation settings should pay attention to patients who are allegedly at a lower risk of falls than more complex patients, and to cardiovascular patients in particular. © 2014 Association of Rehabilitation Nurses.

Identifying High-Risk Patients without Labeled Training Data: Anomaly Detection Methodologies to Predict Adverse Outcomes

PubMed Central

Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan

2010-01-01

For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083

Identifying at-risk children at school entry: the usefulness of multibehavioral problem profiles.

PubMed

Flanagan, Kelly S; Bierman, Karen L; Kam, Chi-Ming

2003-09-01

Found that 1st-grade teacher ratings of aggressive, hyperactive-inattentive, and low levels of prosocial behaviors made unique contributions to the prediction of school outcomes (measured 2 years later) for 755 children. Person-oriented analyses compared the predictive utility of 5 screening strategies based on child problem profiles to identify children at risk for school problems. A broad screening strategy, in which children with elevations in any 1 of the 3 behavior problem dimensions were identified as "at-risk," showed lower specificity but superior sensitivity, odds ratios, and overall accuracy in the prediction of school outcomes than the other screening strategies that were more narrowly focused or were based on a total problem score. Results are discussed in terms of implications for the screening and design of preventive interventions.

An investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

PubMed Central

Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Perez, José Ignacio Arias; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Investigators, kConFab; Group, AOCS; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon-Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Chang-Claude, Jenny

2014-01-01

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) <1.1×10−3. None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170cm (OR=1.22, p=0.017), but inversely associated with ER-negative BC risk in women <160cm (OR=0.83, p=0.039, pint=1.9×10−4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR=0.85, p=2.0×10−4), and absent in women who had had just one (OR=0.96, p=0.19, pint = 6.1×10−4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR=0.93, p=2.8×10−5), but no association was observed in current smokers (OR=1.07, p=0.14, pint = 3.4×10−4). In conclusion, recently identified breast cancer susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies. PMID:25227710

Identifying risk factors for Plasmodium infection and anaemia in Kinshasa, Democratic Republic of Congo.

PubMed

Ferrari, Giovanfrancesco; Ntuku, Henry M T; Ross, Amanda; Schmidlin, Sandro; Kalemwa, Didier M; Tshefu, Antoinette K; Lengeler, Christian

2016-07-15

There is little data on the risk factors for malaria infection in large cities in central Africa and in all age groups. There may be different associations with the risk factors for areas with different malaria transmission intensities such as the effect of fever or age. This study aimed at identifying risk factors associated with Plasmodium infection and anaemia among children 6-59 months and individuals aged older than 5 years in Kinshasa, a large city with heterogeneity in malaria prevalence. This study analysed data from 3342 children aged 6-59 months from 25 non-rural health zones (HZs) and for 816 individuals aged older than 5 years from two HZs in Kinshasa (non-rural), collected during a cross sectional malaria survey in 2011. Logistic regression with random effects was used to investigate predictors for malaria and anaemia. Differences in risk factors in areas with a prevalence of less than 10 and 10 % or greater were investigated. There was evidence of a different age-pattern in the two transmission settings. For children under 5 years, the highest prevalence of malaria was observed in the 48-59 months group in both transmission settings, but it increased more gently for the lower transmission HZs (p = 0.009). In a separate analysis in children over 5 years in two selected HZs, the peak prevalence was in 5-9 years old in the higher transmission setting and in 15-19 years old in the lower transmission setting. Reported fever was associated with malaria in both transmission strata, with no evidence of a difference in these associations (p = 0.71); however in children older than 5 years there was a significant interaction with a stronger association in the low transmission HZ. Insecticide-treated net (ITN) use was associated with a lower risk of malaria infection in children 6-59 months in the high transmission HZs. Similar estimates were found in children over 5 years and the lower transmission HZ but the associations there were not

Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: a case control study.

PubMed

Zhuang, Ke; Zhang, Wencai; Zhang, Xiaobo; Wu, Fangqin; Cheng, Longxian

2011-08-01

Associations between "lipid-related" candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

Sexual harassment: identifying risk factors.

PubMed

O'Hare, E A; O'Donohue, W

1998-12-01

A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

Identifying gender specific risk/need areas for male and female juvenile offenders: Factor analyses with the Structured Assessment of Violence Risk in Youth (SAVRY).

PubMed

Hilterman, Ed L B; Bongers, Ilja; Nicholls, Tonia L; van Nieuwenhuizen, Chijs

2016-02-01

By constructing risk assessment tools in which the individual items are organized in the same way for male and female juvenile offenders it is assumed that these items and subscales have similar relevance across males and females. The identification of criminogenic needs that vary in relevance for 1 of the genders, could contribute to more meaningful risk assessments, especially for female juvenile offenders. In this study, exploratory factor analyses (EFA) on a construction sample of male (n = 3,130) and female (n = 466) juvenile offenders were used to aggregate the 30 items of the Structured Assessment of Violence Risk in Youth (SAVRY) into empirically based risk/need factors and explore differences between genders. The factor models were cross-validated through confirmatory factor analyses (CFA) on a validation sample of male (n = 2,076) and female (n = 357) juvenile offenders. In both the construction sample and the validation sample, 5 factors were identified: (a) Antisocial behavior; (b) Family functioning; (c) Personality traits; (d) Social support; and (e) Treatability. The male and female models were significantly different and the internal consistency of the factors was good, both in the construction sample and the validation sample. Clustering risk/need items for male and female juvenile offenders into meaningful factors may guide clinicians in the identification of gender-specific treatment interventions. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Self-Identified Sexual Orientation and Sexual Risk Behavior Among HIV-Infected Latino Males.

PubMed

Champion, Jane Dimmitt; Szlachta, Alaina

2016-01-01

The HIV testing, disclosure, and sexual practices of ethnic minority men suggest that addressing sexual risk behavior and the underlying reasons for not receiving HIV testing or disclosing HIV-infection status-unique to differing populations-would improve public health interventions. Descriptive behaviors and underlying perspectives reported in our study suggest that public health interventions for HIV-infected Latino men who self-identify as heterosexual should explicitly identify substance use, needle sharing, and unprotected sex to current partners as behaviors placing both oneself and one's partners at high risk for contracting HIV. However, diversity of sexual behavior among gay, straight, and bisexual HIV-infected Latino men in our study ultimately suggested that clinicians should not rely on simplistic conceptions of sexuality in assessment of self-care needs. Care in presentation and discussion of self-identified sexual preference and sexual behavior is indicated, as these do not determine actual sexual orientation or behavior and vice versa. Copyright © 2016 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Drake, Christopher L.

2016-01-01

Study Objectives: A primary focus of the National Institute of Mental Health's current strategic plan is “predicting” who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. Methods: A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Results: Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49–1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. Conclusions: The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts

Poverty, AIDS and child health: identifying highest-risk children in South Africa.

PubMed

Cluver, Lucie; Boyes, Mark; Orkin, Mark; Sherr, Lorraine

2013-10-11

Identifying children at the highest risk of negative health effects is a prerequisite to effective public health policies in Southern Africa. A central ongoing debate is whether poverty, orphanhood or parental AIDS most reliably indicates child health risks. Attempts to address this key question have been constrained by a lack of data allowing distinction of AIDS-specific parental death or morbidity from other causes of orphanhood and chronic illness. To examine whether household poverty, orphanhood and parental illness (by AIDS or other causes) independently or interactively predict child health, developmental and HIV-infection risks. We interviewed 6 002 children aged 10 - 17 years in 2009 - 2011, using stratified random sampling in six urban and rural sites across three South African provinces. Outcomes were child mental health risks, educational risks and HIV-infection risks. Regression models that controlled for socio-demographic co-factors tested potential impacts and interactions of poverty, AIDS-specific and other orphanhood and parental illness status. Household poverty independently predicted child mental health and educational risks, AIDS orphanhood independently predicted mental health risks and parental AIDS illness independently predicted mental health, educational and HIV-infection risks. Interaction effects of poverty with AIDS orphanhood and parental AIDS illness were found across all outcomes. No effects, or interactions with poverty, were shown by AIDS-unrelated orphanhood or parental illness. The identification of children at highest risk requires recognition and measurement of both poverty and parental AIDS. This study shows negative impacts of poverty and AIDS-specific vulnerabilities distinct from orphanhood and adult illness more generally. Additionally, effects of interaction between family AIDS and poverty suggest that, where these co-exist, children are at highest risk of all.

Hospital readmission following transplantation: identifying risk factors and designing preventive measures.

PubMed

McKenna, Dorothy R; Sullivan, Matthew R; Hill, John M; Lowrey, Christopher H; Brown, Jeremiah R; Hickman, Joshua; Meehan, Kenneth R

2015-09-01

About 1 in 7 of all hospitalized patients is readmitted within 30 days of discharge. The cost of readmissions is significant, with Medicare readmissions alone costing the health care system an estimated $28 billion a year. To identify the rates of and causes for readmission within 100 days of patients receiving a hematopoietic stem cell transplant. We performed a retrospective review of 235 consecutive transplant recipients (autologous, n = 144; allogeneic, n = 91) to determine rates and causes for readmission within 100 days of patients receiving a transplant. Medical records and hospital readmissions were reviewed for each patient. 36 allogeneic patients accounted for 56 readmissions. 23 autologous patients accounted for 26 readmissions. Autologous transplant recipients were most commonly readmitted for the development of a fever (n = 15 patients) or cardiopulmonary issues (n = 4). The most prevalent reasons for readmission in the allogeneic recipients included a fever (n = 21) or the development or exacerbation of graft-versus-host disease (n = 5). The readmission length of stay was 6 days (median range, 1-91 days) for allogeneic patients and 4 days (median range, 1-22 days) for autologous patients. There was no difference in survival between the readmitted and the non-readmitted cohorts ( = .55 for allogeneic patients; = .24 for autologous patients). Although allogeneic graft recipients demonstrated a higher readmission rate (39.6%) compared with autologous recipients (16%), none of the variables examined, including age, gender, performance status, diagnosis, remission status at the time of transplant, comorbidities, type of preparative chemotherapy regimen or donor type, identified patients at increased risk for readmission. Variations in clinical care, physician practices, and patient characteristics need to be considered when examining readmission rates. Most of the allogeneic patient population included unrelated donor recipients (65%) who received

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2011 CFR

2011-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

40 CFR 141.723 - Requirements to respond to significant deficiencies identified in sanitary surveys performed by EPA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... deficiencies identified in sanitary surveys performed by EPA. 141.723 Section 141.723 Protection of Environment... REGULATIONS Enhanced Treatment for Cryptosporidium Requirements for Sanitary Surveys Performed by Epa § 141.723 Requirements to respond to significant deficiencies identified in sanitary surveys performed by...

Identifying the women at risk of antenatal anxiety and depression: A systematic review.

PubMed

Biaggi, Alessandra; Conroy, Susan; Pawlby, Susan; Pariante, Carmine M

2016-02-01

Pregnancy is a time of increased vulnerability for the development of anxiety and depression. This systematic review aims to identify the main risk factors involved in the onset of antenatal anxiety and depression. A systematic literature analysis was conducted, using PubMed, PsychINFO, and the Cochrane Library. Original papers were included if they were written in English and published between 1st January 2003 and 31st August 2015, while literature reviews and meta-analyses were consulted regardless of publication date. A final number of 97 papers were selected. The most relevant factors associated with antenatal depression or anxiety were: lack of partner or of social support; history of abuse or of domestic violence; personal history of mental illness; unplanned or unwanted pregnancy; adverse events in life and high perceived stress; present/past pregnancy complications; and pregnancy loss. The review does not include a meta-analysis, which may have added additional information about the differential impact of each risk factor. Moreover, it does not specifically examine factors that may influence different types of anxiety disorders, or the recurrence or persistence of depression or anxiety from pregnancy to the postpartum period. The results show the complex aetiology of antenatal depression and anxiety. The administration of a screening tool to identify women at risk of anxiety and depression during pregnancy should be universal practice in order to promote the long-term wellbeing of mothers and babies, and the knowledge of specific risk factors may help creating such screening tool targeting women at higher risk. Copyright © 2016 Elsevier B.V. All rights reserved.

Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma

PubMed Central

Li, Ying; Wang, Jiaxing; Allingham, R. Rand; Hauser, Michael A.; Wiggs, Janey L.; Geisert, Eldon E.

2018-01-01

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60–100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP

Assessing urban potential flooding risk and identifying effective risk-reduction measures.

PubMed

Cherqui, Frédéric; Belmeziti, Ali; Granger, Damien; Sourdril, Antoine; Le Gauffre, Pascal

2015-05-01

Flood protection is one of the traditional functions of any drainage system, and it remains a major issue in many cities because of economic and health impact. Heavy rain flooding has been well studied and existing simulation software can be used to predict and improve level of protection. However, simulating minor flooding remains highly complex, due to the numerous possible causes related to operational deficiencies or negligent behaviour. According to the literature, causes of blockages vary widely from one case to another: it is impossible to provide utility managers with effective recommendations on how to improve the level of protection. It is therefore vital to analyse each context in order to define an appropriate strategy. Here we propose a method to represent and assess the flooding risk, using GIS and data gathered during operation and maintenance. Our method also identifies potential management responses. The approach proposed aims to provide decision makers with clear and comprehensible information. Our method has been successfully applied to the Urban Community of Bordeaux (France) on 4895 interventions related to flooding recorded during the 2009-2011 period. Results have shown the relative importance of different issues, such as human behaviour (grease, etc.) or operational deficiencies (roots, etc.), and lead to identify corrective and proactive. This study also confirms that blockages are not always directly due to the network itself and its deterioration. Many causes depend on environmental and operating conditions on the network and often require collaboration between municipal departments in charge of roads, green spaces, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Assessment of postmenopausal women and significant risk factors for osteoporosis.

PubMed

Schnatz, Peter F; Marakovits, Kimberly A; O'Sullivan, David M

2010-09-01

The assessment of osteoporosis risk factors can help guide early intervention. The objective of this study was to analyze numerous potential risk factors to see which were associated with postmenopausal osteoporosis. Women aged 49 or greater presenting for dual-energy x-ray absorptiometry bone scans were recruited from radiology sites in the Hartford, Connecticut, area between January 2007 and March 2009, inclusive. Information was collected regarding primary and secondary risk factors for osteoporosis development, as well as family history and history of pregnancy and breast-feeding. Survey results were subsequently correlated with each woman's dual-energy x-ray absorptiometry scan results. In a sample of 619 women, history of fracture (odds ratio [OR], 12.49), weight less than 127 pounds (OR, 3.50), and use of anticoagulants (OR, 5.40) increased the chance of developing osteoporosis. In contrast, multiparity (OR, 0.45) and history of breast-feeding (OR, 0.38) decreased the development of osteoporosis in postmenopausal women. In women aged 49 to 54, breast-feeding was significantly protective, while low body mass index was most indicative of osteoporosis in women ages 55 to 64. Both previous fracture and low body mass index were associated with osteoporosis in women over age 64. The current results are consistent with other studies suggesting that previous fracture, low body weight, and use of anticoagulants increase the risk of osteoporosis. Our results also suggest that a history of pregnancy and breast-feeding protects against the development of postmenopausal osteoporosis, especially in women aged 49 to 54.

High-Risk Carotid Plaques Identified by CT-Angiogram can Predict Acute Myocardial Infarction

PubMed Central

Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C

2016-01-01

Purpose Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. Methods We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign (NRS). Adjusted relative risks were calculated for each plaque features. Results Patients with speckled (<3mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within one year compared to patients without [adjusted RR of 7.51, 95%CI 1.26 to 73.42, P= 0.001]. Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within one year than patients without [adjusted RR of 2.73, 95%CI 1.19 to 8.50, P= 0.021]. Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100% and 79.17%, respectively) for the development of acute MI. Conclusions Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events. PMID:27866279

High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

PubMed

Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C

2017-04-01

Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

Submicroscopic and Asymptomatic Plasmodium Parasitaemia Associated with Significant Risk of Anaemia in Papua, Indonesia

PubMed Central

Handayuni, Irene; Trianty, Leily; Utami, Retno A. S.; Tirta, Yusrifar Kharisma; Kenangalem, Enny; Lampah, Daniel; Kusuma, Andreas; Wirjanata, Grennady; Kho, Steven; Simpson, Julie A.; Auburn, Sarah; Douglas, Nicholas M.; Noviyanti, Rintis; Anstey, Nicholas M.; Poespoprodjo, Jeanne R.; Marfurt, Jutta

2016-01-01

Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasmodium parasitaemia was determined by blood film microscopy and PCR. Between April and July 2013, 800 households and 2,830 individuals were surveyed. Peripheral parasitaemia was detected in 37.7% (968/2,567) of individuals, 36.8% (357) of whom were identified by blood film examination. Overall the prevalence of P. falciparum parasitaemia was 15.4% (396/2567) and that of P. vivax 18.3% (471/2567). In parasitaemic individuals, submicroscopic infection was significantly more likely in adults (adjusted odds ratio (AOR): 3.82 [95%CI: 2.49–5.86], p<0.001) compared to children, females (AOR = 1.41 [1.07–1.86], p = 0.013), individuals not sleeping under a bednet (AOR = 1.4 [1.0–1.8], p = 0.035), and being afebrile (AOR = 3.2 [1.49–6.93], p = 0.003). The risk of anaemia (according to WHO guidelines) was 32.8% and significantly increased in those with asymptomatic parasitaemia (AOR 2.9 [95% 2.1–4.0], p = 0.007), and submicroscopic P. falciparum infections (AOR 2.5 [95% 1.7–3.6], p = 0.002). Asymptomatic and submicroscopic infections in this area co-endemic for P. falciparum and P. vivax constitute two thirds of detectable parasitaemia and are associated with a high risk of anaemia. Novel public health strategies are needed to detect and eliminate these parasite reservoirs, for the benefit both of the patient and the community. PMID:27788243

Plasma triglyceride determination can identify increased risk of statin-induced type 2 diabetes: a hypothesis.

PubMed

Armato, J; Ruby, R; Reaven, G

2015-04-01

To evaluate the ability of plasma triglyceride (TG) measurements to identify statin-treated persons at accentuated risk of statin-induced type 2 diabetes (T2DM). The experimental population consisted of nondiabetic, statin-treated patients (n = 469), classified as being at high risk for T2DM, subdivided on the basis of a plasma TG concentration of 1.7 mmol/L. Comparisons were made of demographic characteristics, concentrations of fasting glucose, insulin, HbA1c, and hs-CRP, oral glucose tolerance tests, estimates of insulin action and secretion, and lipid/lipoprotein profiles. Despite similar fasting glucose and HbA1c concentrations, patients with elevated TG concentrations displayed markers of increased risk of T2DM (insulin resistance and compensatory hyperinsulinemia), more adverse lipid/lipoprotein profiles, and increased prevalence of abnormal hs-CRP values. These findings demonstrate that plasma TG concentrations ≥ 1.7 mmol/L identified a subset of individuals at enhanced risk of developing statin-induced diabetes within a population classified prior to statin treatment as being at high risk of T2DM. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer

PubMed Central

Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

2017-01-01

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients. PMID:28321054

Identifying Trajectories of Adolescents' Depressive Phenomena: An Examination of Early Risk Factors

ERIC Educational Resources Information Center

Mazza, James J.; Fleming, Charles B.; Abbott, Robert D.; Haggerty, Kevin P.; Catalano, Richard F.

2010-01-01

Few studies have examined risk factors of childhood and early adolescent depressive symptomatology trajectories. This study examined self-report depressive symptomatology across a 6-year time period from 2nd to 8th grade to identify latent groups of individuals with similar patterns of depressive phenomena in a sample of 951 children (440 girls,…

Predicting disease risk, identifying stakeholders, and informing control strategies: A case study of anthrax in Montana

PubMed Central

Morris, Lillian R.; Blackburn, Jason K.

2018-01-01

Infectious diseases that affect wildlife and livestock are challenging to manage, and can lead to large scale die offs, economic losses, and threats to human health. The management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high risk landscapes. This study focuses on anthrax, caused by the bacterium Bacillus anthracis, risk to wildlife and livestock in Montana. There is a history of anthrax in Montana, but the spatial extent of disease risk and subsequent wildlife species at risk are not known. Our objective was to predict the potential geographic distribution of anthrax risk across Montana, identify wildlife species at risk and their distributions, and define stakeholders. We used an ecological niche model to predict the potential distribution of anthrax risk. We overlaid susceptible wildlife species distributions and land ownership delineations on our risk map. We found that there was an extensive region across Montana predicted as potential anthrax risk. These potentially risky landscapes overlapped the ranges of all 6 ungulate species considered in the analysis and livestock grazing allotments, and this overlap was on public and private land for all species. Our findings suggest that there is the potential for a multi species anthrax outbreak on multiple landscapes across Montana. Our potential anthrax risk map can be used to prioritize landscapes for surveillance and for implementing livestock vaccination programs. PMID:27169560

Predicting Disease Risk, Identifying Stakeholders, and Informing Control Strategies: A Case Study of Anthrax in Montana.

PubMed

Morris, Lillian R; Blackburn, Jason K

2016-06-01

Infectious diseases that affect wildlife and livestock are challenging to manage and can lead to large-scale die-offs, economic losses, and threats to human health. The management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high-risk landscapes. This study focuses on anthrax, caused by the bacterium Bacillus anthracis, risk to wildlife and livestock in Montana. There is a history of anthrax in Montana, but the spatial extent of disease risk and subsequent wildlife species at risk are not known. Our objective was to predict the potential geographic distribution of anthrax risk across Montana, identify wildlife species at risk and their distributions, and define stakeholders. We used an ecological niche model to predict the potential distribution of anthrax risk. We overlaid susceptible wildlife species distributions and land ownership delineations on our risk map. We found that there was an extensive region across Montana predicted as potential anthrax risk. These potentially risky landscapes overlapped the ranges of all 6 ungulate species considered in the analysis and livestock grazing allotments, and this overlap was on public and private land for all species. Our findings suggest that there is the potential for a multi-species anthrax outbreak on multiple landscapes across Montana. Our potential anthrax risk map can be used to prioritize landscapes for surveillance and for implementing livestock vaccination programs.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance.

PubMed

Nooij, Linda S; Ter Haar, Natalja T; Ruano, Dina; Rakislova, Natalia; van Wezel, Tom; Smit, Vincent T H B M; Trimbos, Baptist J B M Z; Ordi, Jaume; van Poelgeest, Mariette I E; Bosse, Tjalling

2017-11-15

Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers. Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort). Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower ( P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV + , HPV - /p53wt, HPV - /p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV + , 16.3% for HPV - /p53wt and 22.6% for HPV - /p53abn tumors ( P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis ( P = 0.020). Conclusions: HPV - and HPV + vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV - /p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV + VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

PubMed

Oltmanns, J; Licht, O; Bitsch, A; Bohlen, M-L; Escher, S E; Silano, V; MacLeod, M; Serafimova, R; Kass, G E N; Merten, C

2018-02-21

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

Identifying Patterns in Extreme Precipitation Risk and the Related Impacts

NASA Astrophysics Data System (ADS)

Schroeer, K.; Tye, M. R.

2017-12-01

Extreme precipitation can harm human life and assets through flooding, hail, landslides, or debris flows. Flood risk assessments typically concentrate on river or mountain torrent channels, using water depth, flow velocity, and/or sediment deposition to quantify the risk. In addition, extreme events with high recurrence intervals are often the main focus. However, damages from short-term and localized convective showers often occur away from watercourses. Also, damages from more frequent small scale extremes, although usually less disastrous, can accumulate to considerable financial burdens. Extreme convective precipitation is expected to intensify in a warmer climate, and vulnerability patterns might change in tandem with changes in the character of precipitation and flood types. This has consequences for adaptation planners who want to establish effective protection measures and reduce the cost from natural hazards. Here we merge hydrological and exposure data to identify patterns of risk under varying synoptic conditions. Exposure is calculated from a database of 76k damage claims reported to the national disaster fund in 480 municipalities in south eastern Austria from 1990-2015. Hydrological data comprise sub-daily precipitation (59 gauges) and streamflow (62 gauges) observations. We use synoptic circulation types to identify typical precipitation patterns. They indicate the character of precipitation even if a gauge is not in close proximity, facilitating potential future research with regional climate model data. Results show that more claims are reported under synoptic conditions favouring convective precipitation (on average 1.5-3 times more than on other days). For agrarian municipalities, convective precipitation damages are among the costliest after long low-intensity precipitation events. In contrast, Alpine communities are particularly vulnerable to convective high-intensity rainfall. In addition to possible observational error, uncertainty is present

Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

PubMed Central

Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

2015-01-01

Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with P<10−6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (P<10−6) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

Spectrum of risk of malignancy in subcategories of 'atypia of undetermined significance'.

PubMed

Olson, Matthew T; Clark, Douglas P; Erozan, Yener S; Ali, Syed Z

2011-01-01

To determine if focal 'nuclear atypia' or 'microfollicular architecture' portends a higher risk of malignancy than other subcategories of atypia of undetermined significance (AUS) in thyroid fine-needle aspirations (FNAs). The frequencies of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories were calculated from 3,956 thyroid FNAs interpreted over a 26-month period at The Johns Hopkins Hospital after adoption of TBSRTC. TBSRTC criteria were applied strictly. The risk of malignancy, specifically for AUS subcategories, was analyzed by cyto-histo correlation. Of the 133 cases diagnosed as AUS, 32% were found to have stageable carcinoma (not incidental microcarcinoma) on resection. When the subset of AUS with 'nuclear atypia' (AUS-N) was separated from other AUS cases, 48% (30/62) of them had stageable carcinoma on resection; of the AUS subset with 'microfollicular architecture' (AUS-F), 27% (8/30) were malignant on resection. The 'suspicious for papillary thyroid carcinoma' (SPTC) group maintained a higher risk of malignancy versus AUS-N (relative risk, RR 1.57; 95% CI 1.23-1.81). The subcategory of 'nuclear atypia' within AUS indicates a higher risk of malignancy than other subcategories of AUS but has a lower risk of malignancy than SPTC does. Thus, it is an important distinction with potential clinical implications. Copyright © 2011 S. Karger AG, Basel.

Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

PubMed

Hu, Liyuan; Gu, Qiufang; Zhu, Zhen; Yang, Chenhao; Chen, Chao; Cao, Yun; Zhou, Wenhao

2014-08-01

Hypoglycaemia is a significant problem in high-risk neonates and predominant parieto-occipital lobe involvement has been observed after severe hypoglycaemic insult. We explored the use of flash visual evoked potentials (FVEP) in detecting parieto-occipital lobe involvement after significant hypoglycaemia. Full-term neonates (n = 15) who underwent FVEP from January 2008 to May 2013 were compared with infants (n = 11) without hypoglycaemia or parietal-occipital lobe injury. Significant hypoglycaemia was defined as being symptomatic or needing steroids, glucagon or a glucose infusion rate of ≥12 mg/kg/min. The hypoglycaemia group exhibited delayed latency of the first positive waveform on FVEP. The initial detected time for hypoglycaemia was later in the eight subjects with seizures (median 51-h-old) than those without (median 22-h-old) (P = 0.003). Magnetic resonance imaging showed that 80% of the hypoglycaemia group exhibited occipital-lobe injuries, and they were more likely to exhibit abnormal FVEP morphology (P = 0.007) than the controls. FVEP exhibited 100% sensitivity, but only 25% specificity, for detecting injuries to the parieto-occipital lobes. Flash visual evoked potential (FVEP) was sensitive, but not sufficiently specific, in identifying parieto-occipital lobe injuries among term neonates exposed to significant hypoglycaemia. Larger studies exploring the potential role of FVEP in neonatal hypoglycaemia are required. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Genetic predictors of antipsychotic response to lurasidone identified in a genome wide association study and by schizophrenia risk genes.

PubMed

Li, Jiang; Yoshikawa, Akane; Brennan, Mark D; Ramsey, Timothy L; Meltzer, Herbert Y

2018-02-01

Biomarkers which predict response to atypical antipsychotic drugs (AAPDs) increases their benefit/risk ratio. We sought to identify common variants in genes which predict response to lurasidone, an AAPD, by associating genome-wide association study (GWAS) data and changes (Δ) in Positive And Negative Syndrome Scale (PANSS) scores from two 6-week randomized, placebo-controlled trials of lurasidone in schizophrenia (SCZ) patients. We also included SCZ risk SNPs identified by the Psychiatric Genomics Consortium using a polygenic risk analysis. The top genomic loci, with uncorrected p<10 -4 , include: 1) synaptic adhesion (PTPRD, LRRC4C, NRXN1, ILIRAPL1, SLITRK1) and scaffolding (MAGI1, MAGI2, NBEA) genes, both essential for synaptic function; 2) other synaptic plasticity-related genes (NRG1/3 and KALRN); 3) the neuron-specific RNA splicing regulator, RBFOX1; and 4) ion channel genes, e.g. KCNA10, KCNAB1, KCNK9 and CACNA2D3). Some genes predicted response for patients with both European and African Ancestries. We replicated some SNPs reported to predict response to other atypical APDs in other GWAS. Although none of the biomarkers reached genome-wide significance, many of the genes and associated pathways have previously been linked to SCZ. Two polygenic modeling approaches, GCTA-GREML and PLINK-Polygenic Risk Score, demonstrated that some risk genes related to neurodevelopment, synaptic biology, immune response, and histones, also contributed to prediction of response. The top hits predicting response to lurasidone did not predict improvement with placebo. This is the first evidence from clinical trials that SCZ risk SNPs are related to clinical response to an AAPD. These results need to be replicated in an independent sample. Copyright © 2017. Published by Elsevier B.V.

Identifying HIV most-at-risk groups in Malawi for targeted interventions. A classification tree model.

PubMed

Emina, Jacques B O; Madise, Nyovani; Kuepie, Mathias; Zulu, Eliya M; Ye, Yazoume

2013-05-28

To identify HIV-socioeconomic predictors as well as the most-at-risk groups of women in Malawi. A cross-sectional survey. Malawi The study used a sample of 6395 women aged 15-49 years from the 2010 Malawi Health and Demographic Surveys. Individual HIV status: positive or not. Findings from the Pearson χ(2) and χ(2) Automatic Interaction Detector analyses revealed that marital status is the most significant predictor of HIV. Women who are no longer in union and living in the highest wealth quintiles households constitute the most-at-risk group, whereas the less-at-risk group includes young women (15-24) never married or in union and living in rural areas. In the light of these findings, this study recommends: (1) that the design and implementation of targeted interventions should consider the magnitude of HIV prevalence and demographic size of most-at-risk groups. Preventive interventions should prioritise couples and never married people aged 25-49 years and living in rural areas because this group accounts for 49% of the study population and 40% of women living with HIV in Malawi; (2) with reference to treatment and care, higher priority must be given to promoting HIV test, monitoring and evaluation of equity in access to treatment among women in union disruption and never married or women in union aged 30-49 years and living in urban areas; (3) community health workers, households-based campaign, reproductive-health services and reproductive-health courses at school could be used as canons to achieve universal prevention strategy, testing, counselling and treatment.

Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A Decision Tree Approach

PubMed Central

Ortega-Campos, Elena; García-García, Juan; Gil-Fenoy, Maria José; Zaldívar-Basurto, Flor

2016-01-01

Research on juvenile justice aims to identify profiles of risk and protective factors in juvenile offenders. This paper presents a study of profiles of risk factors that influence young offenders toward committing sanctionable antisocial behavior (S-ASB). Decision tree analysis is used as a multivariate approach to the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders in Spain. The study sample was made up of the set of juveniles who were charged in a court case in the Juvenile Court of Almeria (Spain). The period of study of recidivism was two years from the baseline. The object of study is presented, through the implementation of a decision tree. Two profiles of risk and protective factors are found. Risk factors associated with higher rates of recidivism are antisocial peers, age at baseline S-ASB, problems in school and criminality in family members. PMID:27611313

RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PubMed

Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

2017-11-01

To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P < 0.05). Within cleft group, the early-onset (<6 months) subgroup had even worse visual outcomes than the late-onset subgroup (P < 0.05). Multiple logistic regression analyses revealed that the incidence of prechoroidal cleft was positively correlated with having received intravitreal gas injection to displace a submacular hemorrhage and a diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration (P < 0.05). Diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

Trabecular bone score as an assessment tool to identify the risk of osteoporosis in axial spondyloarthritis: a case-control study.

PubMed

Kang, Kwi Young; Goo, Hye Yeon; Park, Sung-Hwan; Hong, Yeon Sik

2018-03-01

To compare the trabecular bone score (TBS) between patients with axial spondyloarthritis (axSpA) and matched normal controls and identify risk factors associated with a low TBS. TBS and BMD were assessed in the two groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory markers were also assessed. Disease activity and radiographic progression in the sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear regression analysis was performed to identify risk factors associated with TBS. In the axSpA group, 248 subjects were enrolled; an equal number of age- and sex-matched subjects comprised the control group. The mean TBS was 1.43 (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001); BMD at the lumbar spine did not differ between the two groups. The TBS was negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001 and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the multivariate analyses, ESR, CRP and spinal radiographic progression were significantly associated with TBS. TBS assessments revealed poor bone quality in patients with axSpA compared with the matched controls. In axSpA, systemic inflammatory markers were negatively correlated with TBS and spinal radiographic progression and inflammatory markers were independently correlated with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk of osteoporosis in patients with axSpA.

Genetic Testing as a Tool to Identify Horses with or at Risk for Ocular Disorders.

PubMed

Bellone, Rebecca R

2017-12-01

Advances in equine genetics and genomics resources have enabled the understanding of some inherited ocular disorders and ocular manifestations. These ocular disorders include congenital stationary night blindness, equine recurrent uveitis, multiple congenital ocular anomalies, and squamous cell carcinoma. Genetic testing can identify horses with or at risk for disease and thus can assist in clinical management. In addition, genetic testing can identify horses that are carriers and thus can inform breeding decisions. Use of genetic tests in management and breeding decisions should aid in reducing the incidence of these disorders and improving the outcomes for horses at highest risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying, screening and engaging high-risk clients in private non-profit child abuse prevention programs.

PubMed

Barth, R P; Ash, J R; Hacking, S

1986-01-01

Child abuse prevention programs rely on varied strategies to identify, screen, obtain referrals of, and engage high risk parents. Available literature on community-based child abuse prevention projects is not conclusive about project outcomes nor sufficiently descriptive about implementation. From the literature, experience and interviews with staff from more than 20 programs, barriers to implementation are identifiable. Barriers arise during identifying and screening at-risk families, referral, continued collaboration with referrers, and engaging clients in services. The paper describes a diverse set of strategies for surmounting these barriers. Staff characteristics and concrete services partially predict the success of program implementation. So does the program's relationship to other agencies. Child abuse prevention programs assume independent, interdependent, and dependent relationships with other agencies and referrers. Interdependent programs appear to have the best chance of obtaining referrals and maintaining clients who match their program's intent.

An Electronic Health Record Data-driven Model for Identifying Older Adults at Risk of Unintentional Falls

PubMed Central

Baus, Adam; Coben, Jeffrey; Zullig, Keith; Pollard, Cecil; Mullett, Charles; Taylor, Henry; Cochran, Jill; Jarrett, Traci; Long, Dustin

2017-01-01

Screening for risk of unintentional falls remains low in the primary care setting because of the time constraints of brief office visits. National studies suggest that physicians caring for older adults provide recommended fall risk screening only 30 to 37 percent of the time. Given prior success in developing methods for repurposing electronic health record data for the identification of fall risk, this study involves building a model in which electronic health record data could be applied for use in clinical decision support to bolster screening by proactively identifying patients for whom screening would be beneficial and targeting efforts specifically to those patients. The final model, consisting of priority and extended measures, demonstrates moderate discriminatory power, indicating that it could prove useful in a clinical setting for identifying patients at risk of falls. Focus group discussions reveal important contextual issues involving the use of fall-related data and provide direction for the development of health systems–level innovations for the use of electronic health record data for fall risk identification. PMID:29118679

[Smoking fewer cigarettes per day may determine a significant risk reduction in developing smoking attributable diseases? Is there a risk reduction for e-cigarette users?].

PubMed

Pieri, Luca; Chellini, Elisabetta; Gorini, Giuseppe

2014-01-01

Among Italian smokers--about 10 millions in 2013--about 600,000 began using electronic cigarettes (e-cigs) in last years. About 10% of e-cig users quitted smoking tobacco, whereas the 90% was dual users. Among them, about three out of four decreased the number of cigarettes smoked per day (cig/day), but did not quit. How many fewer cigarettes a smoker has to smoke to obtain significant health benefits? Is there a threshold? In order to observe a significant 27% reduction in the risk of developing lung cancer, a smoker must reduce the number of cig/day by at least 50%, while for the other smoking-related diseases (acute myocardial infarction - AMI, stroke, chronic obstructive pulmonary diseases), halving the number of cig/day did not drive to a significant risk reduction. Even smoking 5 cig/day increases the risk of AMI, whereas it significantly lowers the risk of lung cancer. Obviously, quitting smoking is the best choice to highly reduce risks for all smoking-related diseases. Therefore, in order to achieve significant risk reductions, e-cig users should quit smoking as first choice, or, if they feel it is impossible to them, reduce the consumption of traditional cigarettes to less than 5 cig/day.

Naturalistic Cycling Study: Identifying Risk Factors for On-Road Commuter Cyclists

PubMed Central

Johnson, Marilyn; Charlton, Judith; Oxley, Jennifer; Newstead, Stuart

2010-01-01

The study aim was to identify risk factors for collisions/near-collisions involving on-road commuter cyclists and drivers. A naturalistic cycling study was conducted in Melbourne, Australia, with cyclists wearing helmet-mounted video cameras. Video recordings captured cyclists’ perspective of the road and traffic behaviours including head checks, reactions and manoeuvres. The 100-car naturalistic driving study analysis technique was adapted for data analysis and events were classified by severity: collision, near-collision and incident. Participants were adult cyclists and each filmed 12 hours of commuter cycling trips over a 4-week period. In total, 127 hours and 38 minutes were analysed for 13 participants, 54 events were identified: 2 collisions, 6 near-collisions and 46 incidents. Prior to events, 88.9% of cyclists travelled in a safe/legal manner. Sideswipe was the most frequent event type (40.7%). Most events occurred at an intersection/intersection-related location (70.3%). The vehicle driver was judged at fault in the majority of events (87.0%) and no post-event driver reaction was observed (83.3%). Cross tabulations revealed significant associations between event severity and: cyclist reaction, cyclist post-event manoeuvre, pre-event driver behaviour, other vehicle involved, driver reaction, visual obstruction, cyclist head check (left), event type and vehicle location (p<0.05). Frequent head checks suggest cyclists had high situational awareness and their reactive behaviour to driver actions led to successful avoidance of collisions/near-collisions. Strategies to improve driver awareness of on-road cyclists and to indicate early before turning/changing lanes when sharing the roadway with cyclists are discussed. Findings will contribute to the development of effective countermeasures to reduce cyclist trauma. PMID:21050610

Naturalistic cycling study: identifying risk factors for on-road commuter cyclists.

PubMed

Johnson, Marilyn; Charlton, Judith; Oxley, Jennifer; Newstead, Stuart

2010-01-01

The study aim was to identify risk factors for collisions/near-collisions involving on-road commuter cyclists and drivers. A naturalistic cycling study was conducted in Melbourne, Australia, with cyclists wearing helmet-mounted video cameras. Video recordings captured cyclists' perspective of the road and traffic behaviours including head checks, reactions and manoeuvres. The 100-car naturalistic driving study analysis technique was adapted for data analysis and events were classified by severity: collision, near-collision and incident. Participants were adult cyclists and each filmed 12 hours of commuter cycling trips over a 4-week period. In total, 127 hours and 38 minutes were analysed for 13 participants, 54 events were identified: 2 collisions, 6 near-collisions and 46 incidents. Prior to events, 88.9% of cyclists travelled in a safe/legal manner. Sideswipe was the most frequent event type (40.7%). Most events occurred at an intersection/intersection-related location (70.3%). The vehicle driver was judged at fault in the majority of events (87.0%) and no post-event driver reaction was observed (83.3%). Cross tabulations revealed significant associations between event severity and: cyclist reaction, cyclist post-event manoeuvre, pre-event driver behaviour, other vehicle involved, driver reaction, visual obstruction, cyclist head check (left), event type and vehicle location (p<0.05). Frequent head checks suggest cyclists had high situational awareness and their reactive behaviour to driver actions led to successful avoidance of collisions/near-collisions. Strategies to improve driver awareness of on-road cyclists and to indicate early before turning/changing lanes when sharing the roadway with cyclists are discussed. Findings will contribute to the development of effective countermeasures to reduce cyclist trauma.

Critical assessment of the use of growth monitoring for identifying high risk children in primary health care programmes.

PubMed Central

Briend, A.; Bari, A.

1989-01-01

OBJECTIVE--To see whether change in weight was a more useful index than weight for age in assessing the risk of dying among malnourished children. DESIGN--Prospective cohort study. SETTING--Rural community in Bangladesh being served by international health organisation. PARTICIPANTS--1011 Children aged under 5, of whom 66 died. END POINT--Efficient screening method for identifying malnourished children at risk of dying. MEASUREMENTS AND MAIN RESULTS--Weight was measured every month. Weight for age and monthly change in weight averaged over one and three months were calculated. Sensitivity and specificity curves were used to compare the values of these two variables in identifying children with a high risk of dying. Weight for age was more sensitive than change in weight at all levels of specificity. Changes in weight, however, were independently related to the risk of dying even when intercurrent diseases and low weight for age were taken into account. CONCLUSIONS--For identifying children with a high risk of dying weight for age is a more efficient screening tool than a recent change in weight. Growth monitoring as currently recommended for primary health care programmes in developing countries does not seem to be the most effective approach in identifying children in need of urgent help. PMID:2503147

Development and validation testing of a short nutrition questionnaire to identify dietary risk factors in preschoolers aged 12–36 months

PubMed Central

Rice, Niamh; Gibbons, Helena; McNulty, Breige A.; Walton, Janette; Flynn, Albert; Gibney, Michael J.; Nugent, Anne P.

2015-01-01

Background Although imbalances in dietary intakes can have short and longer term influences on the health of preschool children, few tools exist to quickly and easily identify nutritional risk in otherwise healthy young children. Objectives To develop and test the validity of a parent-administered questionnaire (NutricheQ) as a means of evaluating dietary risk in young children (12–36 months). Design Following a comprehensive development process and internal reliability assessment, the NutricheQ questionnaire was validated in a cohort of 371 Irish preschool children as part of the National Preschool Nutrition Survey. Dietary risk was rated on a scale ranging from 0 to 22 from 11 questions, with a higher score indicating higher risk. Results Children with higher NutricheQ scores had significantly (p<0.05) lower mean daily intakes of key nutrients such as iron, zinc, vitamin D, riboflavin, niacin, folate, phosphorous, potassium, carotene, retinol, and dietary fibre. They also had lower (p<0.05) intakes of vegetables, fish and fish dishes, meat and infant/toddler milks and higher intakes of processed foods and non-milk beverages, confectionery, sugars and savoury snack foods indicative of poorer dietary quality. Areas under the curve values of 84.7 and 75.6% were achieved for ‘medium’ and ‘high’ dietary risk when compared with expert risk ratings indicating good consistency between the two methods. Conclusion NutricheQ is a valid method of quickly assessing dietary quality in preschoolers and in identifying those at increased nutritional risk. In Context Analysis of data from national food and nutrition surveys typically identifies shortfalls in dietary intakes or quality of young children. This can relate to intakes of micronutrients such as iron or vitamin D as well as to the balance of macronutrients they consume (e.g. fat or sugar). Alongside this lie concerns regarding overweight and obesity and physical inactivity. This combination of risk factors has

Applying an Evidence-Based Assessment Model to Identify Students at Risk for Perceived Academic Problems following Concussion.

PubMed

Ransom, Danielle M; Burns, Alison R; Youngstrom, Eric A; Vaughan, Christopher G; Sady, Maegan D; Gioia, Gerard A

2016-11-01

The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Latent class analysis categorized participants into "high" (44%) and "low" (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038-1049).

Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health.

PubMed

Abbate, V; Kicman, A T; Evans-Brown, M; McVeigh, J; Cowan, D A; Wilson, C; Coles, S J; Walker, C J

2015-07-01

Twenty-four products suspected of containing anabolic steroids and sold in fitness equipment shops in the United Kingdom (UK) were analyzed for their qualitative and semi-quantitative content using full scan gas chromatography-mass spectrometry (GC-MS), accurate mass liquid chromatography-mass spectrometry (LC-MS), high pressure liquid chromatography with diode array detection (HPLC-DAD), UV-Vis, and nuclear magnetic resonance (NMR) spectroscopy. In addition, X-ray crystallography enabled the identification of one of the compounds, where reference standard was not available. Of the 24 products tested, 23 contained steroids including known anabolic agents; 16 of these contained steroids that were different to those indicated on the packaging and one product contained no steroid at all. Overall, 13 different steroids were identified; 12 of these are controlled in the UK under the Misuse of Drugs Act 1971. Several of the products contained steroids that may be considered to have considerable pharmacological activity, based on their chemical structures and the amounts present. This could unwittingly expose users to a significant risk to their health, which is of particular concern for naïve users. Copyright © 2014 John Wiley & Sons, Ltd.

Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

PubMed

Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

2011-09-23

Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD.

PubMed

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p -benzoquinone ( p -BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p -BQ is also derived from CS in smokers and it elicits the production of anti- p -BQ antibody in humans. We therefore hypothesized that anti- p -BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti- p -BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Serum anti- p -BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A significant difference was observed in the serum anti- p -BQ antibody level between smokers with and without COPD (Mann-Whitney U -test =4,632.5, P =0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913-0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15-101.99) were considered to be at risk for COPD. Our results indicate that serum anti- p -BQ antibody level may be used as a

Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

PubMed

Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

2013-01-01

To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

Identifying risk factors for refractory febrile neutropenia in patients with lung cancer.

PubMed

Fujita, Masaki; Tokunaga, Shoji; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Watanabe, Kentaro; Nakanishi, Yoichi

2012-02-01

Information about the development of febrile neutropenia in patients with solid tumors remains insufficient. In this study, we tried to identify the risk factors for refractory febrile neutropenia in patients with lung cancer. A total of 59 neutropenic fever episodes associated with anti-tumor chemotherapy for lung cancer were retrospectively analyzed. We compared patient characteristics according to their initial response to treatment with antibiotics. For 34 of 59 (58%) episodes a response to initial antibiotics was obtained whereas 25 of 59 (42%) were refractory to treatment. Multivariate analysis demonstrated independent risk factors for refractory febrile neutropenia with lung cancer. These risk factors were the severity of febrile neutropenia (odds ratio (OR) 6.11; 95% confidence interval (CI) 1.85-20.14) and C-reactive protein more than 10 mg/dl (OR 4.39; 95% CI 1.22-15.74). These factors could predict outcome for patients with lung cancer who develop refractory febrile neutropenia.

A genome-wide association study identifies risk loci to equine recurrent uveitis in German warmblood horses.

PubMed

Kulbrock, Maike; Lehner, Stefanie; Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

2013-01-01

Equine recurrent uveitis (ERU) is a common eye disease affecting up to 3-15% of the horse population. A genome-wide association study (GWAS) using the Illumina equine SNP50 bead chip was performed to identify loci conferring risk to ERU. The sample included a total of 144 German warmblood horses. A GWAS showed a significant single nucleotide polymorphism (SNP) on horse chromosome (ECA) 20 at 49.3 Mb, with IL-17A and IL-17F being the closest genes. This locus explained a fraction of 23% of the phenotypic variance for ERU. A GWAS taking into account the severity of ERU, revealed a SNP on ECA18 nearby to the crystalline gene cluster CRYGA-CRYGF. For both genomic regions on ECA18 and 20, significantly associated haplotypes containing the genome-wide significant SNPs could be demonstrated. In conclusion, our results are indicative for a genetic component regulating the possible critical role of IL-17A and IL-17F in the pathogenesis of ERU. The associated SNP on ECA18 may be indicative for cataract formation in the course of ERU.

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

PubMed Central

Permuth, Jennifer B.; Pirie, Ailith; Ann Chen, Y.; Lin, Hui-Yi; Reid, Brett M.; Chen, Zhihua; Monteiro, Alvaro; Dennis, Joe; Mendoza-Fandino, Gustavo; Anton-Culver, Hoda; Bandera, Elisa V.; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E.; Chenevix-Trench, Georgia; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; D’Aloisio, Aimee A.; Anne Doherty, Jennifer; Earp, Madalene; Edwards, Robert P.; Fridley, Brooke L.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Goodman, Marc T.; Gronwald, Jacek; Hogdall, Estrid; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Karlan, Beth Y.; Kelemen, Linda E.; Kjaer, Suzanne K.; Kraft, Peter; Le, Nhu D.; Levine, Douglas A.; Lissowska, Jolanta; Lubinski, Jan; Matsuo, Keitaro; Menon, Usha; Modugno, Rosemary; Moysich, Kirsten B.; Nakanishi, Toru; Ness, Roberta B.; Olson, Sara; Orlow, Irene; Pearce, Celeste L.; Pejovic, Tanja; Poole, Elizabeth M.; Ramus, Susan J.; Anne Rossing, Mary; Sandler, Dale P.; Shu, Xiao-Ou; Song, Honglin; Taylor, Jack A.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tworoger, Shelley S.; Webb, Penelope M.; Wentzensen, Nicolas; Wilkens, Lynne R.; Winham, Stacey; Woo, Yin-Ling; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Phelan, Catherine M.; Schildkraut, Joellen M.; Berchuck, Andrew; Goode, Ellen L.; Pharoah, Paul D. P.; Sellers, Thomas A.

2016-01-01

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P < 5.0 × 10 − 7). One of the most significant signals (Pall histologies = 1.01 × 10 − 13;Pserous = 3.54 × 10 − 14) occurred at 3q25.31 for rs62273959, a missense variant mapping to the LEKR1 gene that is in LD (r2 = 0.90) with a previously identified ‘best hit’ (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 × 10 − 5 > P≥5.0 ×10 − 7) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 − 5; PSKAT-o = 9.23 × 10 − 4) and KRT13 (PAML = 1.67 × 10 − 4; PSKAT-o = 1.07 × 10 − 5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk.

PubMed

Permuth, Jennifer B; Pirie, Ailith; Ann Chen, Y; Lin, Hui-Yi; Reid, Brett M; Chen, Zhihua; Monteiro, Alvaro; Dennis, Joe; Mendoza-Fandino, Gustavo; Anton-Culver, Hoda; Bandera, Elisa V; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E; Chenevix-Trench, Georgia; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; D'Aloisio, Aimee A; Anne Doherty, Jennifer; Earp, Madalene; Edwards, Robert P; Fridley, Brooke L; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Goodman, Marc T; Gronwald, Jacek; Hogdall, Estrid; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kjaer, Suzanne K; Kraft, Peter; Le, Nhu D; Levine, Douglas A; Lissowska, Jolanta; Lubinski, Jan; Matsuo, Keitaro; Menon, Usha; Modugno, Rosemary; Moysich, Kirsten B; Nakanishi, Toru; Ness, Roberta B; Olson, Sara; Orlow, Irene; Pearce, Celeste L; Pejovic, Tanja; Poole, Elizabeth M; Ramus, Susan J; Anne Rossing, Mary; Sandler, Dale P; Shu, Xiao-Ou; Song, Honglin; Taylor, Jack A; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Tworoger, Shelley S; Webb, Penelope M; Wentzensen, Nicolas; Wilkens, Lynne R; Winham, Stacey; Woo, Yin-Ling; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Phelan, Catherine M; Schildkraut, Joellen M; Berchuck, Andrew; Goode, Ellen L; Pharoah, Paul D P; Sellers, Thomas A

2016-08-15

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P < 5.0 × 10  -   7 ). One of the most significant signals (P all histologies  =   1.01 × 10  -   13 ;P serous  =   3.54 × 10  -   14 ) occurred at 3q25.31 for rs62273959, a missense variant mapping to the LEKR1 gene that is in LD (r 2  =   0.90) with a previously identified 'best hit' (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 × 10  -   5  >   P≥5.0 ×10  -   7 ) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (P AML  =   3.23 × 10  -   5 ; P SKAT-o  =   9.23 × 10  -   4 ) and KRT13 (P AML  =   1.67 × 10  -   4 ; P SKAT-o  =   1.07 × 10  -   5 ), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed

Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

ERIC Educational Resources Information Center

Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

2011-01-01

Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

Prevalence of HIV in pregnant women identified with a risk factor at a tertiary care hospital.

PubMed

Mahmud, Ghazala; Abbas, Shazra

2009-01-01

HIV is an epidemic quite unlike any other, combining the problems of a lifelong medical disease with immense social, psychological, economic and public health consequences. Since we are living in a global village where human interactions has become fast and frequent, diseases like HIV are no more alien to us. HIV/AIDS in Pakistan is slowly gaining recognition as a public health issue of great importance. Objectives of this study were to determine the prevalence of HIV in pregnant women identified with a high risk factor/behaviour at a tertiary care hospital. It is a Descriptive study. All pregnant women attending antenatal booking clinic were assessed via a pre-designed 'Risk assessment questionnaire'. Women identified with a risk factor were offered HIV Rapid screening test (Capillus HIV1/2). Positive (reactive) results on screening test were confirmed with ELISA. During the study period (March 2007-May 2008), out of 5263 antenatal bookings 785 (14%) women were identified with a risk factor. HIV screening test was done in 779 (99%), and 6 women refused testing. Three women (0.3%) were found positive (reactive) on screening. Two out of 3 women were confirmed positive (0.2%) on ELISA. Husbands of both women were tested and one found positive (migrant from Dubai). Second women had history of blood transfusion. Her husband was HIV negative. During the study period, in addition to 2 pregnant women diagnosed as HIV positive through ANC risk screening, 6 confirmed HIV positive women, found pregnant were referred from 'HIV Treatment Centre', Pakistan Institute of Medical Sciences (PIMS) to Prevention of Parent to Child Transmission (PPTCT) centre for obstetric care. Spouses of 5 out of 6 had history of working abroad and extramarital sexual relationships. All positive (8) women were referred to PPTCT centre for further management. A simple 'Risk Assessment Questionnaire' can help us in identifying women who need HIV screening. Sexual transmission still remains the

Five endometrial cancer risk loci identified through genome-wide association analysis.

PubMed

Cheng, Timothy Ht; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica Mj; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Consortium, Chibcha; Jun Li, Mulin; Yip, Shun H; Wang, Junwen; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Dunlop, Malcolm; Houlston, Richard; Palles, Claire; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Cunningham, Julie M; Pharoah, Paul D P; Dunning, Alison M; Edwards, Stacey L; Easton, Douglas F; Tomlinson, Ian; Spurdle, Amanda B

2016-06-01

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.

To identify or not to identify parathyroid glands during total thyroidectomy.

PubMed

Chang, Yuk Kwan; Lang, Brian H H

2017-12-01

Hypoparathyroidism is one of the most common complications after total thyroidectomy and may impose a significant burden to both the patient and clinician. The extent of thyroid resection, surgical techniques, concomitant central neck dissection, parathyroid gland (PG) autotransplantation and inadvertent parathyroidectomy have long been some of the risk factors for postoperative hypoparathyroidism. Although routine identification of PGs has traditionally been advocated by surgeons, recent evidence has suggested that perhaps identifying fewer number of in situ PGs during surgery (i.e., selective identification) may further lower the risk of hypoparathyroidism. One explanation is that visual identification may often lead to subtle damages to the nearby blood supply of the in situ PGs and that may increase the risk of hypoparathyroidism. However, it is worth highlighting the current literature supporting either approach (i.e., routine vs. selective) remains scarce and because of the significant differences in study design, inclusions, definitions and management protocol between studies, a pooled analysis on this important but controversial topic remains an impossible task. Furthermore, it is worth nothing that identification of PGs does not equal safe preservation, as some studies demonstrated that it is not the number of PGs identified, but the number of PG preserved in situ that matters. Therefore a non-invasive, objective and reliable way to localize PGs and assess their viability intra-operatively is warranted. In this aspect, modern technology such as the indocyanine green (ICG) as near-infrared fluorescent dye for real-time in situ PG perfusion monitoring may have a potential role in the future.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

PubMed

Warren, Helen R; Evangelou, Evangelos; Cabrera, Claudia P; Gao, He; Ren, Meixia; Mifsud, Borbala; Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Lepe, Marcelo P Segura; O'Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-03-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

PubMed Central

Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Segura Lepe, Marcelo P; O’Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-01-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. Combined with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure raising genetic variants on future cardiovascular disease risk. PMID:28135244

School-Based Screening to Identify At-Risk Students Not Already Known to School Professionals: The Columbia Suicide Screen

PubMed Central

Wilcox, Holly C.; Schonfeld, Irvin Sam; Davies, Mark; Hicks, Roger C.; Turner, J. Blake; Shaffer, David

2009-01-01

Objectives. We sought to determine the degree of overlap between students identified through school-based suicide screening and those thought to be at risk by school administrative and clinical professionals. Methods. Students from 7 high schools in the New York metropolitan area completed the Columbia Suicide Screen; 489 of the 1729 students screened had positive results. The clinical status of 641 students (73% of those who had screened positive and 23% of those who had screened negative) was assessed with modules from the Diagnostic Interview Schedule for Children. School professionals nominated by their principal and unaware of students' screening and diagnostic status were asked to indicate whether they were concerned about the emotional well-being of each participating student. Results. Approximately 34% of students with significant mental health problems were identified only through screening, 13.0% were identified only by school professionals, 34.9% were identified both through screening and by school professionals, and 18.3% were identified neither through screening nor by school professionals. The corresponding percentages among students without mental health problems were 9.1%, 24.0%, 5.5%, and 61.3%. Conclusions. School-based screening can identify suicidal and emotionally troubled students not recognized by school professionals. PMID:19059865

Identifying Trajectories of Borderline Personality Features in Adolescence: Antecedent and Interactive Risk Factors.

PubMed

Haltigan, John D; Vaillancourt, Tracy

2016-03-01

To examine trajectories of adolescent borderline personality (BP) features in a normative-risk cohort (n = 566) of Canadian children assessed at ages 13, 14, 15, and 16 and childhood predictors of trajectory group membership assessed at ages 8, 10, 11, and 12. Data were drawn from the McMaster Teen Study, an on-going study examining relations among bullying, mental health, and academic achievement. Participants and their parents completed a battery of mental health and peer relations questionnaires at each wave of the study. Academic competence was assessed at age 8 (Grade 3). Latent class growth analysis, analysis of variance, and logistic regression were used to analyze the data. Three distinct BP features trajectory groups were identified: elevated or rising, intermediate or stable, and low or stable. Parent- and child-reported mental health symptoms, peer relations risk factors, and intra-individual risk factors were significant predictors of elevated or rising and intermediate or stable trajectory groups. Child-reported attention-deficit hyperactivity disorder (ADHD) and somatization symptoms uniquely predicted elevated or rising trajectory group membership, whereas parent-reported anxiety and child-reported ADHD symptoms uniquely predicted intermediate or stable trajectory group membership. Child-reported somatization symptoms was the only predictor to differentiate the intermediate or stable and elevated or rising trajectory groups (OR 1.15, 95% CI 1.04 to 1.28). Associations between child-reported reactive temperament and elevated BP features trajectory group membership were 10.23 times higher among children who were bullied, supporting a diathesis-stress pathway in the development of BP features for these youth. Findings demonstrate the heterogeneous course of BP features in early adolescence and shed light on the potential prodromal course of later borderline personality disorder. © The Author(s) 2015.

Identifying Children at Risk for Language Impairment or Dyslexia with Group-Administered Measures

ERIC Educational Resources Information Center

Adlof, Suzanne M.; Scoggins, Joanna; Brazendale, Allison; Babb, Spencer; Petscher, Yaacov

2017-01-01

Purpose: The study aims to determine whether brief, group-administered screening measures can reliably identify second-grade children at risk for language impairment (LI) or dyslexia and to examine the degree to which parents of affected children were aware of their children's difficulties. Method: Participants (N = 381) completed screening tasks…

Hazard proximity and risk perception of tsunamis in coastal cities: Are people able to identify their risk?

PubMed

Arias, Juan Pablo; Bronfman, Nicolás C; Cisternas, Pamela C; Repetto, Paula B

2017-01-01

Researchers have previously reported that hazard proximity can influence risk perception among individuals exposed to potential hazards. Understanding this relationship among coastline communities at risk of flood events caused by storms and/or tsunamis, is important because hazard proximity, should be recognized when planning and implementing preparation and mitigation actions against these events. Yet, we are not aware of studies that have examined this relationship among coastline inhabitants facing the risk of a tsunami. Consequently, the aim of this study was to examine the relationship between hazard proximity and perceived risk from tsunamis among coastline inhabitants. Participants were 487 residents of the coastal city of Iquique, Chile. They completed a survey during the spring of 2013 that assessed their perceived risk from several natural and non-natural hazards. We found that hazard proximity maintains a negative relationship with the perception of tsunami risk among coastline inhabitants. While this result confirms the general trend obtained in previous studies, this one is conclusive and significant. In contradiction with previous findings, we found that participants from the highest socioeconomic status reported the highest levels of risk perception. This finding can be explained by the fact that most participants from the highest socioeconomic status live closer to the coastline areas, so their risk perception reflects the place where they live, that is in a tsunami inundation zone. Once again, hazard proximity proved to be a determinant factor of risk perception. Our findings have important implications for the development of plans and programs for tsunami preparedness and mitigation. These indicate that individuals do use environmental cues to evaluate their own risk and can potentially make correct choices when having or not to evacuate. Also suggest that preparedness should incorporate how hazard proximity is recognized by individuals and

Hazard proximity and risk perception of tsunamis in coastal cities: Are people able to identify their risk?

PubMed Central

Arias, Juan Pablo; Bronfman, Nicolás C.; Cisternas, Pamela C.; Repetto, Paula B.

2017-01-01

Researchers have previously reported that hazard proximity can influence risk perception among individuals exposed to potential hazards. Understanding this relationship among coastline communities at risk of flood events caused by storms and/or tsunamis, is important because hazard proximity, should be recognized when planning and implementing preparation and mitigation actions against these events. Yet, we are not aware of studies that have examined this relationship among coastline inhabitants facing the risk of a tsunami. Consequently, the aim of this study was to examine the relationship between hazard proximity and perceived risk from tsunamis among coastline inhabitants. Participants were 487 residents of the coastal city of Iquique, Chile. They completed a survey during the spring of 2013 that assessed their perceived risk from several natural and non-natural hazards. We found that hazard proximity maintains a negative relationship with the perception of tsunami risk among coastline inhabitants. While this result confirms the general trend obtained in previous studies, this one is conclusive and significant. In contradiction with previous findings, we found that participants from the highest socioeconomic status reported the highest levels of risk perception. This finding can be explained by the fact that most participants from the highest socioeconomic status live closer to the coastline areas, so their risk perception reflects the place where they live, that is in a tsunami inundation zone. Once again, hazard proximity proved to be a determinant factor of risk perception. Our findings have important implications for the development of plans and programs for tsunami preparedness and mitigation. These indicate that individuals do use environmental cues to evaluate their own risk and can potentially make correct choices when having or not to evacuate. Also suggest that preparedness should incorporate how hazard proximity is recognized by individuals and

Value of laboratory tests in employer-sponsored health risk assessments for newly identifying health conditions: analysis of 52,270 participants.

PubMed

Kaufman, Harvey W; Williams, Fred R; Odeh, Mouneer A

2011-01-01

Employer-sponsored health risk assessments (HRA) may include laboratory tests to provide evidence of disease and disease risks for common medical conditions. We evaluated the ability of HRA-laboratory testing to provide new disease-risk information to participants. We performed a cross-sectional analysis of HRA-laboratory results for participating adult employees and their eligible spouses or their domestic partners, focusing on three common health conditions: hyperlipidemia, diabetes mellitus, and chronic kidney disease. HRA with laboratory results of 52,270 first-time participants were analyzed. Nearly all participants had access to health insurance coverage. Twenty-four percent (12,392) self-reported one or more of these medical conditions: 21.1% (11,017) self-identified as having hyperlipidemia, 4.7% (2,479) self-identified as having diabetes, and 0.7% (352) self-identified as having chronic kidney disease. Overall, 36% (n = 18,540) of participants had laboratory evidence of at least one medical condition newly identified: 30.7% (16,032) had laboratory evidence of hyperlipidemia identified, 1.9% (984) had laboratory evidence of diabetes identified, and 5.5% (2,866) had laboratory evidence of chronic kidney disease identified. Of all participants with evidence of hyperlipidemia 59% (16,030 of 27,047), were newly identified through the HRA. Among those with evidence of diabetes 28% (984 of 3,463) were newly identified. The highest rate of newly identified disease risk was for chronic kidney disease: 89% (2,866 of 3,218) of participants with evidence of this condition had not self-reported it. Men (39%) were more likely than women (33%) to have at least one newly identified condition (p<0.0001). Among men, lower levels of educational achievement were associated with modestly higher rates of newly identified disease risk (p<0.0001); the association with educational achievement among women was unclear. Even among the youngest age range (20 to 29 year olds

Classroom Dynamics and Young Children Identified as At Risk for the Development of Serious Emotional Disturbance.

ERIC Educational Resources Information Center

Lago-Delello, Ellie

This study examined differences between kindergarten and first-grade children identified as at risk (AR) or not at risk (NAR) for the development of severe emotional disturbance on selected factors of classroom dynamics. Screening, using the Systematic Screening for Behavior Disorders measure, of all 628 kindergarten and first-grade children at…

Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States.

PubMed

Slattery, Martha L; Baumgartner, Kathy B; Giuliano, Anna R; Byers, Tim; Herrick, Jennifer S; Wolff, Roger K

2011-09-01

Genome-wide association studies (GWAS) have identified several loci as being associated with breast cancer in mostly European populations. We focus on TNRC9 rs3803662, FGFR2 rs1219648 and rs2981582, MAP3K1 rs889312, and 2q35 rs13387042, to replicate in the 4-Corner's Breast Cancer Study of Hispanic (N = 565 cases and 714 controls) and non-Hispanic white (NHW) women (N = 1177 cases and 1330 controls). We evaluate associations by ethnicity, menopausal status, and tumor ER/PR status after adjusting for genetic admixture. TNRC9 AA genotype was associated with significant increased risk among NHW women (OR 1.54, 95% CI 1.14, 2.08; P trend 0.003). Both polymorphisms of FGFR2 were associated with statistically significant increased risk for NHW and Hispanic women; MAP3K1 was not associated with risk among either ethnic group. The polymorphism on 2q35 was associated with a statistically significant increased risk among Hispanic women (OR 1.53, 95% CI 1.08, 2.15 for the AA genotype; P trend = 0.004). Associations were significantly different among pre/peri-menopausal women for TNRC9 (P heterogeneity 0.008) and for 2q35 (P heterogeneity 0.08) for NHW and Hispanic women. Both FGFR2 polymorphisms reduced risk of ER-/PR- tumors in the presence of the minor allele among NHW women. Among Hispanic women, polymorphisms of the FGFR2 gene were associated with almost a twofold increase risk of an ER+/PR+ tumor, while non-significantly inversely associated with ER-/PR- tumors. Our data replicated some of the previously reported GWAS findings. Differences in associations were detected for NHW and Hispanic women by menopausal status and by ER/PR status of tumors.

A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia

PubMed Central

2013-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) represents an important pathogen in healthcare-associated pneumonia (HCAP). The concept of HCAP, though, may not perform well as a screening test for MRSA and can lead to overuse of antibiotics. We developed a risk score to identify patients presenting to the hospital with pneumonia unlikely to have MRSA. Methods We identified patients admitted with pneumonia (Apr 2005 – Mar 2009) at 62 hospitals in the US. We only included patients with lab evidence of bacterial infection (e.g., positive respiratory secretions, blood, or pleural cultures or urinary antigen testing). We determined variables independently associated with the presence of MRSA based on logistic regression (two-thirds of cohort) and developed a risk prediction model based on these factors. We validated the model in the remaining population. Results The cohort included 5975 patients and MRSA was identified in 14%. The final risk score consisted of eight variables and a potential total score of 10. Points were assigned as follows: two for recent hospitalization or ICU admission; one each for age < 30 or > 79 years, prior IV antibiotic exposure, dementia, cerebrovascular disease, female with diabetes, or recent exposure to a nursing home/long term acute care facility/skilled nursing facility. This study shows how the prevalence of MRSA rose with increasing score after stratifying the scores into Low (0 to 1 points), Medium (2 to 5 points) and High (6 or more points) risk. When the score was 0 or 1, the prevalence of MRSA was < 10% while the prevalence of MRSA climbed to > 30% when the score was 6 or greater. Conclusions MRSA represents a cause of pneumonia presenting to the hospital. This simple risk score identifies patients at low risk for MRSA and in whom anti-MRSA therapy might be withheld. PMID:23742753

Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity.

PubMed

Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

2017-04-01

Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p < 0.0001); 1225 (10.1%) beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p < 0.0001); and 16 (0.13%) beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

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

Hsieh, Yi-Chen; Lien, Li-Ming; School of Medicine, Taipei Medical University, Taipei, Taiwan

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study.more » Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis

Microarray-based SNP genotyping to identify genetic risk factors of triple-negative breast cancer (TNBC) in South Indian population.

PubMed

Aravind Kumar, M; Singh, Vineeta; Naushad, Shaik Mohammad; Shanker, Uday; Lakshmi Narasu, M

2018-05-01

In the view of aggressive nature of Triple-Negative Breast cancer (TNBC) due to the lack of receptors (ER, PR, HER2) and high incidence of drug resistance associated with it, a case-control association study was conducted to identify the contributing genetic risk factors for Triple-negative breast cancer (TNBC). A total of 30 TNBC patients and 50 age and gender-matched controls of Indian origin were screened for 9,00,000 SNP markers using microarray-based SNP genotyping approach. The initial PLINK association analysis (p < 0.01, MAF 0.14-0.44, OR 10-24) identified 28 non-synonymous SNPs and one stop gain mutation in the exonic region as possible determinants of TNBC risk. All the 29 SNPs were annotated using ANNOVAR. The interactions between these markers were evaluated using Multifactor dimensionality reduction (MDR) analysis. The interactions were in the following order: exm408776 > exm1278309 > rs316389 > rs1651654 > rs635538 > exm1292477. Recursive partitioning analysis (RPA) was performed to construct decision tree useful in predicting TNBC risk. As shown in this analysis, rs1651654 and exm585172 SNPs are found to be determinants of TNBC risk. Artificial neural network model was used to generate the Receiver operating characteristic curves (ROC), which showed high sensitivity and specificity (AUC-0.94) of these markers. To conclude, among the 9,00,000 SNPs tested, CCDC42 exm1292477, ANXA3 exm408776, SASH1 exm585172 are found to be the most significant genetic predicting factors for TNBC. The interactions among exm408776, exm1278309, rs316389, rs1651654, rs635538, exm1292477 SNPs inflate the risk for TNBC further. Targeted analysis of these SNPs and genes alone also will have similar clinical utility in predicting TNBC.

Patient selection for day case-eligible surgery: identifying those at high risk for major complications.

PubMed

Mathis, Michael R; Naughton, Norah N; Shanks, Amy M; Freundlich, Robert E; Pannucci, Christopher J; Chu, Yijia; Haus, Jason; Morris, Michelle; Kheterpal, Sachin

2013-12-01

Due to economic pressures and improvements in perioperative care, outpatient surgical procedures have become commonplace. However, risk factors for outpatient surgical morbidity and mortality remain unclear. There are no multicenter clinical data guiding patient selection for outpatient surgery. The authors hypothesize that specific risk factors increase the likelihood of day case-eligible surgical morbidity or mortality. The authors analyzed adults undergoing common day case-eligible surgical procedures by using the American College of Surgeons' National Surgical Quality Improvement Program database from 2005 to 2010. Common day case-eligible surgical procedures were identified as the most common outpatient surgical Current Procedural Terminology codes provided by Blue Cross Blue Shield of Michigan and Medicare publications. Study variables included anthropometric data and relevant medical comorbidities. The primary outcome was morbidity or mortality within 72 h. Intraoperative complications included adverse cardiovascular events; postoperative complications included surgical, anesthetic, and medical adverse events. Of 244,397 surgeries studied, 232 (0.1%) experienced early perioperative morbidity or mortality. Seven independent risk factors were identified while controlling for surgical complexity: overweight body mass index, obese body mass index, chronic obstructive pulmonary disease, history of transient ischemic attack/stroke, hypertension, previous cardiac surgical intervention, and prolonged operative time. The demonstrated low rate of perioperative morbidity and mortality confirms the safety of current day case-eligible surgeries. The authors obtained the first prospectively collected data identifying risk factors for morbidity and mortality with day case-eligible surgery. The results of the study provide new data to advance patient-selection processes for outpatient surgery.

Identifying At-Risk Individuals for Insomnia Using the Ford Insomnia Response to Stress Test.

PubMed

Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Drake, Christopher L

2016-02-01

A primary focus of the National Institute of Mental Health's current strategic plan is "predicting" who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49-1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts. © 2016 Associated Professional Sleep Societies, LLC.

Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

NASA Astrophysics Data System (ADS)

Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.

PubMed

Ryan, Joanne; Artero, Sylvaine; Carrière, Isabelle; Maller, Jerome J; Meslin, Chantal; Ritchie, Karen; Ancelin, Marie-Laure

2016-01-01

A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Risk factors identified for certain lymphoma subtypes

Cancer.gov

In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

Suicidal Ideation in Anxiety-Disordered Youth: Identifying Predictors of Risk

PubMed Central

O'Neil Rodriguez, Kelly A.; Kendall, Philip C.

2014-01-01

Objective Evidence is mixed regarding an independent association between anxiety and suicidality. Beyond associations with demographic factors and depression, do anxiety disorders increase risk for suicidality in youth? Given that not all anxiety-disordered youth experience suicidal ideation, potential predictors of risk also require investigation. Method The present study examined (a) the independent relationship between anxiety and suicidal ideation and (b) emotion dysregulation and distress intolerance as predictors of risk for suicidal ideation in a sample of anxiety-disordered youth aged 7-17 (N = 86, M = 11.5). Youth and their parents reported on suicidality, emotion dysregulation, and distress intolerance. Distress tolerance was also measured by a computerized behavioral task. Results Results support an independent relationship between anxiety symptomatology and youth-reported suicidal ideation, controlling for depressive symptoms. Youth self-report of emotion dysregulation and distress intolerance predicted higher levels of suicidal ideation in univariate analyses. In a multivariate analysis including all significant predictors, only anxiety symptomatology uniquely predicted suicidal ideation. Conclusions Results provide recommendations for the assessment and treatment of suicidality in anxiety-disordered youth. Suggestions for future research investigating the relationship between anxiety and suicidal ideation are offered. PMID:24156368

Use of a risk scoring tool to identify higher-risk HIV-1 serodiscordant couples for an antiretroviral-based HIV-1 prevention intervention.

PubMed

Irungu, Elizabeth M; Heffron, Renee; Mugo, Nelly; Ngure, Kenneth; Katabira, Elly; Bulya, Nulu; Bukusi, Elizabeth; Odoyo, Josephine; Asiimwe, Stephen; Tindimwebwa, Edna; Celum, Connie; Baeten, Jared M

2016-10-17

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) reduce HIV-1 transmission within heterosexual HIV-1 serodiscordant couples. Prioritizing couples at highest HIV-1 transmission risk for ART and PrEP would maximize impact and minimize costs. The Partners Demonstration Project is an open-label, delivery study of integrated PrEP and ART for HIV-1 prevention among high risk HIV-1 serodiscordant couples in Kenya and Uganda. We evaluated the feasibility of using a validated risk score that weighs a combination of easily measurable factors (age, children, marital status, male circumcision status, condom use, plasma HIV-1 levels) to identify couples at highest risk for HIV-1 transmission for enrollment. Couples scoring ≥5 met the risk score eligibility criteria. We screened 1694 HIV-1 serodiscordant couples and enrolled 1013. Of the screened couples, 1331 (78.6 %) scored ≥5 (with an expected incidence >3 % per year) and 76 % of these entered the study. The median age of the HIV-1 uninfected partner was 29 years [IQR 26, 36] and 20 % were <25 years of age. The HIV-1 uninfected partner was male in 67 % of partnerships, 33 % of whom were uncircumcised, 57 % of couples had no children, and 65 % reported unprotected sex in the month prior to enrollment. Among HIV-1 infected partners, 41 % had plasma viral load >50,000 copies/ml. A risk scoring tool identified HIV-1 serodiscordant couples for a demonstration project of PrEP and ART with high HIV-1 risk. The tool may be feasible for research and public health settings to maximize efficiency and minimize HIV-1 prevention costs.

Using the personal background preparation survey to identify health science professions students at risk for adverse academic events.

PubMed

Johnson, Craig W; Johnson, Ronald; McKee, John C; Kim, Mira

2009-12-01

In the first predictive validity study of a diagnostic and prescriptive instrument for averting adverse academic status events (AASE) among multiple populations of diverse health science professions students, entering matriculates' personal background and preparation survey (PBPS) scores consistently significantly predicted 1st- or 2nd-year AASE. During 1st-year orientations, 441 entering matriculates in four southwestern schools from dental, medical, and nursing disciplines completed the 2004 PBPS. The following year during 1st-year orientations, 526 entering matriculates in five schools from dental, medical, nursing, and biomedical science disciplines completed the 2005 PBPS. The PBPS identifies and quantifies a student's noncognitive and cognitive academic performance risks. One standard deviation increments in PBPS risks consistently multiplied 1st- or 2nd-year AASE odds by approximately 140% (p < .05), controlling for underrepresented minority student (URMS) status and school affiliation. Odds of 2nd-year AASE for URMS one standard deviation above the 2004 PBPS mean reached 494% of odds for nonURMS at the mean. PBPS total risks, school affiliation, and URMS status together provided 70-76% correct predictions of 1st- or 2nd-year AASE. PBPS predictive validity did not differ significantly among dental, medical, nursing, or biomedical science schools, or URMS/nonURMS. PBPS sensitivity and specificity approached those for FDA-approved screening mammograms for breast cancer and PSA tests for prostate cancer. PBPS positive predictive values of 42-60% exceeded those for both. The diagnostic and prescriptive PBPS can facilitate proactive targeting of corrective interventions aimed at reducing AASE and attrition among health science education students at risk for academic difficulties.

Cloud-based solution to identify statistically significant MS peaks differentiating sample categories.

PubMed

Ji, Jun; Ling, Jeffrey; Jiang, Helen; Wen, Qiaojun; Whitin, John C; Tian, Lu; Cohen, Harvey J; Ling, Xuefeng B

2013-03-23

Mass spectrometry (MS) has evolved to become the primary high throughput tool for proteomics based biomarker discovery. Until now, multiple challenges in protein MS data analysis remain: large-scale and complex data set management; MS peak identification, indexing; and high dimensional peak differential analysis with the concurrent statistical tests based false discovery rate (FDR). "Turnkey" solutions are needed for biomarker investigations to rapidly process MS data sets to identify statistically significant peaks for subsequent validation. Here we present an efficient and effective solution, which provides experimental biologists easy access to "cloud" computing capabilities to analyze MS data. The web portal can be accessed at http://transmed.stanford.edu/ssa/. Presented web application supplies large scale MS data online uploading and analysis with a simple user interface. This bioinformatic tool will facilitate the discovery of the potential protein biomarkers using MS.

Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

PubMed

Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

2008-08-15

Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

School-based Screening to Identify Children At Risk for Attention-Deficit/Hyperactivity Disorder: Barriers and Implications

PubMed Central

Barry, Tammy D.; Sturner, Raymond A.; Seymour, Karen; Howard, Barbara H.; McGoron, Lucy; Bergmann, Paul; Kent, Ronald; Sullivan, Casey; Tomeny, Theodore S.; Pierce, Jessica S.; Coin, Kristen L.; Goodlad, James K.; Werle, Nichole

2014-01-01

This report describes a school-based screening project to improve early identification of children at risk for attention-deficit/hyperactivity disorder (ADHD) and communicate these concerns to parents, recommending that they contact their child’s primary care provider (PCP). Of 17,440 eligible children in first through fifth grades in five school districts, 47.0% of parents provided required written consent, and teachers completed 70.4% of the online screeners (using the Vanderbilt AD/HD Diagnostic Teacher Rating Scale). Of 5,772 screeners completed, 18.1% of children (n = 1,044) were identified as at risk. Parents of at-risk children were contacted to explain risk status and recommended to visit their child’s PCP for further evaluation. It was not possible to contact 39.1% of parents of at-risk children. Of the 636 parents of at-risk children who could be contacted, 53.1% (n = 338) verbally accepted the recommendation to follow-up with their PCP, which was not related to ADHD symptom severity. Parents of children with IEPs or related services were more likely to accept the recommendation to visit the PCP. Our exploration of the potential for school-based screening for ADHD identified a number of barriers to successful execution, but the data also indicated that this is an important problem to address. PMID:27642209

Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials.

PubMed

Harrington, John S; Schenck, Edward J; Oromendia, Clara; Choi, Augustine M K; Siempos, Ilias I

2018-06-02

We examined whether patients with acute respiratory distress syndrome (ARDS) lacking risk factors are enrolled in therapeutic trials and assessed their clinical characteristics and outcomes. We performed a secondary analysis of patient-level data pooled from the ARMA, ALVEOLI, FACTT, ALTA and EDEN ARDSNet randomized controlled trials obtained from the Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung and Blood Institute. We compared baseline characteristics and clinical outcomes (before and after adjustment using Poisson regression model) of ARDS patients with versus without risk factors. Of 3733 patients with ARDS, 81 (2.2%) did not have an identifiable risk factor. Patients without risk factors were younger, had lower baseline severity of illness, were more likely to have the ARDS resolve rapidly (i.e., within 24 h) (p < 0.001) and they had more ventilator-free days (median 21; p = 0.003), more intensive care unit-free days (18; p = 0.010), and more non-pulmonary organ failure-free days (24; p < 0.001) than comparators (17, 14 and 18, respectively). Differences persisted after adjustment for potential confounders. Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials and may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors. Copyright © 2018. Published by Elsevier Inc.

Risk assessment tools to identify women with increased risk of osteoporotic fracture: complexity or simplicity? A systematic review.

PubMed

Rubin, Katrine Hass; Friis-Holmberg, Teresa; Hermann, Anne Pernille; Abrahamsen, Bo; Brixen, Kim

2013-08-01

A huge number of risk assessment tools have been developed. Far from all have been validated in external studies, more of them have absence of methodological and transparent evidence, and few are integrated in national guidelines. Therefore, we performed a systematic review to provide an overview of existing valid and reliable risk assessment tools for prediction of osteoporotic fractures. Additionally, we aimed to determine if the performance of each tool was sufficient for practical use, and last, to examine whether the complexity of the tools influenced their discriminative power. We searched PubMed, Embase, and Cochrane databases for papers and evaluated these with respect to methodological quality using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) checklist. A total of 48 tools were identified; 20 had been externally validated, however, only six tools had been tested more than once in a population-based setting with acceptable methodological quality. None of the tools performed consistently better than the others and simple tools (i.e., the Osteoporosis Self-assessment Tool [OST], Osteoporosis Risk Assessment Instrument [ORAI], and Garvan Fracture Risk Calculator [Garvan]) often did as well or better than more complex tools (i.e., Simple Calculated Risk Estimation Score [SCORE], WHO Fracture Risk Assessment Tool [FRAX], and Qfracture). No studies determined the effectiveness of tools in selecting patients for therapy and thus improving fracture outcomes. High-quality studies in randomized design with population-based cohorts with different case mixes are needed. Copyright © 2013 American Society for Bone and Mineral Research.

Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease.

PubMed

Ertekin-Taner, Nilüfer; Allen, Mariet; Fadale, Daniel; Scanlin, Leah; Younkin, Linda; Petersen, Ronald C; Graff-Radford, Neill; Younkin, Steven G

2004-04-01

Risk for late onset Alzheimer disease (LOAD) and plasma amyloid beta levels (Abeta42; encoded by APP), an intermediate phenotype for LOAD, show linkage to chromosome 10q. Several strong candidate genes (VR22, PLAU, IDE) lie within the 1-lod support interval for linkage. Others have independently identified haplotypes in the chromosome 10q region harboring IDE that show highly significant association with intermediate AD phenotypes and with risk for AD. To pursue these associations, we analyzed the same haplotypes for association with plasma Abeta42 in 24 extended LOAD families and for association with LOAD in two independent case-control series. One series (MCR, 188 age-matched case-control pairs) did not show association (p=0.64) with the six haplotypes in the 276-kb region spanning three genes (IDE, KNSL1, and HHEX) previously shown to associate with LOAD. The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes. In the MCJ series, the H4 (odds ratio [OR]=5.1, p=0.003) and H2(H7) haplotypes (OR=0.60, p=0.04) had the same effects previously reported. In this series, the H8 haplotype (OR=2.7, p=0.098) also had an effect similar as in one previous case control series but not in others. In the extended families, the H8 haplotype was associated with significantly elevated plasma Abeta42 (p=0.02). In addition, the H5(H10) haplotype, which is associated with reduced risk for AD in the other study is associated with reduced plasma Abeta42 (p=0.007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD. Copyright 2004 Wiley-Liss, Inc.

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Using association rule mining to identify risk factors for early childhood caries.

PubMed

Ivančević, Vladimir; Tušek, Ivan; Tušek, Jasmina; Knežević, Marko; Elheshk, Salaheddin; Luković, Ivan

2015-11-01

Early childhood caries (ECC) is a potentially severe disease affecting children all over the world. The available findings are mostly based on a logistic regression model, but data mining, in particular association rule mining, could be used to extract more information from the same data set. ECC data was collected in a cross-sectional analytical study of the 10% sample of preschool children in the South Bačka area (Vojvodina, Serbia). Association rules were extracted from the data by association rule mining. Risk factors were extracted from the highly ranked association rules. Discovered dominant risk factors include male gender, frequent breastfeeding (with other risk factors), high birth order, language, and low body weight at birth. Low health awareness of parents was significantly associated to ECC only in male children. The discovered risk factors are mostly confirmed by the literature, which corroborates the value of the methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

PubMed

Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

2017-04-01

To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying areas under potential risk of illegal construction and demolition waste dumping using GIS tools.

PubMed

Seror, Nissim; Portnov, Boris A

2018-05-01

Construction and demolition (C&D) waste, dumped illegally in ravines and open areas, contaminates soil and can cause underground water pollution and forests fires. Yet, effective monitoring of illegal C&D waste dumping and enforcing legislation against the offenders are often a difficult task due to the large size of geographic areas that need to be monitored, and limited human and financial resources available to environmental law enforcement agencies. In this study, we use Geographic Information System (GIS) tools and geo-statistical modelling to identify the areas under potentially elevated risk of illegal C&D waste dumping in the Haifa district of Israel. As our analysis shows, locational factors, significantly associated with the accumulated amount of waste in the existing illegal C&D waste sites, include: distance to the nearest main road, depth of the ravine present at the site (p<0.01), and forest proximity (p<0.05). Using the model incorporating these locational parameters, we mapped the areas under the elevated risk of illegal C&D waste dumping for future monitoring. As we suggest, the proposed approach may be useful for environmental law enforcement authorities, by helping them to focus on specific sites for inspection, save resources, and act against the offenders more efficiently. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identifying areas of high risk of human exposure to coccidioidomycosis in Texas using serology data from dogs.

PubMed

Gautam, R; Srinath, I; Clavijo, A; Szonyi, B; Bani-Yaghoub, M; Park, S; Ivanek, R

2013-03-01

Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF. © 2012 Blackwell Verlag GmbH.

Identifying HIV most-at-risk groups in Malawi for targeted interventions. A classification tree model

PubMed Central

Emina, Jacques B O; Madise, Nyovani; Kuepie, Mathias; Zulu, Eliya M; Ye, Yazoume

2013-01-01

Objectives To identify HIV-socioeconomic predictors as well as the most-at-risk groups of women in Malawi. Design A cross-sectional survey. Setting Malawi Participants The study used a sample of 6395 women aged 15–49 years from the 2010 Malawi Health and Demographic Surveys. Interventions N/A Primary and secondary outcome measures Individual HIV status: positive or not. Results Findings from the Pearson χ2 and χ2 Automatic Interaction Detector analyses revealed that marital status is the most significant predictor of HIV. Women who are no longer in union and living in the highest wealth quintiles households constitute the most-at-risk group, whereas the less-at-risk group includes young women (15–24) never married or in union and living in rural areas. Conclusions In the light of these findings, this study recommends: (1) that the design and implementation of targeted interventions should consider the magnitude of HIV prevalence and demographic size of most-at-risk groups. Preventive interventions should prioritise couples and never married people aged 25–49 years and living in rural areas because this group accounts for 49% of the study population and 40% of women living with HIV in Malawi; (2) with reference to treatment and care, higher priority must be given to promoting HIV test, monitoring and evaluation of equity in access to treatment among women in union disruption and never married or women in union aged 30–49 years and living in urban areas; (3) community health workers, households-based campaign, reproductive-health services and reproductive-health courses at school could be used as canons to achieve universal prevention strategy, testing, counselling and treatment. PMID:23793677

Can we use subchondral bone thickness on high-field magnetic resonance images to identify Thoroughbred racehorses at risk of catastrophic lateral condylar fracture?

PubMed

Tranquille, C A; Murray, R C; Parkin, T D H

2017-03-01

Fractures of the lateral condyle of the third metacarpus (MC3) are a significant welfare concern in horseracing worldwide. The primary aim of this work was to identify magnetic resonance (MR) image-detectable prefracture markers that have the potential for use as a screening tool to identify horses at significant risk of catastrophic fracture. Case-control study of bone-level risk factors for fracture in racehorses. A total of 191 MC3s from horses, with and without lateral condylar fracture of MC3, were subjected to MR imaging. The depth of dense subchondral/trabecular bone was measured at several sites around the distal end of the bone and regression analyses were conducted to identify differences in this depth between horses with and without lateral condylar fracture. Greater depth of dense subchondral/trabecular bone in the palmar half of the lateral parasagittal groove of distal MC3 was associated with an increased likelihood of being from a horse that had sustained a fracture. Receiver operator characteristic analysis was used to identify the optimal cut-off in the depth of dense subchondral/trabecular bone at this site to best discriminate fracture status. Positive and negative predictive values were calculated using the prevalence of fracture within the current study and also a prevalence estimate for the wider racehorse population. There is a requirement to identify suitable prescreening test(s) to eliminate many true negative horses and increase the prevalence of prefracture pathology in the sub population that would be screened using MR imaging, in turn maximising the positive predictive value of this test. © 2016 EVJ Ltd.

Genome-wide pathway-based association analysis identifies risk pathways associated with Parkinson's disease.

PubMed

Zhang, Mingming; Mu, Hongbo; Shang, Zhenwei; Kang, Kai; Lv, Hongchao; Duan, Lian; Li, Jin; Chen, Xinren; Teng, Yanbo; Jiang, Yongshuai; Zhang, Ruijie

2017-01-06

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is generally believed that it is influenced by both genetic and environmental factors, but the precise pathogenesis of PD is unknown to date. In this study, we performed a pathway analysis based on genome-wide association study (GWAS) to detect risk pathways of PD in three GWAS datasets. We first mapped all SNP markers to autosomal genes in each GWAS dataset. Then, we evaluated gene risk values using the minimum P-value of the tagSNPs. We took a pathway as a unit to identify the risk pathways based on the cumulative risks of the genes in the pathway. Finally, we combine the analysis results of the three datasets to detect the high risk pathways associated with PD. We found there were five same pathways in the three datasets. Besides, we also found there were five pathways which were shared in two datasets. Most of these pathways are associated with nervoussystem. Five pathways had been reported to be PD-related pathways in the previous literature. Our findings also implied that there was a close association between immune response and PD. Continued investigation of these pathways will further help us explain the pathogenesis of PD. Copyright © 2016. Published by Elsevier Ltd.

Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci

NASA Astrophysics Data System (ADS)

Law, Philip J.; Sud, Amit; Mitchell, Jonathan S.; Henrion, Marc; Orlando, Giulia; Lenive, Oleg; Broderick, Peter; Speedy, Helen E.; Johnson, David C.; Kaiser, Martin; Weinhold, Niels; Cooke, Rosie; Sunter, Nicola J.; Jackson, Graham H.; Summerfield, Geoffrey; Harris, Robert J.; Pettitt, Andrew R.; Allsup, David J.; Carmichael, Jonathan; Bailey, James R.; Pratt, Guy; Rahman, Thahira; Pepper, Chris; Fegan, Chris; von Strandmann, Elke Pogge; Engert, Andreas; Försti, Asta; Chen, Bowang; Filho, Miguel Inacio Da Silva; Thomsen, Hauke; Hoffmann, Per; Noethen, Markus M.; Eisele, Lewin; Jöckel, Karl-Heinz; Allan, James M.; Swerdlow, Anthony J.; Goldschmidt, Hartmut; Catovsky, Daniel; Morgan, Gareth J.; Hemminki, Kari; Houlston, Richard S.

2017-01-01

B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.

A Genome-Wide Association Study Identifies Risk Loci to Equine Recurrent Uveitis in German Warmblood Horses

PubMed Central

Kulbrock, Maike; Lehner, Stefanie; Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

2013-01-01

Equine recurrent uveitis (ERU) is a common eye disease affecting up to 3–15% of the horse population. A genome-wide association study (GWAS) using the Illumina equine SNP50 bead chip was performed to identify loci conferring risk to ERU. The sample included a total of 144 German warmblood horses. A GWAS showed a significant single nucleotide polymorphism (SNP) on horse chromosome (ECA) 20 at 49.3 Mb, with IL-17A and IL-17F being the closest genes. This locus explained a fraction of 23% of the phenotypic variance for ERU. A GWAS taking into account the severity of ERU, revealed a SNP on ECA18 nearby to the crystalline gene cluster CRYGA-CRYGF. For both genomic regions on ECA18 and 20, significantly associated haplotypes containing the genome-wide significant SNPs could be demonstrated. In conclusion, our results are indicative for a genetic component regulating the possible critical role of IL-17A and IL-17F in the pathogenesis of ERU. The associated SNP on ECA18 may be indicative for cataract formation in the course of ERU. PMID:23977091

Identifying mismatches between institutional perceptions of water-related risk drivers and water management strategies in three river basin areas

NASA Astrophysics Data System (ADS)

Räsänen, Aleksi; Juhola, Sirkku; Monge Monge, Adrián; Käkönen, Mira; Kanninen, Markku; Nygren, Anja

2017-07-01

Water-related risks and vulnerabilities are driven by variety of stressors, including climate and land use change, as well as changes in socio-economic positions and political landscapes. Hence, water governance, which addresses risks and vulnerabilities, should target multiple stressors. We analyze the institutional perceptions of the drivers and strategies for managing water-related risks and vulnerabilities in three regionally important river basin areas located in Finland, Mexico, and Laos. Our analysis is based on data gathered through participatory workshops and complemented by qualitative content analysis of relevant policy documents. The identified drivers and proposed risk reduction strategies showed the multidimensionality and context-specificity of water-related risks and vulnerabilities across study areas. Most of the identified drivers were seen to increase risks, but some of the drivers were positive trends, and drivers also included also policy instruments that can both increase or decrease risks. Nevertheless, all perceived drivers were not addressed with suggested risk reduction strategies. In particular, most of the risk reduction strategies were incremental adjustments, although many of the drivers classified as most important were large-scale trends, such as climate change, land use changes and increase in foreign investments. We argue that there is a scale mismatch between the identified drivers and suggested strategies, which questions the opportunity to manage the drivers by single-scale incremental adjustments. Our study suggests that for more sustainable risk and vulnerability reduction, the root causes of water-related risks and vulnerabilities should be addressed through adaptive multi-scale governance that carefully considers the context-specificity and the multidimensionality of the associated drivers and stressors.

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD

PubMed Central

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Background and objective Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p-benzoquinone (p-BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p-BQ is also derived from CS in smokers and it elicits the production of anti-p-BQ antibody in humans. We therefore hypothesized that anti-p-BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti-p-BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Methods Serum anti-p-BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Results and discussion A significant difference was observed in the serum anti-p-BQ antibody level between smokers with and without COPD (Mann–Whitney U-test =4,632.5, P=0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913–0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15–101.99) were considered to be at risk for COPD. Conclusion and future directions

Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

PubMed

Beck, Alexander; Eberherr, Corinna; Hagemann, Michaela; Cairo, Stefano; Häberle, Beate; Vokuhl, Christian; von Schweinitz, Dietrich; Kappler, Roland

2016-11-01

Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option. Subsequent expression analysis of primary HB and HB cell lines revealed a general overexpression of HDAC1 and HDAC2, which has been suggested to be predictive for the efficacy of HDAC inhibition. Accordingly, treatment of HB cells with the HDAC inhibitors SAHA and MC1568 resulted in a potent reduction of cell viability, induction of apoptosis, reactivation of epigenetically suppressed tumor suppressor genes, and the reversion of the 16-gene HB classifier toward the more favorable expression signature. Most importantly, the combination of HDAC inhibitors and cisplatin - a major chemotherapeutic agent of HB treatment - revealed a strong synergistic effect, even at significantly reduced doses of cisplatin. Our findings suggest that HDAC inhibitors skew HB cells toward a more favorable prognostic phenotype through changes in gene expression, thus indicating a targeted molecular mechanism that seems to enhance the anti-proliferative effects of conventional chemotherapy. Thus, adding HDAC inhibitors to the treatment regimen of high risk HB could potentially improve outcomes and reduce severe late effects.

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

PubMed

van Leeuwen, Pim J; Hayen, Andrew; Thompson, James E; Moses, Daniel; Shnier, Ron; Böhm, Maret; Abuodha, Magdaline; Haynes, Anne-Maree; Ting, Francis; Barentsz, Jelle; Roobol, Monique; Vass, Justin; Rasiah, Krishan; Delprado, Warick; Stricker, Phillip D

2017-12-01

To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Identifying Emergency Department Patients at Low Risk for a Variceal Source of Upper Gastrointestinal Hemorrhage.

PubMed

Klein, Lauren R; Money, Joel; Maharaj, Kaveesh; Robinson, Aaron; Lai, Tarissa; Driver, Brian E

2017-11-01

Assessing the likelihood of a variceal versus nonvariceal source of upper gastrointestinal bleeding (UGIB) guides therapy, but can be difficult to determine on clinical grounds. The objective of this study was to determine if there are easily ascertainable clinical and laboratory findings that can identify a patient as low risk for a variceal source of hemorrhage. This was a retrospective cohort study of adult ED patients with UGIB between January 2008 and December 2014 who had upper endoscopy performed during hospitalization. Clinical and laboratory data were abstracted from the medical record. The source of the UGIB was defined as variceal or nonvariceal based on endoscopic reports. Binary recursive partitioning was utilized to create a clinical decision rule. The rule was internally validated and test characteristics were calculated with 1,000 bootstrap replications. A total of 719 patients were identified; mean age was 55 years and 61% were male. There were 71 (10%) patients with a variceal UGIB identified on endoscopy. Binary recursive partitioning yielded a two-step decision rule (platelet count > 200 × 10 9 /L and an international normalized ratio [INR] < 1.3), which identified patients who were low risk for a variceal source of hemorrhage. For the bootstrapped samples, the rule performed with 97% sensitivity (95% confidence interval [CI] = 91%-100%) and 49% specificity (95% CI = 44%-53%). Although this derivation study must be externally validated before widespread use, patients presenting to the ED with an acute UGIB with platelet count of >200 × 10 9 /L and an INR of <1.3 may be at very low risk for a variceal source of their upper gastrointestinal hemorrhage. © 2017 by the Society for Academic Emergency Medicine.

Nutritional markers may identify patients with greater risk of re-admission after geriatric hip fractures.

PubMed

Stone, Austin V; Jinnah, Alexander; Wells, Brian J; Atkinson, Hal; Miller, Anna N; Futrell, Wendell M; Lenoir, Kristin; Emory, Cynthia L

2018-02-01

Osteoporotic hip fractures are increasing in prevalence with the growing elderly population. Morbidity and mortality remain high following osteoporotic hip fractures despite advances in medical and surgical treatments. The associated costs and medical burdens are increased with a re-admission following hip fracture treatment. This study sought to identify demographic and clinical values that may be a predictive model for 30-day re-admission risk following operative management of an isolated hip fracture. Between January 1, 2013 and April 30, 2015 all patients admitted to a single academic medical centre for treatment of a hip fracture were reviewed. Candidate variables included standard demographics, common laboratory values, and markers of comorbid conditions and nutrition status. A 30-day, all-cause re-admission model was created utilizing multivariate logistic regression. A total of 607 patients with hip fractures were identified and met the inclusion criteria; of those patients, 67 were re-admitted within 30 days. Univariate analysis indicates that the re-admission group had more comorbidities (p < 0.001) and lower albumin (p = 0.038) and prealbumin (p < 0.001). The final, reduced model contained 12 variables and incorporated four out of five nutritional makers with an internally, cross-validated C-statistic of 0.811 (95% CI: 0.754, 0.867). Our results indicate that specific nutritional laboratory markers at the index admission may identify patients that have a greater risk of re-admission after hip fracture. This model identifies potentially modifiable risk factors and may allow orthogeriatricians to better educate patients and better treat post-operative nutritional status and care.

Significant factors of aviation insurance and risk management strategy: an empirical study of Taiwanese airline carriers.

PubMed

Lin, Yi Hsin; Chang, Yu Hern

2008-04-01

Aviation insurance premiums have become a heavy burden for the airline industry since September 11, 2001. Although the industry must constantly balance its operations between profitability and safety, the reality is that airlines are in the business of making money. Therefore, their ability to reduce cost and manage risk is a key factor for success. Unlike past research, which used subjective judgment methods, this study applied quantitative historical data (1999-2000) and gray relation analysis to identify the primary factors influencing ratemaking for aviation insurance premiums. An empirical study of six airlines in Taiwan was conducted to determine these factors and to analyze the management strategies used to deal with them. Results showed that the loss experience and performance of individual airlines were the key elements associated with aviation insurance premiums paid by each airline. By identifying and understanding the primary factors influencing ratemaking for aviation insurance, airlines will better understand their relative operational strengths and weaknesses, and further help top management identify areas for further improvement. Knowledge of these factors combined with effective risk management strategies, may result in lower premiums and operating costs for airline companies.

A case-control study to identify risk factors for totally implantable central venous port-related bloodstream infection.

PubMed

Lee, Guk Jin; Hong, Sook Hee; Roh, Sang Young; Park, Sa Rah; Lee, Myung Ah; Chun, Hoo Geun; Hong, Young Seon; Kang, Jin Hyoung; Kim, Sang Il; Kim, Youn Jeong; Chun, Ho Jong; Oh, Jung Suk

2014-07-01

To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

HIV risk behaviors among African American men in Los Angeles County who self-identify as heterosexual.

PubMed

Wohl, Amy Rock; Johnson, Denise F; Lu, Sharon; Jordan, Wilbert; Beall, Gildon; Currier, Judith; Simon, Paul A

2002-11-01

There are limited data on high-risk behaviors among heterosexual African American men with HIV infection. Risk behaviors were examined in a case-control study of HIV-infected (n = 90) and uninfected (n = 272) African American men who self-identified as heterosexual. Of men who self-identified as heterosexual, 31% (n = 28) of the infected men and 16% (n = 43) of the uninfected men reported having had anal sex with men. Among the heterosexual men reporting anal sex with men, 100% of the infected and 67% of the uninfected men reported inconsistent condom use during anal sex with men. Few of the infected (12%) and uninfected (2%) men reported oral sex with other men. Of the men who self-identified as heterosexual, 46% of those who were HIV-positive and 37% of those who were HIV-negative reported anal sex with women with infrequent condom use. An increasing risk for HIV was associated with decreasing age at first sexual experience (chi2, 9.3; p = .002). A history of injecting drugs (odds ratio [OR], 3.1; 95% confidence intervals [CIs], 1.8, 5.4) and amphetamine (OR, 4.3; 95% CIs, 1.1, 16.7) and methamphetamine (OR, 2.9; 95% CIs, 1.4, 6.3) use were associated with HIV. Innovative HIV prevention strategies are needed that move beyond the traditional gay versus straight model to effectively access hard-to-reach African American men who self-identify as heterosexual.

Identifying Children in Middle Childhood Who Are at Risk for Reading Problems.

PubMed

Speece, Deborah L; Ritchey, Kristen D; Silverman, Rebecca; Schatschneider, Christopher; Walker, Caroline Y; Andrusik, Katryna N

2010-06-01

The purpose of this study was to identify and evaluate a universal screening battery for reading that is appropriate for older elementary students in a response to intervention model. Multiple measures of reading and reading correlates were administered to 230 fourth-grade children. Teachers rated children's reading skills, academic competence, and attention. Children were classified as not-at-risk or at-risk readers based on a three-factor model reflecting reading comprehension, word recognition/decoding, and word fluency. Predictors of reading status included group-administered tests of reading comprehension, silent word reading fluency, and teacher ratings of reading problems. Inclusion of individually administered tests and growth estimates did not add substantial variance. The receiver-operator characteristic curve analysis yielded an area under the curve index of 0.90, suggesting this model may both accurately and efficiently screen older elementary students with reading problems.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

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

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe

2016-08-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET andmore » CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

PubMed

Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

2016-08-01

To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high-risk

Risk factors for persistent fatigue with significant school absence in children and adolescents.

PubMed

Bakker, Robert J; van de Putte, Elise M; Kuis, Wietse; Sinnema, Gerben

2009-07-01

To assess children and adolescents with severe fatigue who are referred to pediatricians and to examine whether factors can be identified at their first visit that predict worse outcomes at 1 year. Ninety-one patients, aged 8 to 18 years completed questionnaires about sleep, somatic symptoms, physical activity, and fatigue. They were reassessed 12 months later. Measurements at baseline and outcome were analyzed by using univariable logistic regression with persistent, severe fatigue (yes/no) and persistent school absence (yes/no) as dependent variables and baseline scores as independent variables. After 12 months, 50.6% of the children and adolescents showed improvement; 29.1% had persistent fatigue, and 20.3% had persistent fatigue with significant school absence. Factors associated with the poorest outcome were sleep problems (odds ratio [OR]: 1.4 [95% confidence interval (CI): 1.1-1.8]), initial fatigue score (OR: 1.1 [95% CI: 1.0-1.2]), somatic complaints such as hot and cold spells (OR: 1.9 [95% CI: 1.2-3.0]), blurred vision (OR: 2.1 [95% CI: 1.1-4.0]), pain in arms and legs (OR: 2.0 [95% CI: 1.0-3.2]), back pain (OR: 1.8 [95% CI: 1.0-3.2]), constipation (OR: 1.7 [95% CI: 1.0-2.7]), and memory deficits (OR: 1.8 [95% CI: 1.0-3.2]). Resolved fatigue was associated with male gender (OR: 5.0 [95% CI: 1.6-15.5]) and a physically active lifestyle (OR: 1.3 [95% CI: 1.1-1.5]). Assessment of predictive factors at the first visit enables the pediatrician to identify those patients with severe fatigue who are at risk of a poor outcome. Female gender, poor sleep quality, physically inactive lifestyle, and specific somatic complaints were important predictive factors.

Comparison of Four Views to Single-view Ultrasound Protocols to Identify Clinically Significant Pneumothorax.

PubMed

Helland, Gregg; Gaspari, Romolo; Licciardo, Samuel; Sanseverino, Alexandra; Torres, Ulises; Emhoff, Timothy; Blehar, David

2016-10-01

Ultrasound (US) has been shown to be effective at identifying a pneumothorax (PTX); however, the additional value of adding multiple views has not been studied. Single- and four-view protocols have both been described in the literature. The objective of this study was to compare the diagnostic accuracy of single-view versus four-view lung US to detect clinically significant PTX in trauma patients. This was a randomized, prospective trial on trauma patients. Adult patients with acute traumatic injury undergoing computed tomography (CT) scan of the chest were eligible for enrollment. Patients were randomized to a single view or four views of each hemithorax prior to any imaging. USs were performed and interpreted by credentialed physicians using a 7.5-Mhz linear array transducer on a portable US machine with digital clips recorded for later review. Attending radiologist interpretation of the chest CT was reviewed for presence or absence of PTX with descriptions of small foci of air or minimal PTX categorized as clinically insignificant. A total of 260 patients were enrolled over a 2-year period. A total of 139 patients received a single view of each chest wall and 121 patients received four views. There were a total of 49 patients that had a PTX (19%), and 29 of these were clinically significant (11%). In diagnosis of any PTX, both single-view and four-view techniques showed poor sensitivity (54.2 and 68%) but high specificity (99 and 98%). For clinically significant PTX, single-view US demonstrated a sensitivity of 93% (95% confidence interval [CI] = 64.1% to 99.6%) and a specificity of 99.2% (95% CI = 95.5% to 99.9%), with sensitivity of 93.3% (95% CI = 66% to 99.7%) and specificity of 98% (95% CI = 92.1% to 99.7%) for four views. Single-view and four-view chest wall USs demonstrate comparable sensitivity and specificity for PTX. The additional time to obtain four views should be weighed against the absence of additional diagnostic yield over a single view when

A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer.

PubMed

Al-Tassan, Nada A; Whiffin, Nicola; Hosking, Fay J; Palles, Claire; Farrington, Susan M; Dobbins, Sara E; Harris, Rebecca; Gorman, Maggie; Tenesa, Albert; Meyer, Brian F; Wakil, Salma M; Kinnersley, Ben; Campbell, Harry; Martin, Lynn; Smith, Christopher G; Idziaszczyk, Shelley; Barclay, Ella; Maughan, Timothy S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Buchannan, Daniel D; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Dunlop, Malcolm G; Tomlinson, Ian P; Cheadle, Jeremy P; Houlston, Richard S

2015-05-20

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10(-8), odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10(-8); OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

Recent trauma is associated with antiretroviral failure and HIV transmission risk behavior among HIV-positive women and female-identified transgenders.

PubMed

Machtinger, E L; Haberer, J E; Wilson, T C; Weiss, D S

2012-11-01

Trauma and posttraumatic stress disorder disproportionally affect HIV-positive women. Studies increasingly demonstrate that both conditions may predict poor HIV-related health outcomes and transmission-risk behaviors. This study analyzed data from a prevention-with-positives program to understand if socio-economic, behavioral, and health-related factors are associated with antiretroviral failure and HIV transmission-risk behaviors among 113 HIV-positive biological and transgender women. An affirmative answer to a simple screening question for recent trauma was significantly associated with both outcomes. Compared to participants without recent trauma, participants reporting recent trauma had over four-times the odds of antiretroviral failure (AOR 4.3; 95% CI 1.1-16.6; p = 0.04), and over three-times the odds of reporting sex with an HIV-negative or unknown serostatus partner (AOR 3.9; 95% CI 1.3-11.9; p = 0.02) and <100% condom use with these partners (AOR 4.5; 95% CI 1.5-13.3; p = 0.007). Screening for recent trauma in HIV-positive biological and transgender women identifies patients at high risk for poor health outcomes and HIV transmission-risk behavior.

Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

PubMed

Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

2016-09-01

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

PubMed Central

Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A.; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A. Keith; Obreja, Mihaela; Moreau, Philippe

2016-01-01

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.

PubMed

Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

2015-05-03

To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Prospective cross-sectional study. Two primary care practices (adult patient population 10,479) in Nottingham, UK. Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study. Published by the BMJ Publishing Group Limited. For permission to use (where