The impact of genetically modified crops on soil microbial communities.

PubMed

Giovannetti, Manuela; Sbrana, Cristiana; Turrini, Alessandra

2005-01-01

Genetically modified (GM) plants represent a potential benefit for environmentally friendly agriculture and human health. Though, poor knowledge is available on potential hazards posed by unintended modifications occurring during genetic manipulation. The increasing amount of reports on ecological risks and benefits of GM plants stresses the need for experimental works aimed at evaluating the impact of GM crops on natural and agro-ecosystems. Major environmental risks associated with GM crops include their potential impact on non-target soil microorganisms playing a fundamental role in crop residues degradation and in biogeochemical cycles. Recent works assessed the effects of GM crops on soil microbial communities on the basis of case-by-case studies, using multimodal experimental approaches involving different target and non-target organisms. Experimental evidences discussed in this review confirm that a precautionary approach should be adopted, by taking into account the risks associated with the unpredictability of transformation events, of their pleiotropic effects and of the fate of transgenes in natural and agro-ecosystems, weighing benefits against costs.

Contribution of European research to risk analysis.

PubMed

Boenke, A

2001-12-01

The European Commission's, Quality of Life Research Programme, Key Action 1-Health, Food & Nutrition is mission-oriented and aims, amongst other things, at providing a healthy, safe and high-quality food supply leading to reinforced consumer confidence in the safety, of European food. Its objectives also include the enhancing of the competitiveness of the European food supply. Key Action 1 is currently supporting a number of different types of European collaborative projects in the area of risk analysis. The objectives of these projects range from the development and validation of prevention strategies including the reduction of consumers risks; development and validation of new modelling approaches, harmonization of risk assessment principles methodologies and terminology; standardization of methods and systems used for the safety evaluation of transgenic food; providing of tools for the evaluation of human viral contamination of shellfish and quality control; new methodologies for assessing the potential of unintended effects of genetically modified (genetically modified) foods; development of a risk assessment model for Cryptosporidium parvum related to the food and water industries, to the development of a communication platform for genetically modified organism, producers, retailers, regulatory authorities and consumer groups to improve safety assessment procedures, risk management strategies and risk communication; development and validation of new methods for safety testing of transgenic food; evaluation of the safety and efficacy of iron supplementation in pregnant women, evaluation of the potential cancer-preventing activity of pro- and pre-biotic ('synbiotic') combinations in human volunteers. An overview of these projects is presented here.

Depressive Symptoms Negate the Beneficial Effects of Physical Activity on Mortality Risk

ERIC Educational Resources Information Center

Lee, Pai-Lin

2013-01-01

The aim of this study is to: (1) compare the association between various levels of physical activity (PA) and mortality; and (2) examine the potential modifying effect of depressive symptoms on the PA-mortality associations. Previous large scale randomized studies rarely assess the association in conjunction with modifying effects of depressive…

Do not fear the Framingham: Practical application to properly evaluate and modify cardiovascular risk in commercial divers.

PubMed

Suresh, Rahul; Pavela, James; Kus, Marcus S; Alleman, Tony; Sanders, Robert

2018-01-01

In April 2016 the Association of Diving Contractors International (ADCI) consensus guidelines began recommending annual cardiovascular risk stratification of commercial divers using the Framingham Risk Score (FRS). For those at elevated risk, further testing is recommended. This approach has raised concerns about potential operational and financial impacts. However, the prevalence of elevated cardiovascular risk and need for additional testing among commercial divers is not known. Clinical data required to calculate the FRS was abstracted for 190 commercial divers in two cohorts. Population demographics, FRS distribution, contributions of risk factors and effect of interventions on reducing risk-factor burden were assessed. Mean FRS score was 1.68 ± 6.35 points, with 13 divers (6.8%) at intermediate risk and none at high 10-year risk. In these 13 divers, the mean contributions to the FRS were from age (6.5 points), cholesterol (3.1 pts.), smoking (1.3 pts.), highdensity lipoprotein (1 pt.), and systolic blood pressure (0.8 pts). The youngest age group had a significantly higher modifiable risk core than the oldest age group (5.87 vs. 1.2 points, P ⟨ 0.001). All 13 intermediate risk divers could have been reclassified as low-risk with successful treatment of modifiable risk factors. The prevalence of elevated cardiovascular risk among commercial divers is low, and treatment of modifiable risk factors could reclassify those at intermediate risk to low risk. Therefore, FRS implementation coupled with intensive risk-reduction strategies for at risk-divers may help improve diver health and prolong the careers of divers while limiting the need for additional testing and adverse operational impact. Copyright© Undersea and Hyperbaric Medical Society.

Modifiable risk factors for impaired fertility in women: what nurse practitioners need to know.

PubMed

Kelly-Weeder, Susan; O'Connor, Alane

2006-06-01

To provide an overview of impaired fertility in childbearing-aged women, to review the current research on modifiable lifestyle risk factors implicated in its development, and to suggest strategies for nurse practitioners (NPs) to assist women in behavioral changes that will allow them to protect their fertility. Original research articles and comprehensive review articles identified through Medline, CINAHL, and OVID databases. Research has shown that advancing age, a history of a sexually transmitted infection and/or pelvic inflammatory disease, extremes of body weight, and tobacco and caffeine use are potentially modifiable risk factors in the development of impaired fertility. NPs must be aware of the link between these behaviors and the development of impaired fertility in order to assist women in preserving their fertility. Individual counseling, education, and community-wide education strategies are discussed.

GM Risk Assessment

NASA Astrophysics Data System (ADS)

Sparrow, Penny A. C.

GM risk assessments play an important role in the decision-making process surrounding the regulation, notification and permission to handle Genetically Modified Organisms (GMOs). Ultimately the role of a GM risk assessment will be to ensure the safe handling and containment of the GMO; and to assess any potential impacts on the environment and human health. A risk assessment should answer all ‘what if’ scenarios, based on scientific evidence.

Modified secondary lithium metal batteries with the polyaniline-carbon nanotube composite buffer layer.

PubMed

Zhang, Ding; Yin, Yanli; Liu, Changhong; Fan, Shoushan

2015-01-07

A modified secondary lithium metal battery inserted with a polyaniline-carbon nanotube nanoporous composite buffer layer was fabricated. This unique and simple design of battery has the great potential to decrease the safety risk of the secondary Li metal battery in cycles of recharging processes and improve its cycle life in the future.

Association Between Cardiovascular Risk Factors and Carpal Tunnel Syndrome in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew Steven; Kapellusch, Jay; Merryweather, Andrew S; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Wertsch, Jacqueline; Foster, James; Garg, Arun; Drury, David L

2016-01-01

The aim of the study was to ascertain if cardiovascular (CVD) risk factors are carpal tunnel syndrome (CTS) risk factors. Analysis of pooled baseline data from two large prospective cohort studies (n = 1824) assessed the relationships between a modified Framingham Heart Study CVD risk score both CTS and abnormal nerve conduction study prevalence. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratio and 95% confidence intervals were calculated for individual risk scores. There was a strong relationship between CVD risk score and both CTS and abnormal nerve conduction study after adjustment for confounders, with odds ratios as high as 4.16 and 7.35, respectively. Dose responses were also observed. In this workplace population, there is a strong association between CVD risk scores and both CTS and abnormal nerve conduction study that persisted after controlling for confounders. These data suggest a potentially modifiable disease mechanism.

Classification of drugs with different risk profiles.

PubMed

Saedder, Eva Aggerholm; Brock, Birgitte; Nielsen, Lars Peter; Bonnerup, Dorthe Krogsgaard; Lisby, Marianne

2015-08-01

A risk stratification approach is needed to identify patients at high risk of medication errors and a resulting high need of medication review. The aim of this study was to perform risk stratification (distinguishing between low-risk, medium-risk and high-risk drugs) for drugs found to cause serious adverse reactions due to medication errors. The study employed a modified Delphi technique. Drugs from a systematic literature search were included into two rounds of a Delphi process. A panel of experts was asked to evaluate each identified drug's potential for harm and for clinically relevant drug-drug interactions on a scale from 1 (low risk) to 9 (high risk). A total of 36 experts were appointed to serve on the panel. Consensus was reached for 29/57 (51%) drugs or drug classes that cause harm, and for 32/57 (56%) of the drugs or drug classes that cause interactions. For the remaining drugs, a decision was made based on the median score. Two lists, one stating the drugs' potential for causing harm and the other stating clinically relevant drug-drug interactions, were stratified into low-risk, medium-risk and high-risk drugs. Based on a modified Delphi technique, we created two lists of drugs stratified into a low-risk, a medium-risk and a high-risk group of clinically relevant interactions or risk of harm to patients. The lists could be incorporated into a risk-scoring tool that stratifies the performance of medication reviews according to patients' risk of experiencing adverse reactions. none. not relevant.

Nest predation risk modifies nestlings' immune function depending on the level of threat.

PubMed

Roncalli, Gianluca; Colombo, Elisa; Soler, Manuel; Tieleman, B Irene; Versteegh, Maaike A; Ruiz-Raya, Fran; Gómez Samblas, Mercedes; Ibáñez-Álamo, Juan Diego

2018-05-20

Predation risk is thought to modify the physiology of prey mainly through the stress response. However, little is known about its potential effects on the immunity of animals, particularly in young individuals, despite the importance of overcoming wounding and pathogen aggression following a predator attack. We investigated the effect of four progressive levels of nest predation risk on several components of the immune system in common blackbird ( Turdus merula ) nestlings by presenting them with four different calls during 1 h: non-predator calls, predator calls, parental alarm calls and conspecific distress calls to induce a null, moderate, high and extreme level of risk, respectively. Nest predation risk induced an increase in ovotransferrin, immunoglobulin and the number of lymphocytes and eosinophils. Thus, the perception of a potential predator per se could stimulate the mobilization of a nestling's immune function and enable the organism to rapidly respond to the immune stimuli imposed by a predator attack. Interestingly, only high and extreme levels of risk caused immunological changes, suggesting that different immunological parameters are modulated according to the perceived level of threat. We also found a mediator role of parasites (i.e. Leucocytozoon ) and the current health status of the individual, as only nestlings not parasitized or in good body condition were able to modify their immune system. This study highlights a previously unknown link between predation risk and immunity, emphasizing the complex relationship among different selective pressures (predation, parasitism) in developing organisms and accentuating the importance of studying predation from a physiological point of view. © 2018. Published by The Company of Biologists Ltd.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Inter-Pregnancy Intervals and the Risk of Autism Spectrum Disorder: Results of a Population-Based Study

ERIC Educational Resources Information Center

Durkin, Maureen S.; DuBois, Lindsay A.; Maenner, Matthew J.

2015-01-01

Recent studies have reported an increased risk of autism among second-born children conceived <12 versus >36 months after the birth of a sibling. Confirmation of this finding would point to inter-pregnancy interval (IPI) as a potentially modifiable risk factor for autism. This study evaluated the relationship between IPI and autism spectrum…

GENE FLOW STUDIES BETWEEN BRASSICA NAPUS AND B. RAPA IN CONSTRUCTED PLANT COMMUNITIES

EPA Science Inventory

The commercial production of genetically modified crops has led to a growing awareness of the difficulties of transgene confinement and of the potential environmental risks associated with the escape of transgenes into naturalized or native plant populations. A potential conseque...

Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age.

PubMed

Shi, Zumin; Johnstone, Daniel; Talseth-Palmer, Bente A; Evans, Tiffany-Jane; Spigelman, Allan D; Groombridge, Claire; Milward, Elizabeth A; Olynyk, John K; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; Scott, Rodney J

2009-07-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.

In Search of Modifiable Risk and Protective Factors for Teen Dating Violence

PubMed Central

Smith-Darden, Joanne P.; Kernsmith, Poco D.; Reidy, Dennis E.; Cortina, Kai S.

2018-01-01

The present research explores the additive and interactive effects of anger or hostility (A/H), acceptance of violence (AoV), and constructive conflict resolution strategies (CRS) on the perpetration of physical and sexual teen dating violence (TDV). Adolescents completed surveys assessing physical and sexual TDV perpetration, A/H, AoV, and positive CRS. While the findings require replication with longitudinal data, the results suggest that developing interventions to modify AoV and A/H may have the potential to prevent instances of TDV perpetration among both boys and girls. The results for CRS were mixed and necessitate further exploration. These cross-sectional data provide insight into potentially fruitful areas of exploration for the development and tailoring of prevention strategies for teens at risk for physical and sexual TDV perpetration. PMID:28876526

DTREEv2, a computer-based support system for the risk assessment of genetically modified plants.

PubMed

Pertry, Ine; Nothegger, Clemens; Sweet, Jeremy; Kuiper, Harry; Davies, Howard; Iserentant, Dirk; Hull, Roger; Mezzetti, Bruno; Messens, Kathy; De Loose, Marc; de Oliveira, Dulce; Burssens, Sylvia; Gheysen, Godelieve; Tzotzos, George

2014-03-25

Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems that can facilitate the risk assessment process. In this paper we describe DTREEv2, a computer-based decision support system for the identification of hazards related to the introduction of GM-crops into the environment. DTREEv2 structures hazard identification and evaluation by means of an Event-Tree type of analysis. The system produces an output flagging identified hazards and potential risks. It is intended to be used for the preparation and evaluation of biosafety dossiers and, as such, its usefulness extends to researchers, risk assessors and regulators in government and industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Association between Epicondylitis and Cardiovascular Risk Factors in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew S; Kapellusch, Jay; Merryweather, Andrew; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Foster, James; Drury, David L; Garg, Arun

2017-05-30

The pathophysiology of lateral epicondylitis (LE) is unclear. Recent evidence suggests some common musculoskeletal disorders may have a basis in cardiovascular disease (CVD) risk factors. Thus, we examined CVD risks as potential LE risks. Workers (n = 1824) were enrolled in two large prospective studies and underwent structured interviews and physical examinations at baseline. Analysis of pooled baseline data assessed the relationships separately between a modified Framingham Heart Study CVD risk score and three prevalence outcomes of: 1) lateral elbow pain, 2) positive resisted wrist or middle finger extension, and 3) a combination of both symptoms and at least one resisted maneuver. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratios (ORs) and 95% Confidence Intervals (CIs) were calculated. There was a strong relationship between CVD risk score and lateral elbow symptoms, resisted wrist or middle finger extension and LE after adjustment for confounders. The adjusted ORs for symptoms were as high as 3.81 (95% CI 2.11, 6.85), for positive examination with adjusted odds ratios as high as 2.85 (95% CI 1.59, 5.12) and for combined symptoms and physical examination 6.20 (95% CI 2.04, 18.82). Relationships trended higher with higher CVD risk scores. These data suggest a potentially modifiable disease mechanism for LE.

Development of an Algorithm for Stroke Prediction: A National Health Insurance Database Study in Korea.

PubMed

Min, Seung Nam; Park, Se Jin; Kim, Dong Joon; Subramaniyam, Murali; Lee, Kyung-Sun

2018-01-01

Stroke is the second leading cause of death worldwide and remains an important health burden both for the individuals and for the national healthcare systems. Potentially modifiable risk factors for stroke include hypertension, cardiac disease, diabetes, and dysregulation of glucose metabolism, atrial fibrillation, and lifestyle factors. We aimed to derive a model equation for developing a stroke pre-diagnosis algorithm with the potentially modifiable risk factors. We used logistic regression for model derivation, together with data from the database of the Korea National Health Insurance Service (NHIS). We reviewed the NHIS records of 500,000 enrollees. For the regression analysis, data regarding 367 stroke patients were selected. The control group consisted of 500 patients followed up for 2 consecutive years and with no history of stroke. We developed a logistic regression model based on information regarding several well-known modifiable risk factors. The developed model could correctly discriminate between normal subjects and stroke patients in 65% of cases. The model developed in the present study can be applied in the clinical setting to estimate the probability of stroke in a year and thus improve the stroke prevention strategies in high-risk patients. The approach used to develop the stroke prevention algorithm can be applied for developing similar models for the pre-diagnosis of other diseases. © 2018 S. Karger AG, Basel.

Reducing sickness absence from work due to low back pain: how well do intervention strategies match modifiable risk factors?

PubMed

Shaw, William S; Linton, Steven J; Pransky, Glenn

2006-12-01

To assess, from the review literature, the extent to which effective strategies for reducing work absence after acute low back pain (LBP) match empirical risk factors. From 17 recent review articles (2000-2005), disability risk factors and interventions were cross-tabulated to assess levels of relative concordance. Potentially modifiable risk factors included 23 variables describing 3 workplace and 3 personal domains. Effective interventions included 25 strategies that were personal (physical or behavioral), engineering, or administrative in nature. There was a strong risk factor concordance for workplace technical and organizational interventions, graded activity exposure, and cognitive restructuring of pain beliefs. There was less risk factor concordance for exercise, back education, and RTW coordination. Few interventions focused on relieving emotional distress or improving job dissatisfaction, two well-supported risk factors. Gaps between the epidemiological and intervention research of back disability prevention could be reduced by testing mediators of intervention effects or by stratifying outcomes according to pre-intervention risk factors.

External validation of the Probability of repeated admission (Pra) risk prediction tool in older community-dwelling people attending general practice: a prospective cohort study.

PubMed

Wallace, Emma; McDowell, Ronald; Bennett, Kathleen; Fahey, Tom; Smith, Susan M

2016-11-14

Emergency admission is associated with the potential for adverse events in older people and risk prediction models are available to identify those at highest risk of admission. The aim of this study was to externally validate and compare the performance of the Probability of repeated admission (Pra) risk model and a modified version (incorporating a multimorbidity measure) in predicting emergency admission in older community-dwelling people. 15 general practices (GPs) in the Republic of Ireland. n=862, ≥70 years, community-dwelling people prospectively followed up for 2 years (2010-2012). Pra risk model (original and modified) calculated for baseline year where ≥0.5 denoted high risk (patient questionnaire, GP medical record review) of future emergency admission. Emergency admission over 1 year (GP medical record review). descriptive statistics, model discrimination (c-statistic) and calibration (Hosmer-Lemeshow statistic). Of 862 patients, a total of 154 (18%) had ≥1 emergency admission(s) in the follow-up year. 63 patients (7%) were classified as high risk by the original Pra and of these 26 (41%) were admitted. The modified Pra classified 391 (45%) patients as high risk and 103 (26%) were subsequently admitted. Both models demonstrated only poor discrimination (original Pra: c-statistic 0.65 (95% CI 0.61 to 0.70); modified Pra: c-statistic 0.67 (95% CI 0.62 to 0.72)). When categorised according to risk-category model, specificity was highest for the original Pra at cut-point of ≥0.5 denoting high risk (95%), and for the modified Pra at cut-point of ≥0.7 (95%). Both models overestimated the number of admissions across all risk strata. While the original Pra model demonstrated poor discrimination, model specificity was high and a small number of patients identified as high risk. Future validation studies should examine higher cut-points denoting high risk for the modified Pra, which has practical advantages in terms of application in GP. The original Pra tool may have a role in identifying higher-risk community-dwelling older people for inclusion in future trials aiming to reduce emergency admissions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

PubMed Central

Okeke, Malachy I.; Okoli, Arinze S.; Offor, Collins; Oludotun, Taiwo G.; Tryland, Morten; Bøhn, Thomas; Moens, Ugo

2017-01-01

Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health. However, key aspects of MVA biology require further research in order to provide data needed to evaluate the potential risks that may occur due to the use of MVA and MVA-vectored vaccines. The purpose of this paper is to identify knowledge gaps in the biology of MVA and recombinant MVA that are of relevance to its hazard characterization and discuss ongoing and future experiments aimed at providing data necessary to fill in the knowledge gaps. In addition, we presented arguments for the inclusion of uncertainty analysis and experimental investigation of verifiable worst-case scenarios in the environmental risk assessment of MVA and recombinant MVA. These will contribute to improved risk assessment of MVA and recombinant MVA vaccines. PMID:29109380

Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

PubMed

Okeke, Malachy I; Okoli, Arinze S; Diaz, Diana; Offor, Collins; Oludotun, Taiwo G; Tryland, Morten; Bøhn, Thomas; Moens, Ugo

2017-10-29

Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health. However, key aspects of MVA biology require further research in order to provide data needed to evaluate the potential risks that may occur due to the use of MVA and MVA-vectored vaccines. The purpose of this paper is to identify knowledge gaps in the biology of MVA and recombinant MVA that are of relevance to its hazard characterization and discuss ongoing and future experiments aimed at providing data necessary to fill in the knowledge gaps. In addition, we presented arguments for the inclusion of uncertainty analysis and experimental investigation of verifiable worst-case scenarios in the environmental risk assessment of MVA and recombinant MVA. These will contribute to improved risk assessment of MVA and recombinant MVA vaccines.

Risk factors for Dandy-Walker malformation: a population-based assessment.

PubMed

Reeder, Matthew R; Botto, Lorenzo D; Keppler-Noreuil, Kim M; Carey, John C; Byrne, Janice L B; Feldkamp, Marcia L

2015-09-01

Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, but its causes are largely unknown. An increasing number of genes associated with congenital cerebellar malformations have been identified; however, few studies have examined the potential role of non-genetic, potentially modifiable risk factors. From the National Birth Defects Prevention Study, we examined maternal, paternal, and infant characteristics and maternal conditions and periconceptional exposures (from 1 month before to 3 months after conception) among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed using logistic regression. Maternal factors associated with DWM included non-Hispanic black race/ethnicity (aOR = 2.0, 95%CI: 1.3-3.2). Among maternal conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4, 95%CI: 1.3-4.6; multiple: aOR = 3.9, 95%CI: 1.7-8.9). The lack of association with many maternal exposures supports the hypothesis of a major contribution of genetic factors to the risk for DWM; however, the observed associations with maternal non-Hispanic black race/ethnicity and maternal history of infertility indicate that further research into factors underlying these characteristics may uncover potentially modifiable risk factors, acting alone or as a component of gene-environment interactions. © 2015 Wiley Periodicals, Inc.

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

PubMed

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

99mTc MDP SPECT-CT-Based Modified Mirels Classification for Evaluation of Risk of Fracture in Skeletal Metastasis: A Pilot Study.

PubMed

Riaz, Saima; Bashir, Humayun; Niazi, Imran Khalid; Butt, Sumera; Qamar, Faisal

2018-06-01

Mirels' scoring system quantifies the risk of sustaining a pathologic fracture in osseous metastases of weight bearing long bones. Conventional Mirels' scoring is based on radiographs. Our pilot study proposes Tc MDP bone SPECT-CT based modified Mirels' scoring system and its comparison with conventional Mirels' scoring. Cortical lysis was noted in 8(24%) by SPECT-CT versus 2 (6.3%) on X-rays. Additional SPECT-CT parameters were; circumferential involvement [1/4 (31%), 1/2 (3%), 3/4 (37.5%), 4/4 (28%)] and extra-osseous soft tissue [3%]. Our pilot study suggests the potential role of SPECT-CT in predicting risk of fracture in osseous metastases.

Non-genetic risk factors and their influence on the management of patients in the clinic.

PubMed

Álvarez, Teresa; Soto, Immaculada; Astermark, Jan

2015-02-01

The development of inhibitors is the most serious iatrogenic complication affecting patients with haemophilia. This complication is associated with impaired vital or functional prognosis, reduced quality of life and increased cost of treatment. The reasons why some patients develop antibodies to factor replacement and others do not remain unclear. It is however clear that inhibitor development results from a complex multifactorial interaction between genetic and non-genetic risk factors. Environmental influences implicated in increasing the risk of inhibitor formation can be viewed as modifiable risk factors. Therefore, identification of the non-genetic risk factors may offer the possibility of personalising haemophilia therapy by modifying treatment strategies in high-risk patients in the critical early phase of factor VIII exposure. In this article, we review the non-genetic factors reported as well as the potential impact of danger signals and the different scores for inhibitor development risk stratification. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A case-crossover study on transient risk factors of work-related eye injuries.

PubMed

Chen, S-Y; Fong, P-C; Lin, S-F; Chang, C-H; Chan, C-C

2009-08-01

To investigate modifiable risk and preventive factors of work-related eye injuries. A case-crossover study conducted to explore the associations between transient risk factors and work-related eye injuries. Patients seen at seven medical centres in Taiwan with work-related eye injuries over a 4-year period were enrolled in the study. Clinical information was collected from medical charts and detailed information on exposure to eight potentially modifiable factors during the 60 minutes prior to the occurrence of each injury, as well as during the same time interval on the last work day prior to the injury, were obtained using questionnaire surveys. Matched-pair interval analysis was adopted to assess the odds ratios (ORs) for work-related eye injuries given exposure to the eight modifiable factors. A total of 283 subjects were interviewed. Most of these injured workers were young, male, and self-employed or small enterprise workers. The most common injury type was photokeratitis (33.2%), mainly caused by welding (30.4%). The OR for a work-related eye injury was increased with the performance of an unfamiliar task (57.0), operation of a faulty tool or piece of equipment (48.5), distractions (24.0), being rushed (13.0), or fatigued (10.0), and a poor work environment (4.3). Wearing eye protection devices was found to have a significant protective effect on workers who might otherwise have been exposed to eye injuries (OR = 0.4; 95% CI 0.2 to 0.7). Potential modifiable risk and preventive factors for work-related eye injuries were identified using a case-crossover study. This information should be helpful in the development of preventive strategies.

Validation of a modified FRAX® tool for improving outpatient efficiency--part of the "Catch Before a Fall" initiative.

PubMed

Parker, Simon; Ciaccio, Maria; Cook, Erica; Davenport, Graham; Cooper, Alun; Grange, Simon; Smitham, Peter

2015-01-01

We have validated our touch-screen-modified FRAX® tool against the traditional healthcare professional-led questionnaire, demonstrating strong concordance between doctor- and patient-derived results. We will use this in outpatient clinics and general practice to increase our capture rate of at-risk patients, making valuable use of otherwise wasted patient waiting times. Outpatient clinics offer an opportunity to collect valuable health information from a captive population. We have previously developed a modified fracture risk assessment (FRAX®) tool, enabling patients to self-assess their osteoporotic fracture risk in a touch-screen computer format and demonstrated its acceptability with patients. We aim to validate the accuracy of our tool against the traditional questionnaire. Fifty patients over 50 years of age within the fracture clinic independently completed a paper equivalent of our touch-screen-modified FRAX® questionnaire. Responses were analysed against the traditional healthcare professional (HCP)-led questionnaire which was carried out afterwards. Correlation was assessed by sensitivity, specificity, Cohen's kappa statistic and Fisher's exact test for each potential FRAX® outcome of "treat", "measure BMD" and "lifestyle advice". Age range was 51-98 years. The FRAX® tool was completed by 88 % of patients; six patients lacked confidence in estimating either their height or weight. Following question adjustment according to patient response and feedback, our tool achieved >95 % sensitivity and specificity for the "treat" and "lifestyle advice" groups, and 79 % sensitivity and 100 % specificity in the "measure BMD" group. Cohen's kappa value ranged from 0.823 to 0.995 across all groups, demonstrating "very good" agreement for all. Fisher's exact test demonstrated significant concordance between doctor and patient decisions. Our modified tool provides a simple, accurate and reliable method for patients to self-report their own FRAX® score outside the clinical contact period, thus releasing the HCP from the time required to complete the questionnaire and potentially increasing our capture rate of at-risk patients.

Bioinformatics analysis to assess potential risks of allergenicity and toxicity of HRAP and PFLP proteins in genetically modified bananas resistant to Xanthomonas wilt disease.

PubMed

Jin, Yuan; Goodman, Richard E; Tetteh, Afua O; Lu, Mei; Tripathi, Leena

2017-11-01

Banana Xanthomonas wilt (BXW) disease threatens banana production and food security throughout East Africa. Natural resistance is lacking among common cultivars. Genetically modified (GM) bananas resistant to BXW disease were developed by inserting the hypersensitive response-assisting protein (Hrap) or/and the plant ferredoxin-like protein (Pflp) gene(s) from sweet pepper (Capsicum annuum). Several of these GM banana events showed 100% resistance to BXW disease under field conditions in Uganda. The current study evaluated the potential allergenicity and toxicity of the expressed proteins HRAP and PFLP based on evaluation of published information on the history of safe use of the natural source of the proteins as well as established bioinformatics sequence comparison methods to known allergens (www.AllergenOnline.org and NCBI Protein) and toxins (NCBI Protein). The results did not identify potential risks of allergy and toxicity to either HRAP or PFLP proteins expressed in the GM bananas that might suggest potential health risks to humans. We recognize that additional tests including stability of these proteins in pepsin assay, nutrient analysis and possibly an acute rodent toxicity assay may be required by national regulatory authorities. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Children and genetically engineered food: potentials and problems.

PubMed

Perr, Hilary A

2002-10-01

Changes in food production and dietary practices are occurring faster than our understanding of their potential impact on children's health. Traditionally, pediatric gastroenterologists have studied food with respect to its nutritive value and digestibility, its influence on metabolism, its growth-promoting characteristics, and its relationship to risk and severity of disease. Biotechnology is now expanding the science of food to include disease prevention and treatment, as well as the feeding of children on a global scale. Bioengineered ("genetically modified", or "transgenic") plants were initially developed to enhance the food supply by increasing crop yields. Such previously developed transgenic plants are now prevalent worldwide and appear in many processed food products. The implementation of the technology of genetic modulation of food plants has led to considerable fear, controversy, and confusion as the understanding of the technology is poor in the general population. This review presents an overview of genetically modified food crops and their potential unique benefits and risks to children's health. Political, economical, and ecological issues related to transgenic crops are not discussed.

Genetic Variation as a Modifier of Association between Therapeutic Exposure and Subsequent Malignant Neoplasms in Cancer Survivors

PubMed Central

Bhatia, Smita

2014-01-01

Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat the primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk, and can possibly explain the observed inter-individual variability. This article provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs. This article also discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as, an appropriate study design, identification of an adequately sized study population together with a reliable plan for collecting and maintaining high quality DNA, clinical validation of the phenotype, and selection of an appropriate approach or platform for genotyping. Understanding the modifiers of risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care of cancer survivors. PMID:25355167

Modifiable Midlife Risk Factors for Late-Life Cognitive Impairment and Dementia

PubMed Central

Hughes, Tiffany F.; Ganguli, Mary

2009-01-01

The baby boom generation is approaching the age of greatest risk for cognitive impairment and dementia. There is growing interest in strategies to modify the environment in midlife to increase the probability of maintaining cognitive health in late life. Several potentially modifiable risk factors have been studied in relation to cognitive impairment and dementia in late life, but methodological limitations of observational research have resulted in some inconsistencies across studies. The most promising strategies are maintaining cardiovascular health, engagement in mental, physical, and social activities, using alcohol in moderation, abstaining from tobacco use, and following a heart-healthy diet. Other factors that may influence cognitive health are occupational attainment, depression, personality, exposure to general anesthesia, head injury, postmenopausal hormone therapy, non-steroidal anti-inflammatory medications, and nutritional supplements such as antioxidants. Some long-term observational studies initiated in midlife or earlier, and some randomized controlled trials, have examined the effects of specific cognitive health promotion behaviors in midlife on the risk of cognitive impairment in late life. Overall, these studies provide limited support for risk reduction at this time. Recommendations and challenges for developing effective strategies to reduce the burden of cognitive impairment and dementia in the future are discussed. PMID:19946443

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

PubMed

Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

2010-12-01

A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat

PubMed Central

Brevik, Asgeir; Joshi, Amit D.; Corral, Román; Onland-Moret, N. Charlotte; Siegmund, Kimberly D.; Le Marchand, Loïc; Baron, John A.; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

2010-01-01

Background A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents, and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Methods Using a family-based study we investigated the role of polymorphisms in four BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between high-red meat or poultry diets and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Results Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared to carriers of the Gln/Gln genotype (OR 0.15, 95% CI 0.03-0.69, p = 0.015). The association between higher red meat intake (>3 servings/week) and CRC was modified by the PARP Val762Ala SNP (case-only interaction p = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction p = 0.0009). Conclusions We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Impact Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a high-red meat diet. PMID:21037106

Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes

PubMed Central

Schludi, Belinda; Moin, Abu Saleh Md; Montemurro, Chiara; Gurlo, Tatyana; Matveyenko, Aleksey V.; Kirakossian, David; Dawson, David W.; Dry, Sarah M.; Butler, Peter C.; Butler, Alexandra E.

2017-01-01

Pancreatitis is more frequent in type 2 diabetes mellitus (T2DM), although the underlying cause is unknown. We tested the hypothesis that ongoing β cell stress and apoptosis in T2DM induces ductal tree proliferation, particularly the pancreatic duct gland (PDG) compartment, and thus potentially obstructs exocrine outflow, a well-established cause of pancreatitis. PDG replication was increased 2-fold in human pancreas from individuals with T2DM, and was associated with increased pancreatic intraepithelial neoplasia (PanIN), lesions associated with pancreatic inflammation and with the potential to obstruct pancreatic outflow. Increased PDG replication in the prediabetic human-IAPP-transgenic (HIP) rat model of T2DM was concordant with increased β cell stress but preceded metabolic derangement. Moreover, the most abundantly expressed chemokines released by the islets in response to β cell stress in T2DM, CXCL1, -4, and -10, induced proliferation in human pancreatic ductal epithelium. Also, the diabetes medications reported as potential modifiers for the risk of pancreatitis in T2DM modulated PDG proliferation accordingly. We conclude that chronic stimulation and proliferation of the PDG compartment in response to islet inflammation in T2DM is a potentially novel mechanism that serves as a link to the increased risk for pancreatitis in T2DM and may potentially be modified by currently available diabetes therapy. PMID:28679961

Math anxiety and exposure to statistics in messages about genetically modified foods: effects of numeracy, math self-efficacy, and form of presentation.

PubMed

Silk, Kami J; Parrott, Roxanne L

2014-01-01

Health risks are often communicated to the lay public in statistical formats even though low math skills, or innumeracy, have been found to be prevalent among lay individuals. Although numeracy has been a topic of much research investigation, the role of math self-efficacy and math anxiety on health and risk communication processing has received scant attention from health communication researchers. To advance theoretical and applied understanding regarding health message processing, the authors consider the role of math anxiety, including the effects of math self-efficacy, numeracy, and form of presenting statistics on math anxiety, and the potential effects for comprehension, yielding, and behavioral intentions. The authors also examine math anxiety in a health risk context through an evaluation of the effects of exposure to a message about genetically modified foods on levels of math anxiety. Participants (N = 323) were randomly assigned to read a message that varied the presentation of statistical evidence about potential risks associated with genetically modified foods. Findings reveal that exposure increased levels of math anxiety, with increases in math anxiety limiting yielding. Moreover, math anxiety impaired comprehension but was mediated by perceivers' math confidence and skills. Last, math anxiety facilitated behavioral intentions. Participants who received a text-based message with percentages were more likely to yield than participants who received either a bar graph with percentages or a combined form. Implications are discussed as they relate to math competence and its role in processing health and risk messages.

Methods for addressing "innocent bystanders" when evaluating safety of concomitant vaccines.

PubMed

Wang, Shirley V; Abdurrob, Abdurrahman; Spoendlin, Julia; Lewis, Edwin; Newcomer, Sophia R; Fireman, Bruce; Daley, Matthew F; Glanz, Jason M; Duffy, Jonathan; Weintraub, Eric S; Kulldorff, Martin

2018-04-01

The need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self-controlled design to investigate the safety of concomitant vaccination. We propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re-examining the known increase in risk of seizure 7 to 10 days after measles-mumps-rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines. Initial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9-1.6), P value = θ.226. We have shown that when using a self-controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time-invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules. Copyright © 2018 John Wiley & Sons, Ltd.

The associations of gender, depression and elder mistreatment in a community-dwelling Chinese population: the modifying effect of social support.

PubMed

Dong, XinQi; Beck, Todd; Simon, Melissa A

2010-01-01

The aims of this study are to: (1) examine the gender differences in the association of depression and elder mistreatment (EM) in a community-dwelling Chinese population; and (2) examine the potential differential modifying effect of greater social support on these associations. We conducted a cross-sectional study of 141 women and 270 men aged 60 years or greater who presented to an urban medical center. EM was assessed using the modified Vulnerability to Abuse Screening Scale (VASS) and depression was assessed using the Geriatric Depression Scale (GDS) and overall social support was measured using the Social Support Index (SSI). After adjusting for potential confounders, depression was associated with 447% increased risk for EM among men (odds ratio, OR = 4.47; 95% confidence intervals (CI) = 1.52-13.13) and 854% increased risk for EM among women (OR = 8.54; 95% CI = 2.85-25.57). After examining the effect of greater social support on depression (social support x depression), depression was no longer associated with increased risk for EM in men (parameter estimate = PE = 0.62 + or - 0.82 (+ or - S.E.M.) = 0.82, p = 0.454). However, among women, depression remained as a significant risk factor for EM (PE = 1.49 + or - 0.68, p = 0.029). Depression is significant risk factor for EM for both men and women. However, effect of greater overall social support may have higher protective effect in men than in women. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

PubMed

Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

2013-02-01

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. © 2012 John Wiley & Sons A/S.

Genetically Modified Plants: Public and Scientific Perceptions

PubMed Central

2013-01-01

The potential of genetically modified plants to meet the requirements of growing population is not being recognized at present. This is a consequence of concerns raised by the public and the critics about their applications and release into the environment. These include effect on human health and environment, biosafety, world trade monopolies, trustworthiness of public institutions, integrity of regulatory agencies, loss of individual choice, and ethics as well as skepticism about the real potential of the genetically modified plants, and so on. Such concerns are enormous and prevalent even today. However, it should be acknowledged that most of them are not specific for genetically modified plants, and the public should not forget that the conventionally bred plants consumed by them are also associated with similar risks where no information about the gene(s) transfer is available. Moreover, most of the concerns are hypothetical and lack scientific background. Though a few concerns are still to be disproved, it is viewed that, with proper management, these genetically modified plants have immense potential for the betterment of mankind. In the present paper, an overview of the raised concerns and wherever possible reasons assigned to explain their intensity or unsuitability are reviewed. PMID:25937981

World War II-related post-traumatic stress disorder and breast cancer risk among Israeli women: a case-control study.

PubMed

Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

2014-03-01

Several studies have suggested that post-traumatic stress disorder (PTSD) is related to adverse health outcomes. There are limited data on PTSD and cancer, which has a long latency period. We investigated the association between World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among Jewish WWII survivors and examined whether this association was modified by exposure to hunger during WWII. We compared 65 BC patients diagnosed in 2005 through 2010 to 200 population-based controls who were members of various organizations for Jewish WWII survivors in Israel. All participants were born in Europe, lived at least six months under Nazi rule during WWII, and immigrated to Israel after the war. We estimated PTSD using the PTSD Inventory and applied logistic regression models to estimate the association between WWII-related PTSD and BC, adjusting for potential confounders. We observed a linear association between WWII-related PTSD and BC risk. This association remained significant following adjustment for potential confounders, including obesity, alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and total number of traumatic life events (OR = 2.89, 95% CI = 1.14-7.31). However, the level of hunger exposure during WWII modified this effect significantly. These findings suggest an independent association between WWII-related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by hunger, a novel finding. Future research is needed to further explore these findings.

Potential bioavailability assessment, source apportionment and ecological risk of heavy metals in the sediment of Brisbane River estuary, Australia.

PubMed

Duodu, Godfred Odame; Goonetilleke, Ashantha; Ayoko, Godwin A

2017-04-15

A weak acid extraction was used to mobilize the loosely bound metals in estuary sediment samples. More than 30% of Ag, As, Ca, Cd, Co, Cu, Hg, Mn Ni, Pb and Zn were leached from the sediment showing that these metals are significantly present in the bioavailable form. PCA/APCS identified three sources of the metals, namely: lithogenic accounting for 72%, shipping related contributing 15% and traffic related representing 13% of the total load. Application of pollution index (PI) and modified pollution index (MPI) revealed that the sediment range from unpolluted to heavily polluted while ecological risk index (RI) classifies the sediment as posing low ecological risk modified ecological risk index (MRI) suggests considerable to very high ecological risk. To provide holistic insights into the ecological risks posed by metals, enrichment factor, MPI and MRI are recommended for the assessment of sediment in complex environments such as estuaries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Framing alters risk-taking behavior on a modified Balloon Analogue Risk Task (BART) in a sex-specific manner.

PubMed

Gabriel, Kara I; Williamson, Ashley

2010-12-01

Framing uncertain scenarios to emphasize potential positive or negative elements influences decision making and behavior. The current experiment investigated sex differences in framing effects on risk-taking propensity in a modified version of the Balloon Analogue Risk Task (BART). Male and female undergraduates completed questionnaires on sensation seeking, impulsiveness, and risk and benefit perception prior to viewing one of three framing conditions for the BART: (1) positively-framed instructions emphasizing the ability to earn money if balloons were inflated to large size; (2) negatively framed instructions emphasizing the possibility that money could be lost if balloons were inflated to bursting; and (3) completely framed instructions noting both possible outcomes. Results revealed correlations between BART performance and impulsiveness for both sexes. Compared to positive and complete framing, negatively framed instructions decreased balloon inflation time in women but not men, indicating sex differences in response to treatments designed to alter risk-taking behavior.

Applying a weed risk assessment approach to GM crops.

PubMed

Keese, Paul K; Robold, Andrea V; Myers, Ruth C; Weisman, Sarah; Smith, Joe

2014-12-01

Current approaches to environmental risk assessment of genetically modified (GM) plants are modelled on chemical risk assessment methods, which have a strong focus on toxicity. There are additional types of harms posed by plants that have been extensively studied by weed scientists and incorporated into weed risk assessment methods. Weed risk assessment uses robust, validated methods that are widely applied to regulatory decision-making about potentially problematic plants. They are designed to encompass a broad variety of plant forms and traits in different environments, and can provide reliable conclusions even with limited data. The knowledge and experience that underpin weed risk assessment can be harnessed for environmental risk assessment of GM plants. A case study illustrates the application of the Australian post-border weed risk assessment approach to a representative GM plant. This approach is a valuable tool to identify potential risks from GM plants.

How CO2 Leakage May Impact the Role of Geologic Carbon Storage in Climate Mitigation

NASA Astrophysics Data System (ADS)

Peters, C. A.; Deng, H.; Bielicki, J. M.; Fitts, J. P.; Oppenheimer, M.

2014-12-01

Among CCUS technologies (Carbon Capture Utilization and Sequestration), geological storage of CO2 has a large potential to mitigate greenhouse gas emissions, but confidence in its deployment is often clouded by the possibility and cost of leakage. In this study, we took the Michigan sedimentary basin as an example to investigate the monetized risks associated with leakage, using the Risk Interference of Subsurface CO2 Storage (RISCS) model. The model accounts for spatial heterogeneity and variability of hydraulic properties of the subsurface system and permeability of potential leaking wells. In terms of costs, the model quantifies the financial consequences of CO2 escaping back to the atmosphere as well as the costs incurred if CO2 or brine leaks into overlying formations and interferes with other subsurface activities or resources. The monetized leakage risks derived from the RISCS model were then used to modify existing cost curves by shifting them upwards and changing their curvatures. The modified cost curves were used in the integrated assessment model - GCAM (Global Change Assessment Model), which provides policy-relevant results to help inform the potential role of CCUS in future energy systems when carbon mitigation targets and incentives are in place. The results showed that the extent of leakage risks has a significant effect on the extent of CCUS deployment. Under more stringent carbon mitigation policies such as a high carbon tax, higher leakage risks can be afforded and incorporating leakage risks will have a smaller impact on CCUS deployment. Alternatively, if the leakage risks were accounted for by charging a fixed premium, similar to how the risk of nuclear waste disposal is treated, the contribution of CCUS in mitigating climate change varies, depending on the value of the premium.

Prioritizing stream types according to their potential risk to receive crop plant material--A GIS-based procedure to assist in the risk assessment of genetically modified crops and systemic insecticide residues.

PubMed

Bundschuh, Rebecca; Kuhn, Ulrike; Bundschuh, Mirco; Naegele, Caroline; Elsaesser, David; Schlechtriemen, Ulrich; Oehen, Bernadette; Hilbeck, Angelika; Otto, Mathias; Schulz, Ralf; Hofmann, Frieder

2016-03-15

Crop plant residues may enter aquatic ecosystems via wind deposition or surface runoff. In the case of genetically modified crops or crops treated with systemic pesticides, these materials may contain insecticidal Bt toxins or pesticides that potentially affect aquatic life. However, the particular exposure pattern of aquatic ecosystems (i.e., via plant material) is not properly reflected in current risk assessment schemes, which primarily focus on waterborne toxicity and not on plant material as the route of uptake. To assist in risk assessment, the present study proposes a prioritization procedure of stream types based on the freshwater network and crop-specific cultivation data using maize in Germany as a model system. To identify stream types with a high probability of receiving crop materials, we developed a formalized, criteria-based and thus transparent procedure that considers the exposure-related parameters, ecological status--an estimate of the diversity and potential vulnerability of local communities towards anthropogenic stress--and availability of uncontaminated reference sections. By applying the procedure to maize, ten stream types out of 38 are expected to be the most relevant if the ecological effects from plant-incorporated pesticides need to be evaluated. This information is an important first step to identifying habitats within these stream types with a high probability of receiving crop plant material at a more local scale, including accumulation areas. Moreover, the prioritization procedure developed in the present study may support the selection of aquatic species for ecotoxicological testing based on their probability of occurrence in stream types having a higher chance of exposure. Finally, this procedure can be adapted to any geographical region or crop of interest and is, therefore, a valuable tool for a site-specific risk assessment of crop plants carrying systemic pesticides or novel proteins, such as insecticidal Bt toxins, expressed in genetically modified crops. Copyright © 2015 Elsevier B.V. All rights reserved.

Individual epigenetic variation: When, why, and so what?

USDA-ARS?s Scientific Manuscript database

Epigenetics provides a potential explanation for how environmental factors modify the risk for common diseases among individuals. Interindividual variation in DNA methylation and epigenetic regulation has been reported at specific genomic regions including transposable elements, genomically imprinte...

Biological and biomedical aspects of genetically modified food.

PubMed

Celec, Peter; Kukucková, Martina; Renczésová, Veronika; Natarajan, Satheesh; Pálffy, Roland; Gardlík, Roman; Hodosy, Július; Behuliak, Michal; Vlková, Barbora; Minárik, Gabriel; Szemes, Tomás; Stuchlík, Stanislav; Turna, Ján

2005-12-01

Genetically modified (GM) foods are the product of one of the most progressive fields of science-biotechnology. There are major concerns about GM foods in the public; some of them are reasonable, some of them are not. Biomedical risks of GM foods include problems regarding the potential allergenicity, horizontal gene transfer, but environmental side effects on biodiversity must also be recognized. Numerous methods have been developed to assess the potential risk of every GM food type. Benefits of the first generation of GM foods were oriented towards the production process and companies, the second generation of GM foods offers, on contrary, various advantages and added value for the consumer. This includes improved nutritional composition or even therapeutic effects. Recombinant probiotics and the principle of alternative gene therapy represent the latest approach of using GM organisms for biomedical applications. This article tries to summarize and to explain the problematic topic of GM food.

Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention1234

PubMed Central

Crozier, Sarah R; Harvey, Nicholas C; Barton, Benjamin D; Law, Catherine M; Godfrey, Keith M; Cooper, Cyrus; Inskip, Hazel M

2015-01-01

Background: Early life may be a “critical period” when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m2) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry–assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity. PMID:25646335

The Role of eHealth in Optimizing Preventive Care in the Primary Care Setting.

PubMed

Carey, Mariko; Noble, Natasha; Mansfield, Elise; Waller, Amy; Henskens, Frans; Sanson-Fisher, Rob

2015-05-22

Modifiable health risk behaviors such as smoking, overweight and obesity, risky alcohol consumption, physical inactivity, and poor nutrition contribute to a substantial proportion of the world's morbidity and mortality burden. General practitioners (GPs) play a key role in identifying and managing modifiable health risk behaviors. However, these are often underdetected and undermanaged in the primary care setting. We describe the potential of eHealth to help patients and GPs to overcome some of the barriers to managing health risk behaviors. In particular, we discuss (1) the role of eHealth in facilitating routine collection of patient-reported data on lifestyle risk factors, and (2) the role of eHealth in improving clinical management of identified risk factors through provision of tailored feedback, point-of-care reminders, tailored educational materials, and referral to online self-management programs. Strategies to harness the capacity of the eHealth medium, including the use of dynamic features and tailoring to help end users engage with, understand, and apply information need to be considered and maximized. Finally, the potential challenges in implementing eHealth solutions in the primary care setting are discussed. In conclusion, there is significant potential for innovative eHealth solutions to make a contribution to improving preventive care in the primary care setting. However, attention to issues such as data security and designing eHealth interfaces that maximize engagement from end users will be important to moving this field forward.

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

PubMed

Pouwels, K B; Van Kleef, E; Vansteelandt, S; Batra, R; Edgeworth, J D; Smieszek, T; Robotham, J V

2017-05-01

Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Association Between Cardiovascular Disease Risk Factors and Rotator Cuff Tendinopathy: A Cross-Sectional Study.

PubMed

Applegate, Kara Arnold; Thiese, Matthew S; Merryweather, Andrew S; Kapellusch, Jay; Drury, David L; Wood, Eric; Kendall, Richard; Foster, James; Garg, Arun; Hegmann, Kurt T

2017-02-01

Recent evidence has found potential associations between cardiovascular disease (CVD) risk factors and common musculoskeletal disorders. We evaluated possible associations between risk factors and both glenohumeral joint pain and rotator cuff tendinopathy. Data from WISTAH hand study participants (n = 1226) were assessed for associations between Framingham Heart Study CVD risk factors and both health outcomes. A strong association was observed between CVD risk scores and both glenohumeral joint pain and rotator cuff tendinopathy. Peak odds ratios (ORs) of the adjusted models were 4.55 [95% confidence interval (95% CI) 1.97 to 10.31] and 5.97 (95% CI 2.12 to 16.83), respectively. The results show a dose-response trend of increasing risk. Individual risk factors were associated with both outcomes. Combined, CVD risk factors demonstrated a strong correlation with glenohumeral joint pain and an even stronger correlation with rotator cuff tendinopathy. Results suggest a potentially modifiable disease mechanism.

A social media approach to inform youth about breast cancer and smoking: an exploratory descriptive study.

PubMed

Bottorff, Joan L; Struik, Laura L; Bissell, Laura J L; Graham, Raquel; Stevens, Jodie; Richardson, Chris G

2014-01-01

Tobacco exposure during periods of breast development has been shown to increase risk of premenopausal breast cancer. An urgent need exists, therefore, to raise awareness among adolescent girls about this new evidence, and for adolescent girls and boys who smoke to understand how their smoking puts their female peers at risk for breast cancer. The purpose of this study was to develop two youth-informed, gender specific YouTube-style videos designed to raise awareness among adolescent girls and boys about tobacco exposure as a modifiable risk factor for breast cancer and to assess youths' responses to the videos and their potential for inclusion on social media platforms. Both videos consisted of a combination of moving text, novel images, animations, and youth-friendly music. A brief questionnaire was used to gather feedback on two videos using a convenience sample of 135 youth in British Columbia, Canada. The overall positive responses by girls and boys to their respective videos and their reported interest in sharing these videos via social networking suggests that this approach holds potential for other types of health promotion messaging targeting youth. The videos offer a promising messaging strategy for raising awareness about tobacco exposure as a modifiable risk factor for breast cancer. Tailored, gender-specific messages for use on social media hold the potential for cost-effective, health promotion and cancer prevention initiatives targeting youth.

Modifying Children's Responses to Unsecured Firearms and Modifying the Keeping and Storage of Firearms in Families of Elementary School Children: A Possible Role for Child Behavior Therapy.

ERIC Educational Resources Information Center

Vacha, Edward F.; McLaughlin, T. F.

2000-01-01

Article outlines potential strategies for reducing the disproportionate rate of firearm accidents among low-income children. Suggests this problem stems from risky gun storage practices that are in response to high rates of victimization and fear of crime. Discusses the role that child behavior therapy can have in reducing the risk of firearm…

Lower Risk Cannabis use Guidelines for Canada (LRCUG): a narrative review of evidence and recommendations.

PubMed

Fischer, Benedikt; Jeffries, Victoria; Hall, Wayne; Room, Robin; Goldner, Elliot; Rehm, Jürgen

2011-01-01

More than one in ten adults--and about one in three young adults--report past year cannabis use in Canada. While cannabis use is associated with a variety of health risks, current policy prohibits all use, rather than adopting a public health approach focusing on interventions to address specific risks and harms as do policies for alcohol. The objective of this paper was to develop 'Lower Risk Cannabis Use Guidelines' (LRCUG) based on research evidence on the adverse health effects of cannabis and factors that appear to modify the risk of these harms. Relevant English-language peer-reviewed publications on health harms of cannabis use were reviewed and LRCUG were drafted by the authors on the basis of a consensus process. The review suggested that health harms related to cannabis use increase with intensity of use although the risk curve is not well characterized. These harms are associated with a number of potentially modifiable factors related to: frequency of use; early onset of use; driving after using cannabis; methods and practices of use and substance potency; and characteristics of specific populations. LRCUG recommending ways to reduce risks related to cannabis use on an individual and population level--analogous to 'Low Risk Drinking Guidelines' for alcohol--are presented. Given the prevalence and age distribution of cannabis use in Canada, a public health approach to cannabis use is overdue. LRCUG constitute a potentially valuable tool in facilitating a reduction of health harms from cannabis use on a population level.

The predictive role of health-promoting behaviours and perceived stress in aneurysmal rupture.

PubMed

Lee, Mi-Sun; Park, Chang G; Hughes, Tonda L; Jun, Sang-Eun; Whang, Kum; Kim, Nahyun

2018-03-01

To examine the roles of two modifiable factors-health-promoting behaviours and perceived stress-in predicting aneurysmal rupture. Unruptured intracranial aneurysm detection produces significant stress and anxiety in patients because of the risk of rupture. Compared to nonmodifiable risk factors for rupture such as age, gender and aneurysm size/location, less attention has been given to modifiable risk factors. Two modifiable factors, health-promoting behaviours and perceived stress, have hardly been examined as potential predictors of rupture. This study used a cross-sectional design. We assessed 155 patients with intracranial aneurysms-that is, subarachnoid haemorrhage (n = 77) or unruptured intracranial aneurysm (n = 78)-to examine (i) baseline characteristics (patient and aneurysmal factors), (ii) health-related factors (lifestyle habits and health-promoting behaviour) and (iii) perceived stress levels (psychological stress and physical stress). Patient records provided medical histories and aneurysmal factors; other data were collected using a structured questionnaire addressing lifestyle habits, the Health-Promoting Lifestyle Profile-II to measure health-promoting behaviour and the Perceived Stress Questionnaire to measure perceived-psychological stress and perceived-physical stress levels. Bivariate analysis indicated that aneurysm rupture risk was associated with female gender, aneurysm size/location, defecation frequency, hyperlipidaemia, sedentary time, low Health-Promoting Lifestyle Profile-II mean scores and high perceived-psychological stress scores. After adjusting for known risk factors, the mean Health-Promoting Lifestyle Profile-II and perceived-psychological stress scores remained robust predictors of rupture. Furthermore, known risk factors combined with these scores had greater predictive power than known risk factors alone. Health-promoting behaviour and psychological stress are promising modifiable factors for reducing risk of aneurysmal rupture. Our findings may stimulate greater understanding of mechanisms underlying aneurysmal rupture and suggest practical strategies for nurses to employ in optimising conservative management of rupture risk by teaching patients how to modify their risk. Both health-promoting behaviour and perceived stress should be addressed when designing preventive nursing interventions for patients with unruptured intracranial aneurysm. © 2017 John Wiley & Sons Ltd.

Personally Modifiable Risk Factors Associated with Pediatric Hearing Loss: A Systematic Review

PubMed Central

Vasconcellos, Adam P.; Kyle, Meghann E.; Gilani, Sapideh; Shin, Jennifer J.

2015-01-01

Background Pediatric hearing loss is an increasingly recognized problem with significant implications. Increasing our quantitative understanding of potentially modifiable environmental risk factors for hearing loss may form the foundation for prevention and screening programs. Objective To determine whether specific threshold exposure levels of personally modifiable risk factors for hearing loss have been defined, with the overarching goal of providing actionable guidance for the prevention of pediatric hearing loss. Data Sources A systematic review was performed. Computerized searches of PubMed, EMBASE, and the Cochrane Library were completed and supplemented with manual searches. Review Methods Inclusion/exclusion criteria were designed to determine specific threshold values of personally modifiable risk factors on hearing loss in the pediatric population. Searches and data extraction were performed by independent reviewers. Results There were 38 criterion-meeting studies, including a total of 50,651 subjects. Threshold noise exposures significantly associated with hearing loss in youth included: (1) more than 4 hours per week or more than 5 years of personal headphone usage, (2) more than 4 visits per month to a discotheque, and (3) working on a mechanized farm. Quantified tobacco levels of concern included any level of in utero smoke exposure as well as secondhand exposure sufficient to elevate serum cotinine. Conclusions Specific thresholds analyses are limited. Future studies would ideally focus on stratifying risk according to clearly defined levels of exposure, in order to provide actionable guidance for children and families. PMID:24671457

Cancer incidence attributable to lifestyle and environmental factors in Alberta in 2012: summary of results

PubMed Central

Grundy, Anne; Poirier, Abbey E.; Khandwala, Farah; Grevers, Xin; Friedenreich, Christine M.; Brenner, Darren R.

2017-01-01

Background: Estimates of the proportion of cancer cases that can be attributed to modifiable risk factors are not available for Canada and, more specifically, Alberta. The purpose of this study was to estimate the total proportion of cancer cases in Alberta in 2012 that could be attributed to a set of 24 modifiable lifestyle and environmental risk factors. Methods: We estimated summary population attributable risk estimates for 24 risk factors (smoking [both passive and active], overweight and obesity, inadequate physical activity, diet [inadequate fruit and vegetable consumption, inadequate fibre intake, excess red and processed meat consumption, salt consumption, inadequate calcium and vitamin D intake], alcohol, hormones [oral contraceptives and hormone therapy], infections [Epstein-Barr virus, hepatitis B and C viruses, human papillomavirus, Helicobacter pylori], air pollution, natural and artificial ultraviolet radiation, radon and water disinfection by-products) by combining population attributable risk estimates for each of the 24 factors that had been previously estimated. To account for the possibility that individual cancer cases were the result of a combination of multiple risk factors, we subtracted the population attributable risk for the first factor from 100% and then applied the population attributable risk for the second factor to the remaining proportion that was not attributable to the first factor. We repeated this process in sequential order for all relevant exposures. Results: Overall, an estimated 40.8% of cancer cases in Alberta in 2012 were attributable to modifiable lifestyle and environmental risk factors. The largest proportion of cancers were estimated to be attributable to tobacco smoking, physical inactivity and excess body weight. The summary population attributable risk estimate was slightly higher among women (42.4%) than among men (38.7%). Interpretation: About 41% of cancer cases in Alberta may be attributable to known modifiable lifestyle and environmental risk factors. Reducing the prevalence of these factors in the Alberta population has the potential to substantially reduce the provincial cancer burden. PMID:28687643

Risks of allergic reactions to biotech proteins in foods: perception and reality.

PubMed

Lehrer, S B; Bannon, G A

2005-05-01

In recent years, significant attention has been paid to the use of biotechnology to improve the quality and quantity of the food supply due in part to the projected growth in the world population, plus limited options available for increasing the amount of land under cultivation. Alterations in the food supply induced by classical breeding and selection methods typically involve the movement of large portions of genomic DNA between different plant varieties to obtain the desired trait. This is in contrast to techniques of genetic engineering which allows the selection and transfers specific genes from one species to another. The primary allergy risk to consumers from genetically modified crops may be placed into one of three categories. The first represents the highest risk to the allergic consumer is the transfer of known allergen or cross-reacting allergen into a food crop. The second category, representing an intermediate risk to the consumer, is the potential for replacing the endogenous allergenicity of a genetically-modified crop. The last category involves expression of novel proteins that may become allergens in man and generally represents a relatively low risk to the consumer, although this possibility has received attention of late. In order to mitigate the three categories of potential allergy risk associated with biotech crops, all genes introduced into food crops undergo a series of tests designed to determine if the biotech protein exhibits properties of known food allergens. The result of this risk assessment process to date is that no biotech proteins in foods have been documented to cause allergic reactions. These results indicate that the current assessment process is robust, although as science of allergy and allergens evolves, new information and new technology should help further the assessment process for potential allergenicity.

Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry.

PubMed

Sapkota, Yadav; Vivo, Immaculata De; Steinthorsdottir, Valgerdur; Fassbender, Amelie; Bowdler, Lisa; Buring, Julie E; Edwards, Todd L; Jones, Sarah; O, Dorien; Peterse, Daniëlle; Rexrode, Kathryn M; Ridker, Paul M; Schork, Andrew J; Thorleifsson, Gudmar; Wallace, Leanne M; Kraft, Peter; Morris, Andrew P; Nyholt, Dale R; Edwards, Digna R Velez; Nyegaard, Mette; D'Hooghe, Thomas; Chasman, Daniel I; Stefansson, Kari; Missmer, Stacey A; Montgomery, Grant W

2017-09-12

Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10 -9 ) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.

Chronic headache and potentially modifiable risk factors: screening and behavioral management of sleep disorders.

PubMed

Rains, Jeanetta C

2008-01-01

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.

Depressive symptoms negate the beneficial effects of physical activity on mortality risk.

PubMed

Lee, Pai-Lin

2013-01-01

The aim of this study is to: (1) compare the association between various levels of physical activity (PA) and mortality; and (2) examine the potential modifying effect of depressive symptoms on the PA-mortality associations. Previous large scale randomized studies rarely assess the association in conjunction with modifying effects of depressive symptoms. In this study, participants consisted of 624 (mean age = 77.35 years) non-institutionalized elderly from the Americans' Changing Lives Longitudinal Study. Depression was measured using the Center for Epidemiological Studies' Depression Scale. Participants in gardening, walking, and sports were first classified into four PA frequency levels, "never," "rarely," "sometimes," and "often." Those who self-reported "often" engaged in activities of gardening and walking and had reduced odds of mortality of 77% and 83%, adjusted odds ratio (ORadj) = .23 and .17, 95% confidence interval (CI) = .09-.59 and.07-.41 when compared to those who reported "never." However, mortality risk was not linked to sports activity. The modifying effects of depressive symptoms on PA (depressive symptoms x PA) were then tested, PA was not associated with increased risk for mortality for gardening (parameter estimates, PE = -.03 +/- .62, p = .958), and for walking (PE = .04 +/- .57, p = .948). Elderly people who engaged in gardening and walking might have protection effects on later risk of mortality. Depressive symptoms showed negative modifying effects that prevent PA predicting later mortality.

Load Carriage: An Integrated Risk Management Approach.

PubMed

Orr, Robin M; Pope, Rodney R

2015-11-01

Military load carriage (LC) gives rise to substantial risks to soldier health, tactical performance, and mission success. The aim of this article was to extract and synthesize the key findings of a series of LC research reports previously published by the authors. Five reviews and 6 studies were included, with key findings extracted and synthesized in tabulated and critical narrative form. The weight of a soldier's load is a source of risk for soldier's injuries and tactical task performance. The resulting level of risk is influenced by risk modifiers (like speed of march, terrain grade, and task type and duration) and risk controls (like administrative controls and physical conditioning). In the Australian context, these risk controls were limited, with soldiers carrying heavier loads than those mandated by doctrine and policy, and LC conditioning not meeting best practice. The diversity of LC contexts, combined with the influence of risk modifiers and risk controls, means that levels of risk associated with LC are not consistent and must be assessed on a case-by-case basis. Load weight and marching routes (terrains, gradients), distances, speed, and duration are all potentially treatable sources of LC-related risk. Potential risk treatments include not only commanders directly addressing these specific sources of risk to the extent feasible, on a case-by-case basis, when planning or conducting LC tasks but also improving administration controls (i.e., doctrine and policies) and personal protection (i.e., the physical conditioning of the soldier) as part of the hierarchy of controls. Practical application would involve commanders developing and implementing dedicated LC doctrine and policies and implementing and enforcing LC conditioning programs that meets best practice.

Genetic polymorphisms associated with breast cancer in malaysian cohort.

PubMed

Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy

2015-04-01

Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ≤ 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction.

Genetically Modified Foods: A Brief Overview of the Risk Assessment Process.

PubMed

Finkelstein, Paige E

2016-02-18

Billions of people worldwide are unable to meet their daily micro nutritional needs. Genetically modified (GM) foods, while initially developed to tolerate herbicides and resist disease and insects, have the potential to help alleviate this issue that is currently posing a serious public health concern. However, there is a negative public perception surrounding GM foods, calling for more research regarding the risks that GM foods could pose to the public, specifically on the topics of allergenicity and gene transfer. The risk assessments of GM foods should be performed on a case-by-case basis, by a process outlined by the WHO. The goal of determining food safety is to obtain reasonable certainty that under normal levels of consumption, there will be no harm to people. Current research has shown that GM foods do not cause increased allergenicity or have a meaningful risk of gene transfer to people. GM foods should become publicly accepted products that can bring significant benefit to people at risk of under nutrition.

"It just goes against the grain." Public understandings of genetically modified (GM) food in the UK.

PubMed

Shaw, Alison

2002-07-01

This paper reports on one aspect of qualitative research on public understandings of food risks, focusing on lay understandings of genetically modified (GM) food in the UK context. A range of theoretical, conceptual, and empirical literature on food, risk, and the public understanding of science are reviewed. The fieldwork methods are outlined and empirical data from a range of lay groups are presented. Major themes include: varying "technical" knowledge of science, the relationship between knowledge and acceptance of genetic modification, the uncertainty of scientific knowledge, genetic modification as inappropriate scientific intervention in "nature", the acceptability of animal and human applications of genetic modification, the appropriate boundaries of scientific innovation, the necessity for GM foods, the uncertainty of risks in GM food, fatalism about avoiding risks, and trust in "experts" to manage potential risks in GM food. Key discussion points relating to a sociological understanding of public attitudes to GM food are raised and some policy implications are highlighted.

Evolution and Implementation of the NASA Robotic Conjunction Assessment Risk Analysis Concept of Operations

NASA Technical Reports Server (NTRS)

Newman, Lauri K.; Frigm, Ryan C.; Duncan, Matthew G.; Hejduk, Matthew D.

2014-01-01

Reacting to potential on-orbit collision risk in an operational environment requires timely and accurate communication and exchange of data, information, and analysis to ensure informed decision-making for safety of flight and responsible use of the shared space environment. To accomplish this mission, it is imperative that all stakeholders effectively manage resources: devoting necessary and potentially intensive resource commitment to responding to high-risk conjunction events and preventing unnecessary expenditure of resources on events of low collision risk. After 10 years of operational experience, the NASA Robotic Conjunction Assessment Risk Analysis (CARA) is modifying its Concept of Operations (CONOPS) to ensure this alignment of collision risk and resource management. This evolution manifests itself in the approach to characterizing, reporting, and refining of collision risk. Implementation of this updated CONOPS is expected to have a demonstrated improvement on the efficacy of JSpOC, CARA, and owner/operator resources.

Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors.

PubMed

Bhatia, Smita

2015-03-01

Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk and may explain the observed interindividual variability. In this review, the author provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs and discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as an appropriate study design, the identification of an adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, clinical validation of the phenotype, and the selection of an appropriate approach or platform for genotyping. Understanding the factors that can modify the risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care for cancer survivors. © 2014 American Cancer Society.

A DELPHI STUDY OF RISK FACTORS FOR ACHILLES TENDINOPATHY- OPINIONS OF WORLD TENDON EXPERTS

PubMed Central

Watson, Paul J.; Barry, Simon

2016-01-01

Background and Purpose Achilles tendinopathy can be a debilitating chronic condition for both active and inactive individuals. The identification of risk facors is important both in preventing but also treating tendinopathy, many factors have been proposed but there is a lack of primary epidemiological data. The purpose of this study was to develop a statement of expert consensus on risk factors for Achilles tendinopathy in active and sedentary patient populations to inform a primary epidemiological study. Study design Delphi study Methods and Measures An online Delphi study was completed inviting participation from world tendon experts. The consensus was developed using three rounds of the Delphi technique. The first round developed a complete list of potential risk factors, the second round refined this list but also separated the factors into two population groups – active/athletic and inactive/sedentary. The third round ranked this list in order of perceived importance. Results Forty-four experts were invited to participate, 16 participated in the first round (response rate 40%) and two dropped out in the second round (resulting in a response rate of 35%). A total of 27 intrinsic and eight extrinsic risk factors were identified during round one. During round two only 12 intrinsic and five extrinsic risk factors were identified as important in active/athletic tendinopathy while 14 intrinsic and three extrinsic factors were identified as important for inactive/sedentary tendinopathy. Conclusions Risk factors for Achilles tendinopathy were identified based on expert consensus, and these factors provide a basis for primary epidemiological studies. Plantarflexor strength was identified as the primary modifiable factor in the active/athletic group while systemic factors were identified as important in the inactive/sedentary group, many of the potential factors suggested for either group were non-modifiable. Non-modifiable factors include: previous tendinopathy, previous injury, advancing age, sex, steroid exposure, and antibiotic treatment. Level of evidence Level V PMID:27757281

[Genetically modified food (food derived from biotechnology): current and future trends in public acceptance and safety assessment].

PubMed

Nishiura, Hiroshi; Imai, Hirohisa; Nakao, Hiroyuki; Tsukino, Hiromasa; Kuroda, Yoshiki; Katoh, Takahiko

2002-11-01

Current and future trends regarding genetically modified (GM) crops and food stuffs were reviewed, with a particular focus on public acceptance and safety assessment. While GM foods, foods derived from biotechnology, are popular with growers and producers, they are still a matter of some concern among consumers. In fact, our recent surveys showed that Japanese consumers had become uneasy about the potential health risks of genetically modified foods. Many Japanese consumers have only vague ideas about the actual health risks, and they appear to be making decisions simply by rejecting GM food because of non-informed doubts. Although the debate about GM foods has increased in the mass media and scientific journals, few articles concerning direct studies on the potential toxicity or adverse health effects of GM foods have appeared. The roles of relevant international regulatory bodies in ensuring that GM crops and food are safe are therefore have summarized. Finally, the current debate on use of GM crops in agriculture and future trends for development of GM foods with enriched nutrients, better functionality, and medicinal ingredients, which will be of direct benefit to the consumer, are covered.

Financial strain and cancer risk behaviors among African Americans.

PubMed

Advani, Pragati S; Reitzel, Lorraine R; Nguyen, Nga T; Fisher, Felicia D; Savoy, Elaine J; Cuevas, Adolfo G; Wetter, David W; McNeill, Lorna H

2014-06-01

African Americans suffer disproportionately from the adverse consequences of behavioral risk factors for cancer relative to other ethnic groups. Recent studies have assessed how financial strain might uniquely contribute to engagement in modifiable behavioral risk factors for cancer, but not among African Americans. The current study examined associations between financial strain and modifiable cancer risk factors (smoking, at-risk alcohol use, overweight/obesity, insufficient physical activity, inadequate fruit and vegetable intake, and multiple risk factors) among 1,278 African American adults (age, 46.5 ± 12.6 years; 77% female) and explored potential mediators (stress and depressive symptoms) of those associations. Logistic regression models were used to examine associations between financial strain and cancer risk factors. Analyses were adjusted for age, sex, partner status, income, educational level, and employment status. Analyses involving overweight/obesity status additionally controlled for fruit and vegetable intake and physical activity. Nonparametric bootstrapping procedures were used to assess mediation. Greater financial strain was associated with greater odds of insufficient physical activity (P < 0.003) and smoking (P = 0.005) and was positively associated with the total number of cancer risk factors (P < 0.0001). There was a significant indirect effect of both stress and depressive symptoms on the relations of financial strain with physical inactivity and multiple risk factors, respectively. Future interventions aimed at reducing cancer disparities should focus on African Americans experiencing higher financial strain while addressing their stress and depressive symptoms. Longitudinal studies are needed to assess the temporal and causal relations between financial strain and modifiable behavioral cancer risk factors among African Americans. ©2014 American Association for Cancer Research.

Level, source identification, and risk analysis of heavy metal in surface sediments from river-lake ecosystems in the Poyang Lake, China.

PubMed

Zhang, Hua; Jiang, Yinghui; Ding, Mingjun; Xie, Zhenglei

2017-09-01

The concentrations, sources, and risks of heavy metals (Fe, Al, Mn, Cr, Co, Ni, Cu, Zn, As, Cd, W, Pb, and Tl) in sediments in five river-lake ecosystems in the Poyang Lake region were studied. The concentrations of the heavy metals varied spatially, with most of the highest concentrations in the Raohe river-lake ecosystem (RH). All heavy metals except As, Cd, W, and Tl were enriched in sediments possessing high total organic carbon contents or in finer sediments. Based on enrichment factors and statistical methods, it was found that Cd in sediments in the Xiushui (XS), Ganjiang (GJ), Xinjiang (XJ) river-lake ecosystems, and RH; Mn in the XS, GJ, and RH; and W in the XS and GJ were greatly affected by anthropogenic inputs. Moreover, the origins of Cu, Zn, and As require more attention due to the high concentrations found. The high enrichment factor of Cd in the sediments indicated that this metal might cause significant pollution in the environment. The results of the modified potential ecological risk index revealed that the XS, GJ, RH, and XJ were at considerable ecological risk, while the sediments in the Fuhe river-lake ecosystem (FH) were at moderate ecological risk, with Cd contributing the highest proportion of risk. The hazard score fundamentally validated the modified potential ecological risk analysis and revealed a mean toxicity of 57.80% to the benthic organisms in the RH.

Incident Risk Factors and Major Bleeding in Patients with Atrial Fibrillation Treated with Oral Anticoagulants: A Comparison of Baseline, Follow-up and Delta HAS-BLED Scores with an Approach Focused on Modifiable Bleeding Risk Factors.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-04-01

 When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the 'delta HAS-BLED score' (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score.  A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean 'delta HAS-BLED score' of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a 'delta HAS-BLED' score ≥1, compared with only 59.0% in patients without major bleeding ( p  < 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49).  In this 'real-world' nationwide AF cohort, follow-up HAS-BLED or 'delta HAS-BLED score' was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of 'modifiable bleeding risk factors'. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to 'flag up' patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits. Schattauer GmbH Stuttgart.

RNAi-based GM plants: food for thought for risk assessors.

PubMed

Ramon, Matthew; Devos, Yann; Lanzoni, Anna; Liu, Yi; Gomes, Ana; Gennaro, Andrea; Waigmann, Elisabeth

2014-12-01

RNA interference (RNAi) is an emerging technology that offers new opportunities for the generation of new traits in genetically modified (GM) plants. Potential risks associated with RNAi-based GM plants and issues specific to their risk assessment were discussed during an international scientific workshop (June 2014) organized by the European Food Safety Authority (EFSA). Selected key outcomes of the workshop are reported here. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

PubMed Central

Houghton, P. W.; Leach, S.; Owen, R. W.; McC Mortensen, N. J.; Hill, M. J.; Williamson, R. C.

1989-01-01

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds. PMID:2765371

A risk assessment approach for fresh fruits.

PubMed

Bassett, J; McClure, P

2008-04-01

To describe the approach used in conducting a fit-for-purpose risk assessment of microbiological human pathogens associated with fresh fruit and the risk management recommendations made. A qualitative risk assessment for microbiological hazards in fresh fruit was carried out based on the Codex Alimentarius (Codex) framework, modified to consider multiple hazards and all fresh (whole) fruits. The assessment determines 14 significant bacterial, viral, protozoal and nematodal hazards associated with fresh produce, assesses the probable level of exposure from fresh fruit, concludes on the risk from each hazard, and considers and recommends risk management actions. A review of potential risk management options allowed the comparison of effectiveness with the potential exposure to each hazard. Washing to a recommended protocol is an appropriate risk management action for the vast majority of consumption events, particularly when good agricultural and hygienic practices are followed and with the addition of refrigerated storage for low acid fruit. Additional safeguards are recommended for aggregate fruits with respect to the risk from protozoa. The potentially complex process of assessing the risks of multiple hazards in multiple but similar commodities can be simplified in a qualitative assessment approach that employs the Codex methodology.

Sleep apnoea and stroke

PubMed Central

Sharma, Sameer; Culebras, Antonio

2016-01-01

Sleep disorders have been known to physicians for a long time. In his famous aphorisms, Hippocrates said “Sleep or watchfulness exceeding that which is customary, augurs unfavorably”. Modern medicine has been able to disentangle some of the phenomena that disturb sleep. Among the most notable offenders is sleep apnoea that has gained prominence in the past few decades. It is being proposed as one of the potentially modifiable risk factors for vascular diseases including stroke. The pathological mechanisms linking sleep apnoea to vascular risk factors include hypoxia, cardiac arrhythmias, dysautonomia, impaired glucose tolerance, hypertension, dyslipidaemia and inflammation. In this article, we review literature linking sleep apnoea and stroke, including sleep apnoea as a risk factor for primary prevention with the potential to improve outcome after acute stroke and as a secondary risk factor, amenable to modification and hence vascular risk reduction. PMID:28959482

Do Elderly Patients Experience Increased Perioperative or Postoperative Morbidity or Mortality When Given Neoadjuvant Chemoradiation Before Esophagectomy?

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

Fogh, Shannon E., E-mail: foghse@radonc.ucsf.edu; Yu, Anthony; Kubicek, Gregory J.

2011-08-01

Background: The use of induction chemoradiotherapy followed by surgery has been widely used for the treatment of esophageal cancer. The presumed risk of increased postoperative morbidity and mortality with this regimen has led to reluctance to offer this therapy to elderly patients. We compared the perioperative morbidity and mortality of patients 70 years old and older with those of patients younger than 70 who received CRT followed by esophagectomy and sought to identify preoperative risk factors that may predict higher risk of postoperative death or complications. Methods and Materials: We identified 260 patients who underwent preoperative chemoradiotherapy followed by esophagectomy.more » The association of age with postoperative death and complications was evaluated. The Charlson index, prior cardiac history, and diabetes were identified as preoperative risk factors and were evaluated as potential confounders or effect modifiers. Results: Cardiac disease and the Charlson index were potential modifiers of the effect of age on length of hospital stay (p = 0.08 and p = 0.07, respectively) and postoperative complications (p = 0.1 and p = 0.2) but were not statistically significant. There was a slight nonsignificant decrease in the risk of death in elderly patients after adjustment for the Charlson index (p = 0.2). Conclusion: No significant differences were detected with respect to morbidity and mortality in elderly patients. The presence of cardiac disease, higher scores on the Charlson index, or diabetes did not significantly influence length of stay, postoperative complications, or postoperative death. Given the potential to improve outcomes, this regimen should not be discounted in elderly patients.« less

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study

PubMed Central

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-01-01

Objective Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Methods Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. Results The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Conclusions Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. PMID:28601831

Risk factors for first time incidence sciatica: a systematic review.

PubMed

Cook, Chad E; Taylor, Jeffrey; Wright, Alexis; Milosavljevic, Steven; Goode, Adam; Whitford, Maureen

2014-06-01

Characteristically, sciatica involves radiating leg pain that follows a dermatomal pattern along the distribution of the sciatic nerve. To our knowledge, there are no studies that have investigated risk factors associated with first time incidence sciatica. The purpose of the systematic review was to identify the longitudinal risk factors associated with first time incidence sciatica and to report incidence rates for the condition. For the purposes of this review, first time incidence sciatica was defined as either of the following: 1) no prior history of sciatica or 2) transition from a pain-free state to sciatica. Studies included subjects of any age from longitudinal, observational, cohort designs. The study was a systematic review. Eight of the 239 articles identified by electronic search strategies met the inclusion criteria. Risk factors and their respective effect estimates were reported using descriptive analysis and the preferred reporting items for systematic reviews and meta-analyses guidelines. Modifiable risk factors included smoking, obesity, occupational factors and health status. Non-modifiable factors included age, gender and social class. Incidence rates varied among the included studies, in part reflecting the variability in the operationalized definition of sciatica but ranged from <1% to 37%. A majority of the identified risk factors associated with first time sciatica are modifiable, suggesting the potential benefits of primary prevention. In addition, those risk factors are also associated with unhealthy lifestyles, which may function concomitantly toward the development of sciatica. Sciatica as a diagnosis is inconsistently defined among studies. © 2013 John Wiley & Sons, Ltd.

Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort.

PubMed

Andersen, Louise B; Jørgensen, Jan S; Jensen, Tina K; Dalgård, Christine; Barington, Torben; Nielsen, Jan; Beck-Nielsen, Signe S; Husby, Steffen; Abrahamsen, Bo; Lamont, Ronald F; Christesen, Henrik T

2015-09-01

Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy. We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58). The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage. We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900. © 2015 American Society for Nutrition.

Mechanical Ventilation and Bronchopulmonary Dysplasia.

PubMed

Keszler, Martin; Sant'Anna, Guilherme

2015-12-01

Mechanical ventilation is an important potentially modifiable risk factor for the development of bronchopulmonary dysplasia. Effective use of noninvasive respiratory support reduces the risk of lung injury. Lung volume recruitment and avoidance of excessive tidal volume are key elements of lung-protective ventilation strategies. Avoidance of oxidative stress, less invasive methods of surfactant administration, and high-frequency ventilation are also important factors in lung injury prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

PubMed

Schiffer, Joshua T; Gottlieb, Sami L

2017-09-25

Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort.

PubMed

Dartigues, Jean-François; Carcaillon, Laure; Helmer, Catherine; Lechevallier, Nathalie; Lafuma, Antoine; Khoshnood, Babak

2007-03-01

To assess the effects of treatment for memory impairment and the Ginkgo biloba extract (EGb 761) on dementia, mortality, and survival without dementia. Prospective community-based cohort study. France. Three thousand five hundred thirty-four subjects aged 65 and older. Information on drug consumption was obtained by interview and visual assessment of patients' medicine chests. Active screening of dementia was performed every 2 years over a 13-year period. The independent effects of treatment for memory impairment and the Ginkgo biloba extract on the risks of dementia and death were estimated using Cox proportional hazards models, adjusted for potentially confounding factors (including comorbidities). The initial consumption of Ginkgo biloba did not modify the risk of dementia (relative risk (RR)=1.16, 95% confidence interval (CI)=0.84-1.60), whereas the consumption of other treatments for memory impairment was associated with a higher risk of dementia (RR=1.35, 95% CI=1.11-1.63). Subjects who took Ginkgo biloba had a significantly lower risk of mortality in the long term (RR=0.76, 95% CI=0.62-0.93), even after adjustment for potentially confounding factors. The initial consumption of treatment for memory impairment other than Ginkgo biloba did not modify the risk of mortality. These results suggest that treatment with EGb 761 may increase the probability of survival in the elderly population. These findings need to be corroborated and further assessed using randomized, controlled trials.

Problem formulation in the environmental risk assessment for genetically modified plants

PubMed Central

Wolt, Jeffrey D.; Keese, Paul; Raybould, Alan; Burachik, Moisés; Gray, Alan; Olin, Stephen S.; Schiemann, Joachim; Sears, Mark; Wu, Felicia

2009-01-01

Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation. PMID:19757133

Modifiable Risk Factors for West Nile Virus Infection during an Outbreak—Arizona, 2010

PubMed Central

Gibney, Katherine B.; Colborn, James; Baty, Steven; Bunko Patterson, Andrean M.; Sylvester, Tammy; Briggs, Graham; Stewart, Tasha; Levy, Craig; Komatsu, Ken; MacMillan, Katherine; Delorey, Mark J.; Mutebi, John-Paul; Fischer, Marc; Staples, J. Erin

2012-01-01

West Nile virus (WNV) is the leading cause of mosquito-borne disease in the United States; however, risk factors for infection are poorly defined. We performed a case-control study to identify modifiable risk factors for WNV infection. Case-patients (N = 49) had laboratory evidence of recent WNV infection, whereas control-subjects (N = 74) had negative WNV serology. We interviewed participants, surveyed households, and assessed environmental data. WNV infection was associated with living in or near Water District X within Gilbert Township (adjusted odds ratio [aOR] 5.2; 95% confidence interval [95% CI] = 1.5–18.1), having water-holding containers in their yard (aOR 5.0; 95% CI = 1.5–17.3), and not working or attending school outside the home (aOR 2.4; 95% CI = 1.1–5.5). During this outbreak, WNV infection was likely primarily acquired peri-domestically with increased risk associated with potential mosquito larval habitats around the home and neighborhood. PMID:22556093

Environmental release of living modified organisms: current approaches and case studies.

PubMed

Thomas, E; Nickson, Ph D

2005-01-01

Agricultural biotechnology is being rapidly adopted as evidenced by the acreage of genetically modified (GM) crops planted and tonnes of product (grain and fiber) harvested. Concurrent with this technological progress, is a growing concern that the worlds biological diversity is coming under increasing threat from human activities. As such, ecological risk assessment approaches are being developed for GM crop plants as international agreements regulating the transboundary movements of these products are being implemented. This paper reviews the ecological risk assessment approach that has been used to date to approve GM crops to date. The process has been case-by-case, using a comparative, science-based approach balancing the potential risks and benefits of the new technology versus those present with the currently accepted practices. The approach used to evaluate and approve these products is consistent with the conditions and requirements outlined in the Cartagena Protocol.

Periodontitis as a Modifiable Risk Factor for Dementia: A Nationwide Population-Based Cohort Study.

PubMed

Lee, Yao-Tung; Lee, Hsin-Chien; Hu, Chaur-Jongh; Huang, Li-Kai; Chao, Shu-Ping; Lin, Chia-Pei; Su, Emily Chia-Yu; Lee, Yi-Chen; Chen, Chu-Chieh

2017-02-01

To determine whether periodontitis is a modifiable risk factor for dementia. Prospective cohort study. National Health Insurance Research Database in Taiwan. Individuals aged 65 and older with periodontitis (n = 3,028) and an age- and sex-matched control group (n = 3,028). Individuals with periodontitis were compared age- and sex-matched controls with for incidence density and hazard ratio (HR) of new-onset dementia. Periodontitis was defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 diagnosed by dentists. To ensure diagnostic validity, only those who had concurrently received antibiotic therapies, periodontal treatment other than scaling, or scaling more than twice per year performed by certified dentists were included. Dementia was defined according to ICD-9-CM codes 290.0-290.4, 294.1, 331.0-331.2. After adjustment for confounding factors, the risk of developing dementia was calculated to be higher for participants with periodontitis (HR = 1.16, 95% confidence interval = 1.01-1.32, P = .03) than for those without. Periodontitis is associated with greater risk of developing dementia. Periodontal infection is treatable, so it might be a modifiable risk factor for dementia. Clinicians must devote greater attention to this potential association in an effort to develop new preventive and therapeutic strategies for dementia. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

The influence of social support and perceived stress on response time inconsistency.

PubMed

Phibbs, Sandi; Stawski, Robert S; MacDonald, Stuart W S; Munoz, Elizabeth; Smyth, Joshua M; Sliwinski, Martin J

2017-11-24

Lack of social support and high levels of stress represent potentially modifiable risk factors for cognitive aging. In this study we examined the relationships between these two risk factors and response time inconsistency (RTI), or trial-to-trial variability in choice response time tasks. RTI is an early indicator of declining cognitive health, and examining the influence of modifiable psychosocial risk factors on RTI is important for understanding and promoting cognitive health during adulthood and old age. Using data from a community sample study (n = 317; M age = 49, range = 19-83), we examined the effects of social support, including size of network and satisfaction with support, global perceived stress, and their interactions on RTI. Neither size of network nor satisfaction with support was associated with RTI independent of perceived stress. Stress was positively associated with increased RTI on all tasks, independent of social support. Perceived stress did not interact with either dimension of social support to predict RTI, and perceived stress effects were invariant across age and sex. Perceived stress, but not social support, may be a unique and modifiable risk factor for normal and pathological cognitive aging. Discussion focuses on the importance of perceived stress and its impact on RTI in supporting cognitive health in adulthood and old age.

What are the real risks of sport-related concussion, and are they modifiable?

PubMed

Randolph, Christopher; Kirkwood, Michael W

2009-07-01

Over the past two decades, the management of sport-related concussion has been the topic of increased attention in the scientific literature and in the popular media. Despite a proliferation of competing guidelines for concussion management, the widespread use of neuropsychological "baseline" testing designed to monitor postinjury recovery, and several prospective controlled studies of the natural history of concussion, there has been virtually no attempt to quantify the risks associated with sport-related concussion or to determine whether these risks are modifiable via management strategies. Using American football as a model, the short- and long-term risks of sport-related concussion are reviewed. It is concluded that serious short-term consequences of sport-related concussion are extremely rare and unlikely to be significantly modified via management strategies that rely on baseline testing. Other less serious short-term adverse outcomes are also quite rare, transient, and not likely to be altered by specific management guidelines. The long-term consequences of multiple sport-related head trauma remain unclear but are potentially of greater public health concern and should be the focus of increased research. Based on available evidence, there is little rationale for the use of rigid strategies or guidelines in the place of individual clinical decision-making in the management of these injuries.

Methodologies for the Detection of BSE Risk Material in Meat and Meat Products

NASA Astrophysics Data System (ADS)

Lücker, Ernst

Soon after the emergence of bovine spongiform encephalopathy (BSE), a fatal disease of the central nervous system (CNS) in cattle, so-called specified bovine offal were legally defined and banned (SBO-ban) in order to reduce the presumed potential BSE exposition risk for British consumers (UK, 1989). Later on the legal definition of risk material was frequently modified according to new scientific results on BSE tissue infectivity (Table 19.1). A European-wide ban on specified risk materials (SRM) was established in 2001 (EC, 2001). In effect, the SRM-ban is still the most important direct measure in reducing potential human BSE exposure risk (EC, 2005). Taking into account the overall and constant reduction of the frequency of BSE cases as well as the very high costs of preventive measures, the European Commission has envisioned a future lifting of the SRM-ban (EC, 2005).

[Foot ulceration risk factors in type 2 diabetes mellitus].

PubMed

Bustos-Saldaña, Rafael; Prieto-Miranda, Sergio

2009-01-01

To identify risk factor prevalence for development of foot ulcers in patients with type 2 diabetes (DM2). A cross sectional study, of 2067 patients with DM2 from seven primary care units was conducted. A questionnaire exploring age, sex, occupation, time from diabetes mellitus diagnosis (DMD), and data concerning neuropathy, vascular changes, and presence of infections, anthropometry, and gait was applied. We found mean age, 59.96 +/- 11.47 years and time from DMD, 10.2 +/- 8.09 years. From 1360 women, 65.8 % presented the following risk factors: age, 34.7 %; schooling, 49.5 %; time from DMD, 38.8 %; occupation, 20 %; smoking, 24.3 %; alcoholism, 4.6 %; fasting glucose disturbance, 78 %; ulcer history, 10 %. In relation to associated diseases, 67.5 % of patients had one or more antecedent. The presence of risk factors in the sample was 9.716 +/- 2.52, of which 6.259 +/- 1.59 were modifiable. Patients studied presented high risk factor prevalence for development of foot ulcer. The majority of RF is potentially modifiable by adjusting patients' customs and habits.

75 FR 68306 - Modification of Significant New Uses of 2-Propen-1-one, 1-(4-morpholinyl)-

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... protective equipment (including gloves demonstrated to be impervious) and respiratory personal protective... remaining potential risks, the modified consent order: Requires the use of dermal personal protective... , including any personal information provided, unless the comment includes information claimed to be...

Changing health behaviors to improve health outcomes after angioplasty: a randomized trial of net present value versus future value risk communication.

PubMed

Charlson, M E; Peterson, J C; Boutin-Foster, C; Briggs, W M; Ogedegbe, G G; McCulloch, C E; Hollenberg, J; Wong, C; Allegrante, J P

2008-10-01

Patients who have undergone angioplasty experience difficulty modifying at-risk behaviors for subsequent cardiac events. The purpose of this study was to test whether an innovative approach to framing of risk, based on 'net present value' economic theory, would be more effective in behavioral intervention than the standard 'future value approach' in reducing cardiovascular morbidity and mortality following angioplasty. At baseline, all patients completed a health assessment, received an individualized risk profile and selected risk factors for modification. The intervention randomized patients into two varying methods for illustrating positive effects of behavior change. For the experimental group, each selected risk factor was assigned a numeric biologic age (the net present value) that approximated the relative potential to improve current health status and quality of life when modifying that risk factor. In the control group, risk reduction was framed as the value of preventing future health problems. Ninety-four percent of patients completed 2-year follow-up. There was no difference between the rates of death, stroke, myocardial infarction, Class II-IV angina or severe ischemia (on non-invasive testing) between the net present value group and the future value group. Our results show that a net present risk communication intervention did not result in significant differences in health outcomes.

Lung cancer risk of airborne particles for Italian population

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

Buonanno, G., E-mail: buonanno@unicas.it; International Laboratory for Air Quality and Health, Queensland University of Technology, 2 George Street 2, 4001 Brisbane, Qld.; Giovinco, G., E-mail: giovinco@unicas.it

Airborne particles, including both ultrafine and supermicrometric particles, contain various carcinogens. Exposure and risk-assessment studies regularly use particle mass concentration as dosimetry parameter, therefore neglecting the potential impact of ultrafine particles due to their negligible mass compared to supermicrometric particles. The main purpose of this study was the characterization of lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation by Italian non-smoking people. A risk-assessment scheme, modified from an existing risk model, was applied to estimate the cancer risk contribution from both ultrafine and supermicrometric particles. Exposure assessment was carried outmore » on the basis of particle number distributions measured in 25 smoke-free microenvironments in Italy. The predicted lung cancer risk was then compared to the cancer incidence rate in Italy to assess the number of lung cancer cases attributed to airborne particle inhalation, which represents one of the main causes of lung cancer, apart from smoking. Ultrafine particles are associated with a much higher risk than supermicrometric particles, and the modified risk-assessment scheme provided a more accurate estimate than the conventional scheme. Great attention has to be paid to indoor microenvironments and, in particular, to cooking and eating times, which represent the major contributors to lung cancer incidence in the Italian population. The modified risk assessment scheme can serve as a tool for assessing environmental quality, as well as setting up exposure standards for particulate matter. - Highlights: • Lung cancer risk for non-smoking Italian population due to particle inhalation. • The average lung cancer risk for Italian population is equal to 1.90×10{sup −2}. • Ultrafine particle is the aerosol metric mostly contributing to lung cancer risk. • B(a)P is the main (particle-bounded) compound contributing to lung cancer risk. • Cooking activities represent the principal contributor to the lung cancer risk.« less

Recurrent Shoulder Dystocia: Risk Factors and Counseling.

PubMed

Gurewitsch Allen, Edith D

2016-12-01

A prior history of delivery complicated by shoulder dystocia confers a 6-fold to nearly 30-fold increased risk of shoulder dystocia recurrence in a subsequent vaginal delivery, with most reported rates between 12% and 17%. Whereas prevention of shoulder dystocia in the general population is neither feasible nor cost-effective, directing intervention efforts at the particular subgroup of women with a prior history of shoulder dystocia has merit. Potentially modifiable risk factors and individualized management strategies that may reduce shoulder dystocia recurrence and its associated significant morbidities are reviewed.

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

PubMed

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

2009-07-01

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

Online assessment of risk factors for dementia and cognitive function in healthy adults.

PubMed

Huntley, J; Corbett, A; Wesnes, K; Brooker, H; Stenton, R; Hampshire, A; Ballard, C

2018-02-01

Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan. Copyright © 2017 John Wiley & Sons, Ltd.

Immunoglobulin E mediated food allergy.Modelling and application of diagnostic and predictive tests for existing and novel foods.

PubMed

Elizabeth I Opara Sarah L Oehlschlager A Bryan Hanley

1998-01-01

It is known that some foods cause an allergenic response in certain individuals. Clinical and immunological tests are available for the diagnosis of food allergy and identification of food allergens. However, there are no valid tests for the prediction of the allergenic potential of foods not normally recognized as allergenic. Such foods include: food products developed from foods which may not be recognizable as allergenic in their modified forms; foods produced using novel processes (novel foods), for example genetically modified foods; and foods not normally consumed but that are being used increasingly as alternatives to more traditional foods. Both the risks associated with food allergy and the fact that foods such as the ones described above will become available to the consumer, highlight the need for methods to screen for potential food allergens. This review provides a general overview of food allergy including mechanism, development and prevalence, but focuses on and discusses: 1) the possible risks (with specific reference to food allergy) associated with new and novel foods; and 2) the development/use of food allergy models (in vivo and in vitro) to assess the allergenic potential of new and novel foods.

Horizontal gene transfer between bacteria.

PubMed

Heuer, Holger; Smalla, Kornelia

2007-01-01

Horizontal gene transfer (HGT) refers to the acquisition of foreign genes by organisms. The occurrence of HGT among bacteria in the environment is assumed to have implications in the risk assessment of genetically modified bacteria which are released into the environment. First, introduced genetic sequences from a genetically modified bacterium could be transferred to indigenous micro-organisms and alter their genome and subsequently their ecological niche. Second, the genetically modified bacterium released into the environment might capture mobile genetic elements (MGE) from indigenous micro-organisms which could extend its ecological potential. Thus, for a risk assessment it is important to understand the extent of HGT and genome plasticity of bacteria in the environment. This review summarizes the present state of knowledge on HGT between bacteria as a crucial mechanism contributing to bacterial adaptability and diversity. In view of the use of GM crops and microbes in agricultural settings, in this mini-review we focus particularly on the presence and role of MGE in soil and plant-associated bacteria and the factors affecting gene transfer.

Research on Potential Environmental Impacts of Oxy-fuel Combustion at EPA

EPA Science Inventory

An existing 35kW laboratory-scale combustor located at the U.S. EPA’s National Risk Management Research Laboratory, Research Triangle Park, North Carolina, has been modified for performing oxy-natural gas and oxy-coal experiments by adding O2 operation and flue gas recycling capa...

Research on Potential Environmental Impacts of Oxyfuel Combustion at EPA

EPA Science Inventory

An existing 35kW laboratory-scale combustor located at the U.S. EPA’s National Risk Management Research Laboratory, Research Triangle Park, North Carolina, has been modified for performing oxy-natural gas and oxy-coal experiments by adding O2 operation and flue gas recyclin...

Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

EPA Science Inventory

Epidemiologic and experimental studies have demonstrated a variety of health effects in response to ozone (O3) exposure. Studies have demonstrated that some populations may be at increased risk of O3-related health effects. Objectives: To identify populations and lifestages pote...

Glyphosate drift promotes changes in fitness and transgene flow in canola (Brassica napus) and hybrids

EPA Science Inventory

1. With the advent of transgenic crops, genetically modified, herbicide resistant B. napus has become a model system for examining the risks of escape of transgenes from cultivation and for evaluating potential ecological consequences of novel genes in wild species. 2. We exam...

Change in lifestyle behaviors and diabetes risk: evidence from a population-based cohort study with 10 year follow-up.

PubMed

Feldman, Adina L; Long, Gráinne H; Johansson, Ingegerd; Weinehall, Lars; Fhärm, Eva; Wennberg, Patrik; Norberg, Margareta; Griffin, Simon J; Rolandsson, Olov

2017-03-29

Promoting positive changes in lifestyle behavior in the whole population may be a feasible and effective approach to reducing type 2 diabetes burden, but the impact of population shifts of modifiable risk factors remains unclear. Currently most of the evidence on modifiable lifestyle behavior and type 2 diabetes risk on a population level comes from studies of between-individual differences. The objective of the study was to investigate the association and potential impact on disease burden for within-individual change in lifestyle behavior and diabetes risk. Population-based prospective cohort study of 35,680 participants aged 30-50 at baseline in 1990-2003 in Västerbotten County, Sweden (follow-up until 2013). Five self-reported modifiable lifestyle behaviors (tobacco use, physical activity, alcohol intake, dietary fiber intake and dietary fat intake) were measured at baseline and 10 year follow-up. Lifestyle behaviors were studied separately, and combined in a score. Incident diabetes was detected by oral glucose tolerance tests. Multivariate logistic regression models and population attributable fractions (PAF) were used to analyze the association between change in lifestyle behavior between baseline and 10 year follow-up, and risk of incident diabetes. Incident diabetes was detected in 1,184 (3.3%) participants at 10 year follow-up. There was a reduced diabetes risk associated with increase in dietary fiber intake, odds ratio (OR) 0.79 (95% confidence interval (CI) 0.66, 0.96) for increase of at least one unit standard deviation (3.0 g/1,000 kcal) of the baseline distribution, PAF 16.0% (95% CI 4.2, 26.4%). Increase in the lifestyle behavior score was associated with reduced diabetes risk, OR 0.92 (95% CI 0.85, 0.99) per unit increase of the score. These results support a causal link between lifestyle behavior and type 2 diabetes incidence. A small shift in lifestyle behaviors, in particular intake of dietary fiber, has the potential to reduce diabetes burden in the population and might be a suitable target for public health intervention.

Gene-by-Environment Interactions in Pancreatic Cancer: Implications for Prevention

PubMed Central

Jansen, Rick J.; Tan, Xiang-Lin; Petersen, Gloria M.

2015-01-01

Pancreatic cancer (PC) has been estimated to have higher incidence and correspondingly higher mortality rates in more developed regions worldwide. Overall, the age-adjusted incidence rate is 4.9/105 and age-adjusted mortality rate is at 4.8/105. We review here our current knowledge of modifiable risk factors (cigarette smoking, obesity, diet, and alcohol) for PC, genetic variants implicated by genome-wide association studies, possible genetic interactions with risk factors, and prevention strategies to provide future research directions that may further our understanding of this complex disease. Cigarette smoking is consistently associated with a two-fold increased PC risk. PC associations with dietary intake have been largely inconsistent, with the potential exception of certain unsaturated fatty acids decreasing risk and well-done red meat or meat mutagens increasing risk. There is strong evidence to support that obesity (and related measures) increase risk of PC. Only the heaviest alcohol drinkers seem to be at an increased risk of PC. Currently, key prevention strategies include avoiding tobacco and excessive alcohol consumption and adopting a healthy lifestyle. Screening technologies and PC chemoprevention are likely to become more sophisticated, but may only apply to those at high risk. Risk stratification may be improved by taking into account gene environment interactions. Research on these modifiable risk factors is key to reducing the incidence of PC and understanding who in the population can be considered high risk. PMID:26029010

Genetically modified crops: success, safety assessment, and public concern.

PubMed

Singh, Om V; Ghai, Shivani; Paul, Debarati; Jain, Rakesh K

2006-08-01

With the emergence of transgenic technologies, new ways to improve the agronomic performance of crops for food, feed, and processing applications have been devised. In addition, ability to express foreign genes using transgenic technologies has opened up options for producing large quantities of commercially important industrial or pharmaceutical products in plants. Despite this high adoption rate and future promises, there is a multitude of concerns about the impact of genetically modified (GM) crops on the environment. Potential contamination of the environment and food chains has prompted detailed consideration of how such crops and the molecules that they produce can be effectively isolated and contained. One of the reasonable steps after creating a transgenic plant is to evaluate its potential benefits and risks to the environment and these should be compared to those generated by traditional agricultural practices. The precautionary approach in risk management of GM plants may make it necessary to monitor significant wild and weed populations that might be affected by transgene escape. Effective risk assessment and monitoring mechanisms are the basic prerequisites of any legal framework to adequately address the risks and watch out for new risks. Several agencies in different countries monitor the release of GM organisms or frame guidelines for the appropriate application of recombinant organisms in agro-industries so as to assure the safe use of recombinant organisms and to achieve sound overall development. We feel that it is important to establish an internationally harmonized framework for the safe handling of recombinant DNA organisms within a few years.

Identifying individuals for primary cardiovascular disease prevention in UK general practice: priorities and resource implications

PubMed Central

Holt, Tim A; Thorogood, Margaret; Griffiths, Frances; Munday, Stephen; Stables, David

2008-01-01

Targeted cardiovascular disease prevention relies on risk-factor information held in primary care records. A risk algorithm, the ‘e-Nudge’, was applied to data from a population of ≥50-year-olds in 19 West Midlands practices, to identify those individuals at risk of cardiovascular disease. Altogether, 5.9% were identified aged 50–74 years at ≥20% 10-year risk based on existing data, and a further 26.4% were potentially at risk but had missing risk-factor information; 9.2% of patients aged over 50 years with established cardiovascular disease had at least one modifiable risk factor outside the audit target of the Quality and Outcomes Framework. Implications for resource allocation are discussed. PMID:18611316

Genetically modified organisms (GMOs) and aquaculture.

PubMed

Beardmore, J A; Porter, Joanne S

2003-01-01

This paper reviews the nature of genetically modified organisms (GMOs), the range of aquatic species in which GMOs have been produced, the methods and target genes employed, the benefits to aquaculture, the problems attached to use of GMOs in aquatic species and the regulatory and other social frameworks surrounding them. A set of recommendations aimed at best practice is appended. This states the potential value of GMOs in aquaculture but also calls for improved knowledge particularly of sites of integration, risk analysis, progress in achieving sterility in fish for production and better dissemination of relevant information.

[The lack of information on genetically modified organisms in Brazil].

PubMed

Ribeiro, Isabelle Geoffroy; Marin, Victor Augustus

2012-02-01

This article presents a review about the labeling of products that have Genetically Modified Organisms (GMO), also called transgenic elements in their composition. It addresses the conventions, laws and regulations relating to such products currently governing the market, the adequacy of these existing standards and their acceptance by society. It also examines the importance of the cautionary principle when assessing the application of new technologies or technologies where little is known or where there is no relevant scientific knowledge about the potential risks to the environment, human health and society.

Association of Asymptomatic Bradycardia With Incident Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Dharod, Ajay; Soliman, Elsayed Z; Dawood, Farah; Chen, Haiying; Shea, Steven; Nazarian, Saman; Bertoni, Alain G

2016-02-01

Bradycardia has been associated with lower cardiovascular disease (CVD) risk in selected populations. There is a paucity of information available about heart rate (HR) less than 50 beats per minute (bpm) among middle-aged or older adults. To determine whether asymptomatic bradycardia was associated with a lower cardiovascular risk profile, less subclinical atherosclerosis, and decreased incident CVD and mortality. This retrospective analysis includes 6733 participants of the Multi-Ethnic Study of Atherosclerosis, which recruited men and women free of clinical cardiovascular disease ages 45 to 84 years from 2000 to 2002 and followed them over 10 years for incident CVD events and mortality. The HR was measured by baseline electrocardiogram. The analysis was performed in June 2014. The association between HR categories with CVD events and all-cause mortality were examined using Cox proportional hazards models adjusted for potential confounders and mediators. The 6733 participants had a mean (SD) age of 62 (10.2) years; 47% were male. The mean (SD) HR was 63 (9.5) bpm among the 5831 participants not taking an HR-modifying drug; 5.3% had an HR lower than 50 bpm. Preliminary results revealed significant interaction for HR categories according to use of HR-modifying drugs for mortality (P = .002); thus, all further analyses were stratified. An HR of less than 50 bpm was not associated with incident CVD in either subgroup (participants taking or not taking HR-modifying drugs). Among participants not taking HR-modifying drugs, the fully adjusted mortality risk was not different for an HR less than 50 bpm (hazard ratio, 0.71 [95% CI, 0.41-1.09]; P = .12) and increased among those with an HR greater than 80 bpm (hazard ratio, 1.49 [95% CI, 1.08-2.05]; P = .01) (reference HR, 60-69 bpm). Among the 902 participants taking HR-modifying drugs there was an elevated mortality risk associated with an HR less than 50 bpm (hazard ratio, 2.42 [95% CI, 1.39-4.20]; P = .002) and with an HR greater than 80 bpm (hazard ratio, 3.55 [95% CI, 1.65-7.65]; P = .001) (reference HR, 60-69 bpm). In a contemporary, community-based cohort, bradycardia was generally not associated with incident CVD or mortality except for a potential adverse association between bradycardia among those taking HR-modifying drugs.

Using spiritually modified cognitive-behavioral therapy in substance dependence treatment: therapists' and clients' perceptions of the presumed benefits and limitations.

PubMed

Hodge, David R; Lietz, Cynthia A

2014-11-01

Cognitive-behavioral therapy (CBT) that has been modified to incorporate clients' spiritual beliefs and practices has been used to treat a variety of problems. This study examines the utility of this modality with the treatment of alcohol dependence and other forms of substance abuse. Toward this end, six focus groups (three therapist groups and three client groups) were conducted to identify the presumed benefits and limitations of using spiritually modified CBT in substance dependence treatment. In terms of benefits, spiritually modified CBT was perceived to enhance outcomes through operationalizing horizontal and vertical sources of social support, divine coping resources, and spiritual motivation. Potential challenges include the risk of therapists inadvertently imposing their own beliefs during the modification process and the possibility of offending clients when conflicts in belief systems emerge, particularly in group setting. The article concludes by providing suggestions for incorporating spiritually modified CBT into treatment and develops a number of illustrative examples of spiritually modified CBT self-statements.

Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

PubMed

Batson, Sarah; Sutton, Alex; Abrams, Keith

2016-01-01

Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional comparators outside of those of primary interest to allow for the exploration of heterogeneity.

76 FR 36544 - Scientific Evaluation of Modified Risk Tobacco Product Applications; Public Workshop; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

... appropriate collection of data regarding the use, consumer perception, and health risks of an MRTP? III...] Scientific Evaluation of Modified Risk Tobacco Product Applications; Public Workshop; Request for Comments... obtain input on specific issues associated with the scientific evaluation of modified risk tobacco...

Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.

PubMed

Yang, Hui; Wang, Qian; Zheng, Lei; Lin, Min; Zheng, Xiang-bin; Lin, Fen; Yang, Li-Ye

2015-01-01

The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

Vascular risk factors and neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study.

PubMed

Steinberg, Martin; Hess, Kyle; Corcoran, Chris; Mielke, Michelle M; Norton, Maria; Breitner, John; Green, Robert; Leoutsakos, Jeannie; Welsh-Bohmer, Kathleen; Lyketsos, Constantine; Tschanz, Joann

2014-02-01

Knowledge of potentially modifiable risk factors for neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is important. This study longitudinally explores modifiable vascular risk factors for NPS in AD. Participants enrolled in the Cache County Study on Memory in Aging with no dementia at baseline were subsequently assessed over three additional waves, and those with incident (new onset) dementia were invited to join the Dementia Progression Study for longitudinal follow-up. A total of 327 participants with incident AD were identified and assessed for the following vascular factors: atrial fibrillation, hypertension, diabetes mellitus, angina, coronary artery bypass surgery, myocardial infarction, cerebrovascular accident, and use of antihypertensive or diabetes medicines. A vascular index (VI) was also calculated. NPS were assessed over time using the Neuropsychiatric Inventory (NPI). Affective and Psychotic symptom clusters were assessed separately. The association between vascular factors and change in NPI total score was analyzed using linear mixed model and in symptom clusters using a random effects model. No individual vascular risk factors or the VI significantly predicted change in any individual NPS. The use of antihypertensive medications more than four times per week was associated with higher total NPI and Affective cluster scores. Use of antihypertensive medication was associated with higher total NPI and Affective cluster scores. The results of this study do not otherwise support vascular risk factors as modifiers of longitudinal change in NPS in AD. Copyright © 2013 John Wiley & Sons, Ltd.

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study.

PubMed

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-06-10

Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Nocturnal Wakefulness as a Previously Unrecognized Risk Factor for Suicide.

PubMed

Perlis, Michael L; Grandner, Michael A; Brown, Gregory K; Basner, Mathias; Chakravorty, Subhajit; Morales, Knashawn H; Gehrman, Philip R; Chaudhary, Ninad S; Thase, Michael E; Dinges, David F

2016-06-01

Suicide is a major public health problem and the 10th leading cause of death in the United States. The identification of modifiable risk factors is essential for reducing the prevalence of suicide. Recently, it has been shown that insomnia and nightmares significantly increase the risk for suicidal ideation, attempted suicide, and death by suicide. While both forms of sleep disturbance may independently confer risk, and potentially be modifiable risk factors, it is also possible that simply being awake at night represents a specific vulnerability for suicide. The present analysis evaluates the frequency of completed suicide per hour while taking into account the percentage of individuals awake at each hour. Archival analyses were conducted estimating the time of fatal injury using the National Violent Death Reporting System for 2003-2010 and the proportion of the American population awake per hour across the 24-hour day using the American Time Use Survey. The mean ± SD incident rate from 06:00-23:59 was 2.2% ± 0.7%, while the mean ± SD incident rate from 00:00-05:59 was 10.3% ± 4.9%. The maximum incident rate was from 02:00-02:59 (16.3%). Hour-by-hour observed values differed from those that would be expected by chance (P < .001), and when 6-hour blocks were examined, the observed frequency at night was 3.6 times higher than would be expected by chance (P < .001). Being awake at night confers greater risk for suicide than being awake at other times of the day, suggesting that disturbances of sleep or circadian neurobiology may potentiate suicide risk. © Copyright 2016 Physicians Postgraduate Press, Inc.

Zolpidem is independently associated with increased risk of inpatient falls.

PubMed

Kolla, Bhanu Prakash; Lovely, Jenna K; Mansukhani, Meghna P; Morgenthaler, Timothy I

2013-01-01

Inpatient falls are associated with significant morbidity and increased healthcare costs. Zolpidem has been reported to decrease balance and is associated with falls. Yet, it is a commonly used hypnotic agent in the inpatient setting. Zolpidem use in hospitalized patients may be a significant and potentially modifiable risk factor for falling. To determine whether inpatients administered zolpidem are at greater risk of falling. Retrospective cohort study. Adult non-intensive care unit (non-ICU) inpatients at a tertiary care center. Adult inpatients who were prescribed zolpidem were identified. Electronic medical records were reviewed to capture demographics and other risk factors for falls. The fall rate was compared in those administered zolpidem versus those only prescribed zolpidem. Multivariate analyses were performed to determine whether zolpidem was independently associated with falls. The fall rate among patients who were prescribed and received zolpidem (n = 4962) was significantly greater than among patients who were prescribed but did not receive zolpidem (n = 11,358) (3.04% vs 0.71%; P < 0.001). Zolpidem use continued to remain significantly associated with increased fall risk after accounting for age, gender, insomnia, delirium status, dose of zolpidem, Charlson comorbidity index, Hendrich's fall risk score, length of hospital stay, presence of visual impairment, gait abnormalities, and dementia/cognitive impairment (adjusted odds ratio [OR] 4.37, 95% confidence interval [CI] = 3.34-5.76; P < 0.001). Additionally, patients taking zolpidem who experienced a fall did not differ from other hospitalized adult patients who fell in terms of age, opioids, antidepressants, sedative-antidepressants, antipsychotics, benzodiazepine, or antihistamine use. Zolpidem use was a strong, independent, and potentially modifiable risk factor for inpatient falls. Copyright © 2012 Society of Hospital Medicine.

Safety factors predictive of job satisfaction and job retention among home healthcare aides.

PubMed

Sherman, Martin F; Gershon, Robyn R M; Samar, Stephanie M; Pearson, Julie M; Canton, Allison N; Damsky, Marc R

2008-12-01

Although many of the well known work characteristics associated with job satisfaction in home health care have been documented, a unique aspect of the home health care aides' (HHA) work environment that might also affect job satisfaction is the fact that their workplace is a household. To obtain a better understanding of the potential impact of the risks/exposures/hazards within the household environment on job satisfaction and job retention in home care, we recently conducted a risk assessment study. Survey data from a convenience sample of 823 New York City HHAs were obtained and analyzed. Household/job-related risks, environmental exposures, transportation issues, threats/verbal and physical abuse, and potential for violence were significantly correlated with HHA job satisfaction and job retention. Addressing the modifiable risk factors in the home health care household may improve job satisfaction and reduce job turnover in this work population.

Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

PubMed

Kirchhoff, Tomas; Gaudet, Mia M; Antoniou, Antonis C; McGuffog, Lesley; Humphreys, Manjeet K; Dunning, Alison M; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H; Hillemanns, Peter; Couch, Fergus J; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W R; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K; Van 't Veer, Laura J; Braaf, Linde M; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C; Hopper, John L; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J; Tollenaar, Robert A E M; Hooning, Maartje J; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L; Arias, José Ignacio; Zamora, M Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A; Caligo, Maria A; Godwin, Andrew K; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L; Domchek, Susan M; Loman, Niklas; Karlsson, Per; Stenmark Askmalm, Marie; Melin, Beatrice; von Wachenfeldt, Anna; Hogervorst, Frans B L; Verheus, Martijn; Rookus, Matti A; Seynaeve, Caroline; Oldenburg, Rogier A; Ligtenberg, Marjolijn J; Ausems, Margreet G E M; Aalfs, Cora M; Gille, Hans J P; Wijnen, Juul T; Gómez García, Encarna B; Peock, Susan; Cook, Margaret; Oliver, Clare T; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D P; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F

2012-01-01

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

PubMed Central

Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Couch, Fergus J.; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W.R.; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K.; Van ‘t Veer, Laura J.; Braaf, Linde M.; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C.; Hopper, John L.; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L.; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I.; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J.; Tollenaar, Robert A.E.M.; Hooning, Maartje J.; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L.; Arias, José Ignacio; Zamora, M. Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G.; kConFab; Group, AOCS Study; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A.; Caligo, Maria A.; Godwin, Andrew K.; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L.; Domchek, Susan M.; SWE-BRCA; Loman, Niklas; Karlsson, Per; Askmalm, Marie Stenmark; Melin, Beatrice; von Wachenfeldt, Anna; HEBON; Hogervorst, Frans B. L.; Verheus, Martijn; Rookus, Matti A.; Seynaeve, Caroline; Oldenburg, Rogier A.; Ligtenberg, Marjolijn J.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; Gille, Hans J.P.; Wijnen, Juul T.; Gómez García, Encarna B.; EMBRACE; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D. Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D.P.; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F.

2012-01-01

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00–1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80–1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk. PMID:22768030

The Fraction of Cancer Attributable to Ways of Life, Infections, Occupation, and Environmental Agents in Brazil in 2020

PubMed Central

Azevedo e Silva, Gulnar; de Moura, Lenildo; Curado, Maria Paula; Gomes, Fabio da Silva; Otero, Ubirani; de Rezende, Leandro Fórnias Machado; Daumas, Regina Paiva; Guimarães, Raphael Mendonça; Meira, Karina Cardoso; Leite, Iuri da Costa; Valente, Joaquim Gonçalves; Moreira, Ronaldo Ismério; Koifman, Rosalina; Malta, Deborah Carvalho; Mello, Marcia Sarpa de Campos; Guedes, Thiago Wagnos Guimarães; Boffetta, Paolo

2016-01-01

Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country. PMID:26863517

Policy-Led Comparative Environmental Risk Assessment of Genetically Modified Crops: Testing for Increased Risk Rather Than Profiling Phenotypes Leads to Predictable and Transparent Decision-Making

PubMed Central

Raybould, Alan; Macdonald, Phil

2018-01-01

We describe two contrasting methods of comparative environmental risk assessment for genetically modified (GM) crops. Both are science-based, in the sense that they use science to help make decisions, but they differ in the relationship between science and policy. Policy-led comparative risk assessment begins by defining what would be regarded as unacceptable changes when the use a particular GM crop replaces an accepted use of another crop. Hypotheses that these changes will not occur are tested using existing or new data, and corroboration or falsification of the hypotheses is used to inform decision-making. Science-led comparative risk assessment, on the other hand, tends to test null hypotheses of no difference between a GM crop and a comparator. The variables that are compared may have little or no relevance to any previously stated policy objective and hence decision-making tends to be ad hoc in response to possibly spurious statistical significance. We argue that policy-led comparative risk assessment is the far more effective method. With this in mind, we caution that phenotypic profiling of GM crops, particularly with omics methods, is potentially detrimental to risk assessment. PMID:29755975

Calcaneal Scoring as an Adjunct to Modified Oxford Hip Scores: Prediction of Contralateral Slipped Capital Femoral Epiphysis.

PubMed

Nicholson, Allen D; Huez, Coridon M; Sanders, James O; Liu, Raymond W; Cooperman, Daniel R

2016-03-01

In 2 recent studies, modified Oxford hip scores of 16 through 18 have been shown to predict an extremely high risk of contralateral slipping in unilateral slipped capital femoral epiphysis (SCFE). However, the modified Oxford system is not widely used. This may be due, in part, to the complexity of the scoring system, difficulty in viewing all 5 radiographic features on a single x-ray and phenotypic variation in the features. Ossification of the calcaneal apophysis provides an osteologic marker of skeletal maturation in relation to peak height velocity and has been described previously. We examine the value of the calcaneal apophyseal ossification sequence for predicting modified Oxford hip scores. We examined 279 pelvis and matching foot x-rays that were taken at the same session from 94 healthy children aged 3 to 18 years. A fellowship-trained pediatric orthopaedist determined the modified Oxford hip score for each hip radiograph. The calcaneal x-rays had been previously graded. Modified Oxford hip scores were compared with calcaneal scores for each set of matched hip and calcaneal x-rays. Stage 0 to 2 calcanei had 94% of corresponding hip radiographs rated as modified Oxford scores of 16 to 18. Stage 3 calcanei had 54% rated as 16 to 18 and 31% rated as scores 19 to 21. Stage 4 calcanei had 31% rated as scores 19 to 21, and 68% rated as scores 22 to 26. Stage 5 calcanei had 100% rated as 22 to 26. Using data from Popejoy and colleagues' study, the weighted risk of contralateral SCFE was 94% for calcaneal stage 0, 86.5% for calcaneal stage 1, 90.3% for calcaneal stage 2, 55.8% for calcaneal stage 3, 6.1% for calcaneal stage 4, and 0 for calcaneal stage 5. Calcaneal stages 0 to 3 correspond entirely to modified Oxford scores indicating elevated risk of contralateral SCFE. The calcaneal scoring system has potential for adjunctive use with the modified Oxford score for prediction of contralateral SCFE.

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

PubMed

Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-09-01

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

Quantifying the risk-reduction potential of new Modified Risk Tobacco Products.

PubMed

Martin, Florian; Vuillaume, Gregory; Baker, Gizelle; Sponsiello-Wang, Zheng; Ricci, Paolo F; Lüdicke, Frank; Weitkunat, Rolf

2018-02-01

Quantitative risk assessment of novel Modified Risk Tobacco Products (MRTP) must rest on indirect measurements that are indicative of disease development prior to epidemiological data becoming available. For this purpose, a Population Health Impact Model (PHIM) has been developed to estimate the reduction in the number of deaths from smoking-related diseases following the introduction of an MRTP. One key parameter of the model, the F-factor, describes the effective dose upon switching from cigarette smoking to using an MRTP. Biomarker data, collected in clinical studies, can be analyzed to estimate the effects of switching to an MRTP as compared to quitting smoking. Based on transparent assumptions, a link function is formulated that translates these effects into the F-factor. The concepts of 'lack of sufficiency' and 'necessity' are introduced, allowing for a parametrization of a family of link functions. These can be uniformly sampled, thus providing different 'scenarios' on how biomarker-based evidence can be translated into the F-factor to inform the PHIM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system

PubMed Central

Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-01-01

Diabetic nephropathy (DN) affects an estimated 20%–40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. PMID:25116004

Potential of chitosan (chemically-modified chitin) for extraction of lead-arsenate contaminated soils

USDA-ARS?s Scientific Manuscript database

Arsenic (As), phosphorous (P), and lead (Pb) contamination in soils represents a health risk to humans and the environment. Chitosan (poly-N-acetyl glucosamine) is a non-toxic and inexpensive food industry byproduct derived from chitin that has been used as an adsorbent of heavy metals. The object...

Educational Awareness of Biotechnology Issues among Undergraduate Students at the United Arab Emirates University

ERIC Educational Resources Information Center

AbuQamar, Synan; Alshannag, Qasim; Sartawi, Abdelaziz; Iratni, Rabah

2015-01-01

Due to its valuable benefits and potential risks, there is a progressing debate among opponents and proponents of biotechnology in recent decades. Previous studies have shown that lack of knowledge about biotechnology remains the concern about genetically modified organisms/food (GMO/GMF). This study assessed levels of educational awareness…

Mapping Risks of Indonesian Tuna Supply Chain

NASA Astrophysics Data System (ADS)

Karningsih, P. D.; Anggrahini, D.; Kurniati, N.; Suef, M.; Fachrur, A. R.; Syahroni, N.

2018-04-01

Due to its high economic value and is produced by many countries, Tuna is considered as one of the world’s popular fish. Demand for Tuna species are very high and it usually sells in three form: fresh, frozen or canned. Competition in Tuna trading is challengin with the potential risk of price and supply fluctuations. With recent focus of Indonesia government that see the future of Indonesia civilization depend on the oceans and as the three biggest Tuna producing country, Ministry of Marine Affairs and Fisheries should ensure sustainability and competitiveness of Indonesian tuna. Therefore, there is a great need to develop a proper and effective strategy to manage potential risks in Indonesian Tuna supply chain. This paper is aimed at identifying and mapping potential Tuna supply chain risks and its interrelationships that would assist government in determining proper strategies to manage Indonesian Tuna. A framework for identifying Tuna supply chain risks is proposed. Generic risk structure of Supply Chain Risk Identification System is adopted and modified to match with particular object, which is Indonesian Tuna. The proposed model consists of hierarchical and causal structure that encompass potential risks of Tuna supply chain operations from fishing, trading, processing and distribution. The causal structure consist of risk events and its risk agents which is the cause of risk events. To ensure the root cause of risk events are identified properly, five why’s analysis is utilized to obtain risk agents. This proposed model also captures risk interrelationship between internal and external environment of Tuna supply chain. Preliminary result of this study identifies 15 risk events and 13 risk factors on fishing and trading operations and maps their interrelationships.

Assessment of endogenous allergenicity of genetically modified plants exemplified by soybean - Where do we stand?

PubMed

Selb, R; Wal, J M; Moreno, F J; Lovik, M; Mills, C; Hoffmann-Sommergruber, K; Fernandez, A

2017-03-01

According to EU regulation, genetically modified (GM) plants considered to be allergenic have to be assessed concerning their endogenous allergens before placement on the EU market, in line with the international standards described in Codex Alimentarius. Under such premises, a quantitative relevant increase in allergens might occur in GM plants as an unintended effect compared with conventionally produced crops, which could pose a risk to consumers. Currently, data showing a connection between dose and allergic sensitisation are scarce since the pathophysiological mechanisms of sensitisation are insufficiently understood. In contrast, data on population dose-distribution relationships acquired by oral food challenge are available showing a connection between quantity of allergenic protein consumed and the population of allergic individuals experiencing reactions. Soybean is currently the only recognised allergenic GM food by law for which EFSA has received applications and was therefore taken as an example for defining an assessment strategy. Identification of potential allergens, methodology for quantification as well as risk assessment considerations, are discussed. A strategy is proposed for the identification, assessment and evaluation of potential hazards/risks concerning endogenous allergenicity in food derived from plants developed by biotechnology. This approach could be expanded to other allergenic foods in the future, whenever required. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

PubMed Central

Altintas, Ayse; Al Jumah, Mohammed; Sahraian, Mohammadali; Alsharoqi, Issa; AlTahan, Abdurahman; Dahdaleh, Maurice; Deleu, Dirk; Fernandez, Oscar; Inshasi, Jihad; Karabudak, Rana; Taha, Karim; Totolyan, Natalia; Yamout, Bassem I.; Zakaria, Magd; Bohlega, Saeed

2016-01-01

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation. PMID:28078140

Alzheimer's disease in people with Down's syndrome: the prospects for and the challenges of developing preventative treatments.

PubMed

Castro, Paula; Zaman, Shahid; Holland, Anthony

2017-04-01

People with Down's syndrome (DS) are at high risk for developing Alzheimer's disease (AD) at a relatively young age. This increased risk is not observed in people with intellectual disabilities for reasons other than DS and for this reason it is unlikely to be due to non-specific effects of having a neurodevelopmental disorder but, instead, a direct consequence of the genetics of DS (trisomy 21). Given the location of the amyloid precursor protein (APP) gene on chromosome 21, the amyloid cascade hypothesis is the dominant theory accounting for this risk, with other genetic and environmental factors modifying the age of onset and the course of the disease. Several potential therapies targeting the amyloid pathway and aiming to modify the course of AD are currently being investigated, which may also be useful for treating AD in DS. However, given that the neuropathology associated with AD starts many years before dementia manifests, any preventative treatment must start well before the onset of symptoms. To enable trials of such interventions, plasma, CSF, brain, and retinal biomarkers are being studied as proxy early diagnostic and outcome measures for AD. In this systematic review, we consider the prospects for the development of potential preventative treatments of AD in the DS population and their evaluation.

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

PubMed

Jóri, Balazs; Kamps, Rick; Xanthoulea, Sofia; Delvoux, Bert; Blok, Marinus J; Van de Vijver, Koen K; de Koning, Bart; Oei, Felicia Trups; Tops, Carli M; Speel, Ernst Jm; Kruitwagen, Roy F; Gomez-Garcia, Encarna B; Romano, Andrea

2015-12-01

The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer. A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis. A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype. A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.

Evaluation of Modified Risk Claim Advertising Formats for Camel Snus

ERIC Educational Resources Information Center

Fix, Brian V.; Adkison, Sarah E.; O'Connor, Richard J.; Bansal-Travers, Maansi; Cummings, K. Michael; Rees, Vaughan W.; Hatsukami, Dorothy K.

2017-01-01

Objectives: The US Food and Drug Administration (FDA) has regulatory authority for modified risk tobacco product advertising claims. To guide future regulatory efforts, we investigated how variations in modified risk claim advertisements influence consumer perceptions of product risk claims for Camel Snus. Methods: Young people and adults (15-65),…

The short-term effect of heat waves on mortality and its modifiers in China: an analysis from 66 communities.

PubMed

Ma, Wenjun; Zeng, Weilin; Zhou, Maigeng; Wang, Lijun; Rutherford, Shannon; Lin, Hualiang; Liu, Tao; Zhang, Yonghui; Xiao, Jianpeng; Zhang, Yewu; Wang, Xiaofeng; Gu, Xin; Chu, Cordia

2015-02-01

Many studies have reported increased mortality risk associated with heat waves. However, few have assessed the health impacts at a nation scale in a developing country. This study examines the mortality effects of heat waves in China and explores whether the effects are modified by individual-level and community-level characteristics. Daily mortality and meteorological variables from 66 Chinese communities were collected for the period 2006-2011. Heat waves were defined as ≥2 consecutive days with mean temperature ≥95th percentile of the year-round community-specific distribution. The community-specific mortality effects of heat waves were first estimated using a Distributed Lag Non-linear Model (DLNM), adjusting for potential confounders. To investigate effect modification by individual characteristics (age, gender, cause of death, education level or place of death), separate DLNM models were further fitted. Potential effect modification by community characteristics was examined using a meta-regression analysis. A total of 5.0% (95% confidence intervals (CI): 2.9%-7.2%) excess deaths were associated with heat waves in 66 Chinese communities, with the highest excess deaths in north China (6.0%, 95% CI: 1%-11.3%), followed by east China (5.2%, 95% CI: 0.4%-10.2%) and south China (4.5%, 95% CI: 1.4%-7.6%). Our results indicate that individual characteristics significantly modified heat waves effects in China, with greater effects on cardiovascular mortality, cerebrovascular mortality, respiratory mortality, the elderly, females, the population dying outside of a hospital and those with a higher education attainment. Heat wave mortality effects were also more pronounced for those living in urban cities or densely populated communities. Heat waves significantly increased mortality risk in China with apparent spatial heterogeneity, which was modified by some individual-level and community-level factors. Our findings suggest adaptation plans that target vulnerable populations in susceptible communities during heat wave events should be developed to reduce health risks. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterizing Stressors and Modifiable Health Risk Factors Among Homeless Smokers: An Exploratory Pilot Study.

PubMed

Kendzor, Darla E; Reitzel, Lorraine R; Businelle, Michael S

2015-10-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were conducted to characterize the sample as well as the relations between relevant stressors (discrimination, chronic stress, and fear and mistrust) and health risk factors. Inadequate daily consumption of fruits, vegetables, and fiber was common. High-fat diet and insufficient physical activity were also prevalent, and the majority of participants were overweight/obese. Participants commonly endorsed discrimination, fear of victimization, mistrust of others, and several other stressors. Greater endorsement of stressors was associated with a high-fat diet. Results suggest that lifestyle interventions and policy changes may be warranted in homeless shelters to attenuate the potential effects of stressors on high-fat dietary consumption among smokers. © 2015 Society for Public Health Education.

Assessment of ecological and human health risks of metals in urban road dust based on geochemical fractionation and potential bioavailability.

PubMed

Jayarathne, Ayomi; Egodawatta, Prasanna; Ayoko, Godwin A; Goonetilleke, Ashantha

2018-09-01

Metals are one of the primary pollutants in the urban environment that pose adverse ecological and human health impacts. Therefore, the accurate quantification of the risk posed by metals is essential for developing effective risk management strategies to safeguard the urban environment. This study assessed the ecological and human health risks of six metals, commonly present in road dust by improving the original risk indices based on their potential bioavailability characteristics. The bioavailability of metals was determined by considering their distribution between the different geochemical phases of exchangeable, reducible, oxidisable and residual. The results of the modified risk analysis indicated that the road dust poses a low ecological risk in most of the study sites. According to the present situation, the non-cancer risk of individual metals for both, children and adults followed the decreasing trend of Pb > Cu > Cr > Zn > Ni > Cd. This study also found that depending on the particle size ranges, the potential of multiple metals being able to cause non-cancer health risk was low at most study sites. In terms of cancer health risk, Cr present at most of the study sites was found to be within the cancer threshold limit, even though the Cr content and the bioavailable fractions were relatively low. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of E-Cigarette Health Warnings and Modified Risk Ad Claims on Adolescent E-Cigarette Craving and Susceptibility.

PubMed

Andrews, J Craig; Mays, Darren; Netemeyer, Richard G; Burton, Scot; Kees, Jeremy

2018-04-16

A between-subjects experiment examines the effects of different warning types and modified risk e-cigarette ad claims on adolescent e-cigarette craving and future e-cigarette susceptibility for two different themes. One theme focuses on nicotine and addiction, and the other on the effects of potentially harmful constituents (e.g., flavored chemicals and lung disease). The effects of warning type (control, text-only, graphic health warning (GHW) and text) and modified risk e-cigarette ad claims (control, exposure reduction, risk reduction) are tested experimentally with two different arms (themes) for a sample of 1,011 adolescents who had tried either e-cigarettes or cigarettes. For addiction, the text-only warning led to significantly less e-cigarette susceptibility than the no warning control condition. As expected, there were no differences between the GHW + text condition and text-only or control conditions for e-cigarette craving. An interaction between warning type and modified risk claims revealed significantly fewer e-cigarette cravings and less susceptibility for the text-only warning and no claim (control) condition than for any other condition. For fatal lung disease, the GHW + text condition led to fewer e-cigarette cravings and less susceptibility than the text-only warning and no warning (control) conditions. Warning type effects can be very different under different themes (e.g., addiction, fatal lung disease). In general, our results point to the effectiveness of the text-only warning for addiction and GHW + text for fatal lung disease. Relative exposure and risk modification claims (e.g., less nicotine; less addicting) tend to undercut addiction warnings. More than one type of e-cigarette warning may be necessary as e-cigarette research evolves. Our results show different warning type effects (e.g., text-only; GHW + text) on e-cigarette craving and future susceptibility for adolescent experimenters depending on the risk theme (e.g., addiction; lung disease) and presence of ad claims (e.g., exposure and risk reduction). As research emerges on risks associated with e-cigarette use, it is important to first know what at-risk populations (e.g., adolescents) believe about such risks. Such research will aid our understanding of what types of warnings might be most effective, especially in the presence of ad claims.

EFSA's scientific activities and achievements on the risk assessment of genetically modified organisms (GMOs) during its first decade of existence: looking back and ahead.

PubMed

Devos, Yann; Aguilera, Jaime; Diveki, Zoltán; Gomes, Ana; Liu, Yi; Paoletti, Claudia; du Jardin, Patrick; Herman, Lieve; Perry, Joe N; Waigmann, Elisabeth

2014-02-01

Genetically modified organisms (GMOs) and derived food and feed products are subject to a risk analysis and regulatory approval before they can enter the market in the European Union (EU). In this risk analysis process, the role of the European Food Safety Authority (EFSA), which was created in 2002 in response to multiple food crises, is to independently assess and provide scientific advice to risk managers on any possible risks that the use of GMOs may pose to human and animal health and the environment. EFSA's scientific advice is elaborated by its GMO Panel with the scientific support of several working groups and EFSA's GMO Unit. This review presents EFSA's scientific activities and highlights its achievements on the risk assessment of GMOs for the first 10 years of its existence. Since 2002, EFSA has issued 69 scientific opinions on genetically modified (GM) plant market registration applications, of which 62 for import and processing for food and feed uses, six for cultivation and one for the use of pollen (as or in food), and 19 scientific opinions on applications for marketing products made with GM microorganisms. Several guidelines for the risk assessment of GM plants, GM microorganisms and GM animals, as well as on specific issues such as post-market environmental monitoring (PMEM) were elaborated. EFSA also provided scientific advice upon request of the European Commission on safeguard clause and emergency measures invoked by EU Member States, annual PMEM reports, the potential risks of new biotechnology-based plant breeding techniques, evaluations of previously assessed GMOs in the light of new scientific publications, and the use of antibiotic resistance marker genes in GM plants. Future challenges relevant to the risk assessment of GMOs are discussed. EFSA's risk assessments of GMO applications ensure that data are analysed and presented in a way that facilitates scientifically sound decisions that protect human and animal health and the environment.

A knowledge-based approach to estimating the magnitude and spatial patterns of potential threats to soil biodiversity.

PubMed

Orgiazzi, Alberto; Panagos, Panos; Yigini, Yusuf; Dunbar, Martha B; Gardi, Ciro; Montanarella, Luca; Ballabio, Cristiano

2016-03-01

Because of the increasing pressures exerted on soil, below-ground life is under threat. Knowledge-based rankings of potential threats to different components of soil biodiversity were developed in order to assess the spatial distribution of threats on a European scale. A list of 13 potential threats to soil biodiversity was proposed to experts with different backgrounds in order to assess the potential for three major components of soil biodiversity: soil microorganisms, fauna, and biological functions. This approach allowed us to obtain knowledge-based rankings of threats. These classifications formed the basis for the development of indices through an additive aggregation model that, along with ad-hoc proxies for each pressure, allowed us to preliminarily assess the spatial patterns of potential threats. Intensive exploitation was identified as the highest pressure. In contrast, the use of genetically modified organisms in agriculture was considered as the threat with least potential. The potential impact of climate change showed the highest uncertainty. Fourteen out of the 27 considered countries have more than 40% of their soils with moderate-high to high potential risk for all three components of soil biodiversity. Arable soils are the most exposed to pressures. Soils within the boreal biogeographic region showed the lowest risk potential. The majority of soils at risk are outside the boundaries of protected areas. First maps of risks to three components of soil biodiversity based on the current scientific knowledge were developed. Despite the intrinsic limits of knowledge-based assessments, a remarkable potential risk to soil biodiversity was observed. Guidelines to preliminarily identify and circumscribe soils potentially at risk are provided. This approach may be used in future research to assess threat at both local and global scale and identify areas of possible risk and, subsequently, design appropriate strategies for monitoring and protection of soil biota. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Towards prevention of ovarian cancer.

PubMed

Ali, Aus Tariq

2018-01-01

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The use of genetically modified mice in cancer risk assessment: challenges and limitations.

PubMed

Eastmond, David A; Vulimiri, Suryanarayana V; French, John E; Sonawane, Babasaheb

2013-09-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53⁺/⁻, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program's conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals.

The use of genetically modified mice in cancer risk assessment: Challenges and limitations*

PubMed Central

Eastmond, David A.; Vulimiri, Suryanarayana V.; French, John E.; Sonawane, Babasaheb

2015-01-01

The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53+/−, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program’s conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals. PMID:23985072

Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality.

PubMed

Nastasi, A J; McAdams-DeMarco, M A; Schrack, J; Ying, H; Olorundare, I; Warsame, F; Mountford, A; Haugen, C E; González Fernández, M; Norman, S P; Segev, D L

2018-01-01

Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Integrating diverse scientific and practitioner knowledge in ecological risk analysis: a case study of biodiversity risk assessment in South Africa.

PubMed

Dana, G V; Kapuscinski, A R; Donaldson, J S

2012-05-15

Ecological risk analysis (ERA) is a structured evaluation of threats to species, natural communities, and ecosystem processes from pollutants and toxicants and more complicated living stressors such as invasive species, genetically modified organisms, and biological control agents. Such analyses are typically conducted by a narrowly-focused group of scientific experts using technical information. We evaluate whether the inclusion of more diverse experts and practitioners in ERA improved the ecological knowledge base about South African biodiversity and the potential impacts of genetically modified (GM) crops. We conducted two participatory ERA workshops in South Africa, analyzing potential impacts of GM maize on biodiversity. The first workshop involved only four biological scientists, who were joined by 18 diverse scientists and practitioners in the second, and we compared the ERA process and results between the two using descriptive statistics and semi-structured interview responses. The addition of diverse experts and practitioners led to a more comprehensive understanding of biological composition of the agro-ecosystem and a more ecologically relevant set of hazards, but impeded hazard prioritization and the generation of precise risk assessment values. Results suggest that diverse participation can improve the scoping or problem formulation of the ERA, by generating an ecologically robust set of information on which to base the subsequent, more technical risk assessment. The participatory ERA process also increased the transparency of the ERA by exposing the logic and rationale for decisions made at each step. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prioritization methodology for the decommissioning of nuclear facilities: a study case on the Iraq former nuclear complex.

PubMed

Jarjies, Adnan; Abbas, Mohammed; Monken Fernandes, Horst; Wong, Melanie; Coates, Roger

2013-05-01

There are a number of sites in Iraq which have been used for nuclear activities and which contain potentially significant amounts of radioactive waste. The principal nuclear site being Al-Tuwaitha. Many of these sites suffered substantial physical damage during the Gulf Wars and have been subjected to subsequent looting. All require decommissioning in order to ensure both radiological and non-radiological safety. However, it is not possible to undertake the decommissioning of all sites and facilities at the same time. Therefore, a prioritization methodology has been developed in order to aid the decision-making process. The methodology comprises three principal stages of assessment: i) a quantitative surrogate risk assessment ii) a range of sensitivity analyses and iii) the inclusion of qualitative modifying factors. A group of Tuwaitha facilities presented the highest risk among the evaluated ones, followed by a middle ranking grouping of Tuwaitha facilities and some other sites, and a relatively large group of lower risk facilities and sites. The initial order of priority is changed when modifying factors are taken into account. It has to be considered the Iraq's isolation from the international nuclear community over the last two decades and the lack of experienced personnel. Therefore it is appropriate to initiate decommissioning operations on selected low risk facilities at Tuwaitha in order to build capacity and prepare for work to be carried out in more complex and potentially high hazard facilities. In addition it is appropriate to initiate some prudent precautionary actions relating to some of the higher risk facilities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Population attributable risk of factors associated with the repetition of self-harm behaviour in young people presenting to clinical services: a systematic review and meta-analysis.

PubMed

Witt, Katrina; Milner, Allison; Spittal, Matthew J; Hetrick, Sarah; Robinson, Jo; Pirkis, Jane; Carter, Gregory

2018-02-03

The repetition of hospital-treated self-harm by young people is common. However, little work has summarised the modifiable factors associated with this. A thorough understanding of those factors most strongly associated with repetition could guide the development of relevant clinical interventions. We systematically reviewed four databases (EMBASE, Medline, PubMed and PsycINFO) until 15 April 2016 to identify all observational studies of factors for the repetition of self-harm or suicide reattempts (together referred to as 'self-harm behaviour') in young people. We quantified the magnitude of association with odds ratios (OR) and 95% confidence intervals (CIs) and calculated the population attributable risk (PAR) and population preventable fraction (PPF) for modifiable factors to provide an indication of the potential impact in reducing subsequent self-harm behaviour in this population. Seventeen studies were included comprising 10,726 participants. Borderline personality disorder (OR 3.47, 95% CI 1.84-6.53; PAR 42.4%), any personality disorder (OR 2.54, 95% CI 1.71-3.78; PAR 16.3%), and any mood disorder (OR 2.16, 95% CI 1.09-4.29; PAR 42.2%) are important modifiable risk factors. Severity of hopelessness (OR 2.95, 95% CI 1.74-5.01), suicidal ideation (OR 2.01, 95% CI 1.43-2.81), and previous sexual abuse (OR 1.52, 95% CI 1.02-2.28; PAR 12.8%) are also associated with repetition of self-harm. We recommend that clinical services should focus on identifying key modifiable risk factors at the individual patient level, whilst the reduction of exposure to child and adolescent sexual abuse would also be a useful goal for public health interventions.

Current (Food) Allergenic Risk Assessment: Is It Fit for Novel Foods? Status Quo and Identification of Gaps

PubMed Central

Mazzucchelli, Gabriel; Holzhauser, Thomas; Cirkovic Velickovic, Tanja; Diaz‐Perales, Araceli; Molina, Elena; Roncada, Paola; Rodrigues, Pedro; Verhoeckx, Kitty

2017-01-01

Abstract Food allergies are recognized as a global health concern. In order to protect allergic consumers from severe symptoms, allergenic risk assessment for well‐known foods and foods containing genetically modified ingredients is installed. However, population is steadily growing and there is a rising need to provide adequate protein‐based foods, including novel sources, not yet used for human consumption. In this context safety issues such as a potential increased allergenic risk need to be assessed before marketing novel food sources. Therefore, the established allergenic risk assessment for genetically modified organisms needs to be re‐evaluated for its applicability for risk assessment of novel food proteins. Two different scenarios of allergic sensitization have to be assessed. The first scenario is the presence of already known allergenic structures in novel foods. For this, a comparative assessment can be performed and the range of cross‐reactivity can be explored, while in the second scenario allergic reactions are observed toward so far novel allergenic structures and no reference material is available. This review summarizes the current analytical methods for allergenic risk assessment, highlighting the strengths and limitations of each method and discussing the gaps in this assessment that need to be addressed in the near future. PMID:28925060

Increasing Prevalence, Changes in Diagnostic Criteria, and Nutritional Risk Factors for Autism Spectrum Disorders

PubMed Central

Neggers, Yasmin H.

2014-01-01

The frequency of autism spectrum disorders (ASD) diagnoses has been increasing for decades, but researchers cannot agree on whether the trend is a result of increased awareness, improved detection, expanding definition, or an actual increase in incidence or a combination of these factors. Though both genetic and multiple environmental risk factors have been studied extensively, many potentially modifiable risk factors including nutritional and immune function related risk factors such as vitamin D, folic acid, and metabolic syndrome have not received sufficient attention. Several recent studies have put forward hypotheses to explain the mechanism of association between both folic acid and vitamin D and autism. A continuous rise in the prevalence of autism in the USA has coincided with a significant enhancement of maternal folate status with FDA mandated folic acid fortification of certain foods starting in 1998. There is also a growing body of research that suggests that vitamin D status either in utero or early in life may be a risk for autism. In this communication, controversies regarding increase in estimate of prevalence, implications of changes in definition, and possible association between some modifiable nutritional risk factors such as folic acid and vitamin D and ASD will be discussed. PMID:24967269

Evaluation of the environmental impact of apple pest control strategies using pesticide risk indicators.

PubMed

Ioriatti, Claudio; Agnello, Arthur M; Martini, Fabrizio; Kovach, Joseph

2011-10-01

Various pesticide risk indicators have been developed for estimating pesticide impact on human health and the environment. The present work applied a pesticide risk indicator to estimate change in pesticide risk in apple production between 2001 and 2009. The "Environmental Impact Quotient" was used, which evaluates potential impacts of pesticide active ingredients on farm workers, consumers, and nontarget organisms. A modified Environmental Impact Quotient was also tested, which accounts for all ingredients in the formulation presenting a health or environmental hazard, as identified in the Security Data Sheet. Irrespective of the rating system applied, an overall average improvement in environmental impact of apple protection strategies was indicated ranging from 23 to 24%. Hazard reduction was more significant when estimated per treatment, and was higher for acaricides and insecticides than for fungicides. Improvement appeared to be a consequence of using more selective and more effective active ingredients, applying alternative pest control techniques, compulsory periodic sprayer calibration, and wider use of dwarfing orchards. The modified Environmental Impact Quotient does not overcome all limitations regarding accuracy of pesticide risk indicators, but its ease of use in relying on official, easily accessible data, and the consistency of its results, makes it a good candidate for monitoring the success of reduced risk policies. Copyright © 2011 SETAC.

Awareness of modifiable acute myocardial infarction risk factors has little impact on risk perception for heart attack among vulnerable patients.

PubMed

Abed, Mona A; Khalil, Amani A; Moser, Debra K

2015-01-01

Poor awareness of modifiable risks for acute myocardial infarction (AMI) may explain the reported weak relationship between patients' actual and perceived risk for AMI. To assess the level of awareness of modifiable risks and perceived vulnerability for AMI among Jordanian patients, and to determine their independent association. This was a cross-sectional correlational study (N = 231). Perceived risk, awareness of risk factors and risk profile were collected by self-reports and medical chart review. Patients were mostly males (80%) and had a mean of 55.3 ± 12.6 years for age. Perceived and actual AMI risks were not highly congruent even though patients had, on average, two modifiable risks and were knowledgeable of them. Awareness of risk factors independently explained 3.5% of the variance in perceived risk. The risk for developing AMI is underestimated among cardiac patients and it is only weakly linked with their awareness of AMI risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance.

PubMed

Lu, Ellen; Wang, Bing Wei; Guimond, Colleen; Synnes, Anne; Sadovnick, A Dessa; Dahlgren, Leanne; Traboulsee, Anthony; Tremlett, Helen

2013-03-01

When contemplating a pregnancy, women treated for multiple sclerosis (MS) with a disease-modifying drug must decide to discontinue their medication before conception or risk exposing their unborn child to potential drug toxicity. Few studies exist as reference for patients and physicians, and of those available, the majority are less than ideal due to real-world constraints, ethical issues and methodological shortcomings. The authors provide a brief summary of existing animal and human data with current recommendations regarding the safety of IFN-β, glatiramer acetate, natalizumab, mitoxantrone, fingolimod and teriflunomide during pregnancy and lactation in women with MS. We also assess the quality, strengths and limitations of the existing studies including challenges with study design. The investigation of outcomes such as spontaneous abortion and congenital anomalies are highlighted with potential methodological improvements for future studies on drug safety in pregnancy suggested. The authors explore the pharmacokinetics and pharmacodynamics of the MS disease-modifying drugs for their possible mechanistic role in fetal harm and discuss the potential role of clinical trials. Future pharmacovigilance studies should continue to pursue multicenter collaboration with an emphasis on appropriate study design.

From accuracy to patient outcome and cost-effectiveness evaluations of diagnostic tests and biomarkers: an exemplary modelling study

PubMed Central

2013-01-01

Background Proper evaluation of new diagnostic tests is required to reduce overutilization and to limit potential negative health effects and costs related to testing. A decision analytic modelling approach may be worthwhile when a diagnostic randomized controlled trial is not feasible. We demonstrate this by assessing the cost-effectiveness of modified transesophageal echocardiography (TEE) compared with manual palpation for the detection of atherosclerosis in the ascending aorta. Methods Based on a previous diagnostic accuracy study, actual Dutch reimbursement data, and evidence from literature we developed a Markov decision analytic model. Cost-effectiveness of modified TEE was assessed for a life time horizon and a health care perspective. Prevalence rates of atherosclerosis were age-dependent and low as well as high rates were applied. Probabilistic sensitivity analysis was applied. Results The model synthesized all available evidence on the risk of stroke in cardiac surgery patients. The modified TEE strategy consistently resulted in more adapted surgical procedures and, hence, a lower risk of stroke and a slightly higher number of life-years. With 10% prevalence of atherosclerosis the incremental cost-effectiveness ratio was €4,651 and €481 per quality-adjusted life year in 55-year-old men and women, respectively. In all patients aged 65 years or older the modified TEE strategy was cost saving and resulted in additional health benefits. Conclusions Decision analytic modelling to assess the cost-effectiveness of a new diagnostic test based on characteristics, costs and effects of the test itself and of the subsequent treatment options is both feasible and valuable. Our case study on modified TEE suggests that it may reduce the risk of stroke in cardiac surgery patients older than 55 years at acceptable cost-effectiveness levels. PMID:23368927

Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

PubMed

Li, N; Hauser, R; Holford, T; Zhu, Y; Zhang, Y; Bassig, B A; Honig, S; Chen, C; Boyle, P; Dai, M; Schwartz, S M; Morey, P; Sayward, H; Hu, Z; Shen, H; Gomery, P; Zheng, T

2015-03-31

No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Application of whole genome shotgun sequencing for detection and characterization of genetically modified organisms and derived products.

PubMed

Holst-Jensen, Arne; Spilsberg, Bjørn; Arulandhu, Alfred J; Kok, Esther; Shi, Jianxin; Zel, Jana

2016-07-01

The emergence of high-throughput, massive or next-generation sequencing technologies has created a completely new foundation for molecular analyses. Various selective enrichment processes are commonly applied to facilitate detection of predefined (known) targets. Such approaches, however, inevitably introduce a bias and are prone to miss unknown targets. Here we review the application of high-throughput sequencing technologies and the preparation of fit-for-purpose whole genome shotgun sequencing libraries for the detection and characterization of genetically modified and derived products. The potential impact of these new sequencing technologies for the characterization, breeding selection, risk assessment, and traceability of genetically modified organisms and genetically modified products is yet to be fully acknowledged. The published literature is reviewed, and the prospects for future developments and use of the new sequencing technologies for these purposes are discussed.

Drug-Induced Thrombophilic or Prothrombotic States: An Underestimated Clinical Problem That Involves Both Legal and Illegal Compounds.

PubMed

Girolami, A; Cosi, E; Tasinato, V; Santarossa, C; Ferrari, S; Girolami, B

2017-10-01

Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases.

Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures.

PubMed

Zhu, Haifeng; Li, Xiaoqin; Zhang, Xiaomei; Chen, Deyu; Li, Dan; Ren, Jin; Gu, Hangang; Shu, Yongqian; Wang, Deqiang

2016-03-15

Epigenetic alterations of DNA mismatch repair (MMR) genes are associated with risk of gastric cancer (GC) by causing microsatellite instability (MSI). Less understood is the association of common polymorphisms in MMR genes with the risk and MSI phenotype of GC. A hospital-based study was conducted in China with 423 cases and 454 matched controls. Four potentially functional polymorphisms were selected and analyzed: rs1800734 in MLH1, rs2303428 in MSH2, rs735943 in EXO1, and rs11797 in TREX1. The rs1800734 G-allele was associated with decreased risk of GC (GA or GG vs AA, OR=0.72; 95% CI: 0.50-1.05; Ptrend=0.029). For combined effects, a dose-response manner was observed in which GC risk was increased with increasing number of at-risk genotypes (Ptrend=0.039); this manner mainly existed in MSI GC (Ptrend=0.047) rather than in microsatellite stability GC, though neither single polymorphism was linked with MSI. For exposures, modified effects were observed from green tea drinking and soy foods intake on rs11797 (P for interaction=0.007 and 0.016, respectively). The MLH1 rs1800734 polymorphism is associated with GC risk. Those at-risk genotypes have a joint effect on GC risk, which contributes to the MSI phenotype of GC. Life exposures modify GC risk, stratified by MMR genotypes. Copyright © 2015 Elsevier B.V. All rights reserved.

mHealth and Mobile Medical Apps: A Framework to Assess Risk and Promote Safer Use

PubMed Central

2014-01-01

The use of mobile medical apps by clinicians and others has grown considerably since the introduction of mobile phones. Medical apps offer clinicians the ability to access medical knowledge and patient data at the point of care, but several studies have highlighted apps that could compromise patient safety and are potentially dangerous. This article identifies a range of different kinds of risks that medical apps can contribute to and important contextual variables that can modify these risks. We have also developed a simple generic risk framework that app users, developers, and other stakeholders can use to assess the likely risks posed by a specific app in a specific context. This should help app commissioners, developers, and users to manage risks and improve patient safety. PMID:25223398

mHealth and mobile medical Apps: a framework to assess risk and promote safer use.

PubMed

Lewis, Thomas Lorchan; Wyatt, Jeremy C

2014-09-15

The use of mobile medical apps by clinicians and others has grown considerably since the introduction of mobile phones. Medical apps offer clinicians the ability to access medical knowledge and patient data at the point of care, but several studies have highlighted apps that could compromise patient safety and are potentially dangerous. This article identifies a range of different kinds of risks that medical apps can contribute to and important contextual variables that can modify these risks. We have also developed a simple generic risk framework that app users, developers, and other stakeholders can use to assess the likely risks posed by a specific app in a specific context. This should help app commissioners, developers, and users to manage risks and improve patient safety.

Use of fall risk increasing drugs in residents of retirement villages: a pilot study of long term care and retirement home residents in Ontario, Canada.

PubMed

Rojas-Fernandez, Carlos; Dadfar, Farzan; Wong, Andrea; Brown, Susan G

2015-10-14

Falls continue to be a problem for older people in long-term care (LTC) and retirement home (RH) settings and are associated with significant morbidity and health care use. Fall-risk increasing drugs (FRIDs) are known to increase fall risk and represent modifiable risk factors. There are limited data regarding the use of FRIDs in contemporary LTC and RH settings, and it has not been well documented to what extent medication regimens are reviewed and modified for those who have sustained falls. The objective of this study is to characterize medication related fall risk factors in LTC and RH residents and on-going use of medications known to increase fall risk. Retrospective chart review of residents aged >65 who sustained one or more falls living in LTC or RH settings. 105 residents who fell one or more times during 2009-2010 were identified with a mean age of 89 years, a mean of nine scheduled medications and seven diagnoses, and 83% were women. Residents in LTC were ostensibly at higher risk for falls relative to those in RH settings as suggested by higher proportion of residents with multiple falls, multiple comorbidities, comorbidities that increase fall risk and visual impairment. Post fall injuries were sustained by 42% of residents, and residents in RH sustained more injuries relative to LTC residents (47 vs 34%). Use of FRIDs such as benzodiazepines, antipsychotic, antidepressant and various antihypertensive drugs was common in the present sample. No medication regimen changes were noted in the 6-month post fall period. The present study documented common use FRIDs by LTC and RH residents with multiple falls. These potentially modifiable falls risk factors are not being adequately addressed in contemporary practice, demonstrating that there is much room for improvement with regards to the safe and appropriate use of medications in LTC and RH residents.

Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature.

PubMed

Zorzela, L; Ardestani, S K; McFarland, L V; Vohra, S

2017-10-13

Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent and treat various diseases. Recent clinical research has focused on living strains of probiotics, but use in high-risk patients and potential adverse reactions including bacteremia has focused interest on alternatives to the use of live probiotics. We searched MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Alt Health Watch, Web of Science, Scopus, PubMed, from inception to February 14, 2017 for randomised controlled trials involving modified probiotic strains. The primary outcome was efficacy to prevent or treat disease and the secondary outcome was incidence of adverse events. A total of 40 trials were included (n=3,913): 14 trials (15 arms with modified probiotics and 20 control arms) for the prevention of diseases and 26 trials (29 arms with modified probiotics and 32 control arms) for treatment of various diseases. Modified microbes were compared to either placebo (44%), or the same living probiotic strain (39%) or to only standard therapies (17%). Modified microbes were not significantly more or less effective than the living probiotic in 86% of the preventive trials and 69% of the treatment trials. Modified probiotic strains were significantly more effective in 15% of the treatment trials. Incidence rates of adverse events were similar for modified and living probiotics and other control groups, but many trials did not collect adequate safety data. Although several types of modified probiotics showed significant efficacy over living strains of probiotics, firm conclusions could not be reached due to the limited number of trials using the same type of modified microbe (strain, daily dose and duration) for a specific disease indication. Further research may illuminate other strains of modified probiotics that may have potential as clinical biotherapeutics.

Diastolic blood pressure is a potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes.

PubMed

Nørgaard, Sidse Kjærhus; Vestgaard, Marianne Jenlev; Jørgensen, Isabella Lindegaard; Ásbjörnsdóttir, Björg; Ringholm, Lene; McIntyre, Harold David; Damm, Peter; Mathiesen, Elisabeth Reinhardt

2018-04-01

To identify early clinical, modifiable risk factors for preeclampsia present at first antenatal visit and assess the prevalence of pregnancy-related hypertensive disorders in women with pre-existing diabetes treated with tight glycemic and blood pressure (BP) control. A population-based cohort study of 494 women with pre-existing diabetes (307 and 187 women with type 1 and type 2 diabetes, respectively), included at their first antenatal visit from 2012 to 2016. The prevalence of chronic hypertension (without diabetic nephropathy or microalbuminuria), gestational hypertension and preeclampsia was recorded. Diabetic microangiopathy included presence of nephropathy, microalbuminuria and/or retinopathy. Treatment target was BP <135/85 mmHg. HbA1c was 6.9 ± 2.4% (50 ± 12 mmol/mol) at first antenatal visit and 6.0 ± 0.6% (43 ± 6 mmol/mol) before delivery with no differences between women with type 1 and type 2 diabetes. At the first antenatal visit, the prevalence of microalbuminuria was 6% (6% vs. 6%), nephropathy 2% (1% vs. 2%) and chronic hypertension 6% (3% vs. 10%, p = 0.03). Gestational hypertension developed in 8% (9% vs. 6%) and preeclampsia developed in 8% (9% vs. 7%). Presence of diabetic microangiopathy (adjusted odds ratio (OR) 4.35 (confidence interval 2.12-8.93)) and diastolic BP (adjusted OR 1.72 per 10 mmHg (1.05-2.82)) at the first antenatal visit were independent risk factors for preeclampsia. At the first antenatal visit, diastolic BP was the only independent, potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes in the context of tight glycemic and BP control. One out of four women had hypertensive disorders during pregnancy. Copyright © 2018 Elsevier B.V. All rights reserved.

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

2015-06-01

Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis

PubMed Central

Lehert, Philippe; Villaseca, Paulina; Hogervorst, Eef; Maki, Pauline M.; Henderson, Victor W.

2016-01-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually-modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For 10 of these, we used PubMed databases for a systematic review of long-duration (at least six months), randomized controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11 to 0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging. PMID:26361790

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.

PubMed

Lehert, P; Villaseca, P; Hogervorst, E; Maki, P M; Henderson, V W

2015-10-01

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long-duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging.

Modified Sainsbury tool: an initial risk assessment tool for primary care mental health and learning disability services.

PubMed

Stein, W

2005-10-01

Risk assessments by health and social care professionals must encompass risk of suicide, of harm to others, and of neglect. The UK's National Confidential Inquiry into Homicide and Suicide paints a picture of failure to predict suicides and homicides, failure to identify opportunities for prevention and a failure to manage these opportunities. Assessing risk at 'first contact' with the mental health service assumes a special place in this regard. The initial opportunity to be alerted to, and thus to influence, risk, usually falls to the general psychiatric service (as opposed to forensic specialists) or to a joint health and local authority community mental health team. The Mental Health and Learning Disabilities Directorate of Renfrewshire & Inverclyde Primary Care NHS Trust, Scotland, determined to standardize their approach to risk assessment and selected a modified version of the Sainsbury Risk Assessment Tool. A year-long pilot revealed general support for its service-wide introduction but also some misgivings to address, including: (i) rejection of the tool by some medical staff; (ii) concerns about limited training; and (iii) a perceived failure on the part of the management to properly resource its use. The tool has the potential to fit well with the computer-networked needs assessment system used in joint-working with partner local authorities to allocate care resources.

Healthy eating and reduced risk of cognitive decline

PubMed Central

Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

2015-01-01

Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

Complex association between body weight and fracture risk in postmenopausal women.

PubMed

Mpalaris, V; Anagnostis, P; Goulis, D G; Iakovou, I

2015-03-01

Osteoporosis is a common disease, characterized by low bone mass with micro-architectural disruption and skeletal fragility, resulting in an increased risk of fracture. A substantial number of studies has examined the possible relationship between body weight, bone mineral density and fracture risk in post-menopausal women, with the majority of them concluding that low body weight correlates with increased risk of fracture, especially hip fracture. Controversies about the potential protective effect of obesity on osteoporosis and consequent fracture risk still exist. Several recent studies question the concept that obesity exerts a protective effect against fractures, suggesting that it stands as a risk factor for fractures at specific skeletal sites, such as upper arm. The association between body weight and fracture risk is complex, differs across skeletal sites and body mass index, and is modified by the interaction between body weight and bone mineral density. Some potential explanations that link obesity with increased fracture risk may be the pattern of falls and impaired mobility in obese individuals, comorbidities, such as asthma, diabetes and early menopause, as well as, increased parathyroid hormone and reduced 25-hydroxy-vitamin D concentrations. © 2015 World Obesity.

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

[Prevention of cardiovascular diseases].

PubMed

Prochaska, J H; Arnold, N; Jünger, C; Münzel, T; Wild, P S

2018-02-01

The incidence of cardiovascular diseases can be reduced by the early detection and targeted treatment of risk factors and subclinical forms of the disease. Primary prevention provides several opportunities for successful interventions. In addition to a drug-based therapy, especially life style-modifying measures, such as physical activity, normalization of body weight, consistent nicotine abstinence and the consideration of psychosocial aspects represent core components of prevention programs. Healthcare data indicate that risk factors still often remain undetected and that the full potential of risk factor management has not yet been fully exploited at a population level. Especially motivation of patients and adherence to therapy represent key elements of successful prevention efforts.

Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.

PubMed

Marino, Miguel; Li, Yi; Pencina, Michael J; D'Agostino, Ralph B; Berkman, Lisa F; Buxton, Orfeu M

2014-08-01

Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Quantifying Cardiometabolic Risk Using Modifiable Non–Self-Reported Risk Factors

PubMed Central

Marino, Miguel; Li, Yi; Pencina, Michael J.; D’Agostino, Ralph B.; Berkman, Lisa F.; Buxton, Orfeu M.

2014-01-01

Background Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. Purpose To develop and validate a cumulative general cardiometabolic risk score that focuses on non–self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut off points for risk categories. Methods We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14–year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender–specific Cox proportional hazards models were considered to evaluate the effects of non–self-reported modifiable risk factors (blood pressure, total cholesterol, high–density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10–year general cardiometabolic risk score functions and evaluated its predictive performance in 2012–2013. Results HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit χ2=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). Conclusions This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk based on modifiable risk factors that can motivate an individual’s commitment to prevention and intervention. PMID:24951039

Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Women in Southeast Asia: A Meta-Analysis

PubMed

Nindrea, Ricvan Dana; Aryandono, Teguh; Lazuardi, Lutfan

2017-12-28

Objective: The aim of this study was to determine breast cancer risk from modifiable and non-modifiable factors among women in Southeast Asia. Methods: This meta-analysis was performed on research articles on breast cancer risk factors in PubMed, ProQuest and EBSCO databases published between 1997 and October 2017. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). Results: From a total of 1,211 articles, 15 studies (1 cohort and 14 case control studies) met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for breast cancer, parity (nulipara) had the highest odd ratio (OR = 1.85 [95% CI 1.47-2.32]) followed by body mass index (overweight) (OR = 1.61 [95% CI 1.43-1.80]) and use of oral contraceptives (OR = 1.27 [95% CI 1.07-1.51]). Of non-modifiable risk factors, family history of breast cancer had the highest odd ratio (OR = 2.53 [95% CI 1.25-5.09]), followed by age (≥ 40 years) (OR = 1.53 [95% CI 1.34-1.76]) and menopausal status (OR = 1.44 [95% CI 1.26-1.65]). Conclusion: This analysis confirmed associations between both modifiable risk factors (parity, body mass index and use of oral contraceptives) and non-modifiable risk factors (family history of breast cancer, age and menopausal status) with breast cancer. Creative Commons Attribution License

Hamstring Graft Preparation Using a Modified Rolling Hitch Technique

PubMed Central

Hong, Chih-Kai; Chang, Chih-Hsun; Chiang, Chen-Hao; Jou, I-Ming; Su, Wei-Ren

2014-01-01

Anterior cruciate ligament reconstruction using double-looped hamstring autograft is a common procedure in orthopaedic practice. However, during placement of the running, locking stitches at each end of the harvested tendons, the surgeon may face several potential obstacles, including the risk of damaging the tendon, predisposing the surgeon to needle-stick injury, and extended time consumption. We report a modified rolling hitch technique for hamstring graft preparation that is quick, cost-saving, and needleless as an alternative method. The original rolling hitch technique uses a traditional knot that attaches a rope to an object; the modified rolling hitch technique was created by adding 1 more turn before finishing with a half-hitch, which may prevent suture slippage off the tendon, thus providing sufficient fixation of the suture-tendon construct. PMID:25126495

Modifiable Prostate Cancer Risk Reduction and Early Detection Behaviors in Black Men

ERIC Educational Resources Information Center

Odedina, Folakemi T.; Scrivens, John J., Jr.; Larose-Pierre, Margareth; Emanuel, Frank; Adams, Angela Denise; Dagne, Getachew A.; Pressey, Shannon Alexis; Odedina, Oladapo

2011-01-01

Objective: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. Methods: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. Results: Modifiable prostate cancer risk-reduction behavior was found…

Age at onset in Huntington's disease: replication study on the association of HAP1.

PubMed

Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

2012-11-01

In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

The phytoremediation potential of native plants on New Zealand dairy farms.

PubMed

Hahner, Jason L; Robinson, Brett H; Hong-Tao, Zhong; Dickinson, Nicholas M

2014-01-01

Ecological restoration of marginal land and riparian zones in agricultural landscapes in New Zealand enhances the provision of above-ground ecosystem services. We investigated whether native endemic plant assemblages have remediation potential, through modifying soil nutrient and trace element mobility. Analysis of native plant foliage in situ indicated that selective uptake of a range of commonly deficient trace elements including Zn, B, Cu, Mn and Co could provide a browse crop to avoid deficiencies of these elements in livestock, although some native plants may enhance the risk of Mo and Cd toxicity. Native plant rhizospheres were found to modify soil physico-chemistry and are likely to influence lateral and vertical fluxes of chemical elements in drainage waters. Native plants on marginal land in agricultural landscapes could add value to dairy production systems whilst helping to resolve topical environmental issues.

Multimorbidity and healthcare utilization among home care clients with dementia in Ontario, Canada: A retrospective analysis of a population-based cohort

PubMed Central

Mondor, Luke; Maxwell, Colleen J.; Hogan, David B.; Gruneir, Andrea

2017-01-01

Background For community-dwelling older persons with dementia, the presence of multimorbidity can create complex clinical challenges for both individuals and their physicians, and can contribute to poor outcomes. We quantified the associations between level of multimorbidity (chronic disease burden) and risk of hospitalization and risk of emergency department (ED) visit in a home care cohort with dementia and explored the role of continuity of physician care (COC) in modifying these relationships. Methods and findings A retrospective cohort study using linked administrative and clinical data from Ontario, Canada, was conducted among 30,112 long-stay home care clients (mean age 83.0 ± 7.7 y) with dementia in 2012. Multivariable Fine–Gray regression models were used to determine associations between level of multimorbidity and 1-y risk of hospitalization and 1-y risk of ED visit, accounting for multiple competing risks (death and long-term care placement). Interaction terms were used to assess potential effect modification by COC. Multimorbidity was highly prevalent, with 35% (n = 10,568) of the cohort having five or more chronic conditions. In multivariable analyses, risk of hospitalization and risk of ED visit increased monotonically with level of multimorbidity: sub-hazards were 88% greater (sub-hazard ratio [sHR] = 1.88, 95% CI: 1.72–2.05, p < 0.001) and 63% greater (sHR = 1.63; 95% CI: 1.51–1.77, p < 0.001), respectively, among those with five or more conditions, relative to those with dementia alone or with dementia and one other condition. Low (versus high) COC was associated with an increased risk of both hospitalization and ED visit in age- and sex-adjusted analyses only (sHR = 1.11, 95% CI: 1.07–1.16, p < 0.001, for hospitalization; sHR = 1.07, 95% CI: 1.03–1.11, p = 0.001, for ED visit) but did not modify associations between multimorbidity and outcomes (Wald test for interaction, p = 0.566 for hospitalization and p = 0.637 for ED visit). The main limitations of this study include use of fixed (versus time-varying) covariates and focus on all-cause rather than cause-specific hospitalizations and ED visits, which could potentially inform interventions. Conclusions Older adults with dementia and multimorbidity pose a particular challenge for health systems. Findings from this study highlight the need to reshape models of care for this complex population, and to further investigate health system and other factors that may modify patients’ risk of health outcomes. PMID:28267802

Aggregate Exposure and Cumulative Risk Assessment—Integrating Occupational and Non-occupational Risk Factors

PubMed Central

Lentz, T. J.; Dotson, G. S.; Williams, P. R.D.; Maier, A.; Gadagbui, B.; Pandalai, S. P.; Lamba, A.; Hearl, F.; Mumtaz, M.

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational. PMID:26583907

Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

PubMed

Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

2015-01-01

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

PHYSICAL ACTIVITY AND THE PELVIC FLOOR

PubMed Central

Nygaard, Ingrid E.; Shaw, Janet M.

2015-01-01

Pelvic floor disorders (PFDs) are common, with one in four U.S. women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review is to summarize studies reporting the association between physical activity and PFDs. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include: Urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this exam finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods. PMID:26348380

Physical activity and the pelvic floor.

PubMed

Nygaard, Ingrid E; Shaw, Janet M

2016-02-01

Pelvic floor disorders are common, with 1 in 4 US women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse, or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review was to summarize studies reporting the association between physical activity and pelvic floor disorders. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include that urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high-intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this examination finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods. Copyright © 2016 Elsevier Inc. All rights reserved.

International migration as a determinant of emergency caesarean.

PubMed

Merry, Lisa; Semenic, Sonia; Gyorkos, Theresa W; Fraser, William; Small, Rhonda; Gagnon, Anita J

2016-10-01

High caesarean rates are of concern given associated risks. International migrant women (women born abroad) represent a substantial proportion of women giving birth in high-income countries (HICs) and face social conditions that may exacerbate childbearing health risks. Among migrant women, emergency rather than planned caesareans, tend to be more prevalent. This method of delivery can be stressful, physically harmful and result in an overall negative birth experience. Research establishing evidence of risk factors for emergency caesareans in migrants is insufficient. (1) Describe potential pathways (with a focus on modifiable factors) by which migration, using internationally recommended migration indicators: country of birth, length of time in country, fluency in receiving-country language, migration classification and ethnicity, may lead to emergency caesarean; and (2) propose a framework to guide future research for understanding "potentially preventable" emergency caesareans in migrant women living in HICs. "Potentially preventable" emergency caesareans in migrant women are likely due to several modifiable, interrelated factors pre-pregnancy, during pregnancy and during labour. Migration itself is a determinant and also shapes other determinants. Complications and ineffective labour progress and/or foetal distress and ultimately the decision to perform an emergency caesarean may be the result of poor health (i.e., physiological effects), lack of support and disempowerment (i.e., psychological effects) and sub-optimal care. Understanding the direct and indirect effects of migration on emergency caesarean is crucial so that targeted strategies can be developed and implemented for reducing unnecessary caesareans in this vulnerable population. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Field trial of insect-resistant and herbicide-tolerant genetically modified cotton (Gossypium hirsutum L.) for environmental risk assessment in Japan.

PubMed

Asanuma, Yoko; Gondo, Takahiro; Ishigaki, Genki; Inoue, Koichi; Zaita, Norihiro; Muguerza, Melody; Akashi, Ryo

2017-04-03

Japan imports cottonseed mainly from Australia and the USA where more than 96% of all cotton varieties grown are genetically modified (GM). GM crops undergo an environmental risk assessment (ERA) under the Law Concerning the Conservation and Sustainable Use of Biological Diversity before import into Japan. Potential adverse effects on biodiversity are comprehensively assessed based on competitiveness, production of harmful substances and outcrossing ability. Even though imported cottonseed is intended for food and feed uses and not for cultivation, the potential risks from seed spillage during transport must be evaluated. In most cases, the ERA requires data collected from in-country field trials to demonstrate how the GM crop behaves in Japan's environment. Confined field trials in Japan were conducted for the ERA of Lepidoptera-resistant and glufosinate-tolerant GM cotton (Gossypium hirsutum L.) lines GHB119 and T304-40. These lines were compared with conventional varieties for growth habit, morphological characteristics, seed dormancy, and allelopathic activity associated with competitiveness and production of harmful substances. Outcrossing ability was not a concern due to the absence of sexually compatible wild relatives in Japan. Although slight statistical differences were observed between the GM line and its conventional comparator for some morphological characteristics, transgenes or transformation were not considered to be responsible for these differences. The trial demonstrated that competitiveness and production of harmful substances by these GM cotton lines were equivalent to conventional cotton varieties that have a long history of safe use, and no potential adverse effects to biosafety in Japan were observed.

Field trial of insect-resistant and herbicide-tolerant genetically modified cotton (Gossypium hirsutum L.) for environmental risk assessment in Japan

PubMed Central

Asanuma, Yoko; Gondo, Takahiro; Ishigaki, Genki; Inoue, Koichi; Zaita, Norihiro; Muguerza, Melody; Akashi, Ryo

2017-01-01

ABSTRACT Japan imports cottonseed mainly from Australia and the USA where more than 96% of all cotton varieties grown are genetically modified (GM). GM crops undergo an environmental risk assessment (ERA) under the Law Concerning the Conservation and Sustainable Use of Biological Diversity before import into Japan. Potential adverse effects on biodiversity are comprehensively assessed based on competitiveness, production of harmful substances and outcrossing ability. Even though imported cottonseed is intended for food and feed uses and not for cultivation, the potential risks from seed spillage during transport must be evaluated. In most cases, the ERA requires data collected from in-country field trials to demonstrate how the GM crop behaves in Japan's environment. Confined field trials in Japan were conducted for the ERA of Lepidoptera-resistant and glufosinate-tolerant GM cotton (Gossypium hirsutum L.) lines GHB119 and T304-40. These lines were compared with conventional varieties for growth habit, morphological characteristics, seed dormancy, and allelopathic activity associated with competitiveness and production of harmful substances. Outcrossing ability was not a concern due to the absence of sexually compatible wild relatives in Japan. Although slight statistical differences were observed between the GM line and its conventional comparator for some morphological characteristics, transgenes or transformation were not considered to be responsible for these differences. The trial demonstrated that competitiveness and production of harmful substances by these GM cotton lines were equivalent to conventional cotton varieties that have a long history of safe use, and no potential adverse effects to biosafety in Japan were observed. PMID:28510512

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

PubMed

Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Real time forest fire warning and forest fire risk zoning: a Vietnamese case study

NASA Astrophysics Data System (ADS)

Chu, T.; Pham, D.; Phung, T.; Ha, A.; Paschke, M.

2016-12-01

Forest fire occurs seriously in Vietnam and has been considered as one of the major causes of forest lost and degradation. Several studies of forest fire risk warning were conducted using Modified Nesterov Index (MNI) but remaining shortcomings and inaccurate predictions that needs to be urgently improved. In our study, several important topographic and social factors such as aspect, slope, elevation, distance to residential areas and road system were considered as "permanent" factors while meteorological data were updated hourly using near-real-time (NRT) remotely sensed data (i.e. MODIS Terra/Aqua and TRMM) for the prediction and warning of fire. Due to the limited number of weather stations in Vietnam, data from all active stations (i.e. 178) were used with the satellite data to calibrate and upscale meteorological variables. These data with finer resolution were then used to generate MNI. The only significant "permanent" factors were selected as input variables based on the correlation coefficients that computed from multi-variable regression among true fire-burning (collected from 1/2007) and its spatial characteristics. These coefficients also used to suggest appropriate weight for computing forest fire risk (FR) model. Forest fire risk model was calculated from the MNI and the selected factors using fuzzy regression models (FRMs) and GIS based multi-criteria analysis. By this approach, the FR was slightly modified from MNI by the integrated use of various factors in our fire warning and prediction model. Multifactor-based maps of forest fire risk zone were generated from classifying FR into three potential danger levels. Fire risk maps were displayed using webgis technology that is easy for managing data and extracting reports. Reported fire-burnings thereafter have been used as true values for validating the forest fire risk. Fire probability has strong relationship with potential danger levels (varied from 5.3% to 53.8%) indicating that the higher potential risk, the more chance of fire happen. By adding spatial factors to continuous daily updated remote sensing based meteo-data, results are valuable for both mapping forest fire risk zones in short and long-term and real time fire warning in Vietnam. Key words: Near-real-time, forest fire warning, fuzzy regression model, remote sensing.

Genetic testing and breach of patient confidentiality: law, ethics, and pragmatics.

PubMed

Minkoff, Howard; Ecker, Jeffrey

2008-05-01

Medical uses of genetic information have multiplied over the last several years. When an individual is a carrier of a clinically important allele, their kindred are at increased risk of carrying the same allele and of sharing the consequent risk of disease. If there were an intervention that could modify the risk of progression to disease, then there would be a clear advantage to kindred to be so informed. However, some probands may resist divulging that information to kindred for any of a variety of reasons, including the potential for discrimination. In this article we will review the manner in which the courts and professional organizations have viewed the conflict between 1 individual's right to privacy and another's right to information that could potentially be life saving or life prolonging. We will then consider the ethics of this issue and suggest an approach that physicians should take when confronting it.

The consequences of modern military deployment on calcium status and bone health.

PubMed

McCarthy, Mary S; Loan, Lori A; Azuero, Andres; Hobbs, Curtis

2010-06-01

This article highlights the potential negative effect of the current combat environment on bone health of young military men and women who may be at risk for stress fractures and future bone disease because of alterations primarily in diet and physical activity level during deployment. A combination of physiologic biomarkers, including bone turnover and bone mineral density, and nutrition and exercise surveys can provide meaningful data on potential health risks related to deployment. Soldiers participating in an investigation into bone health before and after deployment did not have decreased bone density but the study did raise awareness about an issue that might otherwise go unnoticed because preventive care is typically focused on older adults. Several risk factors may be modifiable and nurses have the necessary skills for counseling and monitoring behaviors that can minimize disabling musculoskeletal injuries that affect quality of life for the individual and unit readiness for the commander. Published by Elsevier Inc.

Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

DOE PAGES

Cologne, John; Grant, Eric J.; Nakashima, Eiji; ...

2012-01-01

Objective . Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods . We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results . Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relativemore » accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions . When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs.« less

Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

PubMed Central

Cologne, John; Grant, Eric J.; Nakashima, Eiji; Chen, Yun; Funamoto, Sachiyo; Katayama, Hiroaki

2012-01-01

Objective. Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods. We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results. Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions. When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs. PMID:22505949

Protecting privacy of shared epidemiologic data without compromising analysis potential.

PubMed

Cologne, John; Grant, Eric J; Nakashima, Eiji; Chen, Yun; Funamoto, Sachiyo; Katayama, Hiroaki

2012-01-01

Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs.

Risk factors for relinquishment of cats to an animal shelter.

PubMed

Patronek, G J; Glickman, L T; Beck, A M; McCabe, G P; Ecker, C

1996-08-01

To identify feline and household characteristics associated with relinquishment of a pet cat to an animal shelter. Case-control study. Households that relinquished cats for adoption (case households) and a random sample of current cat-owning households in the same community (control households). Potentially modifiable risk factors with the highest population attributable risk for relinquishment were owners having specific expectations about the cat's role in the household, allowing the cat outdoors, owning a sexually intact cat, never having read a book about cat behavior, cats having daily or weekly inappropriate elimination, and inappropriate care expectations. Frequency of inappropriate elimination and aggression toward people were not associated with declaw status, but these behaviors were more common among sexually intact cats, compared with sterilized cats. Owners of cats in case households were more likely than owners in control households to cite cost of sterilization as a reason a cat was sexually intact. Cats found as strays and cats acquired with minimal planning were at decreased risk of relinquishment. The identified risk factors can be modified by cat owners and veterinarians to decrease the estimated 4 million cats euthanatized annually in animal shelters. Owner education programs are needed as well as increased awareness on the part of cat owners and veterinarians of the importance of resolving feline inappropriate elimination problems.

Pelvic inflammatory disease: a clinical syndrome with social causes.

PubMed

Brabin, L; Raleigh, V S; Dumella, S

1992-08-01

Prevalence of pelvic inflammatory disease (PID) reflects community and individual risk factors. Cultural and behavioural factors influence community prevalence of sexually transmitted disease (STD), illegal abortion, puerperal sepsis and contraceptive usage--all of which influence risk of PID. The relative importance of these factors will vary by region. Individual risk factors for the ascent of a lower genital tract infection are still poorly understood but are thought to be behavioural and immunological. Prevention of PID must be undertaken at several levels. At primary level, it requires a reduction in community risk. At secondary level, individual risk can be modified by ensuring diagnosis and treatment of STD before damage of the upper genital tract occurs. More attention to cultural factors should increase the potential for prevention at both levels.

Mediation and Moderation of the Association between Cynical Hostility and Systolic Blood Pressure in Low-Income Women

ERIC Educational Resources Information Center

Versey, H. Shellae; Kaplan, George A.

2012-01-01

Hostility may be related to risk factors for cardiovascular disease (CVD), such as blood pressure. However, the process by which hostility affects blood pressure is not fully understood. The current study sought to evaluate abdominal obesity (waist-to-hip ratio [WHR]) as a potential mediator and modifier of the relationship between cynical…

Concussion Education in U.S. Collegiate Sport: What Is Happening and What Do Athletes Want?

ERIC Educational Resources Information Center

Kroshus, Emily; Baugh, Christine M.

2016-01-01

Concussion education for athletes has the potential to play a role in reducing the health burden of concussions from sport by modifying individual risk-related behaviors. In U.S. collegiate sport, decisions about content and delivery of concussion education are left up to the individual institution. This may result in a high degree of variability…

Cigarette Smoking among Medical Students in China and Modifiable Risk Factors for Smoking Prevention

ERIC Educational Resources Information Center

Chen, Xinguang; Tang, Xiaolan; Stanton, Bonita; Li, Hanwu; Chen, Weiqing

2012-01-01

Purpose: The reduction of tobacco use among medical students is a potentially powerful strategy to reduce tobacco use among future health professionals, who in turn, can have significant impact on tobacco use among patients as well as the general population in China. The goal of this study is to update information on the prevalence of cigarette…

ENVIRONMENTAL REACTIVITY OF SOLID STATE HYDRIDE MATERIALS: MODELING AND TESTING FOR AIR AND WATER EXPOSURE

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

Anton, D.; James, C.; Cortes-Concepcion, J.

2010-05-18

To make commercially acceptable condensed phase hydrogen storage systems, it is important to understand quantitatively the risks involved in using these materials. A rigorous set of environmental reactivity tests have been developed based on modified testing procedures codified by the United Nations for the transportation of dangerous goods. Potential hydrogen storage material, 2LiBH4{center_dot}MgH2 and NH3BH3, have been tested using these modified procedures to evaluate the relative risks of these materials coming in contact with the environment in hypothetical accident scenarios. It is apparent that an ignition event will only occur if both a flammable concentration of hydrogen and sufficient thermalmore » energy were available to ignite the hydrogen gas mixture. In order to predict hydride behavior for hypothesized accident scenarios, an idealized finite element model was developed for dispersed hydride from a breached system. Empirical thermodynamic calculations based on precise calorimetric experiments were performed in order to quantify the energy and hydrogen release rates and to quantify the reaction products resulting from water and air exposure. Both thermal and compositional predictions were made with identification of potential ignition event scenarios.« less

The Impact of an Incentive-Based Worksite Health Promotion Program on Modifiable Health Risk Factors.

ERIC Educational Resources Information Center

Poole, Kathleen; Kumpfer, Karol; Pett, Marjorie

2001-01-01

Examined the impact of participating in an incentive-based employee health promotion program on modifiable health risk factors over 4 years. Data from physiological and self-report measures indicated that modifiable health risks improved over time (smoking, physical activity, systolic and diastolic blood pressure, and seat belt use). Cholesterol…

Workshop overview: approaches to the assessment of the allergenic potential of food from genetically modified crops.

PubMed

Ladics, Gregory S; Holsapple, Michael P; Astwood, James D; Kimber, Ian; Knippels, Leon M J; Helm, Ricki M; Dong, Wumin

2003-05-01

There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allergens. Instead, the evaluation focuses on risk factors such as source of the gene (i.e., allergenic vs. nonallergenic sources), physicochemical and genetic comparisons to known allergens, and exposure assessments. The purpose of this workshop was to gather together researchers working on various strategies for assessing protein allergenicity: (1) to describe the current state of knowledge and progress that has been made in the development and evaluation of appropriate testing strategies and (2) to identify critical issues that must now be addressed. This overview begins with a consideration of the current issues involved in assessing the allergenicity of GM foods. The second section presents information on in vitro models of digestibility, bioinformatics, and risk assessment in the context of clinical prevention and management of food allergy. Data on rodent models are presented in the next two sections. Finally, nonrodent models for assessing protein allergenicity are discussed. Collectively, these studies indicate that significant progress has been made in developing testing strategies. However, further efforts are needed to evaluate and validate the sensitivity, specificity, and reproducibility of many of these assays for determining the allergenicity potential of GM foods.

Occupational health and safety among commercial sex workers.

PubMed

Ross, Michael W; Crisp, Beth R; Månsson, Sven-Axel; Hawkes, Sarah

2012-03-01

The concept of occupational health and safety (OHS) for commercial sex workers has rarely been investigated, perhaps because of the often informal nature of the workplace, the associated stigma, and the frequently illegal nature of the activity. We reviewed the literature on health, occupational risks, and safety among commercial sex workers. Cultural and local variations and commonalities were identified. Dimensions of OHS that emerged included legal and policing risks, risks associated with particular business settings such as streets and brothels, violence from clients, mental health risks and protective factors, alcohol and drug use, repetitive strain injuries, sexually transmissible infections, risks associated with particular classes of clients, issues associated with male and transgender commercial sex workers, and issues of risk reduction that in many cases are associated with lack of agency or control, stigma, and legal barriers. We further discuss the impact and potential of OHS interventions for commercial sex workers. The OHS of commercial sex workers covers a range of domains, some potentially modifiable by OHS programs and workplace safety interventions targeted at this population. We argue that commercial sex work should be considered as an occupation overdue for interventions to reduce workplace risks and enhance worker safety.

Fuzzy risk analysis of a modern γ-ray industrial irradiator.

PubMed

Castiglia, F; Giardina, M

2011-06-01

Fuzzy fault tree analyses were used to investigate accident scenarios that involve radiological exposure to operators working in industrial γ-ray irradiation facilities. The HEART method, a first generation human reliability analysis method, was used to evaluate the probability of adverse human error in these analyses. This technique was modified on the basis of fuzzy set theory to more directly take into account the uncertainties in the error-promoting factors on which the methodology is based. Moreover, with regard to some identified accident scenarios, fuzzy radiological exposure risk, expressed in terms of potential annual death, was evaluated. The calculated fuzzy risks for the examined plant were determined to be well below the reference risk suggested by International Commission on Radiological Protection.

Risk Factors of Periodontal Disease: Review of the Literature

PubMed Central

AlJehani, Yousef A.

2014-01-01

Objectives. This paper aims to review the evidence on the potential roles of modifiable and nonmodifiable risk factors associated with periodontal disease. Data. Original articles that reported on the risk factors for periodontal disease were included. Sources. MEDLINE (1980 to Jan 2014), PubMed (using medical subject headings), and Google Scholar were searched using the following terms in different combinations: “periodontal disease,” “periodontitis,” “risk factors,” and “causal.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Conclusions. It is important to understand the etiological factors and the pathogenesis of periodontal disease to recognize and appreciate the associated risk factors. As periodontal disease is multifactorial, effective disease management requires a clear understanding of all the associated risk factors. PMID:24963294

A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences.

PubMed

Ji, Yuelong; Hong, Xiumei; Wang, Guoying; Chatterjee, Nilanjan; Riley, Anne W; Lee, Li-Ching; Surkan, Pamela J; Bartell, Tami R; Zuckerman, Barry; Wang, Xiaobin

2018-05-08

To investigate the prospective associations between early childhood lead exposure and subsequent risk of attention deficit hyperactivity disorder (ADHD) in childhood and its potential effect modifiers. We analyzed data from 1479 mother-infant pairs (299 ADHD, 1180 neurotypical) in the Boston Birth Cohort. The child's first blood lead measurement and physician-diagnosed ADHD was obtained from electronic medical records. Graphic plots and multiple logistic regression were used to examine dose-response associations between lead exposure and ADHD and potential effect modifiers, adjusting for pertinent covariables. We found that 8.9% of the children in the Boston Birth Cohort had elevated lead levels (5-10 µg/dL) in early childhood, which was associated with a 66% increased risk of ADHD (OR, 1.66; 95% CI, 1.08-2.56). Among boys, the association was significantly stronger (OR, 2.49; 95% CI, 1.46-4.26); in girls, the association was largely attenuated (P value for sex-lead interaction = .017). The OR of ADHD associated with elevated lead levels among boys was reduced by one-half if mothers had adequate high-density lipoprotein levels compared with low high-density lipoprotein, or if mothers had low stress compared with high stress during pregnancy. Elevated early childhood blood lead levels increased the risk of ADHD. Boys were more vulnerable than girls at a given lead level. This risk of ADHD in boys was reduced by one-half if the mother had adequate high-density lipoprotein levels or low stress. These findings shed new light on the sex difference in ADHD and point to opportunities for early risk assessment and primary prevention of ADHD. Copyright © 2018 Elsevier Inc. All rights reserved.

Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment

PubMed Central

Benjamin, Daniel K.; Stoll, Barbara J.; Gantz, Marie G.; Walsh, Michele C.; Sanchez, Pablo J.; Das, Abhik; Shankaran, Seetha; Higgins, Rosemary D.; Auten, Kathy J.; Miller, Nancy A.; Walsh, Thomas J.; Laptook, Abbot R.; Carlo, Waldemar A.; Kennedy, Kathleen A.; Finer, Neil N.; Duara, Shahnaz; Schibler, Kurt; Chapman, Rachel L.; Van Meurs, Krisa P.; Frantz, Ivan D.; Phelps, Dale L.; Poindexter, Brenda B.; Bell, Edward F.; O’Shea, T. Michael; Watterberg, Kristi L.; Goldberg, Ronald N.

2011-01-01

OBJECTIVE Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low-birth-weight (<1000 g) infants. We quantify risk factors predicting infection in high-risk premature infants and compare clinical judgment with a prediction model of invasive candidiasis. METHODS The study involved a prospective observational cohort of infants <1000 g birth weight at 19 centers of the NICHD Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: 1) potentially modifiable risk factors and 2) a clinical model at time of blood culture to predict candidiasis. RESULTS Invasive candidiasis occurred in 137/1515 (9.0%) infants and was documented by positive culture from ≥ 1 of these sources: blood (n=96), cerebrospinal fluid (n=9), urine obtained by catheterization (n=52), or other sterile body fluid (n=10). Mortality was not different from infants who had positive blood culture compared to those with isolated positive urine culture. Incidence varied from 2–28% at the 13 centers enrolling ≥ 50 infants. Potentially modifiable risk factors (model 1) included central catheter, broad-spectrum antibiotics (e.g., third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model (model 2) had an area under the receiver operating characteristic curve of 0.79, and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis. Performance of clinical judgment did not vary significantly with level of training. CONCLUSION Prior antibiotics, presence of a central catheter, endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment. PMID:20876174

Applications of Capstone depleted uranium aerosol risk data to military combat risk management.

PubMed

Daxon, Eric G; Parkhurst, Mary Ann; Melanson, Mark A; Roszell, Laurie E

2009-03-01

Risks to personnel engaged in military operations include not only the threat of enemy firepower but also risks from exposure to other hazards such as radiation. Combatant commanders of the U.S. Army carefully weigh risks of casualties before implementing battlefield actions using an established paradigm that takes these risks into consideration. As a result of the inclusion of depleted uranium (DU) anti-armor ammunition in the conventional (non-nuclear) weapons arsenal, the potential for exposure to DU aerosols and its associated chemical and radiological effects becomes an element of the commanders' risk assessment. The Capstone DU Aerosol Study measured the range of likely DU oxide aerosol concentrations created inside a combat vehicle perforated with a DU munition, and the Capstone Human Health Risk Assessment (HHRA) estimated the associated doses and calculated risks. This paper focuses on the development of a scientific approach to adapt the risks from DU's non-uniform dose distribution within the body using the current U.S. Department of Defense radiation risk management approach. The approach developed equates the Radiation Exposure Status categories to the estimated radiological risks of DU and makes use of the Capstone-developed Renal Effects Group as a measure of chemical risk from DU intake. Recommendations are provided for modifying Army guidance and policy in order to better encompass the potential risks from DU aerosol inhalation during military operations.

Graphite fiber surface treatment to improve char retention and increase fiber clumping

NASA Technical Reports Server (NTRS)

Paul, J. T., Jr.; Weldy, W. E.

1980-01-01

Composites containing carbon and graphite fibers can release fibers into the atmosphere during a fire. This release can potentially cause failure in some types of electrical equipment. Reduced fiber dispersion during and after combustion will reduce risks. Epoxidized char forming systems were synthesized which will react with commercially available surface treated carbon fiber. Fibers modified with these char formers retained adhesion in a specific epoxy matrix resin. Small scale combustion testing indicates that using these char former modified fibers in laminates will help to reduce the dispersement of fibers resulting from exposure to fire without sacrificing resin to fiber adhesion.

Extended Endoscopic and Open Sinus Surgery for Refractory Chronic Rhinosinusitis.

PubMed

Eloy, Jean Anderson; Marchiano, Emily; Vázquez, Alejandro

2017-02-01

This review discusses extended endoscopic and open sinus surgery for refractory chronic rhinosinusitis. Extended maxillary sinus surgery including endoscopic maxillary mega-antrostomy, endoscopic modified medial maxillectomy, and inferior meatal antrostomy are described. Total/complete ethmoidectomy with mucosal stripping (nasalization) is discussed. Extended endoscopic sphenoid sinus procedures as well as their indications and potential risks are reviewed. Extended endoscopic frontal sinus procedures, such the modified Lothrop procedure, are described. Extended open sinus surgical procedures, such as the Caldwell-Luc approach, frontal sinus trephine procedure, external frontoethmoidectomy, frontal sinus osteoplastic flap with or without obliteration, and cranialization, are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

[The public perception of information about the potential risks of genetically modified crops in the food chain].

PubMed

Furnival, Ariadne Chloë; Pinheiro, Sônia Maria

2008-01-01

At a time when genetically modified (GM) crops are entering the Brazilian food chain, we present the findings of a study that makes use of a qualitative technique involving focal groups to look into the public's interpretation of the information available about this biotechnological innovation. This methodology produced results that revealed the interconnections drawn by the research subjects between this form of biotechnology, changes to the environment, and food production in general. The mistrust expressed about GM crops was particularly attributed by the participants to the non-availability of comprehensible information in the mass media or on product labels.

Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults.

PubMed

Aigner, Annette; Grittner, Ulrike; Rolfs, Arndt; Norrving, Bo; Siegerink, Bob; Busch, Markus A

2017-07-01

As stroke in young adults is assumed to have different etiologies and risk factors than in older populations, the aim of this study was to examine the contribution of established potentially modifiable cardiovascular risk factors to the burden of stroke in young adults. A German nationwide case-control study based on patients enrolled in the SIFAP1 study (Stroke In Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 was performed. Cases were 2125 consecutive patients aged 18 to 55 years with acute first-ever stroke from 26 clinical stroke centers; controls (age- and sex-matched, n=8500, without previous stroke) were from a nationwide community sample. Adjusted population-attributable risks of 8 risk factors (hypertension, hyperlipidemia, diabetes mellitus, coronary heart disease, smoking, heavy episodic alcohol consumption, low physical activity, and obesity) and their combinations for all stroke, ischemic stroke, and primary intracerebral hemorrhage were calculated. Low physical activity and hypertension were the most important risk factors, accounting for 59.7% (95% confidence interval, 56.3-63.2) and 27.1% (95% confidence interval, 23.6-30.6) of all strokes, respectively. All 8 risk factors combined explained 78.9% (95% confidence interval, 76.3-81.4) of all strokes. Population-attributable risks of all risk factors were similar for all ischemic stroke subtypes. Population-attributable risks of most risk factors were higher in older age groups and in men. Modifiable risk factors previously established in older populations also account for a large part of stroke in younger adults, with 4 risk factors explaining almost 80% of stroke risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2017 American Heart Association, Inc.

Lower-Risk Cannabis Use Guidelines: A Comprehensive Update of Evidence and Recommendations.

PubMed

Fischer, Benedikt; Russell, Cayley; Sabioni, Pamela; van den Brink, Wim; Le Foll, Bernard; Hall, Wayne; Rehm, Jürgen; Room, Robin

2017-08-01

Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health outcomes. Cannabis control regimes are evolving, for example toward a national legalization policy in Canada, with the aim to improve public health, and thus require evidence-based interventions. As cannabis-related health outcomes may be influenced by behaviors that are modifiable by the user, evidence-based Lower-Risk Cannabis Use Guidelines (LRCUG)-akin to similar guidelines in other health fields-offer a valuable, targeted prevention tool to improve public health outcomes. To systematically review, update, and quality-grade evidence on behavioral factors determining adverse health outcomes from cannabis that may be modifiable by the user, and translate this evidence into revised LRCUG as a public health intervention tool based on an expert consensus process. We used pertinent medical search terms and structured search strategies, to search MEDLINE, EMBASE, PsycINFO, Cochrane Library databases, and reference lists primarily for systematic reviews and meta-analyses, and additional evidence on modifiable risk factors for adverse health outcomes from cannabis use. We included studies if they focused on potentially modifiable behavior-based factors for risks or harms for health from cannabis use, and excluded studies if cannabis use was assessed for therapeutic purposes. We screened the titles and abstracts of all studies identified by the search strategy and assessed the full texts of all potentially eligible studies for inclusion; 2 of the authors independently extracted the data of all studies included in this review. We created Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow-charts for each of the topical searches. Subsequently, we summarized the evidence by behavioral factor topic, quality-graded it by following standard (Grading of Recommendations Assessment, Development, and Evaluation; GRADE) criteria, and translated it into the LRCUG recommendations by the author expert collective on the basis of an iterative consensus process. For most recommendations, there was at least "substantial" (i.e., good-quality) evidence. We developed 10 major recommendations for lower-risk use: (1) the most effective way to avoid cannabis use-related health risks is abstinence, (2) avoid early age initiation of cannabis use (i.e., definitively before the age of 16 years), (3) choose low-potency tetrahydrocannabinol (THC) or balanced THC-to-cannabidiol (CBD)-ratio cannabis products, (4) abstain from using synthetic cannabinoids, (5) avoid combusted cannabis inhalation and give preference to nonsmoking use methods, (6) avoid deep or other risky inhalation practices, (7) avoid high-frequency (e.g., daily or near-daily) cannabis use, (8) abstain from cannabis-impaired driving, (9) populations at higher risk for cannabis use-related health problems should avoid use altogether, and (10) avoid combining previously mentioned risk behaviors (e.g., early initiation and high-frequency use). Evidence indicates that a substantial extent of the risk of adverse health outcomes from cannabis use may be reduced by informed behavioral choices among users. The evidence-based LRCUG serve as a population-level education and intervention tool to inform such user choices toward improved public health outcomes. However, the LRCUG ought to be systematically communicated and supported by key regulation measures (e.g., cannabis product labeling, content regulation) to be effective. All of these measures are concretely possible under emerging legalization regimes, and should be actively implemented by regulatory authorities. The population-level impact of the LRCUG toward reducing cannabis use-related health risks should be evaluated. Public health implications. Cannabis control regimes are evolving, including legalization in North America, with uncertain impacts on public health. Evidence-based LRCUG offer a potentially valuable population-level tool to reduce the risk of adverse health outcomes from cannabis use among (especially young) users in legalization contexts, and hence to contribute to improved public health outcomes.

Lessons from obesity prevention for the prevention of mental disorders: the primordial prevention approach.

PubMed

Hayward, Joshua; Jacka, Felice N; Waters, Elizabeth; Allender, Steven

2014-09-10

Emerging evidence supports a relationship between risk factors for obesity and the genesis of the common mental disorders, depression and anxiety. This suggests common mental disorders should be considered as a form of non-communicable disease, preventable through the modification of lifestyle behaviours, particularly diet and physical activity. Obesity prevention research since the 1970's represents a considerable body of knowledge regarding strategies to modify diet and physical activity and so there may be clear lessons from obesity prevention that apply to the prevention of mental disorders. For obesity, as for common mental disorders, adolescence represents a key period of vulnerability. In this paper we briefly discuss relationships between modifiable lifestyle risk factors and mental health, lifestyle risk factor interventions in obesity prevention research, the current state of mental health prevention, and the implications of current applications of systems thinking in obesity prevention research for lifestyle interventions. We propose a potential focus for future mental health promotion interventions and emphasise the importance of lessons available from other lifestyle modification intervention programmes.

A risk-based classification scheme for genetically modified foods. III: Evaluation using a panel of reference foods.

PubMed

Chao, Eunice; Krewski, Daniel

2008-12-01

This paper presents an exploratory evaluation of four functional components of a proposed risk-based classification scheme (RBCS) for crop-derived genetically modified (GM) foods in a concordance study. Two independent raters assigned concern levels to 20 reference GM foods using a rating form based on the proposed RBCS. The four components of evaluation were: (1) degree of concordance, (2) distribution across concern levels, (3) discriminating ability of the scheme, and (4) ease of use. At least one of the 20 reference foods was assigned to each of the possible concern levels, demonstrating the ability of the scheme to identify GM foods of different concern with respect to potential health risk. There was reasonably good concordance between the two raters for the three separate parts of the RBCS. The raters agreed that the criteria in the scheme were sufficiently clear in discriminating reference foods into different concern levels, and that with some experience, the scheme was reasonably easy to use. Specific issues and suggestions for improvements identified in the concordance study are discussed.

Polychlorinated biphenyls and links to cardiovascular disease.

PubMed

Perkins, Jordan T; Petriello, Michael C; Newsome, Bradley J; Hennig, Bernhard

2016-02-01

The pathology of cardiovascular disease is multi-faceted, with links to many modifiable and non-modifiable risk factors. Epidemiological evidence now implicates exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), with an increased risk of developing diabetes, hypertension, and obesity; all of which are clinically relevant to the onset and progression of cardiovascular disease. PCBs exert their cardiovascular toxicity either directly or indirectly via multiple mechanisms, which are highly dependent on the type and concentration of PCBs present. However, many PCBs may modulate cellular signaling pathways leading to common detrimental outcomes including induction of chronic oxidative stress, inflammation, and endocrine disruption. With the abundance of potential toxic pollutants increasing globally, it is critical to identify sensible means of decreasing associated disease risks. Emerging evidence now implicates a protective role of lifestyle modifications such as increased exercise and/or nutritional modulation via anti-inflammatory foods, which may help to decrease the vascular toxicity of PCBs. This review will outline the current state of knowledge linking coplanar and non-coplanar PCBs to cardiovascular disease and describe the possible molecular mechanism of this association.

Dynamics of Diabetes and Obesity: Epidemiological Perspective

PubMed Central

Boles, Annette; Kandimalla, Ramesh; Reddy, P. Hemachandra

2017-01-01

The purpose of this review article is to understand the current literature on obesity, diabetes and therapeutic avenues across the world. Diabetes is a chronic lifestyle condition that affects millions of people worldwide and it is a major health concern in our society. Diabetes and obesity are associated with various conditions, including non-modifiable and modifiable risk factors. Early detectable markers are not well established to detect pre-diabetes and as a result, it becomes diabetes. Several published epidemiological studies were assessed and the findings were summarized. Resources from published studies were used to identify criteria used for pre-diabetes, the role of diet in pre-diabetics and potential risks and characteristics associated with pre-diabetes. Preventive strategies are needed to combat diabetes. Individuals diagnosed with pre-diabetes need detailed education, need to fully understand the risk factors and have the ability to manage diabetes. Interventions exist that include chronic disease self-management programs, lifestyle interventions and pharmacological strategies. Obesity plays a large role in causing pre-diabetes and diabetes. Critical analysis of existing epidemiological research data suggests that additional research is needed to determine the efficacy of interventions. PMID:28130199

Can species traits predict the susceptibility of riverine fish to water resource development? An Australian case study.

PubMed

Rolls, Robert J; Sternberg, David

2015-06-01

Water resource developments alter riverine environments by disrupting longitudinal connectivity, transforming lotic habitats, and modifying in-stream hydraulic conditions. Effective management of anthropogenic disturbances therefore requires an understanding of the range of potential ecosystem effects and the inherent traits symptomatic of elevated vulnerability to disturbance. Using 42 riverine fish native to South Eastern Australia as a case study, we quantified six morphological, behavioral, and life-history traits to classify species into groups reflecting potential differences in their response to ecosystem changes as a result of water resource development. Classification analysis identified five strategies based on fish life-history dispersal requirements, climbing potential, and habitat preference. These strategies in turn highlight the potential species at risk from the separate impacts of water resource development and inform management decisions to mitigate those risks. Swimming ability did not contribute to distinguishing species into functional groups, likely due to methodological inconsistencies in quantifying swimming performance that may ultimately hinder the ability of fish passage facilities to function within the physical capabilities of species at risk of habitat fragmentation. This study improves our ability to predict the performance of groups of species at risk from the multiple environmental changes imposed by humans and goes beyond broad-scale dispersal requirements as a predictor of individual species response.

Current (Food) Allergenic Risk Assessment: Is It Fit for Novel Foods? Status Quo and Identification of Gaps.

PubMed

Mazzucchelli, Gabriel; Holzhauser, Thomas; Cirkovic Velickovic, Tanja; Diaz-Perales, Araceli; Molina, Elena; Roncada, Paola; Rodrigues, Pedro; Verhoeckx, Kitty; Hoffmann-Sommergruber, Karin

2018-01-01

Food allergies are recognized as a global health concern. In order to protect allergic consumers from severe symptoms, allergenic risk assessment for well-known foods and foods containing genetically modified ingredients is installed. However, population is steadily growing and there is a rising need to provide adequate protein-based foods, including novel sources, not yet used for human consumption. In this context safety issues such as a potential increased allergenic risk need to be assessed before marketing novel food sources. Therefore, the established allergenic risk assessment for genetically modified organisms needs to be re-evaluated for its applicability for risk assessment of novel food proteins. Two different scenarios of allergic sensitization have to be assessed. The first scenario is the presence of already known allergenic structures in novel foods. For this, a comparative assessment can be performed and the range of cross-reactivity can be explored, while in the second scenario allergic reactions are observed toward so far novel allergenic structures and no reference material is available. This review summarizes the current analytical methods for allergenic risk assessment, highlighting the strengths and limitations of each method and discussing the gaps in this assessment that need to be addressed in the near future. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

PubMed

de Vathaire, Florent; Haddy, Nadia; Allodji, Rodrigue S; Hawkins, Mike; Guibout, Catherine; El-Fayech, Chiraz; Teinturier, Cécile; Oberlin, Odile; Pacquement, Hélène; Diop, Fara; Kalhouche, Amar; Benadjaoud, Mohamedamine; Winter, David; Jackson, Angela; Bezin Mai-Quynh, Giao; Benabdennebi, Aymen; Llanas, Damien; Veres, Cristina; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Deutsch, Eric; Lefkopoulos, Dimitri; Schlumberger, Martin; Diallo, Ibrahima; Rubino, Carole

2015-11-01

Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. This study aimed to investigate the role of potential modifiers of the dose response. We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

A comparative evaluation of the regulation of GM crops or products containing dsRNA and suggested improvements to risk assessments.

PubMed

Heinemann, Jack A; Agapito-Tenfen, Sarah Zanon; Carman, Judy A

2013-05-01

Changing the nature, kind and quantity of particular regulatory-RNA molecules through genetic engineering can create biosafety risks. While some genetically modified organisms (GMOs) are intended to produce new regulatory-RNA molecules, these may also arise in other GMOs not intended to express them. To characterise, assess and then mitigate the potential adverse effects arising from changes to RNA requires changing current approaches to food or environmental risk assessments of GMOs. We document risk assessment advice offered to government regulators in Australia, New Zealand and Brazil during official risk evaluations of GM plants for use as human food or for release into the environment (whether for field trials or commercial release), how the regulator considered those risks, and what that experience teaches us about the GMO risk assessment framework. We also suggest improvements to the process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior.

PubMed

Bokslag, Anouk; Hermes, Wietske; de Groot, Christianne J M; Teunissen, Pim W

2016-11-01

To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as "chance of health" or "risk of disease". 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence.

Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

PubMed Central

Jakubowska, A; Rozkrut, D; Antoniou, A; Hamann, U; Scott, R J; McGuffog, L; Healy, S; Sinilnikova, O M; Rennert, G; Lejbkowicz, F; Flugelman, A; Andrulis, I L; Glendon, G; Ozcelik, H; Thomassen, M; Paligo, M; Aretini, P; Kantala, J; Aroer, B; von Wachenfeldt, A; Liljegren, A; Loman, N; Herbst, K; Kristoffersson, U; Rosenquist, R; Karlsson, P; Stenmark-Askmalm, M; Melin, B; Nathanson, K L; Domchek, S M; Byrski, T; Huzarski, T; Gronwald, J; Menkiszak, J; Cybulski, C; Serrano, P; Osorio, A; Cajal, T R; Tsitlaidou, M; Benítez, J; Gilbert, M; Rookus, M; Aalfs, C M; Kluijt, I; Boessenkool-Pape, J L; Meijers-Heijboer, H E J; Oosterwijk, J C; van Asperen, C J; Blok, M J; Nelen, M R; van den Ouweland, A M W; Seynaeve, C; van der Luijt, R B; Devilee, P; Easton, D F; Peock, S; Frost, D; Platte, R; Ellis, S D; Fineberg, E; Evans, D G; Lalloo, F; Eeles, R; Jacobs, C; Adlard, J; Davidson, R; Eccles, D; Cole, T; Cook, J; Godwin, A; Bove, B; Stoppa-Lyonnet, D; Caux-Moncoutier, V; Belotti, M; Tirapo, C; Mazoyer, S; Barjhoux, L; Boutry-Kryza, N; Pujol, P; Coupier, I; Peyrat, J-P; Vennin, P; Muller, D; Fricker, J-P; Venat-Bouvet, L; Johannsson, O Th; Isaacs, C; Schmutzler, R; Wappenschmidt, B; Meindl, A; Arnold, N; Varon-Mateeva, R; Niederacher, D; Sutter, C; Deissler, H; Preisler-Adams, S; Simard, J; Soucy, P; Durocher, F; Chenevix-Trench, G; Beesley, J; Chen, X; Rebbeck, T; Couch, F; Wang, X; Lindor, N; Fredericksen, Z; Pankratz, V S; Peterlongo, P; Bonanni, B; Fortuzzi, S; Peissel, B; Szabo, C; Mai, P L; Loud, J T; Lubinski, J

2012-01-01

Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID:22669161

[Nematodes with zoonotic potential in parks of the city of Tunja, Colombia].

PubMed

Díaz-Anaya, Adriana María; Pulido-Medellín, Martín Orlando; Giraldo-Forero, Julio César

2015-01-01

To identify the presence of parasites with zoonotic potential in major parks in the city of Tunja, Boyacá. Twenty eight parks in the city were selected, where 124 samples of feces of dogs and soil were collected with the help of a spatula, gathering approximately 150 g per sample. They were processed by the method of concentration of Ritchie modified making the identification of parasitic forms in an optical microscope. A 60.7% of the parks were positive to nematodes in samples of canine fecal material and 100% on soil. Found nematodes were eggs and larvae of Toxocara spp., Ancylostoma spp., Trichuris vulpis and Strongiloides spp. This study demonstrated the potential risk of transmission of zoonoses caused by nematodes in canines and for the need to strengthen public health measures to reduce the risk shows the population exposed to such zoonoses.

Risk Factors for Rapid Kidney Function Decline Among African Americans: The Jackson Heart Study (JHS)

PubMed Central

Young, Bessie A.; Katz, Ronit; Boulware, Ebony; Kestenbaum, Bryan; de Boer, Ian H.; Wang, Wei; Fülöp, Tibor; Bansal, Nisha; Robinson-Cohen, Cassianne; Griswold, Michael; Powe, Neil N.; Himmelfarb, Jonathan; Correa, Adolfo

2016-01-01

Background Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. A greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population. Study Design Prospective cohort study. Setting & Participants 3653 African-American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from two of three examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation. Predictors Demographics, socioeconomic status, lifestyle, clinical risk factors for kidney failure. Outcomes Rapid decline was defined as a ≥ 30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models. Measurements Clinical (systolic blood pressure, albuminuria [albumin-creatinine ratio]) and modifiable risk factors. Results Mean age was 54 ± 12 (SD) years, 37% were male, average body mass index was 31.8 ± 7.1 kg/m2, 19% had diabetes mellitus (DM) and mean eGFR was 96.0 ±20 ml/min/1.73m2 with an annual rate of decline of 1.27 ml/min/1.73m2. Those with rapid decline (11.5%) were older, more likely to be of low/middle income, had higher systolic blood pressure, and greater DM than those with non-rapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71); cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17 mm Hg greater, 1.22; 95% CI, 1.06-1.41); DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30 mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein, and physical activity with rapid decline. Limitations No mid study creatinine measurement at examination 2 (2005-2008). Conclusions Rapid decline heterogeneity existed among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure. PMID:27066930

Risk Factors for Rapid Kidney Function Decline Among African Americans: The Jackson Heart Study (JHS).

PubMed

Young, Bessie A; Katz, Ronit; Boulware, L Ebony; Kestenbaum, Bryan; de Boer, Ian H; Wang, Wei; Fülöp, Tibor; Bansal, Nisha; Robinson-Cohen, Cassianne; Griswold, Michael; Powe, Neil R; Himmelfarb, Jonathan; Correa, Adolfo

2016-08-01

Racial differences in rapid kidney function decline exist, but less is known regarding factors associated with rapid decline among African Americans. Greater understanding of potentially modifiable risk factors for early kidney function loss may help reduce the burden of kidney failure in this high-risk population. Prospective cohort study. 3,653 African American participants enrolled in the Jackson Heart Study (JHS) with kidney function data from 2 of 3 examinations (2000-2004 and 2009-2013). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the CKD-EPI creatinine equation. Demographics, socioeconomic status, lifestyle, and clinical risk factors for kidney failure. Rapid decline was defined as a ≥30% decline in eGFR during follow-up. We quantified the association of risk factors with rapid decline in multivariable models. Clinical (systolic blood pressure and albuminuria [albumin-creatinine ratio]) and modifiable risk factors. Mean age was 54±12 (SD) years, 37% were men, average body mass index was 31.8±7.1kg/m(2), 19% had diabetes mellitus (DM), and mean eGFR was 96.0±20mL/min/1.73m(2) with an annual rate of decline of 1.27mL/min/1.73m(2). Those with rapid decline (11.5%) were older, were more likely to be of low/middle income, and had higher systolic blood pressures and greater DM than those with nonrapid decline. Factors associated with ≥30% decline were older age (adjusted OR per 10 years older, 1.51; 95% CI, 1.34-1.71), cardiovascular disease (adjusted OR, 1.53; 95% CI, 1.12-2.10), higher systolic blood pressure (adjusted OR per 17mmHg greater, 1.22; 95% CI, 1.06-1.41), DM (adjusted OR, 2.63; 95% CI, 2.02-3.41), smoking (adjusted OR, 1.60; 95% CI, 1.10-2.31), and albumin-creatinine ratio > 30mg/g (adjusted OR, 1.55; 95% CI, 1.08-1.21). Conversely, results did not support associations of waist circumference, C-reactive protein level, and physical activity with rapid decline. No midstudy creatinine measurement at examination 2 (2005-2008). Rapid decline heterogeneity exists among African Americans in JHS. Interventions targeting potentially modifiable factors may help reduce the incidence of kidney failure. Published by Elsevier Inc.

Probabilistic Human Health Risk Assessment of Chemical Mixtures: Hydro-Toxicological Interactions and Controlling Factors

NASA Astrophysics Data System (ADS)

Henri, C.; Fernandez-Garcia, D.; de Barros, F.

2014-12-01

Improper disposals of hazardous wastes in most industrial countries give rise to severe groundwater contamination problems that can lead to adverse health effects in humans. Therefore risk assessment methods play an important role in population protection by (1) quantifying the impact on human health of an aquifer contamination and (2) aiding the decision making process of to better manage our groundwater resources. Many reactive components such as chlorinated solvent or nitrate potentially experience attenuation processes under common geochemical conditions. Based on this, monitored natural attenuation has become nowadays an attractive remediation solution. However, in some cases, intermediate degradation products can constitute noxious chemical compounds before reaching a harmless chemical form. In these cases, the joint effect of advection-dispersion transport and the species-dependent kinetic reactions and toxicity will dictate the relative importance of the degradation byproducts to the total risk. This renders the interpretation of risk a non-trivial task. In this presentation, we quantify, through a probabilistic framework, the human health risk posed by a chemical mixture in a heterogeneous aquifer. This work focuses on a Perchloroethylene contamination problem followed by the first-order production/biodegradation of its daughter species Trichloroethylene, Dichloroethylene and Vinyl Chlorine that is known to be highly toxic. Uncertainty on the hydraulic conductivity field is considered through a Monte Carlo scheme. A comparative description of human health risk metrics as a function of aquifer heterogeneity and contaminant injection mode is provided by means of a spatial characterization of the lower-order statistical moments and empirical probability density functions of both individual and total risks. Interestingly, we show that the human health risk of a chemical mixture is mainly controlled by a modified Damköhler number that express the joint effect of contaminant mean travel times, reaction kinetics and chemical toxicity. From this, connectivity is shown to produce a significant and non-trivial impact on risk measures. The impact of connectivity can be potentially beneficial or detrimental on the magnitude of human health risk depending on the modified Damköhler number.

Characterization of the ecological interactions of Roundup Ready 2 Yield® soybean, MON 89788, for use in ecological risk assessment

PubMed Central

Horak, Michael J; Rosenbaum, Eric W; Phillips, Samuel L; Kendrick, Daniel L; Carson, David; Clark, Pete L; Nickson, Thomas E

2015-01-01

Abstract As part of an ecological risk assessment, Roundup Ready 2 Yield® soybean (MON 89788) was compared to a conventional control soybean variety, A3244, for disease and arthropod damage, plant response to abiotic stress and cold, effects on succeeding plant growth (allelopathic effects), plant response to a bacterial symbiont, and effects on the ability of seed to survive and volunteer in a subsequent growing season. Statistically significant differences between MON 89788 and A3244 were considered in the context of the genetic variation known to occur in soybean and were assessed for their potential impact on plant pest (weed) potential and adverse environmental impact. The results of these studies revealed no effects of the genetic modification that would result in increased pest potential or adverse environmental impact of MON 89788 compared with A3244. This paper illustrates how such characterization studies conducted in a range of environments where the crop is grown are used in an ecological risk assessment of the genetically modified (GM) crop. Furthermore, risk assessors and decision makers use this information when deciding whether to approve a GM crop for cultivation in—or grain import into—their country. PMID:26177011

Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis.

PubMed

Sørensen, Per Soelberg

2011-12-01

Balancing efficacy versus burden of therapy is essential for the choice of disease-modifying therapy in every MS patient. The first-line therapies, interferon-? and glatiramer acetate, have well-established efficacy and present no major safety concerns. Certain second-line therapies, such as natalizumab, offer potentially greater efficacy, but are associated with an increased level of risk. Over the last year, the first two oral treatments of relapsing-remitting multiple sclerosis, cladribine and fingolimod, have been marketed in certain countries, although cladribine was subsequently withdrawn. In the Phase III clinical development programme, both drugs appeared effective and reasonably safe. However, there were cases of serious adverse events (malignancies and fatal infections) whose relationship with treatment was unclear. Specific postmarketing studies will be necessary to assess the risks of these new oral therapies. Indeed, both natalizumab and mitoxantrone are known today to be associated with rare adverse drug reactions (progressive multifocal leukoencephalopathy for natalizumab and treatment-related leukaemia for mitoxantrone), which were not identified before the treatments were approved. The use of therapies carrying potential serious risks is justified in patients who cannot be treated effectively with safe first-line therapies, but probably not in the average relapsing-remitting multiple sclerosis or clinical isolated syndrome patient. Pivotal Phase III clinical trials, on which basis drug approval is generally granted, are designed to demonstrate clinical efficacy and reveal frequently occurring adverse effects of a new drug. However, post-approval trials with extensive patient exposure are needed to generate knowledge of more patient-specific clinical effectiveness and long-term safety, in particular with respect to rare adverse reactions. Other post-approval measures, such as risk management programmes, pharmacovigilance studies, or phased launch of the drug, may be useful to ensure that risks associated with new treatments are identified and minimised. The final evaluation of the benefits to risks balance of a drug should be made in every patient by weighing benefits in disease activity and progression, quality of life and health economy against both commonly occurring mild side-effects and rare potentially life-threatening adverse drug effects. This decision should be shared between the physician and patient, who may not share the same perceptions of acceptable risk. Copyright © 2011 Elsevier B.V. All rights reserved.

Implications of Risk Factors for Alzheimer’s Disease in Canada’s Indigenous Population

PubMed Central

MacDonald, Julia Petrasek; Barnes, Deborah E.; Middleton, Laura E.

2015-01-01

Background Indigenous peoples in Canada have higher prevalence of modifiable risk factors for Alzheimer’s disease (AD). The relative importance of these risk factors on AD risk management is poorly understood. Methods Relative risks from literature and prevalence of risk factors from Statistics Canada or the First Nations Regional Health Survey were used to determine projected population attributable risk (PAR) associated with modifiable risk factors for AD (low education and vascular risk factors) among on- and off-reserve Indigenous and non-Indigenous people in Canada using the Levin formula. Results Physical inactivity had the highest PAR for AD among Indigenous and non-Indigenous peoples in Canada (32.5% [10.1%–51.1%] and 30.5% [9.2%–48.8%] respectively). The PAR for most modifiable risk factors was higher among Indigenous peoples in Canada, particularly among on-reserve groups. The greatest differences in PAR were for low educational attainment and smoking, which were approximately 10% higher among Indigenous peoples in Canada. The combined PAR for AD for all six modifiable risk factors was 79.6% among on-reserve Indigenous, 74.9% among off-reserve Indigenous, and 67.1% among non-Indigenous peoples in Canada. (All differences significant to p < .001.) Conclusions Modifiable risk factors are responsible for the most AD cases among Indigenous peoples in Canada. Further research is necessary to determine the prevalence of AD and the impact of risk factor modification among Indigenous peoples in Canada. PMID:26495049

Aquaculture: Incorporating risk assessment and risk management into public policies on genetically modified finfish and shellfish

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

Hallerman, E.M.; Kapuscinski, A.R.

Genetically modified finfish and shellfish pose economic benefits to aquaculture, but also pose ecological and genetic risks to ecosystems receiving such organisms. Realization of benefits with minimization of risks posed by a new technology can be addressed through the processes of risk assessment and risk management. Public policies adopted by individual countries will reflect differences in the outocme of risk assessment and risk management processes resulting from differences among the receiving ecosystems and sets of human values at issue. A number of countries and international institutions have begun development of policies for oversight of genetically modified aquatic organisms. In themore » United States, a working group commissioned by the U.S. Department of Agriculture incorporated risk assessment and risk management principles into draft performance standards for safely conducting research with genetically modified finfish and shellfish. The performance standards address research with a broad range of aquatic GMO`s and compliance is intended to be voluntary. In contrast, the Canadian policy mandates adherence to specified guidelines for experiments with transgenic aquatic organisms; establishment as national policy is expended soon.« less

[Impacts of genetically modified soybean leaf residues on Folsomia candida.

PubMed

Zhou, Lin; Wang, Bai Feng; Liu, Xin Ying; Jiang, Ying; Wang, Da Ming; Feng, Shu Dan; Song, Xin Yuan

2016-09-01

When the genetically modified soybean is planted in the field, the expression product of exogenous gene could be exposed in the soil ecosystem and bring potential risk to the soil fauna, with the form of leaves and other debris. A few of genetically modified soybeans developed by China independently were used in our study as materials. They were Phytophthora-resistant soybean harboring hrpZm gene (B4J8049), leaf-feeding insect-resistant soybean harboring Cry1C gene (A2A8001) and Leguminivora glycinivorella-resistant soybean harboring Cry1Iem gene (C802). By feeding Folsomia candida with the three genetically modified soybeans for continuous 60 days, the surviving rate, reproductive rate and changes on the body length of F. candida were studied. The results showed that all the three genetically modified soybeans of B4J8049, A2A8001 and C802 had no significant adverse effects on the growth of F. candida, as an environmental indicator organism. It was initially inferred that they were environmentally safe under short-term exposure, which provided basic data of ecological safety for their wide cultivation.

Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist.

PubMed

Shankar, Rohit; Cox, David; Jalihal, Virupakshi; Brown, Scott; Hanna, Jane; McLean, Brendan

2013-12-01

The incidence of sudden death appears to be 20 times higher in patients with epilepsy compared with the general population. Epilepsy-related death, particularly sudden unexpected death in epilepsy (SUDEP), is still underestimated by healthcare professionals and this may reflect the mistaken belief that epilepsy is a benign condition. The risk of death associated with epilepsy appeared rarely to have been discussed with patients or their families. It appears the decision to discuss SUDEP and also to peg SUDEP risk is arbitrary and clinical. Unfortunately there is no structured evidenced mechanism at present to represent person centered risk of SUDEP and there is currently no easy manner or template to have this discussion with the family and the patient. We conducted a detailed literature review in Medline, Embase and Psychinfo databases to extract the common risk factors as evidenced from literature till date. Research into risk factors has identified a number of risk factors for SUDEP, some of which are potentially modifiable. Based on the literature review, we believe that the ascertained risk factors could be employed in clinical practice as a checklist to reduce an individual patient's risk of SUDEP. The SUDEP safety checklist may be of practical use in reducing risks in some individuals and is definitely of use in helping communication. An evidence based checklist identifying the major risk factors can help both clinicians and patients to focus on minimizing certain risk factors and promote safety by focusing on the modifiable factors and guide treatment. It can be a tool to open a person centered discussion with patients and to outline how individual behaviors could impact on risk. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Facile preparation of heparinized polysulfone membrane assisted by polydopamine/polyethyleneimine co-deposition for simultaneous LDL selectivity and biocompatibility

NASA Astrophysics Data System (ADS)

Wang, Liwei; Fang, Fei; Liu, Yang; Li, Jing; Huang, Xiaojun

2016-11-01

Low-density lipoprotein (LDL) gains worldwide attention for decades as the key risk factor to atherosclerosis that progressively deteriorating into cardiovascular diseases. Until recent years, LDL-apheresis comes to be extensively used as a direct and efficient LDL removal method, with LDL adsorption materials particularly important. In this paper, a new strategy based on the co-deposition of polydopamine (PDA) with polyethylenimine (PEI) onto polysulfone (PSf) membranes, then subsequent heparinization by amino-carbonyl reactions, to achieve LDL selectivity and simultaneous biocompatibility, is proposed. Surface properties of modified PSf membranes are characterized by ATR-FTIR, XPS, FESEM, Zeta potential and WCA measurements. LDL adsorption ability is investigated by ELISA, while blood biocompatibility is evaluated by platelet adhesion experiments. Results suggest that heparin-modified PSf membranes show high selectivity for LDL removal and fine biocompatibility in contact with plasma, as excellent potential materials for LDL-apheresis.

Safety assessment, detection and traceability, and societal aspects of genetically modified foods. European Network on Safety Assessment of Genetically Modified Food Crops (ENTRANSFOOD). Concluding remarks.

PubMed

Kuiper, H A; König, A; Kleter, G A; Hammes, W P; Knudsen, I

2004-07-01

The most important results from the EU-sponsored ENTRANSFOOD Thematic Network project are reviewed, including the design of a detailed step-wise procedure for the risk assessment of foods derived from genetically modified crops based on the latest scientific developments, evaluation of topical risk assessment issues, and the formulation of proposals for improved risk management and public involvement in the risk analysis process. Copyright 2004 Elsevier Ltd.

Family-oriented cardiac risk estimator: a Java web-based applet.

PubMed

Crouch, Michael A; Jadhav, Ashwin

2003-01-01

We developed a Java applet that calculates four different estimates of a person's 10-year risk for heart attack: (1) Estimate based on Framingham equation (2) Framingham equation estimate modified by C-reactive protein (CRP) level (3) Framingham estimate modified by family history of heart disease in parents or siblings (4) Framingham estimate modified by both CRP and family heart disease history. This web-based, family-oriented cardiac risk estimator uniquely considers family history and CRP while estimating risk.

Risk factors for child maltreatment in an Australian population-based birth cohort.

PubMed

Doidge, James C; Higgins, Daryl J; Delfabbro, Paul; Segal, Leonie

2017-02-01

Child maltreatment and other adverse childhood experiences adversely influence population health and socioeconomic outcomes. Knowledge of the risk factors for child maltreatment can be used to identify children at risk and may represent opportunities for prevention. We examined a range of possible child, parent and family risk factors for child maltreatment in a prospective 27-year population-based birth cohort of 2443 Australians. Physical abuse, sexual abuse, emotional abuse, neglect and witnessing of domestic violence were recorded retrospectively in early adulthood. Potential risk factors were collected prospectively during childhood or reported retrospectively. Associations were estimated using bivariate and multivariate logistic regressions and combined into cumulative risk scores. Higher levels of economic disadvantage, poor parental mental health and substance use, and social instability were strongly associated with increased risk of child maltreatment. Indicators of child health displayed mixed associations and infant temperament was uncorrelated to maltreatment. Some differences were observed across types of maltreatment but risk profiles were generally similar. In multivariate analyses, nine independent risk factors were identified, including some that are potentially modifiable: economic disadvantage and parental substance use problems. Risk of maltreatment increased exponentially with the number of risk factors experienced, with prevalence of maltreatment in the highest risk groups exceeding 80%. A cumulative risk score based on the independent risk factors allowed identification of individuals at very high risk of maltreatment, while a score that incorporated all significant risk and protective factors provided better identification of low-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

The relevance of gene transfer to the safety of food and feed derived from genetically modified (GM) plants.

PubMed

van den Eede, G; Aarts, H; Buhk, H-J; Corthier, G; Flint, H J; Hammes, W; Jacobsen, B; Midtvedt, T; van der Vossen, J; von Wright, A; Wackernagel, W; Wilcks, A

2004-07-01

In 2000, the thematic network ENTRANSFOOD was launched to assess four different topics that are all related to the testing or assessment of food containing or produced from genetically modified organisms (GMOs). Each of the topics was linked to a European Commission (EC)-funded large shared cost action (see http://www.entransfood.com). Since the exchange of genetic information through horizontal (lateral) gene transfer (HGT) might play a more important role, in quantity and quality, than hitherto imagined, a working group dealing with HGT in the context of food and feed safety was established. This working group was linked to the GMOBILITY project (GMOBILITY, 2003) and the results of the deliberations are laid down in this review paper. HGT is reviewed in relation to the potential risks of consuming food or feed derived from transgenic crops. First, the mechanisms for obtaining transgenic crops are described. Next, HGT mechanisms and its possible evolutionary role are described. The use of marker genes is presented in detail as a special case for genes that may pose a risk. Furthermore, the exposure to GMOs and in particular to genetically modified (GM) deoxyribonucleic acid (DNA) is discussed as part of the total risk assessment. The review finishes off with a number of conclusions related to GM food and feed safety. The aim of this paper is to provide a comprehensive overview to assist risk assessors as well as regulators and the general public in understanding the safety issues related to these mechanisms. Copryright 2004 Elsevier Ltd.

[Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

PubMed

Aris, A; Paris, K

2010-12-01

Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Established and novel disease-modifying treatments in multiple sclerosis.

PubMed

Cross, A H; Naismith, R T

2014-04-01

Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e.g. fingolimod or natalizumab if JC virus antibody-negative). The aim of this review is to discuss the clinical benefits, mechanisms of action, safety profiles and monitoring strategies of current MS disease-modifying therapies in clinical practice and of those expected to enter the market in the near future. © 2014 The Association for the Publication of the Journal of Internal Medicine.

Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.

PubMed

Voon, Valerie; Droux, Fabien; Chabardes, Stephan; Bougerol, Thierry; Kohl, Sina; David, Olivier; Krack, Paul; Polosan, Mircea

2018-07-01

Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. STN DBS decreased risk taking to rewards (p = 0.02) and greater risk taking to rewards was positively correlated with OCD severity (p = 0.01) and disease duration (p = 0.01). STN DBS was also associated with impaired subjective discrimination of loss magnitude (p < 0.05), an effect mediated by acute DBS rather than chronic DBS. We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioral symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders. Copyright © 2018. Published by Elsevier Ltd.

Potential use of an arthropod database to support the non-target risk assessment and monitoring of transgenic plants.

PubMed

Romeis, Jörg; Meissle, Michael; Alvarez-Alfageme, Fernando; Bigler, Franz; Bohan, David A; Devos, Yann; Malone, Louise A; Pons, Xavier; Rauschen, Stefan

2014-12-01

Worldwide, plants obtained through genetic modification are subject to a risk analysis and regulatory approval before they can enter the market. An area of concern addressed in environmental risk assessments is the potential of genetically modified (GM) plants to adversely affect non-target arthropods and the valued ecosystem services they provide. Environmental risk assessments are conducted case-by-case for each GM plant taking into account the plant species, its trait(s), the receiving environments into which the GM plant is to be released and its intended uses, and the combination of these characteristics. To facilitate the non-target risk assessment of GM plants, information on arthropods found in relevant agro-ecosystems in Europe has been compiled in a publicly available database of bio-ecological information during a project commissioned by the European Food Safety Authority (EFSA). Using different hypothetical GM maize case studies, we demonstrate how the information contained in the database can assist in identifying valued species that may be at risk and in selecting suitable species for laboratory testing, higher-tier studies, as well as post-market environmental monitoring.

Selection bias in rheumatic disease research.

PubMed

Choi, Hyon K; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing

2014-07-01

The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias--a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic--in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the 'risk factor paradox'--a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research.

Selection bias in rheumatic disease research

PubMed Central

Choi, Hyon K.; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing

2014-01-01

The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias—a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic—in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the ‘risk factor paradox’—a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research. PMID:24686510

Modifiable risk factors of hypertension: A hospital-based case-control study from Kerala, India.

PubMed

Pilakkadavath, Zarin; Shaffi, Muhammed

2016-01-01

Hypertension is a major cause of cardiovascular morbidity and mortality in Kerala. Excess dietary salt, low dietary potassium, overweight and obesity, physical inactivity, excess alcohol, smoking, socioeconomic status, psychosocial stressors, and diabetes are considered as modifiable risk factors for hypertension. To estimate and compare the distribution of modifiable risk factors among hypertensive (cases) and nonhypertensive (controls) patients and to estimate the effect relationship of risk factors. Age- and sex-matched case-control study was conducted in a tertiary care hospital in Kerala using a pretested interviewer-administered structured questionnaire based on the WHO STEPS instrument for chronic disease risk factor surveillance. Bivariate and multiple logistic regression analyses were done. A total of 296 subjects were included in the study. The mean age of study sample was 50.13 years. All modifiable risk factors studied vis-ΰ-vis obesity, lack of physical activity, inadequate fruits and vegetable intake, diabetes, smoking, and alcohol use were significantly different in proportion among cases and controls. Obesity, lack of physical activity, smoking, and diabetes were found to be significant risk factors for hypertension after adjusting for other risk factors. Hypertension is strongly driven by a set of modifiable risk factors. Massive public awareness campaign targeting risk factors is essential in controlling hypertension in Kerala, especially focusing on physical exercise and control of diabetes, obesity, and on quitting smoking.

Potential effects of reclassifying CKD as a coronary heart disease risk equivalent in the US population.

PubMed

Foster, Meredith C; Rawlings, Andreea M; Marrett, Elizabeth; Neff, David; Grams, Morgan E; Kasiske, Bertram L; Willis, Kerry; Inker, Lesley A; Coresh, Josef; Selvin, Elizabeth

2014-05-01

Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. Nationally representative cross-sectional study. 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. CKD and LDL cholesterol defined using a single laboratory value. Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Risk profiles of Alzheimer disease.

PubMed

Bilbul, Melanie; Schipper, Hyman M

2011-07-01

Alzheimer disease (AD) is a dementing, neurodegenerative disorder that affects approximately 500,000 Canadians and its prevalence is expected to double over the next 30 years. Although several medications may temporarily augment cognitive abilities in AD, there presently exists no proven method to avoid the inevitable clinical deterioration in this devastating condition. The delineation of risk factors for the development of AD offers hope for the advent of effective prevention or interventions that might retard the onset of symptoms. In this article, we provide a comprehensive review of midlife risk factors implicated in the etiopathogenesis of sporadic AD. Although some risk factors are heritable and largely beyond our control, others are determined by lifestyle or environment and are potentially modifiable. In a companion paper, we introduce the concept of an Alzheimer Risk Assessment Clinic for ascertainment and mitigation of these and other putative dementia risk factors in middle-aged adults.

Development of economic consequence methodology for process risk analysis.

PubMed

Zadakbar, Omid; Khan, Faisal; Imtiaz, Syed

2015-04-01

A comprehensive methodology for economic consequence analysis with appropriate models for risk analysis of process systems is proposed. This methodology uses loss functions to relate process deviations in a given scenario to economic losses. It consists of four steps: definition of a scenario, identification of losses, quantification of losses, and integration of losses. In this methodology, the process deviations that contribute to a given accident scenario are identified and mapped to assess potential consequences. Losses are assessed with an appropriate loss function (revised Taguchi, modified inverted normal) for each type of loss. The total loss is quantified by integrating different loss functions. The proposed methodology has been examined on two industrial case studies. Implementation of this new economic consequence methodology in quantitative risk assessment will provide better understanding and quantification of risk. This will improve design, decision making, and risk management strategies. © 2014 Society for Risk Analysis.

Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers.

PubMed

Milne, Roger L; Antoniou, Antonis C

2016-10-01

Pathogenic mutations in BRCA1 and BRCA2 are associated with high risks of breast and ovarian cancer. However, penetrance estimates for mutation carriers have been found to vary substantially between studies, and the observed differences in risk are consistent with the hypothesis that genetic and environmental factors modify cancer risks for women with these mutations. Direct evidence that this is the case has emerged in the past decade, through large-scale international collaborative efforts. Here, we describe the methodological challenges in the identification and characterisation of these risk-modifying factors, review the latest evidence on genetic and lifestyle/hormonal risk factors that modify breast and ovarian cancer risks for women with BRCA1 and BRCA2 mutations and outline the implications of these findings for cancer risk prediction. We also review the unresolved issues in this area of research and identify strategies of clinical implementation so that women with BRCA1 and BRCA2 mutations are no longer counselled on the basis of 'average' risk estimates. © 2016 Society for Endocrinology.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Communication of uncertainty regarding individualized cancer risk estimates: effects and influential factors.

PubMed

Han, Paul K J; Klein, William M P; Lehman, Tom; Killam, Bill; Massett, Holly; Freedman, Andrew N

2011-01-01

To examine the effects of communicating uncertainty regarding individualized colorectal cancer risk estimates and to identify factors that influence these effects. Two Web-based experiments were conducted, in which adults aged 40 years and older were provided with hypothetical individualized colorectal cancer risk estimates differing in the extent and representation of expressed uncertainty. The uncertainty consisted of imprecision (otherwise known as "ambiguity") of the risk estimates and was communicated using different representations of confidence intervals. Experiment 1 (n = 240) tested the effects of ambiguity (confidence interval v. point estimate) and representational format (textual v. visual) on cancer risk perceptions and worry. Potential effect modifiers, including personality type (optimism), numeracy, and the information's perceived credibility, were examined, along with the influence of communicating uncertainty on responses to comparative risk information. Experiment 2 (n = 135) tested enhanced representations of ambiguity that incorporated supplemental textual and visual depictions. Communicating uncertainty led to heightened cancer-related worry in participants, exemplifying the phenomenon of "ambiguity aversion." This effect was moderated by representational format and dispositional optimism; textual (v. visual) format and low (v. high) optimism were associated with greater ambiguity aversion. However, when enhanced representations were used to communicate uncertainty, textual and visual formats showed similar effects. Both the communication of uncertainty and use of the visual format diminished the influence of comparative risk information on risk perceptions. The communication of uncertainty regarding cancer risk estimates has complex effects, which include heightening cancer-related worry-consistent with ambiguity aversion-and diminishing the influence of comparative risk information on risk perceptions. These responses are influenced by representational format and personality type, and the influence of format appears to be modifiable and content dependent.

Sports participation in long QT syndrome.

PubMed

Aziz, Peter F; Saarel, Elizabeth V

2017-01-01

Untreated congenital long QT syndrome may result in potentially lethal ventricular tachycardia. In the most common type, risk of such an event has been linked to exercise. This originally resulted in very restrictive guidelines for sports participation in affected individuals. Although the complex interactions of a specific genotype, modifying cofactors, and risk are only now being explored, scientific evidence based on clinical experience now suggests that in many instances such restrictive guidelines are unwarranted. In particular, patients with this condition who are compliant with β-blocker therapy and who have never had symptoms during exertion are now enjoying the benefits of athletic activity.

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

PubMed Central

Østergaard, Søren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.

2015-01-01

Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). Methods and Findings We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, N SNPs = 49), fasting glucose (N SNPs = 36), insulin resistance (N SNPs = 10), body mass index (BMI, N SNPs = 32), total cholesterol (N SNPs = 73), HDL-cholesterol (N SNPs = 71), LDL-cholesterol (N SNPs = 57), triglycerides (N SNPs = 39), systolic blood pressure (SBP, N SNPs = 24), smoking initiation (N SNPs = 1), smoking quantity (N SNPs = 3), university completion (N SNPs = 2), and years of education (N SNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP–AD associations from the International Genomics of Alzheimer’s Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62–0.91]; p = 3.4 × 10−3). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10−8). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51–0.89]; p = 6.5 × 10−3), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Conclusions Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure—or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications—may reduce AD risk. PMID:26079503

Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: the modifying role of other workplace lung carcinogens.

PubMed

Cocco, P; Rice, C H; Chen, J Q; McCawley, M A; McLaughlin, J K; Dosemeci, M

2001-12-01

Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer. We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred. Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica. Copyright 2001 Wiley-Liss, Inc

Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism, modifies postmenopausal breast cancer risk associated with menopausal hormone therapy.

PubMed

Hein, R; Abbas, S; Seibold, P; Salazar, R; Flesch-Janys, D; Chang-Claude, J

2012-01-01

Menopausal hormone therapy (MHT) is associated with an increased breast cancer risk in postmenopausal women, with combined estrogen-progestagen therapy posing a greater risk than estrogen monotherapy. However, few studies focused on potential effect modification of MHT-associated breast cancer risk by genetic polymorphisms in the progesterone metabolism. We assessed effect modification of MHT use by five coding single nucleotide polymorphisms (SNPs) in the progesterone metabolizing enzymes AKR1C3 (rs7741), AKR1C4 (rs3829125, rs17134592), and SRD5A1 (rs248793, rs3736316) using a two-center population-based case-control study from Germany with 2,502 postmenopausal breast cancer patients and 4,833 matched controls. An empirical-Bayes procedure that tests for interaction using a weighted combination of the prospective and the retrospective case-control estimators as well as standard prospective logistic regression were applied to assess multiplicative statistical interaction between polymorphisms and duration of MHT use with regard to breast cancer risk assuming a log-additive mode of inheritance. No genetic marginal effects were observed. Breast cancer risk associated with duration of combined therapy was significantly modified by SRD5A1_rs3736316, showing a reduced risk elevation in carriers of the minor allele (p (interaction,empirical-Bayes) = 0.006 using the empirical-Bayes method, p (interaction,logistic regression) = 0.013 using logistic regression). The risk associated with duration of use of monotherapy was increased by AKR1C3_rs7741 in minor allele carriers (p (interaction,empirical-Bayes) = 0.083, p (interaction,logistic regression) = 0.029) and decreased in minor allele carriers of two SNPs in AKR1C4 (rs3829125: p (interaction,empirical-Bayes) = 0.07, p (interaction,logistic regression) = 0.021; rs17134592: p (interaction,empirical-Bayes) = 0.101, p (interaction,logistic regression) = 0.038). After Bonferroni correction for multiple testing only SRD5A1_rs3736316 assessed using the empirical-Bayes method remained significant. Postmenopausal breast cancer risk associated with combined therapy may be modified by genetic variation in SRD5A1. Further well-powered studies are, however, required to replicate our finding.

State infant mortality: an ecologic study to determine modifiable risks and adjusted infant mortality rates.

PubMed

Paul, David A; Mackley, Amy; Locke, Robert G; Stefano, John L; Kroelinger, Charlan

2009-05-01

To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization procedures. Final risk adjusted IMR's were standardized and states were compared with the United States adjusted rates. Models for IMR in individual states in 2001 (r2 = 0.66, P < 0.01) and 2002 (r2 = 0.81, P < 0.01) were tested. African-American race, teen birth rate, and smoking during pregnancy remained independently associated with state infant mortality rates for 2001 and 2002. Ninety five percent confidence intervals (CI) were calculated around the regression lines to model the expected IMR. After adjustment, some states maintained a consistent IMR; for instance, Vermont and New Hampshire remained low, while Delaware and Louisiana remained high. However, other states such as Mississippi, which have traditionally high infant mortality rates, remained within the expected 95% CI for IMR after adjustment indicating confounding affected the initial unadjusted rates. Non-modifiable demographic variables, including the percentage of non-Hispanic African-American and Hispanic populations of the state are major factors contributing to individual variation in state IMR. Race and ethnicity may confound or modify the IMR in states that shifted inside or outside the 95% CI following adjustment. Other factors including smoking during pregnancy and teen birth rate, which are potentially modifiable, significantly contributed to differences in state IMR. State risk adjusted IMR indicate that other factors impact infant mortality after adjustment by race/ethnicity and other risk factors.

Finasteride Inhibits the Disease-Modifying Activity of Progesterone in the Hippocampus Kindling Model of Epileptogenesis

PubMed Central

Reddy, Doodipala Samba; Ramanathan, G.

2012-01-01

Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively epileptic due to precipitating risk factors. P has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. P markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully-kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy. PMID:22835430

Obesity and Sex Interact in the Regulation of Alzheimer’s Disease

PubMed Central

Moser, V. Alexandra; Pike, Christian J.

2015-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Interestingly, both obesity and AD exhibit sex differences and are regulated by sex steroid hormones. Accumulating evidence suggests interactions between obesity and sex in regulation of AD risk, although the pathways underlying this relationship are unclear. Inflammation and the E4 allele of apolipoprotein E have been identified as independent risk factors for AD and both interact with obesity and sex steroid hormones. We review the individual and cooperative effects of obesity and sex on development of AD and examine the potential contributions of apolipoprotein E, inflammation, and their interactions to this relationship. PMID:26708713

Increased risk of asthma in overweight children born large for gestational age.

PubMed

Pinto, L A; Guerra, S; Anto, J M; Postma, D; Koppelman, G H; de Jongste, J C; Gehring, U; Smit, H A; Wijga, A H

2017-08-01

Being born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non-LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma. © 2017 John Wiley & Sons Ltd.

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

PubMed Central

Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, François; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Investigators, kConFab; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Ewart Toland, Amanda; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmaña, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; Teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie H.; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Gómez Garcia, Encarna B.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnès; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Léoné, Mélanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perłowska, Elżbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Shimon Paluch, Shani; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jønson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teulé, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomäki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Antoniou, Antonis C.

2013-01-01

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10−8, HR = 1.14, 95% CI: 1.09–1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10−8, HR = 1.27, 95% CI: 1.17–1.38) and 4q32.3 (rs4691139, P = 3.4×10−8, HR = 1.20, 95% CI: 1.17–1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10−4). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. PMID:23544013

Breast cancer epidemic in the early twenty-first century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures.

PubMed

Golubnitschaja, Olga; Debald, Manuel; Yeghiazaryan, Kristina; Kuhn, Walther; Pešta, Martin; Costigliola, Vincenzo; Grech, Godfrey

2016-10-01

Rapidly increasing incidence of breast cancer is a new social challenge resulting from a spectrum of internal and external risk factors which appear to be well accepted as an attribute of the early twenty-first century, being, however, new for female sub-populations compared to the past. These include altered socio-economical conditions such as occupational exposure, rotating shift work, specific environmental factors (increased pollution and environmental toxicity, altered dietary habits, quality and composition of meal) as well as consequently shifted and/or adapted physiologic factors such as lower age at menarche, late age of first full-term pregnancy, if any, shorter periods of breastfeeding and later menopause. Consolidated expert statements suggest that over 50 % of all breast cancer cases may be potentially prevented by risk reduction strategy such as regulation of modifiable risk factors. Currently available risk assessment models may estimate potential breast cancer predisposition, in general; however, they are not able to predict the disease manifestation individually. Further, current deficits in risk assessment and effective breast cancer prevention have been recently investigated and summarised as follows: gaps in risk estimation, preventive therapy, lifestyle prevention, understanding of the biology of breast cancer risk and implementation of known preventive measures. This paper overviews the most relevant risk factors, provides recommendations for improved risk assessment and proposes an extended questionnaire for effective preventive measures.

Applications of Capstone Depleted Uranium Aerosol Risk Data to Military Combat Risk Management

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

Daxon, Eric G.; Parkhurst, MaryAnn; Melanson, Mark A.

2009-03-01

Risks to personnel engaged in military operations include not only the threat of enemy firepower but also risks from exposure to other hazards such as radiation. Combatant commanders of the U. S. Army carefully weigh risks of casualties before implementing battlefield actions using an established paradigm that take these risks into consideration. As a result of the inclusion of depleted uranium (DU) anti-armor ammunition in the conventional (non-nuclear) weapons arsenal, the potential for exposure to DU aerosols and its associated chemical and radiological effects becomes an element of the commanders’ risk assessment. The Capstone DU Aerosol Study measured the rangemore » of likely DU oxide aerosol concentrations created inside a combat vehicle perforated with a DU munition, and the Capstone Human Health Risk Assessment (HHRA) estimated the associated doses and calculated risks. This paper focuses on the development of a scientific approach to adapt the risks from DU’s non uniform dose distribution within the body using the current U.S. Department of Defense (DoD) radiation risk management approach. The approach developed equates the Radiation Exposure Status (RES) categories to the estimated radiological risks of DU and makes use of the Capstone-developed Renal Effects Group (REG) as a measure of chemical risk from DU intake. Recommendations are provided for modifying Army guidance and policy in order to better encompass the potential risks from DU aerosol inhalation during military operations.« less

Association between floods and infectious diarrhea and their effect modifiers in Hunan province, China: A two-stage model.

PubMed

Liu, Zhidong; Zhang, Feifei; Zhang, Ying; Li, Jing; Liu, Xuena; Ding, Guoyong; Zhang, Caixia; Liu, Qiyong; Jiang, Baofa

2018-06-01

Understanding the potential links between floods and infectious diarrhea is important under the context of climate change. However, little is known about the risk of infectious diarrhea after floods and what factors could modify these effects in China. This study aims to quantitatively examine the relationship between floods and infectious diarrhea and their effect modifiers. Weekly number of infectious diarrhea cases from 2004 to 2011 during flood season in Hunan province were supplied by the National Notifiable Disease Surveillance System. Flood and meteorological data over the same period were obtained. A two-stage model was used to estimate a provincial average association and their effect modifiers between floods and infectious diarrhea, accounting for other confounders. A total of 134,571 cases of infectious diarrhea were notified from 2004 to 2011. After controlling for seasonality, long-term trends, and meteorological factors, floods were significantly associated with infectious diarrhea in the provincial level with a cumulative RR of 1.22 (95% CI: 1.05, 1.43) with a lagged effect of 0-1 week. Geographic locations and economic levels were identified as effect modifiers, with a higher impact of floods on infectious diarrhea in the western and regions with a low economic level of Hunan. Our study provides strong evidence of a positive association between floods and infectious diarrhea in the study area. Local control strategies for public health should be taken in time to prevent and reduce the risk of infectious diarrhea after floods, especially for the vulnerable regions identified. Copyright © 2018 Elsevier B.V. All rights reserved.

External validation of the modified Glasgow prognostic score for renal cancer

PubMed Central

Tai, Caroline G.; Johnson, Timothy V.; Abbasi, Ammara; Herrell, Lindsey; Harris, Wayne B.; Kucuk, Omer; Canter, Daniel J.; Ogan, Kenneth; Pattaras, John G.; Nieh, Peter T.; Master, Viraj A.

2014-01-01

Purpose: The modified Glasgow prognostic Score (mGPS) incorporates C-reactive protein and albumin as a clinically useful marker of tumor behavior. The ability of the mGPS to predict metastasis in localized renal cell carcinoma (RCC) remains unknown in an external validation cohort. Patients and Methods: Patients with clinically localized clear cell RCC were followed for 1 year post-operatively. Metastases were identified radiologically. Patients were categorized by mGPS score as low-risk (mGPS = 0 points), intermediate-risk (mGPS = 1 point) and high-risk (mGPS = 2 points). Univariate, Kaplan-Meier and multivariate Cox regression analyses examined Recurrence -free survival (RFS) across patient and disease characteristics. Results: Of the 129 patients in this study, 23.3% developed metastases. Of low, intermediate and high risk patients, 10.1%, 38.9% and 89.9% recurred during the study. After accounting for various patient and tumor characteristics in multivariate analysis including stage and grade, only mGPS was significantly associated with RFS. Compared with low-risk patients, intermediate- and high-risk patients experienced a 4-fold (hazard ratios [HR]: 4.035, 95% confidence interval [CI]: 1.312-12.415, P = 0.015) and 7-fold (HR: 7.012, 95% CI: 2.126-23.123 P < 0.001) risk of metastasis, respectively. Conclusions: mGPS is a robust predictor of metastasis following potentially curative nephrectomy for localized RCC. Clinicians may consider mGPS as an adjunct to identify high-risk patients for possible enrollment into clinical trials or for patient counseling PMID:24497679

Regulated Apoptosis of Genetically-Modified Hematopoietic Stem and Progenitor Cells via an Inducible Caspase-9 Suicide Gene in Rhesus Macaques

PubMed Central

Barese, Cecilia N.; Felizardo, Tania C.; Sellers, Stephanie E.; Keyvanfar, Keyvan; Di Stasi, Antonio; Metzger, Mark E.; Krouse, Allen E.; Donahue, Robert E.; Spencer, David M.; Dunbar, Cynthia E.

2014-01-01

The high risk of insertional oncogenesis reported in clinical trials utilizing integrating retroviral vectors to genetically-modify hematopoietic stem and progenitor cells (HSPC) requires the development of safety strategies to minimize risks associated with novel cell and gene therapies. The ability to ablate genetically modified cells in vivo is desirable, should an abnormal clone emerge. Inclusion of “suicide genes” in vectors to facilitate targeted ablation of vector-containing abnormal clones in vivo is one potential safety approach. We tested whether the inclusion of the “inducible Caspase-9” (iCasp9) suicide gene in a gamma-retroviral vector facilitated efficient elimination of vector-containing HSPCs and their hematopoietic progeny in vivo long-term, in an autologous non-human primate transplantation model. Following stable engraftment of iCasp9 expressing hematopoietic cells in rhesus macaques, administration of AP1903, a chemical inducer of dimerization able to activate iCasp9, specifically eliminated vector-containing cells in all hematopoietic lineages long-term, suggesting activity at the HSPC level. Between 75–94% of vector-containing cells were eliminated by well-tolerated AP1903 dosing, but lack of complete ablation was linked to lower iCasp9 expression in residual cells. Further investigation of resistance mechanisms demonstrated upregulation of Bcl-2 in hematopoietic cell lines transduced with the vector and resistant to AP1903 ablation. These results demonstrate both the potential and the limitations of safety approaches utilizing iCasp9 to HSPC-targeted gene therapy settings, in a model with great relevance to clinical development. PMID:25330775

Influence of deprivation on health care use, health care costs, and mortality in COPD.

PubMed

Collins, Peter F; Stratton, Rebecca J; Kurukulaaratchy, Ramesh J; Elia, Marinos

Deprivation is associated with the incidence of COPD, but its independent impact on clinical outcomes is still relatively unknown. This study aimed to explore the influence of deprivation on health care use, costs, and survival. A total of 424 outpatients with COPD were assessed for deprivation across two hospitals. The English Index of Multiple Deprivation (IMD) was used to establish a deprivation score for each patient. The relationship between deprivation and 1-year health care use, costs, and mortality was examined, controlling for potential confounding variables (age, malnutrition risk, COPD severity, and smoking status). IMD was significantly and independently associated with emergency hospitalization (β-coefficient 0.022, SE 0.007; p =0.001), length of hospital stay, secondary health care costs (β-coefficient £101, SE £30; p =0.001), and mortality (HR 1.042, 95% CI 1.015-1.070; p =0.002). IMD was inversely related to participation in exercise rehabilitation (OR 0.961, 95% CI 0.930-0.994; p =0.002) and secondary care appointments. Deprivation was also significantly related to modifiable risk factors (smoking status and malnutrition risk). Deprivation in patients with COPD is associated with increased emergency health care use, health care costs, and mortality. Tackling deprivation is complex; however, strategies targeting high-risk groups and modifiable risk factors, such as malnutrition and smoking, could reduce the clinical and economic burden.

Importance of investigating epigenetic alterations for industry and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute.

PubMed

Miousse, Isabelle R; Currie, Richard; Datta, Kaushik; Ellinger-Ziegelbauer, Heidrun; French, John E; Harrill, Alison H; Koturbash, Igor; Lawton, Michael; Mann, Derek; Meehan, Richard R; Moggs, Jonathan G; O'Lone, Raegan; Rasoulpour, Reza J; Pera, Renee A Reijo; Thompson, Karol

2015-09-01

Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled "Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals" in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dementia Prevention: optimizing the use of observational data for personal, clinical, and public health decision-making.

PubMed

Dacks, Penny A; Andrieu, Sandrine; Blacker, Deborah; Carman, Aaron J; Green, Allan M; Grodstein, Francine; Henderson, Victor W; James, Bryan D; Lane, Rachel F; Lau, Joseph; Lin, Pei-Jung; Reeves, Barnaby C; Shah, Raj C; Vellas, Bruno; Yaffe, Kristine; Yurko-Mauro, Karin; Shineman, Diana W; Bennett, David A; Fillit, Howard M

2014-02-01

Worldwide, over 35 million people suffer from Alzheimer's disease and related dementias. This number is expected to triple over the next 40 years. How can we improve the evidence supporting strategies to reduce the rate of dementia in future generations? The risk of dementia is likely influenced by modifiable factors such as exercise, cognitive activity, and the clinical management of diabetes and hypertension. However, the quality of evidence is limited and it remains unclear whether specific interventions to reduce these modifiable risk factors can, in turn, reduce the risk of dementia. Although randomized controlled trials are the gold-standard for causality, the majority of evidence for long-term dementia prevention derives from, and will likely continue to derive from, observational studies. Although observational research has some unavoidable limitations, its utility for dementia prevention might be improved by, for example, better distinction between confirmatory and exploratory research, higher reporting standards, investment in effectiveness research enabled by increased data-pooling, and standardized exposure and outcome measures. Informed decision-making by the general public on low-risk health choices that could have broad potential benefits could be enabled by internet-based tools and decision-aids to communicate the evidence, its quality, and the estimated magnitude of effect.

Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

PubMed

Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

2016-10-01

As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.

PubMed

Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J

2010-10-01

To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.

A Site Characterization Protocol for Evaluating the Potential for Triggered or Induced Seismicity Resulting from Wastewater Injection and Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Walters, R. J.; Zoback, M. D.; Gupta, A.; Baker, J.; Beroza, G. C.

2014-12-01

Regulatory and governmental agencies, individual companies and industry groups and others have recently proposed, or are developing, guidelines aimed at reducing the risk associated with earthquakes triggered by waste water injection or hydraulic fracturing. While there are a number of elements common to the guidelines proposed, not surprisingly, there are also some significant differences among them and, in a number of cases, important considerations that are not addressed. The goal of this work is to develop a comprehensive protocol for site characterization based on a rigorous scientific understanding of the responsible processes. Topics addressed will include the geologic setting (emphasizing faults that might be affected), historical seismicity, hydraulic characterization of injection and adjacent intervals, geomechanical characterization to identify potentially active faults, plans for seismic monitoring and reporting, plans for monitoring and reporting injection (pressure, volumes, and rates), other factors contributing to risk (potentially affected population centers, structures, and facilities), and implementing a modified Probabilistic Seismic Hazard Analysis (PSHA). The guidelines will be risk based and adaptable, rather than prescriptive, for a proposed activity and region of interest. They will be goal oriented and will rely, to the degree possible, on established best practice procedures, referring to existing procedures and recommendations. By developing a risk-based site characterization protocol, we hope to contribute to the development of rational and effective measures for reducing the risk posed by activities that potentially trigger earthquakes.

Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

PubMed

Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B; Pastinen, Tomi; Droit, Arnaud; Lemaçon, Audrey; Adlard, Julian; Aittomäki, Kristiina; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Azzollini, Jacopo; Bane, Anita; Barjhoux, Laure; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Blok, Marinus J; Bobolis, Kristie; Bonadona, Valérie; Bonanni, Bernardo; Bradbury, Angela R; Brewer, Carole; Buecher, Bruno; Buys, Saundra S; Caligo, Maria A; Chiquette, Jocelyne; Chung, Wendy K; Claes, Kathleen B M; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; De la Hoya, Miguel; De Leeneer, Kim; Diez, Orland; Ding, Yuan Chun; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Eccles, Diana; Eeles, Ros; Einbeigi, Zakaria; Ejlertsen, Bent; Engel, Christoph; Gareth Evans, D; Feliubadalo, Lidia; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fountzilas, George; Friedman, Eitan; Frost, Debra; Ganschow, Pamela; Ganz, Patricia A; Garber, Judy; Gayther, Simon A; Gerdes, Anne-Marie; Glendon, Gord; Godwin, Andrew K; Goldgar, David E; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hays, John L; Hogervorst, Frans B L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Joseph, Vijai; Just, Walter; Kaczmarek, Katarzyna; Karlan, Beth Y; Kets, Carolien M; Kirk, Judy; Kriege, Mieke; Laitman, Yael; Laurent, Maïté; Lazaro, Conxi; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loman, Niklas; Loud, Jennifer T; Manoukian, Siranoush; Mariani, Milena; Mazoyer, Sylvie; McGuffog, Lesley; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Oosterwijk, Jan C; Osorio, Ana; Papi, Laura; Park, Sue Kyung; Pedersen, Inge Sokilde; Peissel, Bernard; Segura, Pedro Perez; Peterlongo, Paolo; Phelan, Catherine M; Radice, Paolo; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Rodriguez, Gustavo C; Rookus, Matti A; Schmutzler, Rita Katharina; Sevenet, Nicolas; Shah, Payal D; Singer, Christian F; Slavin, Thomas P; Snape, Katie; Sokolowska, Johanna; Sønderstrup, Ida Marie Heeholm; Southey, Melissa; Spurdle, Amanda B; Stadler, Zsofia; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Tan, Yen; Tea, Muy-Kheng; Teixeira, Manuel R; Teulé, Alex; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda Ewart; Tung, Nadine; van den Ouweland, Ans M W; van der Luijt, Rob B; van Engelen, Klaartje; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wijnen, Juul T; Rebbeck, Timothy; Chenevix-Trench, Georgia; Offit, Kenneth; Couch, Fergus J; Nord, Silje; Easton, Douglas F; Antoniou, Antonis C; Simard, Jacques

2017-01-01

Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10 -6 ). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

A climate risk assessment of clean water supply in an urban area: A case study of South Tangerang city, Indonesia

NASA Astrophysics Data System (ADS)

Nastiti, S. I. W.; Kusnoputranto, H.; Boer, R.; Utomo, S. W.

2018-03-01

The demand for clean water in South Tangerang, Indonesia, is very high. At present, this demand is mostly met by groundwater that is much influenced by climate variability, land cover change, and human activities. The local company on water services (PDAM) provides clean water services for only about 9% of the population. The climate risk assessment conducted by South Tangerang Government in 2016 indicates that several areas are potentially exposed to a high risk of climate change. Survey and in-depth interview with communities and sectoral officers suggest that a risk to clean water supply in this city is increasing. This study aims to assess climate potential risks on clean water supply based on the 2016 study. We adopted the method of that study by modifying some of the vulnerability indicators that can represent clean water access and supply. The results of the study demonstrate that many wards in South Tangerang would be exposed to high climate risks of clean water supply. By 2021, about 54% of wards would be exposed from high to the very very high risk of clean water supply. These results signify the tangible need of adaptation actions, to prevent the worsening impacts of climate on clean water supply.

Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction

PubMed Central

Yang, Qin; He, Yong-Ming; Cai, Dong-Ping; Yang, Xiang-Jun; Xu, Hai-Feng

2016-01-01

Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven’t been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle. PMID:27748452

Experiences in sub-Saharan Africa with GM crop risk communication: outcome of a workshop.

PubMed

Racovita, Monica; Obonyo, Dennis Ndolo; Abdallah, Roshan; Anguzu, Robert; Bamwenda, Gratian; Kiggundu, Andrew; Maganga, Harrison; Muchiri, Nancy; Nzeduru, Chinyere; Otadoh, Jane; Rumjaun, Anwar; Suleiman, Iro; Sunil, Manjusha; Tepfer, Mark; Timpo, Samuel; van der Walt, Wynand; Kaboré-Zoungrana, Chantal; Nfor, Lilian; Craig, Wendy

2013-01-01

In tackling agricultural challenges, policy-makers in sub-Saharan Africa (SSA) have increasingly considered genetically modified (GM) crops as a potential tool to increase productivity and to improve product quality. Yet, as elsewhere in the world, the adoption of GM crops in SSA has been marked by controversy, encompassing not only the potential risks to animal and human health, and to the environment, but also other concerns such as ethical issues, public participation in decision-making, socio-economic factors and intellectual property rights. With these non-scientific factors complicating an already controversial situation, disseminating credible information to the public as well as facilitating stakeholder input into decision-making is essential. In SSA, there are various and innovative risk communication approaches and strategies being developed, yet a comprehensive analysis of such data is missing. This gap is addressed by giving an overview of current strategies, identifying similarities and differences between various country and institutional approaches and promoting a way forward, building on a recent workshop with risk communicators working in SSA.

Mouth cancer in inflammatory bowel diseases.

PubMed

Giagkou, E; Christodoulou, D K; Katsanos, K H

2016-05-01

Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using a modified dredging elutriate testing approach to evaluate potential aquatic impacts associated with dredging a large freshwater industrial harbor.

PubMed

Watson-Leung, Trudy; Graham, Matt; Hartman, Erin; Welsh, Paul G

2017-01-01

Potential adverse impacts to the aquatic environment should be minimized whenever possible during an environmental dredging project by selecting realistic and technically feasible environmental targets. These targets need to balance short term impacts with the longer term benefit of removing contaminated sediments from the environment. Environmental dredging is part of the planned remediation of Randle Reef (a 60 hectare zone of mostly PAH-contaminated sediments) in Hamilton, Ontario, Canada. In this study, we describe the results of dredging elutriate toxicity testing (DETE) to assess the potential risks from dredging this PAH contaminated site. A modified elutriate preparation method intended as an alternative measure of conditions within the dredging plume was assessed with both standard water column species (Daphnia magna and fathead minnow [Pimephales promelas]) and alternative benthic and epibenthic test organisms (Chironomus dilutus and Hyalella azteca). The standard DETE test was also conducted with H. azteca to compare with the modified DETE results. The greatest toxic response was seen in the alternative test species; however, the modified DETE method resulted in less toxicity than the standard protocol. The relationship between toxicity results and chemical and/or physical characteristics of the samples was examined, but differences in toxicity could only be explained by differences in the total suspended solids concentrations in the elutriate samples. Challenges associated with DETE assessment of PAH-contaminated sediments and the implications for establishing dredging benchmarks are discussed. Integr Environ Assess Manag 2017;13:155-166. © 2016 SETAC. © 2016 SETAC.

Temporal association between hospitalization and rate of falls after discharge.

PubMed

Mahoney, J E; Palta, M; Johnson, J; Jalaluddin, M; Gray, S; Park, S; Sager, M

2000-10-09

Evidence suggests that acute illness and hospitalization may increase the risk for falls. To evaluate the rate of falls, and associated risk factors, for 90 days following hospital discharge. We consecutively enrolled 311 patients, aged 65 years and older, discharged from the hospital after an acute medical illness and receiving home-nursing services. Patients were assessed within 5 days of discharge for prehospital and current functioning by self-report, and balance, vision, cognition, and delirium by objective measures. Patients were followed up weekly for 13 weeks for falls, injuries, and health care use. The rate of falls was significantly higher in the first 2 weeks after hospitalization (8.0 per 1000 person-days) compared with 3 months later (1.7 per 1000 person-days) (P =.002). Fall-related injuries accounted for 15% of all hospitalizations in the first month after discharge. Independent prehospital risk factors significantly associated with falls included dependency in activities of daily living, use of a standard walker, 2 or more falls, and more hospitalizations in the year prior. Posthospital risk factors included use of a tertiary amine tricyclic antidepressant, probable delirium, and poorer balance, while use of a cane was protective. The rate of falls is substantially increased in the first month after medical hospitalization, and is an important cause of injury and morbidity. Posthospital risk factors may be potentially modifiable. Efforts to assess and modify risk factors should be integral to the hospital and posthospital care of older adults (those aged >/=65 years).

Medical Reserve Corps Volunteers’ Ability and Willingness to Report to Work for the Department of Health During Catastrophic Disasters

DTIC Science & Technology

2007-03-01

National Security Affairs iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT Local public health systems ...assist in fulfilling their MRC role. As key enablers and modifiers of risk perception, these two manageable characteristics of potential emergency...Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188

Genetically modified plants and human health.

PubMed

Key, Suzie; Ma, Julian K-C; Drake, Pascal Mw

2008-06-01

Genetically modified (or GM) plants have attracted a large amount of media attention in recent years and continue to do so. Despite this, the general public remains largely unaware of what a GM plant actually is or what advantages and disadvantages the technology has to offer, particularly with regard to the range of applications for which they can be used. From the first generation of GM crops, two main areas of concern have emerged, namely risk to the environment and risk to human health. As GM plants are gradually being introduced into the European Union there is likely to be increasing public concern regarding potential health issues. Although it is now commonplace for the press to adopt 'health campaigns', the information they publish is often unreliable and unrepresentative of the available scientific evidence. We consider it important that the medical profession should be aware of the state of the art, and, as they are often the first port of call for a concerned patient, be in a position to provide an informed opinion. This review will examine how GM plants may impact on human health both directly - through applications targeted at nutrition and enhancement of recombinant medicine production - but also indirectly, through potential effects on the environment. Finally, it will examine the most important opposition currently facing the worldwide adoption of this technology: public opinion.

Evaluation of the modified FINDRISC to identify individuals at high risk for diabetes among middle-aged white and black ARIC study participants.

PubMed

Kulkarni, Manjusha; Foraker, Randi E; McNeill, Ann M; Girman, Cynthia; Golden, Sherita H; Rosamond, Wayne D; Duncan, Bruce; Schmidt, Maria Ines; Tuomilehto, Jaakko

2017-09-01

To evaluate a modified Finnish Diabetes Risk Score (FINDRISC) for predicting the risk of incident diabetes among white and black middle-aged participants from the Atherosclerosis Risk in Communities (ARIC) study. We assessed 9754 ARIC cohort participants who were free of diabetes at baseline. Logistic regression and receiver operator characteristic (ROC) curves were used to evaluate a modified FINDRISC for predicting incident diabetes after 9 years of follow-up, overall and by race/gender group. The modified FINDRISC used comprised age, body mass index, waist circumference, blood pressure medication and family history. The mean FINDRISC (range, 2 [lowest risk] to 17 [highest risk]) for black women was higher (9.9 ± 3.6) than that for black men (7.6 ± 3.9), white women (8.0 ± 3.6) and white men (7.6 ± 3.5). The incidence of diabetes increased generally across deciles of FINDRISC for all 4 race/gender groups. ROC curve statistics for the FINDRISC showed the highest area under the curve for white women (0.77) and the lowest for black men (0.70). We used a modified FINDRISC to predict the 9-year risk of incident diabetes in a biracial US population. The modified risk score can be useful for early screening of incident diabetes in biracial populations, which may be helpful for early interventions to delay or prevent diabetes. © 2017 John Wiley & Sons Ltd.

Cocoa extracts reduce oligomerization of amyloid-β: implications for cognitive improvement in Alzheimer's disease.

PubMed

Wang, Jun; Varghese, Merina; Ono, Kenjiro; Yamada, Masahito; Levine, Samara; Tzavaras, Nikos; Gong, Bing; Hurst, William J; Blitzer, Robert D; Pasinetti, Giulio Maria

2014-01-01

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, characterized by pathological aggregates of amyloid peptide-β (Aβ) and tau protein. Currently available therapies mediate AD symptoms without modifying disease progression. Polyphenol-rich diets are reported to reduce the risk for AD. In the present study, we investigated the AD disease-modifying effects of cocoa, a rich source of flavanols, which are a class of polyphenols. We hypothesized that cocoa extracts interfere with amyloid-β oligomerization to prevent synaptic deficits. We tested the effects of three different cocoa extracts, viz. Natural, Dutched, and Lavado extracts, on Aβ42 and Aβ40 oligomerization, using photo-induced cross-linking of unmodified proteins technique. To assess the effects of cocoa extracts on synaptic function, we measured long term potentiation in mouse brain hippocampal slices exposed to oligomeric Aβ. Our results indicate that cocoa extracts are effective in preventing the oligomerization of Aβ, with Lavado extract being most effective. Lavado extract, but not Dutched extract, was effective in restoring the long term potentiation response reduced by oligomeric Aβ. Our findings indicate that cocoa extracts have multiple disease-modifying properties in AD and present a promising route of therapeutic and/or preventative initiatives.

Advantages and applications of CAR-expressing natural killer cells

PubMed Central

Glienke, Wolfgang; Esser, Ruth; Priesner, Christoph; Suerth, Julia D.; Schambach, Axel; Wels, Winfried S.; Grez, Manuel; Kloess, Stephan; Arseniev, Lubomir; Koehl, Ulrike

2015-01-01

In contrast to donor T cells, natural killer (NK) cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD). In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR) expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy. PMID:25729364

A scoping review of anorexia of aging correlates and their relevance to population health interventions.

PubMed

Roy, Mathieu; Gaudreau, Pierrette; Payette, Hélène

2016-10-01

Anorexia of aging (AA, i.e., loss of appetite and/or reduction of food intake with aging) is an important public health issue. It leads to unintentional weight loss, which is an independent risk factor for morbidity and mortality among seniors. AA has mainly been studied from a biological perspective and regarded as a normal physiological consequence of aging, rather than a negative health outcome with underlying determinants. Some potentially modifiable correlates have however been found to be associated with this geriatric condition. Here, we conducted a scoping review of the literature to: 1) identify AA correlates, and 2) discuss their relevance to population health interventions. Our results indicate two main categories of AA correlates, namely, physiopathological and non-physiopathological. The first category relates to physiological dysfunctions, pathologies involving (or culminating in) biomarker dysregulation, and polypharmacy. These correlates are difficult to modify, especially through population health interventions. The second category, which contains fewer correlates, includes potentially modifiable public health targets, such as food-related properties, psychological, sociocultural, and environmental issues. We conclude that there are several AA correlates. Some of them are modifiable and could be targeted for development and implementation as appropriate population health interventions to prevent appetite loss and promote maintenance of adequate food intake in aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conventional consent with opting in versus simplified consent with opting out: an exploratory trial for studies that do not increase patient risk.

PubMed

Rogers, C G; Tyson, J E; Kennedy, K A; Broyles, R S; Hickman, J F

1998-04-01

The objective of this study was to assess a modified consent procedure allowed under federal regulations and developed for studies, particularly clinical trials, that are judged by the Institutional Review Board to reduce or have no effect on patient risk. This was a randomized trial of a conventional consent procedure that required parental signature to give consent (opting in) after a comprehensive disclosure of the rights of participants in research versus a modified consent procedure that required parental signature to refuse consent (opting out) after specific disclosures appropriate when risk is not increased. Consent was sought for a trial of primary follow-up care for disadvantaged infants at high risk, a trial judged by our Institutional Review Board to increase access to care for both groups. A blinded assessor interviewed mothers within 24 hours of the consent decision. Among the 44 mothers interviewed, the modified consent group scored higher than the conventional consent group in recall and understanding of study purpose and methods (47% vs 30%; p < 0.02). Other comparisons provided no evidence that the modified consent procedure was less desirable. Virtually all mothers reported satisfaction. The modified approach may improve communication and facilitate studies judged by the Institutional Review Board to be risk-neutral or risk-reducing. Further evaluation of a modified consent procedure for such studies is warranted.

Osteoporosis Risk Factors in Eighth Grade Students.

ERIC Educational Resources Information Center

Lysen, Victoria C.; Walker, Robert

1997-01-01

Presents findings from food frequency questionnaires and surveys of 138 Midwestern eighth-grade student-parent pairs. The study examined the incidence of modifiable and nonmodifiable osteoporosis risk factors and compared gender differences. Data analysis indicated that many adolescents possessed several modifiable and nonmodifiable risk factors…

Are joint injury, sport activity, physical activity, obesity, or occupational activities predictors for osteoarthritis? A systematic review.

PubMed

Richmond, Sarah A; Fukuchi, Reginaldo K; Ezzat, Allison; Schneider, Kathryn; Schneider, Geoff; Emery, Carolyn A

2013-08-01

Systematic review with meta-analysis. To identify risk factors for osteoarthritis (OA) of the knee, hip, and ankle, including joint injury, sport, physical activity, overweight/obesity, and occupational activity, in all age groups. OA is a significant health problem worldwide, affecting up to 10% of men and 18% of women over 60 years of age. There has not been a comprehensive review examining modifiable physical risk factors associated with the onset of OA. This evidence is important to inform the physiotherapy management of individuals following onset of OA. Twelve electronic databases were systematically reviewed. The studies selected met the following criteria: (1) original data; (2) joint injury, sport activity, physical activity, overweight/obesity, and/or occupational activity investigated as risk factors; (3) outcomes included OA (hip, knee, and/or ankle); and (4) analytic component of study design. The data extracted included study design, years of follow-up, study population, OA definition, risk factors, and results (effect estimates reported or calculated where available). The quality of evidence was assessed based on a modified version of the Downs and Black checklist. Joint injury, obesity, and occupational activity were associated with an increased risk of OA of the knee and hip. Sport and physical activity produced inconsistent findings. Joint injury was identified as a significant risk factor for knee OA (combined odds ratio = 3.8; 95% confidence interval: 2.0, 7.2) and hip OA (combined odds ratio = 5.0; 95% confidence interval: 1.4, 18.2), as was previous meniscectomy with or without anterior cruciate ligament injury for knee OA (combined odds ratio = 7.4; 95% confidence interval: 4.0, 13.7). There is a paucity of research examining risk factors associated with ankle OA; this review identified only 2 studies with this outcome. Joint injury, obesity, and occupational activity are associated with an increased risk of knee and hip OA. Some findings remain inconclusive, including levels of physical activity and sport specificity in individuals who do not suffer an injury. Early identification of individuals at risk for OA provides an opportunity for physiotherapy management or other interventions to modify risk-related behavior. There is a need in the literature for additional high-quality studies, such as prospective cohort studies, that minimize potential bias in examining the relationship between physical risk factors and OA. Prognosis, level 2a-.

Trends in selected chronic conditions and behavioral risk factors among women of reproductive age, behavioral risk factor surveillance system, 2001-2009.

PubMed

Hayes, Donald K; Fan, Amy Z; Smith, Ruben A; Bombard, Jennifer M

2011-11-01

Some potentially modifiable risk factors and chronic conditions cause significant disease and death during pregnancy and promote the development of chronic disease. This study describes recent trends of modifiable risk factors and controllable chronic conditions among reproductive-aged women. Data from the 2001 to 2009 Behavioral Risk Factor Surveillance System, a representative state-based telephone survey of health behavior in US adults, was analyzed for 327,917 women of reproductive age, 18 to 44 years. We calculated prevalence ratios over time to assess trends for 4 selected risk factors and 4 chronic conditions, accounting for age, race/ethnicity, education, health care coverage, and individual states. From 2001 to 2009, estimates of 2 risk factors improved: smoking declined from 25.9% to 18.8%, and physical inactivity declined from 25.0% to 23.0%. One risk factor, heavy drinking, did not change. From 2003 to 2009, the estimates for 1 risk factor and 4 chronic conditions worsened: obesity increased from 18.3% to 24.7%, diabetes increased from 2.1% to 2.9%, high cholesterol increased from 10.3% to 13.6%, asthma increased from 13.5% to 16.2%, and high blood pressure increased from 9.0% to 10.1%. All trends were significant after adjustment, except that for heavy drinking. Among women of reproductive age, prevalence of smoking and physical inactivity improved, but prevalence of obesity and all 4 chronic conditions worsened. Understanding reasons for the improvements in smoking and physical activity may support the development of targeted interventions to reverse the trends and help prevent chronic disease and adverse reproductive outcomes among women in this age group.

A Prospective Study of Different Types of Dietary Fiber and Risk of Cardiovascular Disease: Tehran Lipid and Glucose Study.

PubMed

Mirmiran, Parvin; Bahadoran, Zahra; Khalili Moghadam, Sajad; Zadeh Vakili, Azita; Azizi, Fereidoun

2016-11-07

This study was designed to examine the hypothesis that dietary of intake different types of fiber could modify the risk of cardiovascular disease (CVD) in a large prospective cohort among Iranian adults. In 2006-2008, we used a validated food frequency questionnaire to assess dietary fiber intake among 2295 health professionals with no previous history of heart disease. Subjects were subsequently followed until 2012 for incidence of CVD events. Multivariate Cox proportional hazard regression models, adjusted for potential confounders were used to estimate the risk of CVD across tertiles of total dietary fiber and different types of fiber. Linear regression models were also used to indicate the association of dietary fiber intakes with changes of cardiovascular risk factors during the follow-up. Mean age of participants (42.8% men) was 38.2 ± 13.4, at baseline. Mean (SD) dietary intake of total fiber was 23.4 (8.9) g/day. After adjustment for cardiovascular risk score and dietary confounders, a significant inverse association was observed between intakes of total, soluble and insoluble dietary fiber and CVD risk, in the highest compared to the lowest tertiles (HR = 0.39, 95% CI = 0.18-0.83, HR = 0.19, 95% CI = 0.09-0.41, and HR = 0.31, 95% CI = 0.14-0.69, respectively). Inverse relations were observed between risk of CVD and dietary fiber from legumes, fruits and vegetables; however, dietary fiber intake from grain and nut sources was not related to risk of CVD. Our findings confirmed that higher intakes of dietary fiber from different sources is associated with CVD events and modify its major risk-related factors.

A Prospective Study of Different Types of Dietary Fiber and Risk of Cardiovascular Disease: Tehran Lipid and Glucose Study

PubMed Central

Mirmiran, Parvin; Bahadoran, Zahra; Khalili Moghadam, Sajad; Zadeh Vakili, Azita; Azizi, Fereidoun

2016-01-01

Background and aim: This study was designed to examine the hypothesis that dietary of intake different types of fiber could modify the risk of cardiovascular disease (CVD) in a large prospective cohort among Iranian adults. Methods: In 2006–2008, we used a validated food frequency questionnaire to assess dietary fiber intake among 2295 health professionals with no previous history of heart disease. Subjects were subsequently followed until 2012 for incidence of CVD events. Multivariate Cox proportional hazard regression models, adjusted for potential confounders were used to estimate the risk of CVD across tertiles of total dietary fiber and different types of fiber. Linear regression models were also used to indicate the association of dietary fiber intakes with changes of cardiovascular risk factors during the follow-up. Results: Mean age of participants (42.8% men) was 38.2 ± 13.4, at baseline. Mean (SD) dietary intake of total fiber was 23.4 (8.9) g/day. After adjustment for cardiovascular risk score and dietary confounders, a significant inverse association was observed between intakes of total, soluble and insoluble dietary fiber and CVD risk, in the highest compared to the lowest tertiles (HR = 0.39, 95% CI = 0.18–0.83, HR = 0.19, 95% CI = 0.09–0.41, and HR = 0.31, 95% CI = 0.14–0.69, respectively). Inverse relations were observed between risk of CVD and dietary fiber from legumes, fruits and vegetables; however, dietary fiber intake from grain and nut sources was not related to risk of CVD. Conclusion: Our findings confirmed that higher intakes of dietary fiber from different sources is associated with CVD events and modify its major risk-related factors. PMID:27827978

Risk factors for musculoskeletal injury in preprofessional dancers: a systematic review.

PubMed

Kenny, Sarah J; Whittaker, Jackie L; Emery, Carolyn A

2016-08-01

Preprofessional dancers partake in rigorous training and have high injury prevalence. Attempts to identify risk factors for dance injuries have focused on a diversity of intrinsic and extrinsic factors. To identify and evaluate the evidence examining risk factors for musculoskeletal injury in preprofessional ballet and modern dancers. Fifteen electronic databases were systematically searched to October 2015. Studies selected met a priori inclusion criteria and investigated musculoskeletal injury risk factors in preprofessional (elite adolescent, student, young adult) ballet and modern dancers. Two reviewers independently assessed the quality and level of evidence using the Downs and Black (DB) criteria and a modified Oxford Centre of Evidence-Based Medicine 2009 model, respectively. Of 1364 potentially relevant studies, 47 were included and scored. Inconsistent injury definition and methodology precluded meta-analysis. The most common modifiable risk factors investigated were anthropometrics (ie, body mass index, adiposity), joint range of motion (ie, lower extremity), dance exposure (ie, years training, exposure hours) and age. The median DB score across studies was 8/33 (range 2-16). The majority of studies were classified as level 3 evidence and few considered risk factor inter-relationships. There is some level 2 evidence that previous injury and poor psychological coping skills are associated with increased injury risk. Because of the lack of high-quality studies, consensus regarding risk factors for musculoskeletal injury in preprofessional dancers remains difficult. There is a need for injury definition consensus and high-quality prospective studies examining the multifactorial relationship between risk factors and injury in preprofessional dance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Perceived Benefits and Challenges of a Risk-Based Approach to Multidisciplinary Chronic Kidney Disease Care: A Qualitative Descriptive Study.

PubMed

Smekal, Michelle D; Tam-Tham, Helen; Finlay, Juli; Donald, Maoliosa; Benterud, Eleanor; Thomas, Chandra; Quinn, Robert R; Tam, Kin; Manns, Braden J; Tonelli, Marcello; Bello, Aminu; Tangri, Navdeep; Hemmelgarn, Brenda R

2018-01-01

The kidney failure risk equation (KFRE) provides an estimate of risk of progression to kidney failure, and may guide clinical care. We aimed to describe patient, family, and health care provider's perspectives of the perceived benefits and challenges of using a risk-based approach to guide care delivery for patients with advanced chronic kidney disease (CKD), and refine implementation based on their input. We used qualitative methodology to explore perceived benefits and challenges of implementing a risk-based approach (using the KFRE) to determine eligibility for multidisciplinary CKD care in Southern Alberta. We obtained perspectives from patients and families through focus groups, as well as input from health care providers through interviews and open-ended responses from an online survey. Twelve patients/family members participated in 2 focus groups, 16 health care providers participated in an interview, and 40 health care providers responded to the survey. Overall, participants felt that a KFRE-based approach had the potential to improve efficiency of the clinics by targeting care to patients at highest risk of kidney failure; however, they also expressed concerns about the impact of loss of services for lower risk individuals. Participants also articulated concerns about a perceived lack of capacity for adequate CKD patient care in the community. Our implementation strategy was modified as a result of participants' feedback. We identified benefits and challenges to implementation of a risk-based approach to guide care of patients with advanced CKD. Based on these results, our implementation strategy has been modified by removing the category of referral back to primary care alone, and instead having that decision made jointly by nephrologists and patients among low-risk patients.

Screening for Prenatal Substance Use

PubMed Central

Yonkers, Kimberly A.; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B.; Rounsaville, Bruce J.

2011-01-01

OBJECTIVE To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. METHODS Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into “training” (n=1,610) and “validation” (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. RESULTS The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike’s Information Criterion=579.75, Nagelkerke R2=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). CONCLUSION The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. PMID:20859145

Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk.

PubMed

ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M; van der Klift, Heleen M; Velthuizen, Mary E; Bernstein, Inge; Capellá Munar, Gabriel; Gomez Garcia, Encarna; Hoogerbrugge, Nicoline; Letteboer, Tom G W; Menko, Fred H; Lindblom, Annika; Mensenkamp, Arjen R; Moller, Pal; van Os, Theo A; Rahner, Nils; Redeker, Bert J W; Sijmons, Rolf H; Spruijt, Liesbeth; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Hes, Frederik J; Vasen, Hans F; Nielsen, Maartje; Wijnen, Juul T

2015-02-01

The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. © 2014 by American Society of Clinical Oncology.

Identification of potentially hazardous human gene products in GMO risk assessment.

PubMed

Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile

2008-01-01

Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

FIASCO II failure to achieve a satisfactory cardiac outcome study: the elimination of system errors.

PubMed

Farid, Shakil; Page, Aravinda; Jenkins, David; Jones, Mark T; Freed, Darren; Nashef, Samer A M

2013-07-01

Death in low-risk cardiac surgical patients provides a simple and accessible method by which modifiable causes of death can be identified. In the first FIASCO study published in 2009, local potentially modifiable causes of preventable death in low-risk patients with a logistic EuroSCORE of 0-2 undergoing cardiac surgery were inadequate myocardial protection and lack of clarity in the chain of responsibility. As a result, myocardial protection was improved, and a formalized system introduced to ensure clarity of the chain of responsibility in the care of all cardiac surgical patients. The purpose of the current study was to re-audit outcomes in low-risk patients to see if improvements have been achieved. Patients with a logistic EuroSCORE of 0-2 who had cardiac surgery from January 2006 to August 2012 were included. Data were prospectively collected and retrospectively analysed. The case notes of patients who died in hospital were subject to internal and external review and classified according to preventability. Two thousand five hundred and forty-nine patients with a logistic EuroSCORE of 0-2 underwent cardiac surgery during the study period. Seven deaths occurred in truly low-risk patients, giving a mortality of 0.27%. Of the seven, three were considered preventable and four non-preventable. Mortality was marginally lower than in our previous study (0.37%), and no death occurred as a result of inadequate myocardial protection or communication failures. We postulate that the regular study of such events in all institutions may unmask systemic errors that can be remedied to prevent or reduce future occurrences. We encourage all units to use this methodology to detect any similarly modifiable factors in their practice.

Risk of childhood otitis media with focus on potentially modifiable factors: A Danish follow-up cohort study.

PubMed

Kørvel-Hanquist, Asbjørn; Koch, Anders; Lous, Jørgen; Olsen, Sjurdur Frodi; Homøe, Preben

2018-03-01

Otitis media is the primary cause of antibiotic prescription in children. Two-thirds of all children experience at least one episode of otitis media before the age of 7 years. The aim of this study was to characterise the attributable effect of several modifiable risk exposures on the risk of >3 episodes of otitis media at age 18 months and 7 years within a large prospective national birth cohort. The study used the Danish National Birth Cohort comprising information about otitis media and risk exposures from more than 50,000 mother-child pairs from the period 1996-2002. Logistic regression models were used to estimate odds ratios for the risk factors and to calculate the population attributable fraction. Short time with breastfeeding, early introduction to daycare, cesarean section, and low compliance to the national vaccination program were all associated with an increased risk of >3 episodes of otitis media at 18 months of age and at 7 years of age. The fraction of children with otitis media attributed from breastfeeding lasting for less than 6 months was 10%. Introduction to daycare before the age of 12 months attributed with 20% of the cases of >3 episodes of otitis media. Short duration of breastfeeding, early introduction into daycare, cesarean section, and low compliance with the national vaccination program increased the risk of experiencing >3 episodes of otitis media at 18 months, and at 7 years of age. These are factors that all can be modulated. Copyright © 2018 Elsevier B.V. All rights reserved.

Regulating genetically modified food. Policy trajectories, political culture, and risk perceptions in the U.S., Canada, and EU.

PubMed

Wohlers, Anton E

2010-09-01

This paper examines whether national differences in political culture add an explanatory dimension to the formulation of policy in the area of biotechnology, especially with respect to genetically modified food. The analysis links the formulation of protective regulatory policies governing genetically modified food to both country and region-specific differences in uncertainty tolerance levels and risk perceptions in the United States, Canada, and European Union. Based on polling data and document analysis, the findings illustrate that these differences matter. Following a mostly opportunistic risk perception within an environment of high tolerance for uncertainty, policymakers in the United States and Canada modified existing regulatory frameworks that govern genetically modified food in their respective countries. In contrast, the mostly cautious perception of new food technologies and low tolerance for uncertainty among European Union member states has contributed to the creation of elaborate and stringent regulatory policies governing genetically modified food.

New EU legislation for risk assessment of GM food: no scientific justification for mandatory animal feeding trials.

PubMed

Kuiper, Harry A; Kok, Esther J; Davies, Howard V

2013-09-01

This commentary focuses on the potential added value of and need for (sub)-chronic testing of whole genetically modified (GM) foods in rodents to assess their safety. Such routine testing should not be required since, due to apparent weaknesses in the approach, it does not add to current risk assessment of GM foods. Moreover, the demand for routine testing using animals is in conflict with the European Union (EU) Commission's efforts to reduce animal experimentation. Regulating agencies in the EU are invited to respect the sound scientific principles applied to the risk assessment of foods derived from GM plants and not to interfere in the risk assessment by introducing extra requirements based on pseudo-scientific or political considerations. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A risk-based classification scheme for genetically modified foods. II: Graded testing.

PubMed

Chao, Eunice; Krewski, Daniel

2008-12-01

This paper presents a graded approach to the testing of crop-derived genetically modified (GM) foods based on concern levels in a proposed risk-based classification scheme (RBCS) and currently available testing methods. A graded approach offers the potential for more efficient use of testing resources by focusing less on lower concern GM foods, and more on higher concern foods. In this proposed approach to graded testing, products that are classified as Level I would have met baseline testing requirements that are comparable to what is widely applied to premarket assessment of GM foods at present. In most cases, Level I products would require no further testing, or very limited confirmatory analyses. For products classified as Level II or higher, additional testing would be required, depending on the type of the substance, prior dietary history, estimated exposure level, prior knowledge of toxicity of the substance, and the nature of the concern related to unintended changes in the modified food. Level III testing applies only to the assessment of toxic and antinutritional effects from intended changes and is tailored to the nature of the substance in question. Since appropriate test methods are not currently available for all effects of concern, future research to strengthen the testing of GM foods is discussed.

The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition.

PubMed

Wallace, Robert G; Twomey, Laura C; Custaud, Marc-Antoine; Turner, Jonathan D; Moyna, Niall; Cummins, Philip M; Murphy, Ronan P

2017-11-16

The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual's overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This 'epigenetic drift' impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well". Copyright © 2017 Elsevier B.V. All rights reserved.

Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

PubMed

Nguyen-Dumont, Tú; Teo, Zhi L; Hammet, Fleur; Roberge, Alexis; Mahmoodi, Maryam; Tsimiklis, Helen; Park, Daniel J; Pope, Bernard J; Lonie, Andrew; Kapuscinski, Miroslav K; Mahmood, Khalid; Goldgar, David E; Giles, Graham G; Winship, Ingrid; Hopper, John L; Southey, Melissa C

2018-02-08

Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p < 0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.

A scoping review of epidemiologic risk factors for pediatric obesity: Implications for future childhood obesity and dental caries prevention research.

PubMed

Chi, Donald L; Luu, Monique; Chu, Frances

2017-06-01

What are the non-modifiable (socioeconomic, genetic) and modifiable factors (physical activity, dietary behaviors) related to childhood (under age 12) obesity? How can this knowledge be applied to oral health professionals' efforts to prevent or manage dental caries in children? Studies have identified risk factors for childhood obesity. The purpose of this scoping review was to develop a conceptual model to identify non-modifiable and modifiable risk factors for childhood obesity and to illustrate how these findings are relevant in developing interventions aimed at preventing obesity and dental caries in children. The authors searched PubMed and Embase and limited the study to English-language publications. A total of 2,572 studies were identified. After de-duplication, 2,479 studies remained and were downloaded into a citation-management tool. Two authors screened the titles and abstracts for relevance. Two hundred and sixty studies remained and were retrieved for a full-text review, and 80 studies were excluded, resulting in 180 studies included in the scoping review. An inductive content analytic methods was used to organize all statistically significant obesity risk factors into seven domains, which were classified as non-modifiable or modifiable; then a conceptual model of common risk factors associated with childhood obesity and dental caries was developed. Non-modifiable obesity risk factors include biological and developmental (e.g., genes, developmental conditions, puberty), sociodemographic and household (e.g., race/ethnicity, socioeconomic status, parent education, unemployment), cultural (e.g., degree of acculturation), and community (e.g., neighborhood composition). Modifiable risk factors included behavioral (e.g., diet, physical activity, weight), psychosocial (e.g., maternal stress, family functioning, parenting practices, child temperament), and medical (e.g., parent smoking, maternal health, child health). Identifying common risk factors has important implications for future oral health research aimed at preventing childhood obesity and dental caries. Epidemiologic knowledge gleaned from the literature can be used to develop rigorous interventions and programs aimed at preventing these highly prevalent diseases and improving health outcomes for children. © 2017 American Association of Public Health Dentistry.

[Strategies for reducing risks in smoking: opportunity or threat].

PubMed

Córdoba, Rodrigo; Nerín, Isabel

2009-12-01

The smoking control policies recommended by the World Health Organisation have achieved a slight decrease in smoking prevalence in the developed countries, although associated mortality is still very high. The use of tobacco products other than cigarettes and even medicinal nicotine (known as nicotine replacement therapy (NRT)) has been proposed as a risk reduction strategy. Among the tobacco products with less individual risk than cigarettes would be any type of tobacco without smoke (smokeless) with a low content in nitrosamines and modified cigarettes; both forms included under the PREP (Potentially Reduced Exposure Products) concept. The idea would be to promote these products among those who cannot quit smoking or wish to reduce their risk without giving up nicotine intake. The possible effects of risk reduction strategies, including PREP, on the decreased prevalence and morbidity and mortality are reviewed, and the possible implications that this measure could have in our country are analysed. Tobacco control measures in Spain are recent and still insufficient. Therefore, the current priority in Spain is the development of policies of control that have shown to more than effective. The marketing and advertising of new tobacco products, even with reduced potential risk, seems more a serious threat than an opportunity for the development of smoking control policies.

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards

PubMed Central

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-01-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards. PMID:28662748

Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards.

PubMed

Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

2017-06-01

Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards.

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

PubMed Central

Vigorito, Elena; Kuchenbaecker, Karoline B.; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A.; Andrulis, Irene L.; Arun, Banu K.; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Chan, Salina B.; Claes, Kathleen B. M.; Cohn, David E.; Cook, Jackie; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F.; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D. Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D.; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K.; Goldgar, David E.; Hake, Christopher R.; Hansen, Thomas V. O.; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B. L.; Houdayer, Claude; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M.; Vijai, Joseph; Karlan, Beth Y.; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R.; Montagna, Marco; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C.; Rookus, Matti A.; Ross, Eric A.; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I.; Tea, Muy-Kheng; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J.; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N.; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J.; Greene, Mark H.; Couch, Fergus J.; Offit, Kenneth; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

2016-01-01

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

PubMed

Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

2016-01-01

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

Perceived peer engagement in HIV-related sexual risk behaviors and self-reported risk-taking among female sex workers in Guangxi, China.

PubMed

Chen, Yiyun; Li, Xiaoming; Zhou, Yuejiao; Wen, Xiaoqing; Wu, Deren

2013-01-01

Searching for modifiable perceptions that are associated with sexual risk behaviors among female sex workers (FSWs) are considered a priority in HIV/sexually transmitted disease preventions. Perception of peers' involvement in risk behaviors, a key correlate of individual risk behaviors, has barely been studied among FSWs. A self-administered questionnaire was completed by 1022 FSWs in Guangxi, China, a country with rapid growth in both HIV epidemic and commercial sex. Multiple imputation using chained equation (MICE) was applied to handle missing values (1-10%) in the data-set. Regression analysis that focused on relationship between perceived peers' risk involvement and FSWs' risk-taking was performed on full data-sets generated by MICE. FSWs who perceived more peer alcohol use was significantly more likely to have sex under the influence of alcohol. Those who perceived more unprotected sex among peers had a higher likelihood to use condom inconsistently with both stable and casual partners. Perceiving more peers engaging in sex after using alcohol was positively associated with having sex with clients who were intoxicated and/or high on drugs, and with having sex under the influence of alcohol. Perceived peer promiscuity, defined as having sex with any types of clients at any price offered, was positively associated with inconsistent condom use with casual partners, but negatively associated with having sex under the influence of alcohol. These data suggest that the potential for intervention programs to address behavioral change among FSWs through modifying perceptions of peer involvement in sexual risk behaviors. Longitudinal studies are needed to confirm these findings and qualitative researches will be essential for the clarification of mechanisms behind associations found in the current study and for the actual design of effective norm-based interventions among FSWs.

Foster care re-entry: Exploring the role of foster care characteristics, in-home child welfare services and cross-sector services.

PubMed

Lee, Sangmoo; Jonson-Reid, Melissa; Drake, Brett

2012-09-01

This study seeks to advance our understanding of how modifiable and non-modifiable factors may impact the likelihood of re-entry into foster care. Children who entered foster care for the first time following at least one report of maltreatment and were then reunified were followed from exit to re-entry, age 18 or the end of the study period using longitudinal administrative data. Risk of re-entry was explored according to a range of modifiable and non-modifiable case and service characteristics. Children removed from homes with parents who had multiple risk factors (e.g., no high school diploma, mental health diagnosis, criminal record, or teen parents) or were receiving AFDC prior to entry were more likely to re-enter. The receipt of in-home child welfare services during or after foster care was associated with reduced risk of re-entry. Having the longest placement with a relative was associated with decreased risk of re-entry. In conclusion, both modifiable and non-modifiable factors are associated with re-entry into foster care. Among modifiable factors, services appear to have a particularly strong relationship to re-entry. Our data also suggest that in-home child welfare services provided during and after foster care may be associated with improved long-term permanency after return home. Given the continued import of caregiver risk factors even among reunified families, services provided to support reunification should include attention to caregiver needs outside parenting.

Foster care re-entry: Exploring the role of foster care characteristics, in-home child welfare services and cross-sector services☆

PubMed Central

Lee, Sangmoo; Jonson-Reid, Melissa; Drake, Brett

2013-01-01

This study seeks to advance our understanding of how modifiable and non-modifiable factors may impact the likelihood of re-entry into foster care. Children who entered foster care for the first time following at least one report of maltreatment and were then reunified were followed from exit to re-entry, age 18 or the end of the study period using longitudinal administrative data. Risk of re-entry was explored according to a range of modifiable and non-modifiable case and service characteristics. Children removed from homes with parents who had multiple risk factors (e.g., no high school diploma, mental health diagnosis, criminal record, or teen parents) or were receiving AFDC prior to entry were more likely to re-enter. The receipt of in-home child welfare services during or after foster care was associated with reduced risk of re-entry. Having the longest placement with a relative was associated with decreased risk of re-entry. In conclusion, both modifiable and non-modifiable factors are associated with re-entry into foster care. Among modifiable factors, services appear to have a particularly strong relationship to re-entry. Our data also suggest that in-home child welfare services provided during and after foster care may be associated with improved long-term permanency after return home. Given the continued import of caregiver risk factors even among reunified families, services provided to support reunification should include attention to caregiver needs outside parenting. PMID:23729947

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

PubMed

Neuberger, James M; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K; Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L; Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Trunečka, Pavel; Tisone, Giuseppe; van Gelder, Teun

2017-04-01

Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

The Modified Hartmann Potential Effects on γ-rigid Bohr Hamiltonian

NASA Astrophysics Data System (ADS)

Suparmi, A.; Cari, C.; Nur Pratiwi, Beta

2018-04-01

In this paper, we present the solution of Bohr Hamiltonian in the case of γ-rigid for the modified Hartmann potential. The modified Hartmann potential was formed from the original Hartmann potential, consists of β function and θ function. By using the separation method, the three-dimensional Bohr Hamiltonian equation was reduced into three one-dimensional Schrodinger-like equation which was solved analytically. The results for the wavefunction were shown in mathematically, while for the binding energy was solved numerically. The numerical binding energy for the presence of the modified Hartmann potential is lower than the binding energy value in the absence of modified Hartmann potential effect.

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis.

PubMed

Nandi, Pradip; Kingsley, Gabrielle H; Scott, David L

2008-05-01

To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.

Clinic Appointment Attendance in Adults with Serious Mental Illness and Diabetes.

PubMed

Gunzler, Douglas D; Morris, Nathan; Dalton, Jarrod E; McCormick, Richard; Dawson, Neal V; Thomas, Charles; Kanuch, Stephanie; Cassidy, Kristin A; Athey, Melanie; Fuentes-Casiano, Edna; Lawless, Mary Ellen; Martin, Siobhan; Einstadter, Douglas; Sajatovic, Martha

2017-11-01

We assessed characteristics that may predict outpatient appointment attendance in outpatient medical clinics among patients comorbid for serious mental illness (SMI) and type 2 diabetes (DM). Baseline covariate data from 200 individuals with SMI-DM enrolled in a randomized controlled trial (RCT) were used to examine characteristics associated with electronic health record-identified clinic appointment attendance using a generalized estimating equations approach. The analyses evaluated the relationship between clinic attendance and potentially modifiable factors including disease knowledge, self-efficacy, social support, physical health, and mental health, as well as demographic information. Demographic and mental health characteristics were most associated with clinic attendance in adults with SMI-DM. Physical health was not associated with clinic attendance. Information on clinical and demographic characteristics and factors potentially modifiable by psychological interventions may be useful in improving adherence to treatment among SMI-DM patients. It is our hope that clinicians and researchers will use these results to help tailor adherence-facilitating interventions among people at particular risk for poor engagement in care.

Decreasing adverse outcomes of unmodified electroconvulsive therapy: suggestions and possibilities.

PubMed

Gallegos, Jesus; Vaidya, Punit; D'Agati, Douglas; Jayaram, Geetha; Nguyen, Thai; Tripathi, Adarsh; Trivedi, Jitendra K; Reti, Irving M

2012-06-01

Electroconvulsive therapy (ECT) is far and away the most effective treatment for depression and quite effective for a range of other psychiatric conditions that are unresponsive to medication. Electroconvulsive therapy in the developed world has been administered with anesthesia, muscle relaxants, and ventilation since the mid-1950s following 20 years of unmodified treatment. However, in much of the developing world, ECT continues to be administered unmodified because of lack of resources. We review the efficacy of unmodified compared with modified treatment. We also review the potential drawbacks of unmodified treatment including fear and anxiety, worse postictal confusion, fracture risk, and the negative effects of unmodified treatment on how ECT is perceived in the general community. Finally, we consider potential solutions in developing countries to minimize adverse outcomes of unmodified treatment by pretreating patients either with low-dose benzodiazepines or sedating, but not anesthetizing, dosages of anesthetic agents. Randomized controlled trials are necessary before either of these options could be considered an acceptable alternative to completely unmodified treatment when modified treatment is unavailable.

[GIS Spatial Distribution and Ecological Risk Assessment of Heavy Metals in Surface Sediments of Shallow Lakes in Jiangsu Province].

PubMed

Li, Ying-jie; Zhang, Lie-yu; Wu, Yi-wen; Li, Cao-le; Yang, Tian-xue; Tang, Jun

2016-04-15

To understand pollution of heavy metals in surface sediments of shallow lakes, surface sediments samples of 11 lakes in Jiangsu province were collected to determine the content of six heavy metals including As, Cr, Cu, Pb, Zn and Ni. GIS was used to analyze the spatial distribution of heavy metals, and geological accumulation index (Igeo), modified contamination index (mCd) pollution load index (PLI) and potential ecological risk index (RI) were used to evaluate heavy metal contamination in the sediments. The results showed that: in the lakes' surface sediments, the average content of As, Cu, Zn, Cr, Pb, Ni in multiples of soil background of Jiangsu province were 1.74-3.85, 0.65-2.66, 0.48-3.56, 0.43-1.52, 0.02-1.49 and 0.12-1.42. According to the evaluation results of Igeo and RI, As, which had high degree of enrichment and great potential ecological risk, was the main pollutant, followed by Cu, and pollution of the rest of heavy metals was relatively light. Combining the results of several evaluation methods, in surface sediments of Sanjiu Lake, Gaoyou Lake and Shaobo Lake, these heavy metals had the most serious pollution, the maximum pollution loading and moderate potential ecological risk; in surface sediments of Gehu Lake, Baima Lake and Hongze Lake, some regions were polluted by certain metals, the overall trend of pollution was aggravating, the pollution loading was large, and the potential ecological risk reached moderate; in the other 5 lakes, the risk of sediments polluted by heavy metals, as well as the pollution loading, was small, and the overall was not polluted.

Principles for the risk assessment of genetically modified microorganisms and their food products in the European Union.

PubMed

Aguilera, Jaime; Gomes, Ana R; Olaru, Irina

2013-10-01

Genetically modified microorganisms (GMMs) are involved in the production of a variety of food and feed. The release and consumption of these products can raise questions about health and environmental safety. Therefore, the European Union has different legislative instruments in place in order to ensure the safety of such products. A key requirement is to conduct a scientific risk assessment as a prerequisite for the product to be placed on the market. This risk assessment is performed by the European Food Safety Authority (EFSA), through its Scientific Panels. The EFSA Panel on Genetically Modified Organisms has published complete and comprehensive guidance for the risk assessment of GMMs and their products for food and/or feed use, in which the strategy and the criteria to conduct the assessment are explained, as well as the scientific data to be provided in applications for regulated products. This Guidance follows the main risk assessment principles developed by various international organisations (Codex Alimentarius, 2003; OECD, 2010). The assessment considers two aspects: the characterisation of the GMM and the possible effects of its modification with respect to safety, and the safety of the product itself. Due to the existing diversity of GMMs and their products, a categorisation is recommended to optimise the assessment and to determine the extent of the required data. The assessment starts with a comprehensive characterisation of the GMM, covering the recipient/parental organism, the donor(s) of the genetic material, the genetic modification, and the final GMM and its phenotype. Evaluation of the composition, potential toxicity and/or allergenicity, nutritional value and environmental impact of the product constitute further cornerstones of the process. The outcome of the assessment is reflected in a scientific opinion which indicates whether the product raises any safety issues. This opinion is taken into account by the different European regulatory authorities prior to a decision regarding authorisation to commercialise the product. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetically modified crops and aquatic ecosystems: considerations for environmental risk assessment and non-target organism testing.

PubMed

Carstens, Keri; Anderson, Jennifer; Bachman, Pamela; De Schrijver, Adinda; Dively, Galen; Federici, Brian; Hamer, Mick; Gielkens, Marco; Jensen, Peter; Lamp, William; Rauschen, Stefan; Ridley, Geoff; Romeis, Jörg; Waggoner, Annabel

2012-08-01

Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.

Falls efficacy, postural balance, and risk for falls in older adults with falls-related emergency department visits: prospective cohort study.

PubMed

Pua, Yong-Hao; Ong, Peck-Hoon; Clark, Ross Allan; Matcher, David B; Lim, Edwin Choon-Wyn

2017-12-21

Risk for falls in older adults has been associated with falls efficacy (self-perceived confidence in performing daily physical activities) and postural balance, but available evidence is limited and mixed. We examined the interaction between falls efficacy and postural balance and its association with future falls. We also investigated the association between falls efficacy and gait decline. Falls efficacy, measured by the Modified Falls Efficacy Scale (MFES), and standing postural balance, measured using computerized posturography on a balance board, were obtained from 247 older adults with a falls-related emergency department visit. Six-month prospective fall rate and habitual gait speed at 6 months post baseline assessment were also measured. In multivariable proportional odds analyses adjusted for potential confounders, falls efficacy modified the association between postural balance and fall risk (interaction P = 0.014): increasing falls efficacy accentuated the increased fall risk related to poor postural balance. Low baseline falls efficacy was strongly predictive of worse gait speed (0.11 m/s [0.06 to 0.16] slower gait speed per IQR decrease in MFES; P < 0.001). Older adults with high falls efficacy but poor postural balance were at greater risk for falls than those with low falls efficacy; however, low baseline falls efficacy was strongly associated with worse gait function at follow-up. Further research into these subgroups of older adults is warranted. ClinicalTrials.gov identifier: NCT01713543 .

RISK COMMUNICATION FOR ES&H PROFESSIONALS AND LINE SUPERVISORS PARTICIPANT MANUAL COURSE NUMBER 004111 REV 0.1 JULY 2011

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

ALDRIDGE PK; ROCKS S

This course will help you successfully apply risk communication principles when interacting with workers regarding work hazards. What Is the Difference Between a Risk and a Hazard? In many cases, the terms 'risk' and 'hazard' are incorrectly used interchangeably. A hazard is a physical condition or practice with the potential for causing harm/adverse effects. A risk is the probability of harm/adverse effects occurring from an exposure to a hazard. It is modified by the severity of harm (the consequence). Once a hazard is identified, a risk assessment is conducted to determine the severity of the risk. It uses scientific methodsmore » and rigorous tests to determine the effects of the risk on people and the environment. Risk Management takes data from the risk assessment and writes policies to help protect people and the environment against the risk. Risk communication is an ongoing process that starts soon after a hazard is identified and continues through the writing of policies. In the past, governing agencies did not do a good job of communicating risk; they would only communicate about risk after studies had been conducted and policies written.« less

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

PubMed

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Modifiable risk factors for chronic back pain: insights using the co-twin control design.

PubMed

Suri, Pradeep; Boyko, Edward J; Smith, Nicholas L; Jarvik, Jeffrey G; Williams, Frances M K; Jarvik, Gail P; Goldberg, Jack

2017-01-01

Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP. This is a cross-sectional co-twin control study in a nationwide sample of male twin members of the Vietnam Era Twin Registry. The sample is composed of 7,108 participants, including 1,308 monozygotic (MZ) pairs and 793 dizygotic pairs. The outcome measure is the self-reported lifetime history of CBP. Lifestyle factors included body mass index (BMI), smoking history, alcohol consumption, habitual physical activity, and typical sleep duration. Psychological factors included depression (Patient Health Questionnaire-9) and posttraumatic stress disorder (PTSD) symptoms (PTSD Checklist). Covariates included age, race, education, and income. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the association of risk factors with lifetime CBP when considering twins as individuals, and a within-pair co-twin control analysis that accounted for familial and genetic factors. Funding was through VA Grant 5IK2RX001515; there were no study-specific conflicts of interest. The mean age of respondents was 62 years and the prevalence of lifetime CBP was 28%. All lifestyle factors were associated with CBP in the individual level analysis. However, none of these persisted in the within-pair analyses, except for severe obesity (BMI ≥35.0), which was associated with lifetime CBP in both individual-level (OR=1.6, 95% CI: 1.3-1.9) and within-pair analyses (MZ analysis: OR=3.7, 95% CI: 1.2-11.4). Symptoms of PTSD and depression were strongly associated with lifetime CBP in both the individual-level (moderate or severe depression: OR=4.2, 95% CI: 3.6-4.9, and severe PTSD: OR=4.8, 95% CI: 4.0-5.7) and within-pair (MZ) analyses (moderate or severe depression: OR=4.6, 95% CI: 2.4-8.7, and severe PTSD: OR=3.2, 95% CI: 1.6-6.5). Many associations between modifiable lifestyle risk factors and CBP are due to confounding by familial and genetic factors. Severe obesity, depression, and PTSD should be considered in the development of intervention strategies to reduce the prevalence of CBP. Published by Elsevier Inc.

Associations between Adolescent Risk Behaviors and Injury: The Modifying Role of Disability

ERIC Educational Resources Information Center

Raman, Sudha R.; Boyce, William F.; Pickett, William

2009-01-01

Background: Adolescents with disabilities are at risk for poor health outcomes including injury. The objective of this study was to examine if disability status modifies the association between risk behavior and injury among adolescents. Methods: The cross-sectional Health Behavior in School-Aged Children Survey was administered to a…

Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue.

PubMed

Murray, Justine V; Jansen, Cassie C; De Barro, Paul

2016-01-01

In an effort to eliminate dengue, a successful technology was developed with the stable introduction of the obligate intracellular bacteria Wolbachia pipientis into the mosquito Aedes aegypti to reduce its ability to transmit dengue fever due to life shortening and inhibition of viral replication effects. An analysis of risk was required before considering release of the modified mosquito into the environment. Expert knowledge and a risk assessment framework were used to identify risk associated with the release of the modified mosquito. Individual and group expert elicitation was performed to identify potential hazards. A Bayesian network (BN) was developed to capture the relationship between hazards and the likelihood of events occurring. Risk was calculated from the expert likelihood estimates populating the BN and the consequence estimates elicited from experts. The risk model for "Don't Achieve Release" provided an estimated 46% likelihood that the release would not occur by a nominated time but generated an overall risk rating of very low. The ability to obtain compliance had the greatest influence on the likelihood of release occurring. The risk model for "Cause More Harm" provided a 12.5% likelihood that more harm would result from the release, but the overall risk was considered negligible. The efficacy of mosquito management had the most influence, with the perception that the threat of dengue fever had been eliminated, resulting in less household mosquito control, and was scored as the highest ranked individual hazard (albeit low risk). The risk analysis was designed to incorporate the interacting complexity of hazards that may affect the release of the technology into the environment. The risk analysis was a small, but important, implementation phase in the success of this innovative research introducing a new technology to combat dengue transmission in the environment.

Risk factors for acute nerve injury after total knee arthroplasty.

PubMed

Shetty, Teena; Nguyen, Joseph T; Sasaki, Mayu; Wu, Anita; Bogner, Eric; Burge, Alissa; Cogsil, Taylor; Dalal, Aashka; Halvorsen, Kristin; Cummings, Kelianne; Su, Edwin P; Lyman, Stephen

2018-06-01

In this we study identified potential risk factors for post-total knee arthroplasty (TKA) nerve injury, a catastrophic complication with a reported incidence of 0.3%-1.3%. Patients who developed post-TKA nerve injury from 1998 to 2013 were identified, and each was matched with 2 controls. A multivariable logistic regression model was built to calculate odds ratios (ORs). Sixty-five nerve injury cases were identified in 39,990 TKAs (0.16%). Females (OR 3.28, P = 0.003) and patients with history of lumbar pathology (OR 6.12, P = 0.026) were associated with increased risk of nerve injury. Tourniquet pressure < 300 mm Hg and longer duration of anesthesia may also be risk factors. Surgical planning for females and patients with lumbar pathology should be modified to mitigate their higher risk of neurologic complications after TKA. Our finding that lower tourniquet pressure was associated with higher risk of nerve injury was unexpected and requires further investigation. Muscle Nerve 57: 946-950, 2018. © 2017 Wiley Periodicals, Inc.

Pre-Diabetes Non-Modifiable Risk Factors

MedlinePlus

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Pre-diabetes Non-modifiable Risk Factors Updated:Nov 9,2015 ... This content was last reviewed August 2015. Pre-diabetes • Introduction • About Pre-diabetes • What's the Problem? Intro ...

Developing a Composite Aquifer Vulnerability Assessment Model Combining DRASTIC with Agricultural Land Use in Choushui River Alluvial Fan, Central Taiwan

NASA Astrophysics Data System (ADS)

Chen, Shih-Kai; Hsieh, Chih-Heng; Tsai, Cheng-Bin

2017-04-01

Aquifer vulnerability assessment is considered to be an effective tool in controlling potential pollution which is critical for groundwater management. The Choushui River alluvial fan, located in central Taiwan, is an agricultural area with complex crop patterns and various irrigation schemes, which increased the difficulties in groundwater resource management. The aim of this study is to propose an integrated methodology to assess shallow groundwater vulnerability by including land-use impact on groundwater potential pollution. The original groundwater vulnerability methodology, DRASTIC, was modified by adding a land-use parameter in order to assess groundwater vulnerability under intense agricultural activities. To examine the prediction capacity of pollution for the modified DRASTIC model, various risk categories of contamination potentials were compared with observed nitrate-N obtained from groundwater monitoring network. It was found that for the original DRASTIC vulnerability map, some areas with low nitrate-N concentrations are covered within the high vulnerability areas, especially in the northern part of mid-fan areas, where rice paddy is the main crop and planted for two crop seasons per year. The low nitrate-N contamination potential of rice paddies may be resulted from the denitrification in the reduced root zone. By reducing the rating for rice paddies, the modified model was proved to be capable of increasing the precise of prediction in study area. The results can provide a basis for groundwater monitoring network design and effective preserve measures formulation in the mixed agricultural area. Keyword:Aquifer Vulnerability, Groundwater, DRASTIC, Nitrate-N

The association between modifiable well-being risks and productivity: a longitudinal study in pooled employer sample.

PubMed

Shi, Yuyan; Sears, Lindsay E; Coberley, Carter R; Pope, James E

2013-04-01

To examine the longitudinal relationship between modifiable well-being risks and productivity. A total of 19,121 employees from five employers participated in baseline and follow-up well-being assessment surveys. Multivariate regressions assessed whether changes in absenteeism, presenteeism, and job performance were associated with changes in 19 modifiable well-being risks. Over time, a 5% reduction in total count of well-being risks was significantly associated with 0.74% decrease in absenteeism, 2.38% decrease in presenteeism, and 0.24% increase in performance. High blood pressure, recurring pain, unhealthy diet, inadequate exercise, poor emotional health, poor supervisor relationship, not utilizing strengths doing job, and organization unsupportive of well-being had greater independent contributions in explaining productivity impairment. The often-ignored well-being risks such as work-related and financial health risks provided incremental explanation of longitudinal productivity variations beyond traditional measures of health-related risks.

An assessment of the barriers to the consumers' uptake of genetically modified foods: a neural network analysis.

PubMed

Rodríguez-Entrena, Macario; Salazar-Ordóñez, Melania; Becerra-Alonso, David

2016-03-30

This paper studies which of the attitudinal, cognitive and socio-economic factors determine the willingness to purchase genetically modified (GM) food, enabling the forecasting of consumers' behaviour in Andalusia, southern Spain. This classification has been made by a standard multilayer perceptron neural network trained with extreme learning machine. Later, an ordered logistic regression was applied to determine whether the neural network can outperform this traditional econometric approach. The results show that the highest relative contributions lie in the variables related to perceived risks of GM food, while the perceived benefits have a lower influence. In addition, an innovative attitude towards food presents a strong link, as does the perception of food safety. The variables with the least relative contribution are subjective knowledge about GM food and the consumers' age. The neural network approach outperforms the correct classification percentage from the ordered logistic regression. The perceived risks must be considered as a critical factor. A strategy to improve the GM food acceptance is to develop a transparent and balanced information framework that makes the potential risk understandable by society, and make them aware of the risk assessments for GM food in the EU. For its success, it is essential to improve the trust in EU institutions and scientific regulatory authorities. © 2015 Society of Chemical Industry.

Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease.

PubMed

McGough, Ellen; Kirk-Sanchez, Neva; Liu-Ambrose, Teresa

2017-07-01

Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability. Through the use of common clinical tests to identify cognitive and noncognitive functional markers of disease, detection and intervention can occur at earlier stages, including preclinical stages of disease. Physical activity and exercise interventions to address modifiable risk factors and impairments can play a pivotal role in the prevention and delay of functional decline, ultimately reducing the incidence of dementia. This article discusses prevention, prediction, plasticity, and participation in the context of preserving brain health and preventing Alzheimer disease and related dementias in aging adults. Rehabilitation professionals have opportunities to slow disease progression through research, practice, and education initiatives. From a clinical perspective, interventions that target brain health through lifestyle changes and exercise interventions show promise for preventing stroke and associated neurovascular diseases in addition to dementia. Physical therapists are well positioned to integrate primary health promotion into practice for the prevention of dementia and other neurological conditions in older adults.

TFOS DEWS II Epidemiology Report.

PubMed

Stapleton, Fiona; Alves, Monica; Bunya, Vatinee Y; Jalbert, Isabelle; Lekhanont, Kaevalin; Malet, Florence; Na, Kyung-Sun; Schaumberg, Debra; Uchino, Miki; Vehof, Jelle; Viso, Eloy; Vitale, Susan; Jones, Lyndon

2017-07-01

The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research. Copyright © 2017 Elsevier Inc. All rights reserved.

Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells.

PubMed

Kogel, U; Gonzalez Suarez, I; Xiang, Y; Dossin, E; Guy, P A; Mathis, C; Marescotti, D; Goedertier, D; Martin, F; Peitsch, M C; Hoeng, J

2015-12-01

Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Allergic risk and role of the Allergy Vigilance Network].

PubMed

Moneret-Vautrin, Denise-Anne

2007-01-01

The recent increase in the incidence of severe anaphylaxis calls for continual assessment of risk factor and dangers associated with food allergy, keeping abreast of changes in the food industry. Allergologists, regulatory bodies and the food industry are all responsible for food safety. The Allergy Vigilance Network, founded by a university research team and comprising 398 French and Belgian allergologists, has developed a three-point strategy. First, reporting cases of severe anaphylaxis of document allergic origin makes it possible to monitor the prevalence of food allergens and to evaluate the quality of management of allergy-related emergencies, thus providing data suitable for estimating the economic burden of anaphylaxis. The second objective of the network is to set up multicenter trials to determine the prevalence of sensitization to risk allergens, such as peanut, lupin and plant pollen, of which transgenic varieties will soon emerge. The third objective is screening and long-term monitoring of dangers related to new foods, ingredients and adjuvant sensitizing factors. Post-marketing monitoring of potential allergic risks arising from genetically modified food is another aim of the network, together with the establishment of a serum bank, following WHO/FAO recommendations. The Allergy Vigilance Network, together with the French National Institute for Food Safety (AFSSA), the Ministry of Consumer Affairs (DGCCRF) and various patient associations, is striving to analyse and deal with dangers related to the allergenicity of natural and modified food proteins.

Identifying Links Between Sexual Violence and Youth Violence Perpetration: New Opportunities for Sexual Violence Prevention

PubMed Central

DeGue, Sarah; Massetti, Greta M.; Holt, Melissa K.; Tharp, Andra Teten; Valle, Linda Anne; Matjasko, Jennifer L.; Lippy, Caroline

2018-01-01

Objective One promising opportunity for advancing sexual violence (SV) research and identifying new avenues for prevention involves examining other forms of violence that may share risk factors with SV. Youth violence (YV) is ideal for consideration given evidence of overlap in SV and YV risk factors, a large set of established YV risk factors across the social ecology, and the number of evidence-based YV prevention strategies available. The current paper identifies shared and unique risk factors for SV and YV and highlights evidence-based YV prevention strategies that impact these shared risk factors. Conclusions Researchers and program developers should consider adapting and evaluating evidence-based YV prevention strategies to prevent SV. Modifying these programs to address SV’s unique risk factors may maximize their potential effectiveness. In addition, expanding SV research at the outer levels of the social ecology is critical to developing community-level prevention strategies. The YV literature suggests several potential risk factors at these levels in need of research for SV, including school connectedness, social disorganization, and availability of alcohol and drugs. Using the YV literature as a starting point for expanding SV research leverages prior investments in YV research, may help identify new SV prevention strategies at a limited cost, and moves the field more quickly toward implementation of cost-effective, multidomain violence prevention strategies in communities. PMID:29644117

Fishing in acid waters: A vulnerability assessment of the Norwegian fishing industry in the face of increasing ocean acidification.

PubMed

Heinrich, Luise; Krause, Torsten

2017-07-01

Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a risk assessment among the Norwegian counties using a modified version of a risk assessment framework introduced in the Intergovernmental Panel on Climate Change's "Special Report: Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation," which considers risk to be the sum of hazard, exposure, and vulnerability. Our results show that about 13 of 19 counties are likely to experience moderate to high risk from OA. We highlight that the success of integrated risk assessments highly depends on the availability of detailed environmental, economic, and societal data. In the case of Norway, modeling data regarding the progress of OA, improved information on potential biological impacts on a larger number of species, and statistical data on social variables are required. We conclude that although still in its infancy, integrated risk assessments are important prerequisites for any form of interdisciplinary research on OA and the development of successful response strategies. Integr Environ Assess Manag 2017;13:778-789. ©2016 SETAC. © 2016 SETAC.

Subclinical Peroneal Neuropathy: A Common, Unrecognized, and Preventable Finding Associated With a Recent History of Falling in Hospitalized Patients.

PubMed

Poppler, Louis H; Groves, Andrew P; Sacks, Gina; Bansal, Anchal; Davidge, Kristen M; Sledge, Jenifer A; Tymkew, Heidi; Yan, Yan; Hasak, Jessica M; Potter, Patricia; Mackinnon, Susan E

2016-11-01

Identification of modifiable risk factors for falling is paramount in reducing the incidence and morbidity of falling. Peroneal neuropathy with an overt foot drop is a known risk factor for falling, but research into subclinical peroneal neuropathy (SCPN) resulting from compression at the fibular head is lacking. The purpose of our study was to determine the prevalence of SCPN in hospitalized patients and establish whether it is associated with a recent history of falling. We conducted a cross-sectional study of 100 medical inpatients at a large academic tertiary care hospital in St Louis, Missouri. General medical inpatients deemed at moderate to high risk for falling were enrolled in the summer of 2013. Patients were examined for findings that suggest peroneal neuropathy, fall risk, and a history of falling. Multivariate logistic regression was used to correlate SCPN with fall risk and a history of falls in the past year. The mean patient age was 53 years (SD = 13 years), and 59 patients (59%) were female. Thirty-one patients had examination findings consistent with SCPN. After accounting for various confounding variables within a multivariate logistic regression model, patients with SCPN were 4.7 times (95% CI, 1.4-15.9) more likely to report having fallen 1 or more times in the past year. Subclinical peroneal neuropathy is common in medical inpatients and is associated with a recent history of falling. Preventing or identifying SCPN in hospitalized patients provides an opportunity to modify activity and therapy, potentially reducing risk. © 2016 Annals of Family Medicine, Inc.

The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload.

PubMed

Trinh, Emilie; Weber, Catherine

2017-01-01

Fluid overload in patients on conventional hemodialysis is a frequent complication, associated with increased cardiovascular morbidity and mortality. The dialysate sodium prescription is a potential modifiable risk factor. Our primary objective was to describe associations between dialysate-to-serum sodium gradient and parameters of fluid status. A secondary objective was to evaluate the 6-month risk of hospitalization and mortality in relation to sodium gradient. We performed a cross-sectional study of 110 prevalent conventional hemodialysis patients at a single center. The associations of sodium gradient with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and blood pressure (BP) were analyzed. The mean serum sodium gradient was 4.6 ± 3.6 mEq/L. There was a direct correlation between sodium gradient and IDWG% ( r = 0.48, p < 0.01) as well as UF rate ( r = 0.44, p < 0.01). In a logistic regression model, a 1 mEq/L higher sodium gradient was associated with increased risk of IDWG% >3% (OR 1.33, p < 0.01) and increased risk of UF rate >10 mL/kg/h (OR 1.16, p = 0.03), but there were no associations with intradialytic hypotension, intradialytic hypertension or BP. No significant differences were found with 6-month hospitalization or mortality risk in relation to sodium gradient. A higher sodium gradient was associated with significant increases in IDWG and UF rates, known to be associated with poor outcomes, but was not associated with intradialytic hypotension. Individualizing the dialysate sodium prescription to minimize sodium gap may lead to less fluid overload in conventional hemodialysis patients.

Climate and environmental triggers of acute myocardial infarction.

PubMed

Claeys, Marc J; Rajagopalan, Sanjay; Nawrot, Tim S; Brook, Robert D

2017-04-01

Over the past few decades, a growing body of epidemiological and clinical evidence has led to heightened concerns about the potential short- and long-term deleterious effects of the environment on cardiovascular health, including the risk for acute myocardial infarction (AMI). This review highlights the increased risk of AMI caused by exposure to air pollution and cold temperatures. These factors should be considered modifiable risk factors in the prevention of cardiovascular disease. The current body of knowledge about the biological mechanisms linking environmental changes to atherothrombotic events and the impact of climate change on cardiovascular health are discussed. Finally, recommendations for prevention and public policy are presented. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression

PubMed Central

Choi, Michael J.; Kao, W.H. Linda; Astor, Brad C.; Scialla, Julia J.; Appel, Lawrence J.; Li, Liang; Lipkowitz, Michael S.; Wolf, Myles; Parekh, Rulan S.; Winkler, Cheryl A.; Estrella, Michelle M.; Crews, Deidra C.

2015-01-01

Background and objectives Common apolipoprotein L1 (APOL1) variants are associated with increased risk of progressive CKD; however, not all individuals with high–risk APOL1 variants experience CKD progression. Identification of factors contributing to heterogeneity has important scientific and clinical implications. Design, setting, participants, & measurements Using multivariable Cox models, we analyzed data from 693 participants in the African American Study of Kidney Disease and Hypertension to identify factors that modify the association between APOL1 genotypes and CKD progression (doubling of serum creatinine or incident ESRD). Results Participant mean age was 54 years old, median GFR was 49 ml/min per 1.73 m2, and 23% had the APOL1 high–risk genotype (two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288 (42%) participants experienced CKD progression. As previously reported, the high-risk genotype was associated with higher risk of CKD progression compared with the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI], 1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI, 1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index ≥30 versus <30 kg/m2; P interaction =0.04) and increased urinary excretion of urea nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30 for urine urea nitrogen ≥8 versus <8 g/d; P interaction =0.04) were associated with lower APOL1–associated risk for CKD progression, these findings were not robust in sensitivity analyses with alternative cut points. No other sociodemographic (e.g., education and income), clinical (e.g., systolic BP and smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or fibroblast growth factor 23) variables modified the association between APOL1 and CKD progression (P interaction >0.05 for each). Conclusions Sociodemographic factors and common risk factors for CKD progression do not seem to alter APOL1–related CKD progression. Additional investigation is needed to identify nontraditional factors that may affect the association between APOL1 and progressive CKD. PMID:26430087

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

PubMed

Esquirol, Yolande; Tully, Mark; Ruidavets, Jean-Bernard; Fogarty, Damian; Ferrieres, Jean; Quinn, Michael; Hughes, Maria; Kee, Frank

2014-12-20

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain. We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease. From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years. For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease. Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Towards a more open debate about values in decision-making on agricultural biotechnology.

PubMed

Devos, Yann; Sanvido, Olivier; Tait, Joyce; Raybould, Alan

2014-12-01

Regulatory decision-making over the use of products of new technology aims to be based on science-based risk assessment. In some jurisdictions, decision-making about the cultivation of genetically modified (GM) plants is blocked supposedly because of scientific uncertainty about risks to the environment. However, disagreement about the acceptability of risks is primarily a dispute over normative values, which is not resolvable through natural sciences. Natural sciences may improve the quality and relevance of the scientific information used to support environmental risk assessments and make scientific uncertainties explicit, but offer little to resolve differences about values. Decisions about cultivating GM plants will thus not necessarily be eased by performing more research to reduce scientific uncertainty in environmental risk assessments, but by clarifying the debate over values. We suggest several approaches to reveal values in decision-making: (1) clarifying policy objectives; (2) determining what constitutes environmental harm; (3) making explicit the factual and normative premises on which risk assessments are based; (4) better demarcating environmental risk assessment studies from ecological research; (5) weighing the potential for environmental benefits (i.e., opportunities) as well as the potential for environmental harms (i.e., risks); and (6) expanding participation in the risk governance of GM plants. Recognising and openly debating differences about values will not remove controversy about the cultivation of GM plants. However, by revealing what is truly in dispute, debates about values will clarify decision-making criteria.

The Interaction between Epigenetics, Nutrition and the Development of Cancer

PubMed Central

Bishop, Karen S.; Ferguson, Lynnette R.

2015-01-01

Unlike the genome, the epigenome can be modified and hence some epigenetic risk markers have the potential to be reversed. Such modifications take place by means of drugs, diet or environmental exposures. It is widely accepted that epigenetic modifications take place during early embryonic and primordial cell development, but it is also important that we gain an understanding of the potential for such changes later in life. These “later life” epigenetic modifications in response to dietary intervention are the focus of this paper. The epigenetic modifications investigated include DNA methylation, histone modifications and the influence of microRNAs. The epigenotype could be used not only to predict susceptibility to certain cancers but also to assess the effectiveness of dietary modifications to reduce such risk. The influence of diet or dietary components on epigenetic modifications and the impact on cancer initiation or progression has been assessed herein. PMID:25647662

Garlic and onions: Their cancer prevention properties

PubMed Central

Nicastro, Holly L.; Ross, Sharon A.; Milner, John A.

2015-01-01

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiological studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biological processes that modify cancer risk. This review discusses the cancer preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps. PMID:25586902

Mediation and moderation of the association between cynical hostility and systolic blood pressure in low-income women.

PubMed

Versey, H Shellae; Kaplan, George A

2012-04-01

Hostility may be related to risk factors for cardiovascular disease (CVD), such as blood pressure. However, the process by which hostility affects blood pressure is not fully understood. The current study sought to evaluate abdominal obesity (waist-to-hip ratio [WHR]) as a potential mediator and modifier of the relationship between cynical hostility and systolic blood pressure (SBP) in a group of disadvantaged women. Path analysis and multiple regression models were used to identify mediating and moderating pathways in the relationship between cynical hostility and SBP. Results indicate a significant interaction between WHR and cynical hostility. WHR was a partial mediator and significant moderator of the association between hostility and blood pressure. These findings highlight the potential importance of examining abdominal obesity and psychosocial factors as conjunctive determinants of CVD and risk factors for related metabolic conditions.

Evaluation of an automatic segmentation algorithm for definition of head and neck organs at risk.

PubMed

Thomson, David; Boylan, Chris; Liptrot, Tom; Aitkenhead, Adam; Lee, Lip; Yap, Beng; Sykes, Andrew; Rowbottom, Carl; Slevin, Nicholas

2014-08-03

The accurate definition of organs at risk (OARs) is required to fully exploit the benefits of intensity-modulated radiotherapy (IMRT) for head and neck cancer. However, manual delineation is time-consuming and there is considerable inter-observer variability. This is pertinent as function-sparing and adaptive IMRT have increased the number and frequency of delineation of OARs. We evaluated accuracy and potential time-saving of Smart Probabilistic Image Contouring Engine (SPICE) automatic segmentation to define OARs for salivary-, swallowing- and cochlea-sparing IMRT. Five clinicians recorded the time to delineate five organs at risk (parotid glands, submandibular glands, larynx, pharyngeal constrictor muscles and cochleae) for each of 10 CT scans. SPICE was then used to define these structures. The acceptability of SPICE contours was initially determined by visual inspection and the total time to modify them recorded per scan. The Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm created a reference standard from all clinician contours. Clinician, SPICE and modified contours were compared against STAPLE by the Dice similarity coefficient (DSC) and mean/maximum distance to agreement (DTA). For all investigated structures, SPICE contours were less accurate than manual contours. However, for parotid/submandibular glands they were acceptable (median DSC: 0.79/0.80; mean, maximum DTA: 1.5 mm, 14.8 mm/0.6 mm, 5.7 mm). Modified SPICE contours were also less accurate than manual contours. The utilisation of SPICE did not result in time-saving/improve efficiency. Improvements in accuracy of automatic segmentation for head and neck OARs would be worthwhile and are required before its routine clinical implementation.

Modifying effect of N-acetyltransferase 2 genotype on the association between systemic lupus erythematosus and consumption of alcohol and caffeine-rich beverages.

PubMed

Kiyohara, Chikako; Washio, Masakazu; Horiuchi, Takahiko; Asami, Toyoko; Ide, Saburo; Atsumi, Tatsuya; Kobashi, Gen; Takahashi, Hiroki; Tada, Yoshifumi

2014-07-01

N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20-0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (Pinteraction = 0.026) or consumption of black tea (Pinteraction = 0.048). The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study. Copyright © 2014 by the American College of Rheumatology.

Detection of Genetically Modified Food: Has Your Food Been Genetically Modified?

ERIC Educational Resources Information Center

Brandner, Diana L.

2002-01-01

Explains the benefits and risks of genetically-modified foods and describes methods for genetically modifying food. Presents a laboratory experiment using a polymerase chain reaction (PCR) test to detect foreign DNA in genetically-modified food. (Contains 18 references.) (YDS)

Derivation and interpretation of hazard quotients to assess ecological risks from the cultivation of insect-resistant transgenic crops.

PubMed

Raybould, Alan; Caron-Lormier, Geoffrey; Bohan, David A

2011-06-08

Cost-effective and rigorous risk assessments for chemicals may be based on hazard quotients (HQs): the ratio of a measure of exposure to a substance and a measure of the effect of that substance. HQs have been used for many years in ecological risk assessments for the use of synthetic pesticides in agriculture, and methods for calculating pesticide HQs have been adapted for use with transgenic crops. This paper describes how laboratory methods for assessing the ecotoxicological effects of synthetic pesticides have been modified for the measurement of effects of insecticidal proteins, and how these effect measures are combined with exposure estimates to derive HQs for assessing the ecological risks from the cultivation of insect-resistant transgenic crops. The potential for ecological modeling to inform the design of laboratory effects tests for insecticidal proteins is also discussed.

Quantification of increased flood risk due to global climate change for urban river management planning.

PubMed

Morita, M

2011-01-01

Global climate change is expected to affect future rainfall patterns. These changes should be taken into account when assessing future flooding risks. This study presents a method for quantifying the increase in flood risk caused by global climate change for use in urban flood risk management. Flood risk in this context is defined as the product of flood damage potential and the probability of its occurrence. The study uses a geographic information system-based flood damage prediction model to calculate the flood damage caused by design storms with different return periods. Estimation of the monetary damages these storms produce and their return periods are precursors to flood risk calculations. The design storms are developed from modified intensity-duration-frequency relationships generated by simulations of global climate change scenarios (e.g. CGCM2A2). The risk assessment method is applied to the Kanda River basin in Tokyo, Japan. The assessment provides insights not only into the flood risk cost increase due to global warming, and the impact that increase may have on flood control infrastructure planning.

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

PubMed

Yamada, Shunsuke; Taniguchi, Masatomo; Tokumoto, Masanori; Yoshitomi, Ryota; Yoshida, Hisako; Tatsumoto, Narihito; Hirakata, Hideki; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. Cross-sectional study and prospective longitudinal cohort study. An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. Bone fracture at any site. In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The French Version of the Modified-Checklist for Autism in Toddlers (M-CHAT): A Validation Study on a French Sample of 24 Month-Old Children

ERIC Educational Resources Information Center

Baduel, Sophie; Guillon, Quentin; Afzali, Mohammad H.; Foudon, Nadège; Kruck, Jeanne; Rogé, Bernadette

2017-01-01

Early ASD screening has the potential to reduce delays between initial parental concerns and diagnosis, and promote early intervention. The aim of this study was to validate the M-CHAT on a French population sample of 24 month-old children. This study included a low-risk sample of 1,227 children. A total of 20 children screened positive on the…

Benefits and risks associated with genetically modified food products.

PubMed

Kramkowska, Marta; Grzelak, Teresa; Czyżewska, Krystyna

2013-01-01

Scientists employing methods of genetic engineering have developed a new group of living organisms, termed 'modified organisms', which found application in, among others, medicine, the pharmaceutical industry and food distribution. The introduction of transgenic products to the food market resulted in them becoming a controversial topic, with their proponents and contestants. The presented study aims to systematize objective data on the potential benefits and risks resulting from the consumption of transgenic food. Genetic modifications of plants and animals are justified by the potential for improvement of the food situation worldwide, an increase in yield crops, an increase in the nutritional value of food, and the development of pharmaceutical preparations of proven clinical significance. In the opinions of critics, however, transgenic food may unfavourably affect the health of consumers. Therefore, particular attention was devoted to the short- and long-lasting undesirable effects, such as alimentary allergies, synthesis of toxic agents or resistance to antibiotics. Examples arguing for the justified character of genetic modifications and cases proving that their use can be dangerous are innumerable. In view of the presented facts, however, complex studies are indispensable which, in a reliable way, evaluate effects linked to the consumption of food produced with the application of genetic engineering techniques. Whether one backs up or negates transgenic products, the choice between traditional and non-conventional food remains to be decided exclusively by the consumers.

Genetically modified plants and human health

PubMed Central

Key, Suzie; Ma, Julian K-C; Drake, Pascal MW

2008-01-01

Summary Genetically modified (or GM) plants have attracted a large amount of media attention in recent years and continue to do so. Despite this, the general public remains largely unaware of what a GM plant actually is or what advantages and disadvantages the technology has to offer, particularly with regard to the range of applications for which they can be used. From the first generation of GM crops, two main areas of concern have emerged, namely risk to the environment and risk to human health. As GM plants are gradually being introduced into the European Union there is likely to be increasing public concern regarding potential health issues. Although it is now commonplace for the press to adopt ‘health campaigns’, the information they publish is often unreliable and unrepresentative of the available scientific evidence. We consider it important that the medical profession should be aware of the state of the art, and, as they are often the first port of call for a concerned patient, be in a position to provide an informed opinion. This review will examine how GM plants may impact on human health both directly – through applications targeted at nutrition and enhancement of recombinant medicine production – but also indirectly, through potential effects on the environment. Finally, it will examine the most important opposition currently facing the worldwide adoption of this technology: public opinion. PMID:18515776

Regulatory challenges for GM crops in developing economies: the African experience.

PubMed

Nang'ayo, Francis; Simiyu-Wafukho, Stella; Oikeh, Sylvester O

2014-12-01

Globally, transgenic or genetically modified (GM) crops are considered regulated products that are subject to regulatory oversight during trans-boundary movement, testing and environmental release. In Africa, regulations for transgenic crops are based on the outcomes of the historic Earth Summit Conference held in Rio, Brazil two decades ago, namely, the adoption of the Convention on Biological Diversity (CBD) and the subsequent adoption of the Cartagena Protocol on Biosafety. To exploit the potential benefits of transgenic crops while safeguarding the potential risks on human health and environment, most African countries have signed and ratified the CBD and the Cartagena Protocol on Biosafety. Consequently, these countries are required to take appropriate legal, administrative and other measures to ensure that the handling and utilization of living modified organisms are undertaken in a manner that reduces the risks to humans and the environment. These countries are also expected to provide regulatory oversight on transgenic crops through functional national biosafety frameworks (NBFs). While in principle this approach is ideal, NBFs in most African countries are steeped in a host of policy, legal and operational challenges that appear to be at cross-purposes with the noble efforts of seeking to access, test and deliver promising GM crops for use by resource-limited farmers in Africa. In this paper we discuss the regulatory challenges faced during the development and commercialization of GM crops based on experiences from countries in Sub-Saharan Africa.

Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.

PubMed

Rhee, Gyu Seek; Cho, Dae Hyun; Won, Yong Hyuck; Seok, Ji Hyun; Kim, Soon Sun; Kwack, Seung Jun; Lee, Rhee Da; Chae, Soo Yeong; Kim, Jae Woo; Lee, Byung Mu; Park, Kui Lea; Choi, Kwang Sik

2005-12-10

Each specific protein has an individual gene encoding it, and a foreign gene introduced to a plant can be used to synthesize a new protein. The identification of potential reproductive and developmental toxicity from novel proteins produced by genetically modified (GM) crops is a difficult task. A science-based risk assessment is needed in order to use GM crops as a conventional foodstuff. In this study, the specific characteristics of GM food and low-level chronic exposure were examined using a five-generation animal study. In each generation, rats were fed a solid pellet containing 5% GM potato and non-GM potato for 10 wk prior to mating in order to assess the potential reproductive and developmental toxic effects. In the multigeneration animal study, there were no GM potato-related changes in body weight, food consumption, reproductive performance, and organ weight. Polymerase chain reaction (PCR) was carried out using extracted genomic DNA to examine the possibility of gene persistence in the organ tissues after a long-term exposure to low levels of GM feed. In each generation, the gene responsible for bar was not found in any of the reproductive organs of the GM potato-treated male and female rats, and the litter-related indexes did not show any genetically modified organism (GMO)-related changes. The results suggest that genetically modified crops have no adverse effects on the multigeneration reproductive-developmental ability.

Characteristics Associated With Severe Perineal and Cervical Lacerations During Vaginal Delivery

PubMed Central

Landy, Helain J.; Laughon, S. Katherine; Bailit, Jennifer; Kominiarek, Michelle A.; Gonzalez-Quintero, Victor Hugo; Ramirez, Mildred; Haberman, Shoshana; Hibbard, Judith; Wilkins, Isabelle; Branch, D. Ware; Burkman, Ronald T.; Gregory, Kimberly; Hoffman, Matthew K.; Learman, Lee A.; Hatjis, Christos; VanVeldhuisen, Paul C.; Reddy, Uma M.; Troendle, James; Sun, Liping; Zhang, Jun

2011-01-01

Objective To characterize potentially modifiable risk factors for third- or fourth-degree perineal lacerations and cervical lacerations in a contemporary U.S. obstetric practice. Methods The Consortium on Safe Labor collected electronic medical records from 19 hospitals within 12 institutions (228,668 deliveries from 2002 to 2008). Information on patient characteristics, prenatal complications, labor and delivery data, and maternal and neonatal outcomes were collected. Only women with successful vaginal deliveries of cephalic singletons at 34 weeks of gestation or later were included; we excluded data from sites lacking information about lacerations at delivery and deliveries complicated by shoulder dystocia; 87,267 and 71,170 women were analyzed for third- or fourth-degree and cervical lacerations, respectively. Multivariable logistic regressions were used to adjust for other factors. Results Third- or fourth-degree lacerations occurred in 2,516 women (2,223 nulliparous [5.8%], 293 [0.6%] multiparous) and cervical lacerations occurred in 536 women (324 nulliparous [1.1%], 212 multiparous [0.5%]). Risks for third or fourth-degree lacerations included nulliparity (7.2-fold risk), being Asian or Pacific Islander, increasing birth weight, operative vaginal delivery, episiotomy, and longer second stage of labor. Increasing body mass index was associated with fewer lacerations. Risk factors for cervical lacerations included young maternal age, vacuum vaginal delivery, and oxytocin use among multiparous women, and cerclage regardless of parity. Conclusion Our large cohort of women with severe obstetric lacerations reflects contemporary obstetric practices. Nulliparity and episiotomy use are important risk factors for third- or fourth-degree lacerations. Cerclage increases the risk for cervical lacerations. Many identified risk factors may not be modifiable. PMID:21343766

Evaluation of copy-number variants as modifiers of breast and ovarian cancer risk for BRCA1 pathogenic variant carriers

PubMed Central

Walker, Logan C; Marquart, Louise; Pearson, John F; Wiggins, George A R; O'Mara, Tracy A; Parsons, Michael T; Barrowdale, Daniel; McGuffog, Lesley; Dennis, Joe; Benitez, Javier; Slavin, Thomas P; Radice, Paolo; Frost, Debra; Godwin, Andrew K; Meindl, Alfons; Schmutzler, Rita Katharina; Isaacs, Claudine; Peshkin, Beth N; Caldes, Trinidad; Hogervorst, Frans BL; Lazaro, Conxi; Jakubowska, Anna; Montagna, Marco; Chen, Xiaoqing; Offit, Kenneth; Hulick, Peter J; Andrulis, Irene L; Lindblom, Annika; Nussbaum, Robert L; Nathanson, Katherine L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Couch, Fergus J; Spurdle, Amanda B

2017-01-01

Genome-wide studies of patients carrying pathogenic variants (mutations) in BRCA1 or BRCA2 have reported strong associations between single-nucleotide polymorphisms (SNPs) and cancer risk. To conduct the first genome-wide association analysis of copy-number variants (CNVs) with breast or ovarian cancer risk in a cohort of 2500 BRCA1 pathogenic variant carriers, CNV discovery was performed using multiple calling algorithms and Illumina 610k SNP array data from a previously published genome-wide association study. Our analysis, which focused on functionally disruptive genomic deletions overlapping gene regions, identified a number of loci associated with risk of breast or ovarian cancer for BRCA1 pathogenic variant carriers. Despite only including putative deletions called by at least two or more algorithms, detection of selected CNVs by ancillary molecular technologies only confirmed 40% of predicted common (>1% allele frequency) variants. These include four loci that were associated (unadjusted P<0.05) with breast cancer (GTF2H2, ZNF385B, NAALADL2 and PSG5), and two loci associated with ovarian cancer (CYP2A7 and OR2A1). An interesting finding from this study was an association of a validated CNV deletion at the CYP2A7 locus (19q13.2) with decreased ovarian cancer risk (relative risk=0.50, P=0.007). Genomic analysis found this deletion coincides with a region displaying strong regulatory potential in ovarian tissue, but not in breast epithelial cells. This study highlighted the need to verify CNVs in vitro, but also provides evidence that experimentally validated CNVs (with plausible biological consequences) can modify risk of breast or ovarian cancer in BRCA1 pathogenic variant carriers. PMID:28145423

CARCINOGEN METABOLISM GENES, RED MEAT AND POULTRY INTAKE, AND COLORECTAL CANCER RISK

PubMed Central

Wang, Jun; Joshi, Amit D.; Corral, Román; Siegmund, Kimberly D.; Le Marchand, Loïc; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

2011-01-01

Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk (p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk. PMID:21618522

Associations between anthropometric characteristics, physical activity, and breast cancer risk in a Canadian cohort.

PubMed

Catsburg, Chelsea; Kirsh, Victoria A; Soskolne, Colin L; Kreiger, Nancy; Bruce, Erin; Ho, Thi; Leatherdale, Scott T; Rohan, Thomas E

2014-06-01

Obesity, physical inactivity, and sedentary behavior, concomitants of the modern environment, are potentially modifiable breast cancer risk factors. This study investigated the association of anthropometric measurements, physical activity and sedentary behavior, with the risk of incident, invasive breast cancer using a prospective cohort of women enrolled in the Canadian Study of Diet, Lifestyle and Health. Using a case-cohort design, an age-stratified subcohort of 3,320 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary questionnaires at baseline. A total of 1,097 incident breast cancer cases were identified from the entire cohort via linkage to the Canadian Cancer Registry. Cox regression models, modified to account for the case-cohort design, were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between anthropometric characteristics, physical activity, and the risk of breast cancer. Weight gain as an adult was positively associated with risk of post-menopausal breast cancer, with a 6 % increase in risk for every 5 kg gained since age 20 (HR 1.06; 95 % CI 1.01-1.11). Women who exercised more than 30.9 metabolic equivalent task (MET) hours per week had a 21 % decreased risk of breast cancer compared to women who exercised less than 3 MET hours per week (HR  0.79; 95 % CI 0.62-1.00), most evident in pre-menopausal women (HR  0.62; 95 % CI 0.43-0.90). As obesity reaches epidemic proportions and sedentary lifestyles have become more prevalent in modern populations, programs targeting adult weight gain and promoting physical activity may be beneficial with respect to reducing breast cancer morbidity.

Platelet function is modified by common sequence variation in megakaryocyte super enhancers

PubMed Central

Petersen, Romina; Lambourne, John J.; Javierre, Biola M.; Grassi, Luigi; Kreuzhuber, Roman; Ruklisa, Dace; Rosa, Isabel M.; Tomé, Ana R.; Elding, Heather; van Geffen, Johanna P.; Jiang, Tao; Farrow, Samantha; Cairns, Jonathan; Al-Subaie, Abeer M.; Ashford, Sofie; Attwood, Antony; Batista, Joana; Bouman, Heleen; Burden, Frances; Choudry, Fizzah A.; Clarke, Laura; Flicek, Paul; Garner, Stephen F.; Haimel, Matthias; Kempster, Carly; Ladopoulos, Vasileios; Lenaerts, An-Sofie; Materek, Paulina M.; McKinney, Harriet; Meacham, Stuart; Mead, Daniel; Nagy, Magdolna; Penkett, Christopher J.; Rendon, Augusto; Seyres, Denis; Sun, Benjamin; Tuna, Salih; van der Weide, Marie-Elise; Wingett, Steven W.; Martens, Joost H.; Stegle, Oliver; Richardson, Sylvia; Vallier, Ludovic; Roberts, David J.; Freson, Kathleen; Wernisch, Lorenz; Stunnenberg, Hendrik G.; Danesh, John; Fraser, Peter; Soranzo, Nicole; Butterworth, Adam S.; Heemskerk, Johan W.; Turro, Ernest; Spivakov, Mikhail; Ouwehand, Willem H.; Astle, William J.; Downes, Kate; Kostadima, Myrto; Frontini, Mattia

2017-01-01

Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits using cell type-matched epigenomic data and promoter long-range interactions. We identify potential regulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we demonstrate, through ex vivo and proof of principle genome editing validation, that variants in super enhancers play an important role in controlling archetypical platelet functions. PMID:28703137

[Surgical treatment of prolapse by abdominal route and effort-related urinary incontinence].

PubMed

Wagner, L; Fatton, B; Delmas, V; Haab, F; Costa, P

2009-12-01

Stress urinary incontinence is often associated with prolapse. The suburethral tapes have modified the indication for a preventive treatment of incontinence. The tapes are necessary in case of patent or masked incontinence, discussed in case of potential incontinence. The diagnosis of incontinence is done on questions to the patient, clinical exam, more than in urodynamic study. There is no absolute sign allowing to predict postoperative incontinence after surgery for prolapse. A continent woman can be incontinent postoperatively. If a potential incontinence is treated in the same as the prolapse, the patient must be informed of risk of obstruction and/or urgency.

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.

A review about the effect of life style modification on diabetes and quality of life.

PubMed

Shrestha, Prabha; Ghimire, Laxmi

2012-10-10

The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required.

A Review about the Effect of Life style Modification on Diabetes and Quality of Life

PubMed Central

Shrestha, Prabha; Ghimire, Laxmi

2012-01-01

The aim of this review is to examine diabetes and quality of life improvements through modifying life style. The data was collected by reviewing published articles from PubMed, Medline, Web of Science, and Google open access publications. The review identified prevention strategies can reduce the risk and complications of diabetes. Life style modification in relation to obesity, eating habit, and physical exercise can play a major role in the prevention of diabetes. Nowadays, there has been progress in the development of behavioural strategies to modify these life style habits and it is not easy to accept for long term basis. If people maintain a balanced diet and physical exercise this can have real and potential benefits for their prevention and control of complications from chronic diseases particularly for cardiovascular risk and diabetes. Healthy life style may best be achieved through public private partnerships involving government, partners organizations, health services providers, community and people living with diabetes. Effective strategies to reduce the incidence of diabetes globally and assist in managing the disease are urgently required. PMID:23121755

Landmarks in the history of cancer epidemiology.

PubMed

Greenwald, Peter; Dunn, Barbara K

2009-03-15

The application of epidemiology to cancer prevention is relatively new, although observations of the potential causes of cancer have been reported for more than 2,000 years. Cancer was generally considered incurable until the late 19th century. Only with a refined understanding of the nature of cancer and strategies for cancer treatment could a systematic approach to cancer prevention emerge. The 20th century saw the elucidation of clues to cancer causation from observed associations with population exposures to tobacco, diet, environmental chemicals, and other exogenous factors. With repeated confirmation of such associations, researchers entertained for the first time the possibility that cancer, like many of the infectious diseases of the time, might be prevented. By the mid-20th century, with antibiotics successfully addressing the majority of infectious diseases and high blood pressure treatment beginning to affect the prevalence of heart disease in a favorable direction, the focus of much of epidemiology shifted to cancer. The early emphasis was on exploring, in greater depth, the environmental, dietary, hormonal, and other exogenous exposures for their potential associations with increased cancer risk. The first major breakthrough in identifying a modifiable cancer risk factor was the documentation of an association between tobacco smoking and lung cancer. During the past four decades, epidemiologic studies have generated population data identifying risk factors for cancers at almost every body site, with many cancers having multiple risk factors. The development of technologies to identify biological molecules has facilitated the incorporation of these molecular manifestations of biological variation into epidemiologic studies, as markers of exposure as well as putative surrogate markers of cancer outcome. This technological trend has, during the past two decades, culminated in emphasis on the identification of genetic variants and their products as correlates of cancer risk, in turn, creating opportunities to incorporate the discipline of molecular/genetic epidemiology into the study of cancer prevention. Epidemiology will undoubtedly continue contributing to cancer prevention by using traditional epidemiologic study designs to address broad candidate areas of interest, with molecular/genetic epidemiology investigations honing in on promising areas to identify specific factors that can be modified with the goal of reducing risk.

Ecological risk assessment of coastal ecosystems: The case of mangrove forests in Hormozgan Province, Iran.

PubMed

Ghasemi, Saber; Moghaddam, Sina Siavash; Rahimi, Amir; Damalas, Christos A; Naji, Abolfazl

2018-01-01

Sediment quality of mangrove forests in Hormozgan Province of Iran with a focus on two distinct habitats - the Hara Protected Area and the area of the Azini Bay - was studied. The accumulation of heavy metals in the sediments of the Hara Protected Area in terms of concentration was in the order of Pb > Zn > Cu > Cd and in those of the Azini Bay in the order of Zn > Cu > Pb > Cd. Based on Pearson's correlation coefficient, no significant correlations were found between concentrations of heavy metals in the sediments of the Hara Protected Area, while Zn and Pb concentrations were positively correlated in the sediments of the Azini Bay, implying a common pollution source. Common pollution indices, such as Contamination factor (Cf), degree of contamination (Cd), modified contamination degree (mCd), potential ecological risk index (RI) and metal pollution index (MPI), were used for assessing contamination status. The value of contamination (Cd) index was lower than 7 across all five stations of each studied region, implying a low degree of contamination. The modified contamination degree (mCd) index was lower than 1.5, showing that the sediment pollution was low in both regions. The potential ecological risk assessment index was 223.89 and 543.97 for the Hara Protected Area and the Azini Bay, respectively. Based on categorization of Hakanson's ecological risk, the Hara Protected Area region was in the range of 150 ≤ RI ≤ 300 (moderate ecological risk) and the Azini Bay region in the range of 300 ≤ RI ≤ 600 (acceptable ecological risk). Findings raise awareness of the contamination status of mangrove forests in Hormozgan Province, provide a valuable benchmark for future comparisons in the area, and are important for the design of appropriate policies and long-term management of those ecosystems by local managers and the national authorities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Academic Achievement and Risk Factors for Adolescents with Attention-Deficit Hyperactivity Disorder in Middle School and Early High School.

PubMed

Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet

Examine academic achievement of students with attention-deficit hyperactivity disorder (ADHD) during the early high school period and identify potentially modifiable risk factors for low achievement. Data were collected through surveys (adolescent, parent, and teacher) and direct assessment of Australian adolescents (12-15 yr; n = 130) with ADHD in early high school (i.e., US middle and high school grades). Academic achievement outcomes were measured by linking to individual performance on the National Assessment Program-Literacy and Numeracy (NAPLAN) tests, direct assessment of reading and math, and teacher report of academic competence. Linear regression models examined associations between adolescent, parent/family, and school factors and NAPLAN domain scores. Students with ADHD had lower NAPLAN scores on all domains and fewer met minimum academic standards in comparison with state benchmarks. The poorest results were for persuasive writing. Poor achievement was associated with lower intelligence quotient across all academic domains. Adolescent inattention, bullying, poor family management, male sex, and attending a low socioeconomic status school were associated with lower achievement on specific domains. Students with ADHD are at increased academic risk during the middle school and early high school period. In addition to academic support, interventions targeting modifiable factors including inattention, bullying, and poor family management may improve academic achievement across this critical period.

Adaptation of the ToxRTool to Assess the Reliability of Toxicology Studies Conducted with Genetically Modified Crops and Implications for Future Safety Testing.

PubMed

Koch, Michael S; DeSesso, John M; Williams, Amy Lavin; Michalek, Suzanne; Hammond, Bruce

2016-01-01

To determine the reliability of food safety studies carried out in rodents with genetically modified (GM) crops, a Food Safety Study Reliability Tool (FSSRTool) was adapted from the European Centre for the Validation of Alternative Methods' (ECVAM) ToxRTool. Reliability was defined as the inherent quality of the study with regard to use of standardized testing methodology, full documentation of experimental procedures and results, and the plausibility of the findings. Codex guidelines for GM crop safety evaluations indicate toxicology studies are not needed when comparability of the GM crop to its conventional counterpart has been demonstrated. This guidance notwithstanding, animal feeding studies have routinely been conducted with GM crops, but their conclusions on safety are not always consistent. To accurately evaluate potential risks from GM crops, risk assessors need clearly interpretable results from reliable studies. The development of the FSSRTool, which provides the user with a means of assessing the reliability of a toxicology study to inform risk assessment, is discussed. Its application to the body of literature on GM crop food safety studies demonstrates that reliable studies report no toxicologically relevant differences between rodents fed GM crops or their non-GM comparators.

The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test.

PubMed

Boonchai, Waranya; Sathaworawong, Angkana; Wongpraparut, Chanisada; Wanitphakdeedecha, Rungsima

2015-10-01

Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

Prevalence and molecular characterization of bovine Cryptosporidium from dairy cows in Northern Thailand.

PubMed

Inpankaew, Tawin; Jiyipong, Tawisa; Sunanta, Chainirun; Kengradomkij, Chanya; Pinyopanuwat, Nongnuch; Jittapalapong, Sathaporn

2017-12-20

Cryptosporidiosis is a common protozoan infection in humans and domestic animals. It is the culprit for significant neonatal morbidity in cattle as well as weight loss and delayed growth, which leads to large economic losses in the farming industry. Furthermore, bovine Cryptosporidium is also a principal source of human Cryptosporidium infections. The purpose of this study is to determine prevalence and genotype of Cryptosporidium spp. from feces of dairy cows from the northern parts of Thailand (Chiang Rai, Chiang Mai, and Lumpang provinces). A total of 500 fecal samples were collected directly from the rectum and they were examined for potential presence of Cryptosporidium infection by using tests such as DMSO-modified acid fast stain, immunofluorescence antibody test (IFAT) and polymerase chain reaction (PCR). The prevalence of Cryptosporidium spp. was 5% by DMSO-modified acid fast stain, 7% by IFAT and 7.6% by PCR respectively. The main genotypes of Cryptosporidium spp. identified were Cryptosporidium parvum and Cryptosporidium bovis. Therefore, as a result of this study, it can be said that, due to the potential cross-species transmission of Cryptosporidium parvum, infected dairy cows may pose a potential zoonotic risk to humans.

Invasive aquarium fish transform ecosystem nutrient dynamics

PubMed Central

Capps, Krista A.; Flecker, Alexander S.

2013-01-01

Trade of ornamental aquatic species is a multi-billion dollar industry responsible for the introduction of myriad fishes into novel ecosystems. Although aquarium invaders have the potential to alter ecosystem function, regulation of the trade is minimal and little is known about the ecosystem-level consequences of invasion for all but a small number of aquarium species. Here, we demonstrate how ecological stoichiometry can be used as a framework to identify aquarium invaders with the potential to modify ecosystem processes. We show that explosive growth of an introduced population of stoichiometrically unique, phosphorus (P)-rich catfish in a river in southern Mexico significantly transformed stream nutrient dynamics by altering nutrient storage and remineralization rates. Notably, changes varied between elements; the P-rich fish acted as net sinks of P and net remineralizers of nitrogen. Results from this study suggest species-specific stoichiometry may be insightful for understanding how invasive species modify nutrient dynamics when their population densities and elemental composition differ substantially from native organisms. Risk analysis for potential aquarium imports should consider species traits such as body stoichiometry, which may increase the likelihood that an invasion will alter the structure and function of ecosystems. PMID:23966642

Discrete two-sex models of population dynamics: On modelling the mating function

NASA Astrophysics Data System (ADS)

Bessa-Gomes, Carmen; Legendre, Stéphane; Clobert, Jean

2010-09-01

Although sexual reproduction has long been a central subject of theoretical ecology, until recently its consequences for population dynamics were largely overlooked. This is now changing, and many studies have addressed this issue, showing that when the mating system is taken into account, the population dynamics depends on the relative abundance of males and females, and is non-linear. Moreover, sexual reproduction increases the extinction risk, namely due to the Allee effect. Nevertheless, different studies have identified diverse potential consequences, depending on the choice of mating function. In this study, we investigate the consequences of three alternative mating functions that are frequently used in discrete population models: the minimum; the harmonic mean; and the modified harmonic mean. We consider their consequences at three levels: on the probability that females will breed; on the presence and intensity of the Allee effect; and on the extinction risk. When we consider the harmonic mean, the number of times the individuals of the least abundant sex mate exceeds their mating potential, which implies that with variable sex-ratios the potential reproductive rate is no longer under the modeller's control. Consequently, the female breeding probability exceeds 1 whenever the sex-ratio is male-biased, which constitutes an obvious problem. The use of the harmonic mean is thus only justified if we think that this parameter should be re-defined in order to represent the females' breeding rate and the fact that females may reproduce more than once per breeding season. This phenomenon buffers the Allee effect, and reduces the extinction risk. However, when we consider birth-pulse populations, such a phenomenon is implausible because the number of times females can reproduce per birth season is limited. In general, the minimum or modified harmonic mean mating functions seem to be more suitable for assessing the impact of mating systems on population dynamics.

Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

PubMed

Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

2017-11-01

To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Impact of a modified carbonated beverage on human dental plaque and salivary pH: an in vivo study.

PubMed

Sardana, V; Balappanavar, A Y; Patil, G B; Kulkarni, N; Sagari, S G; Gupta, K D

2012-01-01

To assess the plaque and salivary pH changes at different time intervals in vivo after consumption of a carbonated beverage modified with sodium fluoride and calcium phosphate. Twenty-four subjects aged 18-25 years were recruited and randomly assigned to three groups (group A, original drink Sprite; group B, Sprite with sodium fluoride; group C, Sprite with calcium phosphate). Collection of pooled plaque and unstimulated saliva was done before and after the drinks were consumed by the subjects at 5-, 10-, 20- and 30-minute intervals. The pH rise was higher with group C for plaque and group B for saliva. Modification of the test carbonated beverage with calcium phosphate and fluoride may exert some protective potential, especially in high caries risk candidates.

Exercise-mediated changes in high-density lipoprotein: impact on form and function.

PubMed

Blazek, Alisa; Rutsky, Jessica; Osei, Kwame; Maiseyeu, Andrei; Rajagopalan, Sanjay

2013-09-01

The goal of this systematic review was to assess the current understanding of the effects of exercise intervention on high-density lipoprotein (HDL) cholesterol (HDL-C) and changes in HDL function as well as modification of these effects by genomic factors. The reviewed studies demonstrate that exercise has modest effects on HDL-C with limited data suggesting an effect on HDL function. Genetic polymorphisms in proteins associated with HDL metabolism play a role in modifying the HDL-C response to exercise and possibly its function. Exercise as an intervention for patients at risk for cardiovascular events can lead to small improvements in HDL-C and potential changes in HDL function. There is an important modifier effect of genetics in determining these changes. Copyright © 2013 Mosby, Inc. All rights reserved.

Neck injury criteria formulation and injury risk curves for the ejection environment: a pilot study.

PubMed

Parr, Jeffrey C; Miller, Michael E; Pellettiere, Joseph A; Erich, Roger A

2013-12-01

Helmet mounted displays provide increased pilot capability, but can also increase the risk of injury during ejection. The National Highway Transportation Safety Administration's (NHTSA's) neck injury criteria (Nij) metric is evaluated for understanding the impact of helmet mass on the risk of injury and modified risk curves are developed which are compatible with the needs of the aviation community. Existent human subject data collected under various accelerative and head loading conditions were applied to understand the sensitivity of the Nij construct to changes in acceleration and helmet mass, as well as its stability with respect to gender, body mass, neck circumference, and sitting height. A portion of this data was combined with data from an earlier postmortem human subject study to create pilot study modified risk curves. These curves were compared and contrasted with the NHTSA risk curves. A statistically significant difference in the peak mean Nij was observed when seat acceleration increased by 2 G, but not when helmet mass was varied from 1.6 kg to 2 kg at a constant seat acceleration of 8 G. Although NHTSA risk curves predict a 13% risk of AIS 2+ injury for the 8-G, 2-kg helmet condition mean Nij of 0.138, no AIS 2+ injuries were observed. Modified risk curves were produced which predict a 0.91% risk of AIS 2+ injury under these conditions. The Nij was shown to be sensitive to changes in acceleration and generally robust to anthropometric differences between individuals. Modified risk curves are proposed which improve risk prediction at lower Nij values.

Early Detection for Dengue Using Local Indicator of Spatial Association (LISA) Analysis.

PubMed

Parra-Amaya, Mayra Elizabeth; Puerta-Yepes, María Eugenia; Lizarralde-Bejarano, Diana Paola; Arboleda-Sánchez, Sair

2016-03-29

Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes . There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for preventing the occurrence of dengue. For this reason, entomological surveillance is recommended by World Health Organization (WHO) to measure dengue risk in endemic areas; however, several works have shown that the current methodology (aedic indices) is not sufficient for predicting dengue. In this work, we modified indices proposed for epidemic periods. The raw value of the epidemiological wave could be useful for detecting risk in epidemic periods; however, risk can only be detected if analyses incorporate the maximum epidemiological wave. Risk classification was performed according to Local Indicators of Spatial Association (LISA) methodology. The modified indices were analyzed using several hypothetical scenarios to evaluate their sensitivity. We found that modified indices could detect spatial and differential risks in epidemic and endemic years, which makes them a useful tool for the early detection of a dengue outbreak. In conclusion, the modified indices could predict risk at the spatio-temporal level in endemic years and could be incorporated in surveillance activities in endemic places.

Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication–Adolescent Supplement Study

PubMed Central

Carliner, Hannah; Keyes, Katherine M.; McLaughlin, Katie A.; Meyers, Jacquelyn L.; Dunn, Erin C.; Martins, Silvia S.

2016-01-01

Objective Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. Method Data were drawn from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A), which included adolescents aged 13-18 years (N=9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. Results Exposure to any PTE prior to age 11 was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR=1.80), other drugs (RR=1.90), and multiple drugs (RR=1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. Conclusion Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention; and that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events. PMID:27453084

Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication-Adolescent Supplement Study.

PubMed

Carliner, Hannah; Keyes, Katherine M; McLaughlin, Katie A; Meyers, Jacquelyn L; Dunn, Erin C; Martins, Silvia S

2016-08-01

Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. Data were drawn from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A), which included adolescents aged 13 to 18 years (N = 9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. Exposure to any PTE before age 11 years was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR = 1.80), other drugs (RR = 1.90), and multiple drugs (RR = 1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention. The results also highlight that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of work experience on fatigue-induced biomechanical changes during repetitive asymmetric lifts/lowers.

PubMed

Lee, Jungyong; Nussbaum, Maury A; Kyung, Gyouhyung

2014-01-01

Repetitive lifting/lowering is associated with an increased risk of work-related low back disorders (WRLBDs), and fatigue may exacerbate such risk. Work methods used by experienced workers are potential models for developing worker training to reduce WRLBDs, though whether experience modifies the effects of fatigue on WRLBD risk is largely unknown. Here, six novices and six experienced workers completed 185 cycles of repetitive, asymmetric lifts/lowers. Physical demands, whole-body balance and torso movement stability were assessed using torso kinematics/kinetics, linear/angular momenta and Lyapunov exponents, respectively. Several fatigue-induced changes in movement strategies were evident. Novices decreased and experienced workers increased peak lumbar moments post-fatigue, suggesting lower WRLBD risks among the former in terms of torso kinetics. Other than lumbar moments, though, fatigue substantially reduced group-level differences in torso twisting velocities and accelerations. Post-fatigue movement strategies of experienced workers thus did not appear to be advantageous in terms of WRLBD risk.

[Drug trials in humans. Risks in the light of the London catastrophe].

PubMed

Otte, A

2007-06-01

London's first-in-man drug trial with the monoclonal anti-CD28 antibody TGN1412 used for the treatment of oncological and autoimmune diseases resulted in a disaster with life-threatening adverse events in the volunteers triggered by an unexpected cytokine storm. Potential mistakes and consequences from this trial are highlighted in the general context of drug development and its risks. Risks in drug testing are not only found for high risk substances, such as TGN1412, or in the critical first-in-man phase, but can sometimes be detected only in later phases of the clinical testing, such as the phase 3 submission studies, or even after market authorization, as for example was the case in the cyclooxygenase-2-inhibitor rofecoxib (Vioxx) used for the treatment of rheumatic diseases and acute pain. Regulatory requirements to minimize risks in drug trials, however, have improved substantially over the last decades. Moreover, in light of the London incident these are being continuously modified with great diligence.

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

PubMed

Davis, D L; Telang, N T; Osborne, M P; Bradlow, H L

1997-04-01

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data.

PubMed

Yelland, Lisa N; Salter, Amy B; Ryan, Philip

2011-10-15

Modified Poisson regression, which combines a log Poisson regression model with robust variance estimation, is a useful alternative to log binomial regression for estimating relative risks. Previous studies have shown both analytically and by simulation that modified Poisson regression is appropriate for independent prospective data. This method is often applied to clustered prospective data, despite a lack of evidence to support its use in this setting. The purpose of this article is to evaluate the performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data, by using generalized estimating equations to account for clustering. A simulation study is conducted to compare log binomial regression and modified Poisson regression for analyzing clustered data from intervention and observational studies. Both methods generally perform well in terms of bias, type I error, and coverage. Unlike log binomial regression, modified Poisson regression is not prone to convergence problems. The methods are contrasted by using example data sets from 2 large studies. The results presented in this article support the use of modified Poisson regression as an alternative to log binomial regression for analyzing clustered prospective data when clustering is taken into account by using generalized estimating equations.

AllergenOnline: A peer-reviewed, curated allergen database to assess novel food proteins for potential cross-reactivity.

PubMed

Goodman, Richard E; Ebisawa, Motohiro; Ferreira, Fatima; Sampson, Hugh A; van Ree, Ronald; Vieths, Stefan; Baumert, Joseph L; Bohle, Barbara; Lalithambika, Sreedevi; Wise, John; Taylor, Steve L

2016-05-01

Increasingly regulators are demanding evaluation of potential allergenicity of foods prior to marketing. Primary risks are the transfer of allergens or potentially cross-reactive proteins into new foods. AllergenOnline was developed in 2005 as a peer-reviewed bioinformatics platform to evaluate risks of new dietary proteins in genetically modified organisms (GMO) and novel foods. The process used to identify suspected allergens and evaluate the evidence of allergenicity was refined between 2010 and 2015. Candidate proteins are identified from the NCBI database using keyword searches, the WHO/IUIS nomenclature database and peer reviewed publications. Criteria to classify proteins as allergens are described. Characteristics of the protein, the source and human subjects, test methods and results are evaluated by our expert panel and archived. Food, inhalant, salivary, venom, and contact allergens are included. Users access allergen sequences through links to the NCBI database and relevant references are listed online. Version 16 includes 1956 sequences from 778 taxonomic-protein groups that are accepted with evidence of allergic serum IgE-binding and/or biological activity. AllergenOnline provides a useful peer-reviewed tool for identifying the primary potential risks of allergy for GMOs and novel foods based on criteria described by the Codex Alimentarius Commission (2003). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Knowledge regarding risk factors of hypertension among entry year students of a medical university

PubMed Central

Shaikh, Rizwana B.; Mathew, Elsheba; Sreedharan, Jayadevan; Muttappallymyalil, Jayakumary; Sharbatti, Shatha Al; Basha, Shaikh A.

2011-01-01

Context: Hypertension in youth is increasing, but there is a dearth of data about the knowledge of risk factors in this age group. Aims: To assess the knowledge of risk factors of hypertension among university students and associate it with the blood pressure, physical activity, family history of cardiovascular disease (CVD), and sociodemographic variables. Materials and Methods: A cross-sectional survey among students enrolled in the first year, in the four academic programs, with the use of a validated, self-administered questionnaire on physical activity in the past 30 days and knowledge of risk factors of hypertension. A score of 6 on 11 was considered as good knowledge for modifiable risk factors. Blood pressure was also measured. The data was analyzed using PASW-17, Chi square test, and binary logistic regression analysis was done. Results: Of the 110 participants, 69.2% were < 20 years of age, 76.4% were females, and 40% were Arabs. Stress, high cholesterol, obesity, and smoking were identified as risk factors by 75.5, 73.6, 77.6, and 71.8%, respectively; 69.1% considered high salt intake and 62.7% considered high calorie diet as risk factors. Energy drink was considered as a risk factor by 64.5%, coffee consumption 35.5%, physical inactivity 47%, and oral contraceptives 13.6%. Half the group did not consider a family history of CVD as a risk factor, 60% did not consider older age as a risk factor, and 88% did not think male gender was a risk factor. Knowledge of modifiable risk factors was better than that of non-modifiable risk factors. Although nationality, course of study, raised blood pressure, and history of diabetes showed significant association with good knowledge, their net effect was not significant by the Adjusted Odd's Ratio. Conclusions: The study identified some gaps in knowledge regarding both modifiable and non-modifiable risk factors of hypertension among students. A larger study would enable health promotion activities tailored to the needs of this age group. PMID:22175039

Impact of Modified System of Objectified Judgement Analysis (SOJA) methodology on prescribing costs of ACE inhibitors.

PubMed

Alabbadi, Ibrahim; Crealey, Grainne; Scott, Michael; Baird, Simon; Trouton, Tom; Mairs, Jill; McElnay, James

2006-01-01

System of Objectified Judgement Analysis (SOJA) is a structured approach to the selection of drugs for formulary inclusion. How- ever, while SOJA is a very important advance in drug selection for formulary purposes, it is hospital based and can only be applied to one indication at a time. In SOJA, cost has been given a primary role in the selection process as it has been included as a selection criterion from the start. Cost may therefore drive the selection of a particular drug product at the expense of other basic criteria such as safety or efficacy. The aims of this study were to use a modified SOJA approach in the selection of ACE inhibitors (ACEIs) for use in a joint formulary that bridges primary and secondary care within a health board in Northern Ireland, and to investigate the potential impact of the joint formulary on prescribing costs of ACEIs in that health board. The modified SOJA approach involved four phases in sequence: an evidence-based pharmacotherapeutic evaluation of all available ACEI drug entities, a separate safety/risk assessment analysis of products containing agents that exceeded the pharmacotherapeutic threshold, a budget-impact analysis and, finally, the selection of product lines. A comprehensive literature review and expert panel judgement informed the selection of criteria (and their relative weighting) for the pharmacotherapeutic evaluation. The resultant criteria/scoring system was circulated (in questionnaire format) to prescribers and stakeholders for comment. Based on statistical analysis of the latter survey results, the final scoring system was developed. Drug entities that exceeded the evidence threshold were sequentially entered into the second and third phases of the process. Five drug entities (11 currently available in the UK) exceeded the evidence threshold and 22 of 26 submitted product lines containing these drug entities satisfied the safety/risk assessment criteria. Three product lines, each containing a different drug entity, were selected for formulary inclusion after budget impact analysis was performed. The estimated potential annual cost savings for ACEIs (based on estimated annual usage in defined daily doses) for this particular health board was 42%. The modified SOJA approach has a significant contribution to make in containing the costs of ACEIs. Applying modified SOJA as a practical method for all indications will allow the development of a unified formulary that bridges secondary and primary care.

Modifiable Lifestyle Risk Factors and Incident Diabetes in African Americans.

PubMed

Joseph, Joshua J; Echouffo-Tcheugui, Justin B; Talegawkar, Sameera A; Effoe, Valery S; Okhomina, Victoria; Carnethon, Mercedes R; Hsueh, Willa A; Golden, Sherita H

2017-11-01

The associations of modifiable lifestyle risk factors with incident diabetes are not well investigated in African Americans (AAs). This study investigated the association of modifiable lifestyle risk factors (exercise, diet, smoking, TV watching, and sleep-disordered breathing burden) with incident diabetes among AAs. Modifiable lifestyle risk factors were characterized among 3,252 AAs in the Jackson Heart Study who were free of diabetes at baseline (2000-2004) using baseline questionnaires and combined into risk factor categories: poor (0-3 points), average (4-7 points), and optimal (8-11 points). Incidence rate ratios (IRR) for diabetes (fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or glycosylated hemoglobin A1c ≥6.5%) were estimated using Poisson regression modeling adjusting for age, sex, education, occupation, systolic blood pressure, and BMI. Outcomes were collected 2005-2012 and data analyzed in 2016. Over 7.6 years, there were 560 incident diabetes cases (mean age=53.3 years, 64% female). An average or optimal compared to poor risk factor categorization was associated with a 21% (IRR=0.79, 95% CI=0.62, 0.99) and 31% (IRR=0.69, 95% CI=0.48, 1.01) lower risk of diabetes. Among participants with BMI <30, IRRs for average or optimal compared to poor categorization were 0.60 (95% CI=0.40, 0.91) and 0.53 (95% CI=0.29, 0.97) versus 0.90 (95% CI=0.67, 1.21) and 0.83 (95% CI=0.51, 1.34) among participants with BMI ≥30. A combination of modifiable lifestyle factors are associated with a lower risk of diabetes among AAs, particularly among those without obesity. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Modifiable health risks in Atlantic Canadian employees: a 5-year report.

PubMed

Makrides, L; Sawatzky, C; Petrie, J; Veinot, P

2010-12-01

A number of modifiable health risks, such as smoking, inactivity and obesity have been linked to increased employer costs, including decreased productivity and increased absenteeism and health claims. The purpose of this paper is to report on the health profile and prevalence of modifiable health risks in an Atlantic Canadian Employee Database. Data were collected over a 5-year period (2001-2006) by the Atlantic Health and Wellness Institute, the research arm of Creative Wellness Solutions, in Halifax, Nova Scotia, Canada. Each employee of 51 workplaces (n = 6067; 2665 males, 3402 females; average age 41.3 years) completed a Health Risk Assessment questionnaire on smoking, nutrition and physical activity behaviours. Clinical data measurements were blood pressure, blood cholesterol, weight and height. Data were compared for private, public and health sectors. Sixteen percent had elevated blood pressure (≥ 140/90 mmHg), 20% smoked cigarettes, 70% were overweight [body mass index (BMI) ≥ 25 kg/m(2)], 31% were obese (BMI ≥ 30 kg/m(2)), 38% had elevated non-fasting cholesterol levels (≥ 5.20 mmol/l) and 49% were inactive (<20-30 min, three to five times per week). Moreover, 50% had two to four major modifiable health risks (i.e. daily tobacco smoking, physical inactivity, overweight and high blood pressure). Health care sector employees were healthier overall, but there was substantial room for improvement. The present analysis identified an alarming prevalence of modifiable health risks in Atlantic Canadian employees. Workplaces need to invest in workplace wellness to reduce the risks and promote better health among employees, thus increasing productivity and decreasing the financial burden on employers.

Modified creatinine index and risk for cardiovascular events and all-cause mortality in patients undergoing hemodialysis: The Q-Cohort study.

PubMed

Arase, Hokuto; Yamada, Shunsuke; Yotsueda, Ryusuke; Taniguchi, Masatomo; Yoshida, Hisako; Tokumoto, Masanori; Nakano, Toshiaki; Tsuruya, Kazuhiko; Kitazono, Takanari

2018-06-02

The modified creatinine (Cr) index, calculated by age, sex, pre-dialysis serum Cr levels, and Kt/V for urea, reflects skeletal muscle mass in patients on hemodialysis. Whether the modified Cr index is associated with cardiovascular events and all-cause mortality remains unknown. A total of 3027 patients registered in the Q-Cohort Study, a multicenter, prospective study of patients on hemodialysis in Japan, were analyzed. The main outcomes were cardiovascular events and all-cause mortality. Associations between sex-specific quartiles of the modified Cr index and outcomes were analyzed by the Cox proportional hazard models and the Fine-Gray proportional subdistribution hazards model. The modified Cr index was correlated with known nutritional and inflammatory markers. During a 4-year follow-up, 499 patients died of any cause, 372 experienced heart disease, and 194 developed stroke. The risk for all-cause mortality was significantly higher in the lower quartiles (Q1 and Q2) than in the highest quartile (Q4) as the reference group (hazard ratios and 95% confidence intervals: Q1, 2.65 [1.69-4.25], Q2, 1.92 [1.27-2.94], and Q3, 1.31 [0.87-2.02]). The risk of heart disease was significantly higher in Q1 than in Q4 (hazard ratios and 95% confidence intervals: Q1, 1.64 [1.04-2.61], Q2, 1.34 [0.91-2.00], and Q3, 1.04 [0.71-1.52]). The risk of stroke was not associated with the modified Cr index. A lower modified Cr index is associated with an increased risk for heart disease and all-cause mortality, but not with the risk for stroke in patients on hemodialysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Implementation of a Worksite Wellness Program Targeting Small Businesses

PubMed Central

Stinson, Kaylan E.; Metcalf, Dianne; Fang, Hai; Brockbank, Claire vS.; Jinnett, Kimberly; Reynolds, Stephen; Trotter, Margo; Witter, Roxana; Tenney, Liliana; Atherly, Adam; Goetzel, Ron Z.

2015-01-01

Objective: To assess small business adoption and need for a worksite wellness program in a longitudinal study of health risks, productivity, workers' compensation rates, and claims costs. Methods: Health risk assessment data from 6507 employees in 260 companies were examined. Employer and employee data are reported as frequencies, with means and standard deviations reported when applicable. Results: Of the 260 companies enrolled in the health risk management program, 71% continued more than 1 year, with 97% reporting that worker wellness improves worker safety. Of 6507 participating employees, 34.3% were overweight and 25.6% obese. Approximately one in five participants reported depression. Potentially modifiable conditions affecting 15% or more of enrollees include chronic fatigue, sleeping problems, headaches, arthritis, hypercholesterolemia, and hypertension. Conclusions: Small businesses are a suitable target for the introduction of health promotion programs. PMID:25563536

Prevention of cardiovascular diseases.

PubMed

Hobbs, F D Richard

2015-10-12

Cardiovascular disease (CVD) is the most important cause of premature death and disability globally. Much is known of the main aetiological risk factors, including elevated blood pressure, dyslipidaemia and smoking, with a raft of additional risks of increasing prevalence, such as obesity and diabetes. Furthermore, some of the most secure evidence-based management strategies in healthcare relate to interventions that modify risk. Yet major gaps remain in the implementation of such evidence, summarized in international guideline recommendations. Some of this gap relates to knowledge deficits amongst clinicians, but also to continued uncertainties over interpretation of the evidence base and areas where data are less available. This article collection in BMC Medicine seeks to offer reflections in each of these areas of uncertainty, spanning issues of better diagnosis, areas of controversy and glimpses of potentially potent future interventions in the prevention of CVD.

Groundwater vulnerability and risk mapping using GIS, modeling and a fuzzy logic tool.

PubMed

Nobre, R C M; Rotunno Filho, O C; Mansur, W J; Nobre, M M M; Cosenza, C A N

2007-12-07

A groundwater vulnerability and risk mapping assessment, based on a source-pathway-receptor approach, is presented for an urban coastal aquifer in northeastern Brazil. A modified version of the DRASTIC methodology was used to map the intrinsic and specific groundwater vulnerability of a 292 km(2) study area. A fuzzy hierarchy methodology was adopted to evaluate the potential contaminant source index, including diffuse and point sources. Numerical modeling was performed for delineation of well capture zones, using MODFLOW and MODPATH. The integration of these elements provided the mechanism to assess groundwater pollution risks and identify areas that must be prioritized in terms of groundwater monitoring and restriction on use. A groundwater quality index based on nitrate and chloride concentrations was calculated, which had a positive correlation with the specific vulnerability index.

Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet

PubMed Central

Curtin, Karen; Slattery, Martha L.; Ulrich, Cornelia M.; Bigler, Jeannette; Levin, Theodore R.; Wolff, Roger K.; Albertsen, Hans; Potter, John D.; Samowitz, Wade S.

2008-01-01

This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case–control study (916 incident colon cancer cases and 1972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylene-tetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP− or CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 and MLH1. The influence of specific dietary factors (folate, methionine, vitamin B12 and alcohol) on these associations was also analyzed. We hypothesized that polymorphisms involved in the provision of methyl groups would be associated with CIMP+ tumors (two or more of five markers methylated), potentially modified by diet. Few associations specific to CIMP+ tumors were observed overall, which does not support the hypothesis that the provision of methyl groups is important in defining a methylator phenotype. However, our data suggest that genetic polymorphisms in MTHFR 1298A > C, interacting with diet, may be involved in the development of highly CpG-methylated colon cancers. AC and CC genotypes in conjunction with a high-risk dietary pattern (low folate and methionine intake and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3–3.4 versus AA/high risk; P-interaction = 0.03). These results provide only limited support for a role of polymorphisms in one-carbon metabolism in the etiology of CIMP colon cancer. PMID:17449906

Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet.

PubMed

Curtin, Karen; Slattery, Martha L; Ulrich, Cornelia M; Bigler, Jeannette; Levin, Theodore R; Wolff, Roger K; Albertsen, Hans; Potter, John D; Samowitz, Wade S

2007-08-01

This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case-control study (916 incident colon cancer cases and 1,972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP- or CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 and MLH1. The influence of specific dietary factors (folate, methionine, vitamin B(12) and alcohol) on these associations was also analyzed. We hypothesized that polymorphisms involved in the provision of methyl groups would be associated with CIMP+ tumors (two or more of five markers methylated), potentially modified by diet. Few associations specific to CIMP+ tumors were observed overall, which does not support the hypothesis that the provision of methyl groups is important in defining a methylator phenotype. However, our data suggest that genetic polymorphisms in MTHFR 1,298A > C, interacting with diet, may be involved in the development of highly CpG-methylated colon cancers. AC and CC genotypes in conjunction with a high-risk dietary pattern (low folate and methionine intake and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3-3.4 versus AA/high risk; P-interaction = 0.03). These results provide only limited support for a role of polymorphisms in one-carbon metabolism in the etiology of CIMP colon cancer.

Saving lives, maintaining safety, and science-based policy: qualitative interview findings from the Blood Donation Rules Opinion Study (Blood DROPS).

PubMed

Hughes, Shana; Sheon, Nicolas; Siedle-Khan, Bob; Custer, Brian

2015-12-01

Indefinite deferral from donation for any man who discloses having had sex with another man even once since 1977 (MSM77) is the US FDA's standing policy. This qualitative component of the Blood Donation Rules and Opinion Study was designed to provide insight into the perceptions and practices of current or previous donors with MSM history. Forty human immunodeficiency virus (HIV)-negative MSM completed an online survey, indicating that they had donated blood and were willing to be interviewed. Semistructured, individual interviews with these key informants covered donation experience and motivations, perceptions of MSM77, policy change preferences, and possible impact of a change to a time-limited deferral. Transcripts were coded deductively and inductively, following a modified Grounded Theory approach. Analysis identified recurrent and divergent themes. Ninety-five percent of participants endorsed modifying MSM77. Preferred deferral length ranged from none to 5 years; a common opinion was that a science-based deferral period would be less than 1 year. Other policy change recommendations included incorporating questions about specific HIV risk behaviors to the donor questionnaire for all potential donors. Interviewees recognized HIV infection rates are higher in MSM than the general US population, but participants considered themselves low-risk for HIV, donated blood "to save lives," and justified their recommendations as being more effective ways to identify donors at risk for HIV. Results suggest that MSM donors are concerned with blood safety; they can be appealed to as such. Communications about a new deferral policy should include scientific explanations and acknowledge altruistic motivations of potential donors. © 2015 AABB.

S219. RISK FACTORS FOR LOW BONE MINERAL DENSITY IN PATIENTS TAKING ANTIPSYCHOTICS

PubMed Central

Jhon, Min; Hong, Ji-Eun; Park, Cheol; Lee, Ju-Yeon; Jo, Anna; Kim, Jae-Min; Shin, Il-Seon; Williams, Lana; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

Abstract Background The aim of this study is to explore potentially modifiable risk factors for low bone mineral density (BMD) in adults with psychotic disorders. Furthermore, we sought to identify gender-specific risk factors. Methods The study included 285 community-dwelling patients with psychotic disorders. Dual-energy x-ray absorptiometry was used to measure BMD. Laboratory examinations included vitamin D and prolactin levels. Low BMD was defined as<1 standard deviation below the mean for young adults. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. Results Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. Discussion Low BMI was risk factor for reduced BMD in both genders. Shorter treatment duration was associated with low BMD in men, whereas higher prolactin levels, lower vitamin D, and the use of serotonergic antidepressants were associated with low BMD in women. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders.

Risk Factors for 30-Day Readmission in Adults with Sickle Cell Disease.

PubMed

Brodsky, Max A; Rodeghier, Mark; Sanger, Maureen; Byrd, Jeannie; McClain, Brandi; Covert, Brittany; Roberts, Dionna O; Wilkerson, Karina; DeBaun, Michael R; Kassim, Adetola A

2017-05-01

Readmission to the hospital within 30 days is a measure of quality care; however, only few modifiable risk factors for 30-day readmission in adults with sickle cell disease are known. We performed a retrospective review of the medical records of adults with sickle cell disease at a tertiary care center, to identify potentially modifiable risk factors for 30-day readmission due to vasoocclusive pain episodes. A total of 88 patients ≥18 years of age were followed for 3.5 years between 2010 and 2013, for 158 first admissions for vasoocclusive pain episodes. Of these, those subsequently readmitted (cases) or not readmitted (controls) within 30 days of their index admissions were identified. Seven risk factors were included in a multivariable model to predict readmission: age, sex, hemoglobin phenotype, median oxygen saturation level, listing of primary care provider, type of health insurance, and number of hospitalized vasoocclusive pain episodes in the prior year. Mean age at admission was 31.7 (18-59) years; median time to readmission was 11 days (interquartile range 20 days). Absence of a primary care provider listed in the electronic medical record (odds ratio 0.38; 95% confidence interval, 0.16-0.91; P = .030) and the number of vasoocclusive pain episodes requiring hospitalization in the prior year were significant risk factors for 30-day readmission (odds ratio 1.30; 95% confidence interval, 1.16-1.44; P <.001). Improved discharge planning and ensuring access to a primary care provider may decrease the 30-day readmission rate in adults with sickle cell disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure.

PubMed

Bouwmeester, Manon C; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; Kamstra, Jorke H; Jelinek, Jaroslav; Issa, Jean-Pierre J; Legler, Juliette; van der Ven, Leo T M

2016-01-15

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

PubMed Central

Cox, David G.; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A.; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S.; Borg, Åke; Karlsson, Per; Stenmark Askmalm, Marie; Barbany Bustinza, Gisela; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Benítez, Javier; Hamann, Ute; Rookus, Matti A.; van den Ouweland, Ans M.W.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; van Asperen, Christi J.; Devilee, Peter; Gille, Hans J.J.P.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Eisinger, François; Bressac de Paillerets, Brigitte; Caron, Olivier; Delnatte, Capucine; Goldgar, David; Miron, Alex; Ozcelik, Hilmi; Buys, Saundra; Southey, Melissa C.; Terry, Mary Beth; Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng; Hansen, Thomas V.O.; Johannsson, Oskar; Piedmonte, Marion; Rodriguez, Gustavo C.; Basil, Jack B.; Blank, Stephanie; Toland, Amanda E.; Montagna, Marco; Isaacs, Claudine; Blanco, Ignacio; Gayther, Simon A.; Moysich, Kirsten B.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Gadzicki, Dorothea; Fiebig, Britta; Caldes, Trinidad; Laframboise, Rachel; Nevanlinna, Heli; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Radice, Paolo; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Sinilnikova, Olga M.

2011-01-01

Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77–0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription. PMID:21890493

Screening for Autism in Older and Younger Toddlers with the Modified Checklist for Autism in Toddlers

ERIC Educational Resources Information Center

Pandey, Juhi; Verbalis, Alyssa; Robins, Diana L.; Boorstein, Hilary; Klin, Ami; Babitz, Tammy; Chawarska, Katarzyna; Volkmar, Fred; Green, James; Barton, Marianne; Fein, Deborah

2008-01-01

The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen younger (16-23 months) versus older (24-30 months) high- and low-risk toddlers. Refusal rates for follow-up interview showed no group differences, but parents of younger/low-risk children were more likely to refuse evaluation than parents of high-risk children. PPP for an…

Parkinson disease and Alzheimer disease: environmental risk factors.

PubMed

Campdelacreu, J

2014-01-01

The purpose of this review is to update and summarise available evidence on environmental risk factors that have been associated with risk of Parkinson disease (PD) or Alzheimer disease (AD) and discuss their potential mechanisms. Evidence consistently suggests that a higher risk of PD is associated with pesticides and that a higher risk of AD is associated with pesticides, hypertension and high cholesterol levels in middle age, hyperhomocysteinaemia, smoking, traumatic brain injury and depression. There is weak evidence suggesting that higher risk of PD is associated with high milk consumption in men, high iron intake, chronic anaemia and traumatic brain injury. Weak evidence also suggests that a higher risk of AD is associated with high aluminium intake through drinking water, excessive exposure to electromagnetic fields from electrical grids, DM and hyperinsulinaemia, obesity in middle age, excessive alcohol consumption and chronic anaemia. Evidence consistently suggests that a lower risk of PD is associated with hyperuricaemia, tobacco and coffee use, while a lower risk of AD is associated with moderate alcohol consumption, physical exercise, perimenopausal hormone replacement therapy and good cognitive reserve. Weak evidence suggests that lower risk of PD is associated with increased vitamin E intake, alcohol, tea, NSAIDs, and vigorous physical exercise, and that lower risk of AD is associated with the Mediterranean diet, coffee and habitual NSAID consumption. Several environmental factors contribute significantly to risk of PD and AD. Some may already be active in the early stages of life, and some may interact with other genetic factors. Population-based strategies to modify such factors could potentially result in fewer cases of PD or AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

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

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.

Effects of modified Pilates on variability of inter-joint coordination during walking in the elderly.

PubMed

Yoon, Sukhoon; Kim, Joo Nyeon; Lim, Hee Sung

2016-12-01

[Purpose] This study aimed to examine the effects of an 8-week modified Pilates program on the variability of inter-joint coordination in the elderly during walking. [Subjects and Methods] Twenty elderly participants with no recent history of orthopedic abnormalities (age, 67.9 ± 2.7 years; height, 163.7 ± 8.9 cm; weight, 67.1 ± 11.6 kg) were recruited for this study and randomly allocated to a modified Pilates exercise group or a control group. Three-dimensional motion analysis was performed on both groups to evaluate the effects of the Pilates exercise. [Results] There was no significant difference in the joint variability of the ankle, knee, and hip joints between the groups, both before training and after training. However, there was a significant increase in the hip-knee deviation phase value in the exercise group after the program was completed, and this increase was also significant when compared with that in the control group. [Conclusion] This study has demonstrated that an 8-week modified Pilates exercise program can have a positive impact on the gait of elderly participants, potentially by enhancing neuromuscular adjustment, which may have positive implications for reducing their fall risk.

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

PubMed

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

Five-year Prognosis after Mild to Moderate Ischemic Stroke by Stroke Subtype: A Multi-Clinic Registry Study

PubMed Central

Lv, Yumei; Fang, Xianghua; Asmaro, Karam; Liu, Hongjun; Zhang, Xinqing; Zhang, Hongmei; Qin, Xiaoming; Ji, Xunming

2013-01-01

Background and Purpose Mild to moderate ischemic stroke is a common presentation in the outpatient setting. Among the various subtypes of stroke, lacunar infarction (LI) is generally very common. Currently, little is known about the long-term prognosis and factors associated with the prognosis between LI and non-LI. This study aims to compare the risk of death and acute cardiovascular events between patients with LI and non-LI, and identify potential risk factors associated with these outcomes. Methods A total of 710 first-ever ischemic stroke patients (LI: 474, non-LI: 263) from 18 clinics were recruited consecutively from 2003 to 2004. They were prospectively followed-up until the end of 2008. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazards regression. Results After a 5-year follow up, 54 deaths and 96 acute cardiovascular events occurred. Recurrent stroke was the most common cause of death (19 cases, 35.18%) and new acute cardiovascular events (75 cases, 78.13%). There were no significant differences between patients with LI and non-LI in their risks of death, new cardiovascular events, and recurrent stroke after adjusting for age, sex, hypertension, diabetes, cardiac diseases, body mass index, dyslipidemia, smoking, alcohol consumption, ADL dependence, and depressive symptoms. Among the modifiable risk factors, diabetes, hypertension, ADL dependency, and symptoms of depression were independent predictors of poor outcomes in patients with LI. In non-LI patients, however, no modifiable risk factors were detected for poor outcomes. Conclusion Long-term outcomes did not differ significantly between LI and non-LI patients. Detecting and managing vascular risk factors and depression as well as functional rehabilitation may improve the prognoses of LI patients. PMID:24223696

The adverse association of diabetes with risk of first acute myocardial infarction is modified by physical activity and body mass index: prospective data from the HUNT Study, Norway.

PubMed

Moe, Børge; Augestad, Liv B; Flanders, W Dana; Dalen, Håvard; Nilsen, Tom I L

2015-01-01

Diabetes increases the risk of acute myocardial infarction (AMI) and effective means for primary prevention are warranted. We prospectively examined the joint association of diabetes and leisure-time physical activity, as well as of diabetes and BMI, with the risk of AMI. A total of 55,534 men and women in the Norwegian HUNT Study were followed-up for first AMI by hospital admission registries and the Cause of Death Registry. Cox proportional adjusted HRs with 95% CIs were estimated. Overall, 1,887 incident AMIs occurred during 12.3 years. Compared with inactive people without diabetes, inactive people with diabetes had an HR of 2.37 (95% CI 1.58, 3.57), whereas the HR among highly active persons with diabetes was 1.04 (95% CI 0.62, 1.74). Normal-weight (BMI 18.5-25 kg/m(2)) persons with diabetes had an HR of 1.60 (95% CI 1.05, 2.44) and obese (BMI > 30 kg/m(2)) persons with diabetes had an HR of 2.55 (95% CI 1.97, 3.29) compared with normal-weight persons without diabetes. The data suggest biological interaction between diabetes and physical activity, with a relative excess risk of inactivity and diabetes of 1.43 (95% CI 0.08, 2.78). For obesity and diabetes, the excess risk due to interaction was smaller (0.67; 95% CI -0.24, 1.58). Body weight and, in particular, physical activity modified the association between diabetes and risk of first AMI. This highlights the potential importance of physical activity and weight maintenance in primary prevention of AMI among people with diabetes.

User Perceptions of a Dementia Risk Reduction Website and Its Promotion of Behavior Change

PubMed Central

2013-01-01

Background Several modifiable health and lifestyle factors are consistently associated with dementia risk and it is estimated that significantly fewer people would develop dementia if the incidence of risk factors could be reduced. Despite this, Australians’ awareness of the health and lifestyle factors associated with dementia risk is low. Within a national community education campaign, Alzheimer’s Australia developed a dementia risk reduction website providing information about modifiable risk or protective factors for dementia. Objective This study aimed to assess the usefulness of the website content in improving knowledge and enabling adoption of recommended strategies, and to examine what additional resources consumers need. Methods Visitors to the website over a 3 month period were invited to complete an online survey, which asked them to rate their knowledge of dementia risk reduction before and after visiting the site, how important monitoring their health related behavior was to them before and after visiting the site, their current behavior related to health and lifestyle factors associated with dementia risk, their intentions to change behavior, and the usefulness of potential additional resources to help them do so. Results For this study, 123 Australian adults responded to the survey. 44.7% (55/122) were aged over 60 and 82.1% (98/119) were female. Respondents’ ratings and comments indicated they generally found the content interesting, informative, and helpful to them. Respondents’ ratings of their knowledge about the links between health and lifestyle factors and dementia risk significantly increased after visiting the website (P<.001). Their ratings of how important monitoring what they do in relation to their health and lifestyle factors were also significantly increased after visiting the website (P<.001). Average ratings for how well respondents felt they were doing at the time in relation to specific risk or protective factors were generally high, suggesting many website visitors already had high levels of health motivation and healthy lifestyle behaviors. 55.6% (45/81) said that after visiting the website their intention to make lifestyle changes was strong. Only 27.1% (22/81) said their intention to visit their doctor to discuss dementia risk reduction was strong. Potential additional resources that would help people assess and address their personal dementia risk factors were rated as more helpful than general information resources. Conclusions A dementia risk reduction website providing information about the current evidence and practical strategies was of interest and was useful to the Australian community. Benefits for visitors included increased knowledge and increased motivation to address relevant behaviors. Many visitors to the site were already health conscious, indicating that more needs to be done to get dementia risk reduction messages to the wider community. More interactive and personalized resources in future interventions may offer additional benefits to individuals. PMID:23608480

The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health

PubMed Central

Lowry, Christopher A.; Smith, David G.; Siebler, Philip H.; Schmidt, Dominic; Stamper, Christopher E.; Hassell, James E.; Yamashita, Paula S.; Fox, James H.; Reber, Stefan O.; Brenner, Lisa A.; Hoisington, Andrew J.; Postolache, Teodor T.; Kinney, Kerry A.; Marciani, Dante; Hernandez, Mark; Hemmings, Sian M.J.; Malan-Muller, Stefanie; Wright, Kenneth P.; Knight, Rob; Raison, Charles L.; Rook, Graham A.W.

2016-01-01

The hygiene or “Old Friends” hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these old friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here we review recent advances in our understanding of the potential for old friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially-derived metabolites, bacterial antigens, and helminthic antigens, through which these inputs promote immunoregulation. Though findings are encouraging, significant human subjects research is required to evaluate the potential impact of old friends, including environmental microbial inputs, on biological signatures and clinically meaningful mental health prevention and intervention outcomes. PMID:27436048

METAL FRACTIONATION IN SOILS AND ASSESSMENT OF ENVIROMENTAL CONTAMINATION IN THE VALLECAMONICA, ITALY

PubMed Central

Borgese, L.; Federici, S.; Zacco, A.; Gianoncelli, A.; Rizzo, L.; Smith, D. R.; Donna, F.; Lucchini, R.; Depero, L. E.; Bontempi, E.

2013-01-01

Metal contamination was investigated in soils of the Vallecamonica, an area in the northern part of the Brescia province (Italy) where ferroalloy industries were active for a century until 2001. The extent in which emissions from ferroalloy plants affected metal concentration in soils is not known in this area. In this study the geogenic and/or anthropogenic origin of metals in soils were estimated. A modified Community Bureau of Reference sequential chemical extraction method followed by inductive coupled plasma optical emission spectroscopy analyses were employed to evaluate the potential bioavailability of Al, Cd, Mn, Fe, Cr, Zn, and Pb in soils. Principal components analysis was used to assess the relationships among metal sources in soil samples from different locations. This approach allowed to distinguish different loadings and mobilities of metals in soils collected in different areas. Results showed high concentrations and readily extractability of Mn in the Vallecamonica soils, which may suggest potential bioavailability for organisms and may create an environmental risk and potential health risk of human exposure. PMID:23338992

Dairy and cardiovascular health: Friend or foe?

PubMed Central

Markey, O; Vasilopoulou, D; Givens, D I; Lovegrove, J A

2014-01-01

Cardiovascular disease (CVD) prevalence at a global level is predicted to increase substantially over the next decade due to the increasing ageing population and incidence of obesity. Hence, there is an urgent requirement to focus on modifiable contributors to CVD risk, including a high dietary intake of saturated fatty acids (SFA). As an important source of SFA in the UK diet, milk and dairy products are often targeted for SFA reduction. The current paper acknowledges that milk is a complex food and that simply focusing on the link between SFA and CVD risk overlooks the other beneficial nutrients of dairy foods. The body of existing prospective evidence exploring the impact of milk and dairy consumption on risk factors for CVD is reviewed. The current paper highlights that high milk consumption may be beneficial to cardiovascular health, while illustrating that the evidence is less clear for cheese and butter intake. The option of manipulating the fatty acid profile of ruminant milk is discussed as a potential dietary strategy for lowering SFA intake at a population level. The review highlights that there is a necessity to perform more well-controlled human intervention-based research that provides a more holistic evaluation of fat-reduced and fat-modified dairy consumption on CVD risk factors including vascular function, arterial stiffness, postprandial lipaemia and markers of inflammation. Additionally, further research is required to investigate the impact of different dairy products and the effect of the specific food matrix on CVD development. PMID:25400508

A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants.

PubMed

Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

2014-04-01

Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided.

A statistical simulation model for field testing of non-target organisms in environmental risk assessment of genetically modified plants

PubMed Central

Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore

2014-01-01

Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided. PMID:24834325

Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers.

PubMed

Madsen, Ida E H; Lange, Theis; Borritz, Marianne; Rugulies, Reiner

2015-06-01

Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout. We used questionnaire data from a three-wave study of Danish human service workers conducted during 1999-2005, linked with national register data on purchases of antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals (81% women) and analysed data by Aalens additive hazards modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted antidepressant treatment. This association was modified by sex (p < 0.01). In men, high vs. intermediate burnout was associated with a 5% increased risk of antidepressant treatment per year of follow-up. This risk difference was 1% for women. Due to the sex specific patterns, we restricted effect modification analyses to women. We found no effect-modification by the examined work environment factors, though a sensitivity analysis indicated a possible stronger association in women of lower occupational position. In conclusion, burnout predicted antidepressant treatment, with a stronger association in men than women. We found no evidence of effect-modification by any of the examined psychosocial work environment factors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modern fat technology: what is the potential for heart health?

PubMed

Upritchard, J E; Zeelenberg, M J; Huizinga, H; Verschuren, P M; Trautwein, E A

2005-08-01

Saturated and trans-fatty acids raise total cholesterol and LDL-cholesterol and are known to increase the risk of CHD, while dietary unsaturated fatty acids play important roles in maintaining cardiovascular health. Replacing saturated fats with unsaturated fats in the diet often involves many complex dietary changes. Modifying the composition of foods high in saturated fat, particularly those foods that are consumed daily, can help individuals to meet the nutritional targets for reducing the risk of CHD. In the 1960s the Dutch medical community approached Unilever about the technical feasibility of producing margarine with a high-PUFA and low-saturated fatty acid composition. Margarine is an emulsion of water in liquid oil that is stabilised by a network of fat crystals. In-depth expertise of fat crystallisation processes allowed Unilever scientists to use a minimum of solid fat (saturated fatty acids) to structure a maximum level of PUFA-rich liquid oil, thus developing the first blood-cholesterol-lowering product, Becel. Over the years the composition of this spread has been modified to reflect new scientific findings and recommendations. The present paper will briefly review the developments in fat technology that have made these improvements possible. Unilever produces spreads that are low in total fat and saturated fat, virtually free of trans-fatty acids and with levels of n-3 and n-6 PUFA that are in line with the latest dietary recommendations for the prevention of CHD. Individuals with the metabolic syndrome have a 2-4-fold increased risk of developing CHD; therefore, these spreads could make a contribution to CHD prevention in this group. In addition, for individuals with the metabolic syndrome the spreads could be further modified to address their unique dyslipidaemia, i.e. elevated blood triacylglycerols and low HDL-cholesterol. Research conducted in the LIPGENE study and other dietary intervention studies will deliver the scientific evidence to justify further modifications in the composition of spreads that are healthy for the heart disease risk factors associated with the metabolic syndrome.

Impact on environment, ecosystem, diversity and health from culturing and using GMOs as feed and food.

PubMed

Tsatsakis, Aristidis M; Nawaz, Muhammad Amjad; Tutelyan, Victor A; Golokhvast, Kirill S; Kalantzi, Olga-Ioanna; Chung, Duck Hwa; Kang, Sung Jo; Coleman, Michael D; Tyshko, Nadia; Yang, Seung Hwan; Chung, Gyuhwa

2017-09-01

Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible environmental, ecological, and health risks. Scientific-and-political debates can even influence legislation and prospective risk assessment procedure. Currently, the scientifically-assessed direct hazardous impacts of GM food and feed on fauna and flora are conflicting; indeed, a review of literature available data provides some evidence of GM environmental and health risks. Although the consequences of gene flow and risks to biodiversity are debatable. Risks to the environment and ecosystems can exist, such as the evolution of weed herbicide resistance during GM cultivation. A matter of high importance is to provide precise knowledge and adequate current information to regulatory agencies, governments, policy makers, researchers, and commercial GMO-releasing companies to enable them to thoroughly investigate the possible risks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endometrial cancer risk factors among Lynch syndrome women: a retrospective cohort study

PubMed Central

Staff, Synnöve; Aaltonen, Mari; Huhtala, Heini; Pylvänäinen, Kirsi; Mecklin, Jukka-Pekka; Mäenpää, Johanna

2016-01-01

Background: Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. Methods: The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model was used to estimate the associations between lifestyle, hormonal, reproductive and medical factors and the risk of EC. Results: Increased EC risk was associated with type II diabetes and hypercholesterolaemia in univariable (HR 3.21, (95% CI 1.34–7.78), P=0.009 and HR 2.08, (95% CI 1.11–3.90), P=0.02; respectively) and with diabetes and duration of hormone replacement therapy (HRT) in multivariable analysis (HR 4.18 (95% CI 1.52–11.52), P=0.006 and HR 1.07 (95% CI 1.02–1.13), P=0.010; respectively). Conclusions: Prevention of diabetes and avoiding long-duration HRT are potential targets for reduction of EC risk in women with LS. PMID:27336600

Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers.

PubMed

Wang, Xianshu; Pankratz, V Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D P; Ponder, Bruce A J; Dunning, Alison M; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B L; Hooning, Maartje J; Ligtenberg, Marjolijn J; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Singer, Christian F; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N; Hunter, David J; Chanock, Stephen J; Easton, Douglas F; Antoniou, Antonis C; Couch, Fergus J

2010-07-15

Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 x 10(-3)) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutation carriers from nine centers. Associations with breast cancer risk were assessed using Cox models weighted for penetrance. Eight SNPs in BRCA1 carriers and 12 SNPs in BRCA2 carriers, representing an enrichment over the number expected, were significantly associated with breast cancer risk (P(trend) < 0.01). The minor alleles of rs6138178 in SNRPB and rs6602595 in CAMK1D displayed the strongest associations in BRCA1 carriers (HR = 0.78, 95% CI: 0.69-0.90, P(trend) = 3.6 x 10(-4) and HR = 1.25, 95% CI: 1.10-1.41, P(trend) = 4.2 x 10(-4)), whereas rs9393597 in LOC134997 and rs12652447 in FBXL7 showed the strongest associations in BRCA2 carriers (HR = 1.55, 95% CI: 1.25-1.92, P(trend) = 6 x 10(-5) and HR = 1.37, 95% CI: 1.16-1.62, P(trend) = 1.7 x 10(-4)). The magnitude and direction of the associations were consistent with the original GWAS. In subsequent risk assessment studies, the loci appeared to interact multiplicatively for breast cancer risk in BRCA1 and BRCA2 carriers. Promising candidate SNPs from GWAS were identified as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. Upon further validation, these SNPs together with other genetic and environmental factors may improve breast cancer risk assessment in these populations.

Nutritional Solutions to Reduce Risks of Negative Health Impacts of Air Pollution

PubMed Central

Péter, Szabolcs; Holguin, Fernando; Wood, Lisa G.; Clougherty, Jane E.; Raederstorff, Daniel; Antal, Magda; Weber, Peter; Eggersdorfer, Manfred

2015-01-01

Air pollution worldwide has been associated with cardiovascular and respiratory morbidity and mortality, particularly in urban settings with elevated concentrations of primary pollutants. Air pollution is a very complex mixture of primary and secondary gases and particles, and its potential to cause harm can depend on multiple factors—including physical and chemical characteristics of pollutants, which varies with fine-scale location (e.g., by proximity to local emission sources)—as well as local meteorology, topography, and population susceptibility. It has been hypothesized that the intake of anti-oxidant and anti-inflammatory nutrients may ameliorate various respiratory and cardiovascular effects of air pollution through reductions in oxidative stress and inflammation. To date, several studies have suggested that some harmful effects of air pollution may be modified by intake of essential micronutrients (such as B vitamins, and vitamins C, D, and E) and long-chain polyunsaturated fatty acids. Here, we review the existing literature related to the potential for nutrition to modify the health impacts of air pollution, and offer a framework for examining these interactions. PMID:26690474

Nutritional Solutions to Reduce Risks of Negative Health Impacts of Air Pollution.

PubMed

Péter, Szabolcs; Holguin, Fernando; Wood, Lisa G; Clougherty, Jane E; Raederstorff, Daniel; Antal, Magda; Weber, Peter; Eggersdorfer, Manfred

2015-12-10

Air pollution worldwide has been associated with cardiovascular and respiratory morbidity and mortality, particularly in urban settings with elevated concentrations of primary pollutants. Air pollution is a very complex mixture of primary and secondary gases and particles, and its potential to cause harm can depend on multiple factors-including physical and chemical characteristics of pollutants, which varies with fine-scale location (e.g., by proximity to local emission sources)-as well as local meteorology, topography, and population susceptibility. It has been hypothesized that the intake of anti-oxidant and anti-inflammatory nutrients may ameliorate various respiratory and cardiovascular effects of air pollution through reductions in oxidative stress and inflammation. To date, several studies have suggested that some harmful effects of air pollution may be modified by intake of essential micronutrients (such as B vitamins, and vitamins C, D, and E) and long-chain polyunsaturated fatty acids. Here, we review the existing literature related to the potential for nutrition to modify the health impacts of air pollution, and offer a framework for examining these interactions.

Early Detection for Dengue Using Local Indicator of Spatial Association (LISA) Analysis

PubMed Central

Parra-Amaya, Mayra Elizabeth; Puerta-Yepes, María Eugenia; Lizarralde-Bejarano, Diana Paola; Arboleda-Sánchez, Sair

2016-01-01

Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes. There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for preventing the occurrence of dengue. For this reason, entomological surveillance is recommended by World Health Organization (WHO) to measure dengue risk in endemic areas; however, several works have shown that the current methodology (aedic indices) is not sufficient for predicting dengue. In this work, we modified indices proposed for epidemic periods. The raw value of the epidemiological wave could be useful for detecting risk in epidemic periods; however, risk can only be detected if analyses incorporate the maximum epidemiological wave. Risk classification was performed according to Local Indicators of Spatial Association (LISA) methodology. The modified indices were analyzed using several hypothetical scenarios to evaluate their sensitivity. We found that modified indices could detect spatial and differential risks in epidemic and endemic years, which makes them a useful tool for the early detection of a dengue outbreak. In conclusion, the modified indices could predict risk at the spatio-temporal level in endemic years and could be incorporated in surveillance activities in endemic places. PMID:28933396

Effect of algal flocculation on dissolved organic matters using cationic starch modified soils.

PubMed

Shi, Wenqing; Bi, Lei; Pan, Gang

2016-07-01

Modified soils (MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch (CS) has been tested as an effective soil modifier, but little is known about its potential impacts on the treated water. This study investigated dissolved organic matters in the bloom water after algal removal using cationic starch modified soils (CS-MSs). Results showed that the dissolved organic carbon (DOC) could be decreased by CS-MS flocculation and the use of higher charge density CS yielded a greater DOC reduction. When CS with the charge density of 0.052, 0.102 and 0.293meq/g were used, DOC was decreased from 3.4 to 3.0, 2.3 and 1.7mg/L, respectively. The excitation-emission matrix fluorescence spectroscopy and UV254 analysis indicated that CS-MS exhibits an ability to remove some soluble organics, which contributed to the DOC reduction. However, the use of low charge density CS posed a potential risk of DOC increase due to the high CS loading for effective algal removal. When CS with the charge density of 0.044meq/g was used, DOC was increased from 3.4 to 3.9mg/L. This study suggested, when CS-MS is used for cyanobacterial bloom removal, the content of dissolved organic matters in the treated water can be controlled by optimizing the charge density of CS. For the settled organic matters, other measures (e.g., capping treatments using oxygen loaded materials) should be jointly applied after algal flocculation. Copyright © 2016. Published by Elsevier B.V.

A Retrospective Analysis of Pressure Ulcer Incidence and Modified Braden Scale Score Risk Classifications.

PubMed

Chen, Hong-Lin; Cao, Ying-Juan; Wang, Jing; Huai, Bao-Sha

2015-09-01

The Braden Scale is the most widely used pressure ulcer risk assessment in the world, but the currently used 5 risk classification groups do not accurately discriminate among their risk categories. To optimize risk classification based on Braden Scale scores, a retrospective analysis of all consecutively admitted patients in an acute care facility who were at risk for pressure ulcer development was performed between January 2013 and December 2013. Predicted pressure ulcer incidence first was calculated by logistic regression model based on original Braden score. Risk classification then was modified based on the predicted pressure ulcer incidence and compared between different risk categories in the modified (3-group) classification and the traditional (5-group) classification using chi-square test. Two thousand, six hundred, twenty-five (2,625) patients (mean age 59.8 ± 16.5, range 1 month to 98 years, 1,601 of whom were men) were included in the study; 81 patients (3.1%) developed a pressure ulcer. The predicted pressure ulcer incidence ranged from 0.1% to 49.7%. When the predicted pressure ulcer incidence was greater than 10.0% (high risk), the corresponding Braden scores were less than 11; when the predicted incidence ranged from 1.0% to 10.0% (moderate risk), the corresponding Braden scores ranged from 12 to 16; and when the predicted incidence was less than 1.0% (mild risk), the corresponding Braden scores were greater than 17. In the modified classification, observed pressure ulcer incidence was significantly different between each of the 3 risk categories (P less than 0.05). However, in the traditional classification, the observed incidence was not significantly different between the high-risk category and moderate-risk category (P less than 0.05) and between the mild-risk category and no-risk category (P less than 0.05). If future studies confirm the validity of these findings, pressure ulcer prevention protocols of care based on Braden Scale scores can be simplified.

DNA barcoding simplifies environmental risk assessment of genetically modified crops in biodiverse regions.

PubMed

Nzeduru, Chinyere V; Ronca, Sandra; Wilkinson, Mike J

2012-01-01

Transgenes encoding for insecticidal crystal (Cry) proteins from the soil-dwelling bacterium Bacillus Thuringiensis have been widely introduced into Genetically Modified (GM) crops to confer protection against insect pests. Concern that these transgenes may also harm beneficial or otherwise valued insects (so-called Non Target Organisms, NTOs) represents a major element of the Environmental Risk Assessments (ERAs) used by all countries prior to commercial release. Compiling a comprehensive list of potentially susceptible NTOs is therefore a necessary part of an ERA for any Cry toxin-containing GM crop. In partly-characterised and biodiverse countries, NTO identification is slowed by the need for taxonomic expertise and time to enable morphological identifications. This limitation represents a potentially serious barrier to timely adoption of GM technology in some developing countries. We consider Bt Cry1A cowpea (Vigna unguiculata) in Nigeria as an exemplar to demonstrate how COI barcoding can provide a simple and cost-effective means of addressing this problem. Over a period of eight weeks, we collected 163 insects from cowpea flowers across the agroecological and geographic range of the crop in Nigeria. These individuals included 32 Operational Taxonomic Units (OTUs) spanning four Orders and that could mostly be assigned to genus or species level. They included 12 Lepidopterans and two Coleopterans (both potentially sensitive to different groups of Cry proteins). Thus, barcode-assisted diagnoses were highly harmonised across groups (typically to genus or species level) and so were insensitive to expertise or knowledge gaps. Decisively, the entire study was completed within four months at a cost of less than 10,000 US$. The broader implications of the findings for food security and the capacity for safe adoption of GM technology are briefly explored.

Eigensolutions, Shannon entropy and information energy for modified Tietz-Hua potential

NASA Astrophysics Data System (ADS)

Onate, C. A.; Onyeaju, M. C.; Ituen, E. E.; Ikot, A. N.; Ebomwonyi, O.; Okoro, J. O.; Dopamu, K. O.

2018-04-01

The Tietz-Hua potential is modified by the inclusion of De ( {{Ch - 1}/{1 - C_{h e^{{ - bh ( {r - re } )}} }}} )be^{{ - bh ( {r - re } )}} term to the Tietz-Hua potential model since a potential of such type is very good in the description and vibrational energy levels for diatomic molecules. The energy eigenvalues and the corresponding eigenfunctions are explicitly obtained using the methodology of parametric Nikiforov-Uvarov. By putting the potential parameter b = 0, in the modified Tietz-Hua potential quickly reduces to the Tietz-Hua potential. To show more applications of our work, we have computed the Shannon entropy and Information energy under the modified Tietz-Hua potential. However, the computation of the Shannon entropy and Information energy is an extension of the work of Falaye et al., who computed only the Fisher information under Tietz-Hua potential.

Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection

PubMed Central

Becker, Andrew E; Hernandez, Yasmin G; Frucht, Harold; Lucas, Aimee L

2014-01-01

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several large-volume centers have initiated such screening protocols, and consensus-based guidelines for screening high-risk groups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields. PMID:25170203

The Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide.

PubMed

Clemens, Kristin K; McArthur, Eric; Dixon, Stephanie N; Fleet, Jamie L; Hramiak, Irene; Garg, Amit X

2015-08-01

The risk for hypoglycemia when taking glyburide compared with modified-release gliclazide remains to be established in older adults in routine care. We investigated the risk of a hospital encounter with hypoglycemia following a new prescription for glyburide compared with modified-release gliclazide. In 2 population-based matched retrospective cohort studies in Ontario, Canada, between 2002 and 2011, we examined older adults who were newly prescribed glyburide or gliclazide as monotherapy or in the presence of metformin. Our primary outcome was a hospital encounter with hypoglycemia assessed within 90 days. The baseline characteristics between matched groups were similar. Initiating glyburide vs. gliclazide as monotherapy was associated with a higher risk for a hospital encounter with hypoglycemia (69 patients of 4374 taking glyburide [1.58%] vs. 8 patients of 4374 taking gliclazide [0.18%], absolute risk increase 1.40% [95% CI 1.01% to 1.79%], number needed to harm 71 [55 to 99], odds ratio 8.63 [95% CI 4.15 to 17.93], p<0.0001). Similar findings were noted when glyburide vs. gliclazide was initiated in the presence of metformin (110 patients of 8038 taking glyburide [1.37%] vs. 19 patients of 8038 taking gliclazide [0.24%], absolute risk increase 1.13% [95% CI 0.86% to 1.40%], number needed to harm 77 [71 to 116], odds ratio 6.06 [95% CI 3.68 to 9.97], p<0.0001). Glyburide was associated with a higher risk for hypoglycemia than modified-release gliclazide. The results of our studies may help to convince healthcare professionals who use glyburide to consider modified-release gliclazide as a safer alternative. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

[Strategies for cardiovascular disease prevention].

PubMed

Gabus, Vincent; Wuerzner, Grégoire; Saubade, Mathieu; Favre, Lucie; Jacot Sadowski, Isabelle; Nanchen, David

2018-02-28

Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

PubMed

Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E; Aalfs, Cora M; Meijers-Heijboer, Hanne E J; van Asperen, Christi J; van Roozendaal, K E P; Hoogerbrugge, Nicoline; Collée, J Margriet; Kriege, Mieke; van der Luijt, Rob B; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J; Walker, Lisa; Porteous, Mary E; Kennedy, M John; Pathak, Harsh; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B; Karlan, Beth Y; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A; Beattie, Mary S; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B; Neuhausen, Susan L; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D P; Gayther, Simon A; Simard, Jacques; Easton, Douglas F; Couch, Fergus J; Chenevix-Trench, Georgia

2012-04-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. © 2012 Wiley Periodicals, Inc.

Criminality and suicide: a longitudinal Swedish cohort study

PubMed Central

Stenbacka, M; Romelsjö, A; Jokinen, J

2014-01-01

Objectives This study aimed to investigate whether violent and non-violent offending were related to elevated risk of suicide. We also investigated whether the risk was higher among those with repeated offences and how experiences of substance misuse and suicide attempt modified the relationship. Design A nationwide prospective cohort study. Setting A register study of 48 834 conscripted men in 1969/1970 in Sweden followed up during a 35-year period in official registers. Participants A birth cohort of 48 834 men who were mandatory conscripted for military service in 1969/70 at the age of 18–20 years. Possible confounders were retrieved from psychological assessments at conscription and the cohort was linked to mortality and hospitalisation and crime records from 1970 onwards. Estimates of suicide risks were calculated as HR with 95% CIs using Cox proportional regression analyses with adjustment for potential confounding by family, psychological and behavioural factors including substance use and psychiatric disorders. Results Of the total cohort, 2671 (5.5%) persons died during the follow-up period. Of these, 615 (23%) persons died due to suicide. Non-violent criminality was evident for 29% and violent criminality for 4.7% of all the participants. In the crude model, the violent offenders had nearly five times higher risk (HR=4.69, 3.56 to 6.19) to die from suicide and non-violent criminals had about two times higher risk (HR=2.08, 1.72 to 2.52). In the fully adjusted model, the HRs were still significant for suicide in the non-violent group. Conclusions Experiences of violent or non-violent criminality were associated with increased risk of suicide. Comorbidity with alcohol and substance use and psychiatric disorders modified the risk, but the suicide risk remained significantly elevated for non-violent criminals. It is crucial to identify offenders and especially repeated offenders who also suffer from alcohol or substance misuse and psychiatric illness in clinical settings in order to prevent suicide. PMID:24491380

Criminality and suicide: a longitudinal Swedish cohort study.

PubMed

Stenbacka, M; Romelsjö, A; Jokinen, J

2014-02-03

This study aimed to investigate whether violent and non-violent offending were related to elevated risk of suicide. We also investigated whether the risk was higher among those with repeated offences and how experiences of substance misuse and suicide attempt modified the relationship. A nationwide prospective cohort study. A register study of 48 834 conscripted men in 1969/1970 in Sweden followed up during a 35-year period in official registers. A birth cohort of 48 834 men who were mandatory conscripted for military service in 1969/70 at the age of 18-20 years. Possible confounders were retrieved from psychological assessments at conscription and the cohort was linked to mortality and hospitalisation and crime records from 1970 onwards. Estimates of suicide risks were calculated as HR with 95% CIs using Cox proportional regression analyses with adjustment for potential confounding by family, psychological and behavioural factors including substance use and psychiatric disorders. Of the total cohort, 2671 (5.5%) persons died during the follow-up period. Of these, 615 (23%) persons died due to suicide. Non-violent criminality was evident for 29% and violent criminality for 4.7% of all the participants. In the crude model, the violent offenders had nearly five times higher risk (HR=4.69, 3.56 to 6.19) to die from suicide and non-violent criminals had about two times higher risk (HR=2.08, 1.72 to 2.52). In the fully adjusted model, the HRs were still significant for suicide in the non-violent group. Experiences of violent or non-violent criminality were associated with increased risk of suicide. Comorbidity with alcohol and substance use and psychiatric disorders modified the risk, but the suicide risk remained significantly elevated for non-violent criminals. It is crucial to identify offenders and especially repeated offenders who also suffer from alcohol or substance misuse and psychiatric illness in clinical settings in order to prevent suicide.

Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers

PubMed Central

Ramus, Susan J.; Antoniou, Antonis C; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E.J.; van Asperen, Christi J.; van Roozendaal, K.E.P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D.P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia

2012-01-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10−4, rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10−4, rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10−4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. PMID:22253144

New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis.

PubMed

Meek, M E; Boobis, A; Cote, I; Dellarco, V; Fotakis, G; Munn, S; Seed, J; Vickers, C

2014-01-01

The World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect the experience acquired in its application and extend its utility to emerging areas in toxicity testing and non-testing methods. The underlying principles have not changed, but the framework's scope has been extended to enable integration of information at different levels of biological organization and reflect evolving experience in a much broader range of potential applications. Mode of action/species concordance analysis can also inform hypothesis-based data generation and research priorities in support of risk assessment. The modified framework is incorporated within a roadmap, with feedback loops encouraging continuous refinement of fit-for-purpose testing strategies and risk assessment. Important in this construct is consideration of dose-response relationships and species concordance analysis in weight of evidence. The modified Bradford Hill considerations have been updated and additionally articulated to reflect increasing experience in application for cases where the toxicological outcome of chemical exposure is known. The modified framework can be used as originally intended, where the toxicological effects of chemical exposure are known, or in hypothesizing effects resulting from chemical exposure, using information on putative key events in established modes of action from appropriate in vitro or in silico systems and other lines of evidence. This modified mode of action framework and accompanying roadmap and case examples are expected to contribute to improving transparency in explicitly addressing weight of evidence considerations in mode of action/species concordance analysis based on both conventional data sources and evolving methods. Copyright © 2013 John Wiley & Sons, Ltd. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Atherosclerosis and clonal hematopoyesis: A new risk factor.

PubMed

Páramo Fernández, José A

Recent research has revealed that clonal hematopoyesis of indeterminate potential (CHIP) characterized by the acquisition of somatic mutations in hematopoietic stem cells, is not only a common age-related disorder and a premalignant condition, but it is also associated with the development of atherosclerotic vascular diseases. Mutations in DNMT3A, TET2 and ASXL1 were each individually associated with coronary heart disease, stroke and coronary calcification. Therefore, CHIP emerges as a new risk factor for atherosclerotic vascular pathologies and its detection may be relevant as a new therapeutic target in order to modify the natural course of the disease. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Nutritional Deficiencies and Sarcopenia in Heart Failure: A Therapeutic Opportunity to Reduce Hospitalization and Death.

PubMed

McCullough, Peter A; Fallahzadeh, Mohammad Kazem; Hegazi, Refaat M

2016-01-01

There is an expanding prevalence pool of heart failure (HF) due to the increasing prevalence of survivors of myocardial infarction, diabetes, hypertension, chronic kidney disease, and obesity. There is increasing interest in the role of nutrition in all forms of HF, given observations concerning micro- and macronutrient deficiencies, loss of lean body mass or sarcopenia, and their relationships with hospitalization and death. This review examines the relationships among loss of lean body mass, macro- and micronutrient intake, and the natural history of HF, particularly in the elderly, in whom the risks for all-cause rehospitalization, infection, falls, and mortality are increased. These risks are potentially modifiable through strategies that improve nutrition in this vulnerable population.

Posttraumatic Stress Disorder and Suicidal Behavior: Indirect Effects of Impaired Social Functioning.

PubMed

Dutton, Courtney E; Rojas, Sasha M; Badour, Christal L; Wanklyn, Sonya G; Feldner, Matthew T

2016-01-01

Social functioning is negatively impacted by the presence of PTSD, while increasing risk of suicidal behavior among individuals with PTSD. However, little research has examined the specific role of social functioning in the association between PTSD and suicidal behavior. Parallel multiple indirect effects analyses were performed to understand the unique indirect effects of four aspects of social functioning. Indirect effects of PTSD on suicidal ideation were significant through three pathways: interpersonal conflict, perceived family support, and interpersonal apprehension. Perceived family support was the only indirect pathway significantly associated with suicide attempt. Findings suggest that social functioning should be assessed and potentially targeted during treatment to help modify the risk for suicidal behavior among individuals with PTSD.

Irresponsible and responsible resource management in obstetrics.

PubMed

Arabin, Birgit

2017-08-01

Low budgets constrain and high budgets stimulate choices. In high-income countries, this economic reality may lead to overuse of healthcare services and pose unnecessary risks for mothers and infants. Options for improvement can be created at different levels of healthcare systems. Pregnancy provides an effective opportunity to profile maternal risks and represents a vulnerable but potentially modifiable period from prenatal life to adulthood. In response to system-inherent false incentives, professional responsibility requires obstetricians to strive to improve the future health of families and their offspring despite disincentives for doing so. This chapter addresses professionally responsible resource management in obstetrics and identifies implications for patients, care givers, communities, policy makers, and academic faculties. Copyright © 2017. Published by Elsevier Ltd.

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Early life factors in the pathogenesis of osteoporosis.

PubMed

Winsloe, Chivon; Earl, Susie; Dennison, Elaine M; Cooper, Cyrus; Harvey, Nicholas C

2009-12-01

Osteoporosis is a major public health burden through associated fragility fractures. Bone mass, a composite of bone size and volumetric density, increases through early life and childhood to a peak in early adulthood. The peak bone mass attained is a strong predictor of future risk of osteoporosis. Evidence is accruing that environmental factors in utero and in early infancy may permanently modify the postnatal pattern of skeletal growth to peak and thus influence risk of osteoporosis in later life. This article describes the latest data in this exciting area of research, including novel epigenetic and translation work, which should help to elucidate the underlying mechanisms and give rise to potential public health interventions to reduce the burden of osteoporotic fracture in future generations.

Increased fear-potentiated startle in major depressive disorder patients with lifetime history of suicide attempt.

PubMed

Ballard, Elizabeth D; Ionescu, Dawn F; Vande Voort, Jennifer L; Slonena, Elizabeth E; Franco-Chaves, Jose A; Zarate, Carlos A; Grillon, Christian

2014-06-01

Suicide is a common reason for psychiatric emergency and morbidity, with few effective treatments. Anxiety symptoms have emerged as potential modifiable risk factors in the time before a suicide attempt, but few studies have been conducted using laboratory measures of fear and anxiety. We operationally defined fear and anxiety as increased startle reactivity during anticipation of predictable (fear-potentiated startle) and unpredictable (anxiety-potentiated startle) shock. We hypothesized that a lifetime history of suicide attempt (as compared to history of no suicide attempt) would be associated with increased fear-potentiated startle. A post-hoc analysis of fear- and anxiety-potentiated startle was conducted in 28 medication-free patients with Major Depressive Disorder (MDD) divided according to suicide attempt history. The magnitude of fear-potentiated startle was increased in depressed patients with lifetime suicide attempts compared to those without a lifetime history of suicide attempt (F(1,26)=5.629, p=.025). There was no difference in anxiety-potentiated startle by suicide attempt history. This is a post-hoc analysis of previously analyzed patient data from a study of depressed inpatients. Further replication of the finding with a larger patient sample is indicated. Increased fear-potentiated startle in suicide attempters suggests the role of amygdala in depressed patients with a suicide attempt history. Findings highlight the importance of anxiety symptoms in the treatment of patients at increased suicide risk. Published by Elsevier B.V.

Pet Ownership and Cancer Risk in the Women's Health Initiative.

PubMed

Garcia, David O; Lander, Eric M; Wertheim, Betsy C; Manson, JoAnn E; Volpe, Stella L; Chlebowski, Rowan T; Stefanick, Marcia L; Lessin, Lawrence S; Kuller, Lewis H; Thomson, Cynthia A

2016-09-01

Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Pet ownership had no association with overall cancer incidence. This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. ©2016 AACR. ©2016 American Association for Cancer Research.

Pet Ownership and Cancer Risk in the Women’s Health Initiative

PubMed Central

Garcia, David O.; Lander, Eric M.; Wertheim, Betsy C.; Manson, JoAnn E.; Volpe, Stella L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Lessin, Lawrence S.; Kuller, Lewis H.; Thomson, Cynthia A.

2016-01-01

Background Pet ownership and cancer are both highly prevalent in the U.S. Evidence suggest associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. Methods A prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women’s Health Initiative (WHI) observational study and clinical trials. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between pet ownership and cancer, adjusted for potential confounders. Results There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Conclusion Pet ownership had no association with overall cancer incidence. Impact This is the first large epidemiological study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. PMID:27365150

Safe sorting of GFP-transduced live cells for subsequent culture using a modified FACS vantage.

PubMed

Sørensen, T U; Gram, G J; Nielsen, S D; Hansen, J E

1999-12-01

A stream-in-air cell sorter enables rapid sorting to a high purity, but it is not well suited for sorting of infectious material due to the risk of airborne spread to the surroundings. A FACS Vantage cell sorter was modified for safe use with potentially HIV infected cells. Safety tests with bacteriophages were performed to evaluate the potential spread of biologically active material during cell sorting. Cells transduced with a retroviral vector carrying the gene for GFP were sorted on the basis of their GFP fluorescence, and GFP expression was followed during subsequent culture. The bacteriophage sorting showed that the biologically active material was confined to the sorting chamber. A failure mode simulating a nozzle blockage resulted in detectable droplets inside the sorting chamber, but no droplets could be detected when an additional air suction from the sorting chamber had been put on. The GFP transduced cells were sorted to 99% purity. Cells not expressing GFP at the time of sorting did not turn on the gene during subsequent culture. Un-sorted cells and cells sorted to be positive for GFP showed a decrease in the fraction of GFP positive cells during culture. Sorting of live infected cells can be performed safely and with no deleterious effects on vector expression using the modified FACS Vantage instrument. Copyright 1999 Wiley-Liss, Inc.

Accuracy and Acceptability of a Screening Tool for Identifying Intimate Partner Violence Perpetration among Women Veterans: A Pre-Implementation Evaluation.

PubMed

Portnoy, Galina A; Haskell, Sally G; King, Matthew W; Maskin, Rachel; Gerber, Megan R; Iverson, Katherine M

2018-06-06

Veterans are at heightened risk for perpetrating intimate partner violence (IPV), yet there is limited evidence to inform practice and policy for the detection of IPV perpetration. The present study evaluated the accuracy and acceptability of a potential IPV perpetration screening tool for use with women veterans. A national sample of women veterans completed a 2016 web-based survey that included a modified 5-item Extended-Hurt/Insult/Threaten/Scream (Modified E-HITS) and the Revised Conflict Tactics Scales (CTS-2). Items also assessed women's perceptions of the acceptability and appropriateness of the modified E-HITS questions for use in healthcare settings. Accuracy statistics, including sensitivity and specificity, were calculated using the CTS-2 as the reference standard. Primary measures included the Modified E-HITS (index test), CTS-2 (reference standard), and items assessing acceptability. This study included 187 women, of whom 31 women veterans (16.6%) reported past-6-month IPV perpetration on the CTS-2. The Modified E-HITS demonstrated good overall accuracy (area under the curve, 0.86; 95% confidence interval, 0.78-0.94). In addition, the majority of women perceived the questions to be acceptable and appropriate. Findings demonstrate that the Modified E-HITS is promising as a low-burden tool for detecting of IPV perpetration among women veterans. This tool may help the Veterans Health Administration and other health care providers detect IPV perpetration and offer appropriate referrals for comprehensive assessment and services. Published by Elsevier Inc.

Investigating the sources and potential health risks of environmental contaminants in the soils and drinking waters from the rural clusters in Thiva area (Greece).

PubMed

Kelepertzis, Efstratios

2014-02-01

The present study investigates the possible influence of human activities on metal loadings of topsoil in a typical small rural city in central Greece and the chemical quality of tap water in surrounding villages. Furthermore, the study aimed to examine potential health risks of naturally enriched heavy metals to exposed population taking into account the soil and drinking water as exposure pathways. The mean concentrations of Ni, Cr, Co, Mn, Pb, Cu, Zn and Cd in the soil were 1777, 285, 99, 946, 30, 26, 78 and 0.67 mg/kg respectively. Combination of pollution indexes based on local reference background soils and statistical analyses (correlation analysis, cluster analysis and principal component analysis) revealed that anthropogenic activities have not modified the natural soil chemistry at least in a large scale. High Hazard Quotient (HQ) values for children were estimated for Ni, Cr and Co based on total metal concentrations for the soil ingestion route (9.26E-01, 9.75E-01 and 3.45E+00 respectively). However, evaluation of HQs based on published bioaccessible concentrations suggested that the population groups would not likely experience potential health risks as a result of exposure to contaminated soils. Concentrations of Cr(VI) in tap waters were within the allowable limits. However, the risk assessment model revealed that local residents (adults) of Eleonas and Neochori villages are at some carcinogenic risks considering lifetime ingestion of water (potential cancer risks 2.05E-04 and 1.29E-04 respectively). Despite the uncertainties accompanying these procedures and the great deal of debate regarding the human carcinogenicity of Cr(VI) by the oral route, results of this study drive attention to remediation measures that should include epidemiological studies for the local population. © 2013 Published by Elsevier Inc.

The relationship between modifiable health risks and group-level health care expenditures. Health Enhancement Research Organization (HERO) Research Committee.

PubMed

Anderson, D R; Whitmer, R W; Goetzel, R Z; Ozminkowski, R J; Dunn, R L; Wasserman, J; Serxner, S

2000-01-01

To assess the relationship between modifiable health risks and total health care expenditures for a large employee group. Risk data were collected through voluntary participation in health risk assessment (HRA) and worksite biometric screenings and were linked at the individual level to health care plan enrollment and expenditure data from employers' fee-for-service plans over the 6-year study period. The setting was worksite health promotion programs sponsored by six large private-sector and public-sector employers. Of the 50% of employees who completed the HRA, 46,026 (74.7%) met all inclusion criteria for the analysis. Eleven risk factors (exercise, alcohol use, eating, current and former tobacco use, depression, stress, blood pressure, cholesterol, weight, and blood glucose) were dichotomized into high-risk and lower-risk levels. The association between risks and expenditures was estimated using a two-part regression model, controlling for demographics and other confounders. Risk prevalence data were used to estimate group-level impact of risks on expenditures. Risk factors were associated with 25% of total expenditures. Stress was the most costly factor, with tobacco use, overweight, and lack of exercise also being linked to substantial expenditures. Modifiable risk factors contribute substantially to overall health care expenditures. Health promotion programs that reduce these risks may be beneficial for employers in controlling health care costs.

Modifiable predictors of depression following childhood maltreatment: a systematic review and meta-analysis

PubMed Central

Braithwaite, E C; O'Connor, R M; Degli-Esposti, M; Luke, N; Bowes, L

2017-01-01

Although maltreatment experiences in childhood increase the risk for depression, not all maltreated children become depressed. This review aims to systematically examine the existing literature to identify modifiable factors that increase vulnerability to, or act as a buffer against, depression, and could therefore inform the development of targeted interventions. Thirteen databases (including Medline, PsychINFO, SCOPUS) were searched (between 1984 and 2014) for prospective, longitudinal studies published in English that included at least 300 participants and assessed associations between childhood maltreatment and later depression. The study quality was assessed using an adapted Newcastle–Ottawa Scale checklist. Meta-analyses (random effects models) were performed on combined data to estimate the effect size of the association between maltreatment and depression. Meta-regressions were used to explore effects of study size and quality. We identified 22 eligible articles (N=12 210 participants), of which 6 examined potential modifiable predictors of depression following maltreatment. No more than two studies examined the same modifiable predictor; therefore, it was not possible to examine combined effects of modifiable predictors with meta-regression. It is thus difficult to draw firm conclusions from this study, but initial findings indicate that interpersonal relationships, cognitive vulnerabilities and behavioral difficulties may be modifiable predictors of depression following maltreatment. There is a lack of well-designed, prospective studies on modifiable predictors of depression following maltreatment. A small amount of initial research suggests that modifiable predictors of depression may be specific to maltreatment subtypes and gender. Corroboration and further investigation of causal mechanisms is required to identify novel targets for intervention, and to inform guidelines for the effective treatment of maltreated children. PMID:28675390

An application of multiattribute decision analysis to the Space Station Freedom program. Case study: Automation and robotics technology evaluation

NASA Technical Reports Server (NTRS)

Smith, Jeffrey H.; Levin, Richard R.; Carpenter, Elisabeth J.

1990-01-01

The results are described of an application of multiattribute analysis to the evaluation of high leverage prototyping technologies in the automation and robotics (A and R) areas that might contribute to the Space Station (SS) Freedom baseline design. An implication is that high leverage prototyping is beneficial to the SS Freedom Program as a means for transferring technology from the advanced development program to the baseline program. The process also highlights the tradeoffs to be made between subsidizing high value, low risk technology development versus high value, high risk technology developments. Twenty one A and R Technology tasks spanning a diverse array of technical concepts were evaluated using multiattribute decision analysis. Because of large uncertainties associated with characterizing the technologies, the methodology was modified to incorporate uncertainty. Eight attributes affected the rankings: initial cost, operation cost, crew productivity, safety, resource requirements, growth potential, and spinoff potential. The four attributes of initial cost, operations cost, crew productivity, and safety affected the rankings the most.

Biosonar behaviour of free-ranging porpoises.

PubMed

Akamatsu, Tomonari; Wang, Ding; Wang, Kexiong; Naito, Yasuhiko

2005-04-22

Detecting objects in their paths is a fundamental perceptional function of moving organisms. Potential risks and rewards, such as prey, predators, conspecifics or non-biological obstacles, must be detected so that an animal can modify its behaviour accordingly. However, to date few studies have considered how animals in the wild focus their attention. Dolphins and porpoises are known to actively use sonar or echolocation. A newly developed miniature data logger attached to a porpoise allows for individual recording of acoustical search efforts and inspection distance based on echolocation. In this study, we analysed the biosonar behaviour of eight free-ranging finless porpoises (Neophocaena phocaenoides) and demonstrated that these animals inspect the area ahead of them before swimming silently into it. The porpoises inspected distances up to 77 m, whereas their swimming distance without using sonar was less than 20 m. The inspection distance was long enough to ensure a wide safety margin before facing real risks or rewards. Once a potential prey item was detected, porpoises adjusted their inspection distance from the remote target throughout their approach.

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

Kapuscinski, A.R.; Hallerman, E.M.

Among the many methodologies encompassing biotechnology in aquaculture, this report addresses: the production of genetically modified aquatic organisms (aquatic GMOs) by gene transfer, chromosome set manipulation, or hybridization or protoplast fusion between species; new health management tools, including DNA-Based diagnostics and recombinant DNA vaccines; Marker-assisted selection; cryopreservation; and stock marking. These methodologies pose a wide range of potential economic benefits for aquaculture by providing improved or new means to affect the mix of necessary material inputs, enhance production efficiency, or improve product quality. Advances in aquaculture through biotechnology could simulate growth of the aquaculture industry to provide a larger proportionmore » of consummer demand, and thereby reduce pressure and natural stocks from over-harvest. Judicious application of gamete cryopreservation and chromosome set manipulations to achieve sterilization could reduce environmental risks of some aquaculture operations. Given the significant losses to disease in many aquaculture enterprises, potential benefits of DNA-based health management tools are very high and appear to pose no major environmental risks or social concerns.« less

Optimizing footwear for older people at risk of falls.

PubMed

Menant, Jasmine C; Steele, Julie R; Menz, Hylton B; Munro, Bridget J; Lord, Stephen R

2008-01-01

Footwear influences balance and the subsequent risk of slips, trips, and falls by altering somatosensory feedback to the foot and ankle and modifying frictional conditions at the shoe/floor interface. Walking indoors barefoot or in socks and walking indoors or outdoors in high-heel shoes have been shown to increase the risk of falls in older people. Other footwear characteristics such as heel collar height, sole hardness, and tread and heel geometry also influence measures of balance and gait. Because many older people wear suboptimal shoes, maximizing safe shoe use may offer an effective fall prevention strategy. Based on findings of a systematic literature review, older people should wear shoes with low heels and firm slip-resistant soles both inside and outside the home. Future research should investigate the potential benefits of tread sole shoes for preventing slips and whether shoes with high collars or flared soles can enhance balance when challenging tasks are undertaken.

Management of statin-intolerant high-risk patients.

PubMed

Tziomalos, Konstantinos; Athyros, Vasilios G; Karagiannis, Asterios; Mikhailidis, Dimitri P

2010-09-01

Statins are an essential part of the management of patients at high vascular risk and are generally well-tolerated. However, statin intolerance will be observed more frequently as more stringent low density lipoprotein cholesterol (LDL-C) targets are pursued in an ever increasing number of patients. We review the management options for high-risk patients intolerant to statin treatment. Potential strategies include switching to a different statin, reducing the frequency of statin administration, substituting statins with other LDL-C-lowering agents (e.g. ezetimibe, colesevelam or nicotinic acid) and combining low-dose statin treatment with other lipid-modifying drugs. A limited number of studies specifically assessed statin-intolerant patients and most were small and of short duration. It is therefore difficult to make evidence-based recommendations for the management of this population. In addition, all treatment options have limitations in terms of safety and/or efficacy.

Electronic Nicotine Delivery Systems (ENDS): What Nurses Need to Know.

PubMed

Essenmacher, Carol; Naegle, Madeline; Baird, Carolyn; Vest, Bridgette; Spielmann, Rene; Smith-East, Marie; Powers, Leigh

Efforts to decrease adverse effects of tobacco use are affected by emergence of new nicotine delivery products. Advertising, product promotion, and social media promote use of these products, yet a lack of evidence regarding safety leaves nurses unprepared to counsel patients. To critically evaluate current research, reviews of literature, expert opinion, and stakeholder policy proposals on use and safety of electronic nicotine delivery systems (ENDS). A targeted examination of literature generated by key stakeholders and subject matter experts was conducted using key words, modified by risk factors, and limited to the past 8 years. Current knowledge gaps in research literature and practice implications of the literature are discussed. The safety of ENDS is questionable and unclear. There are clear health risks of nicotine exposure to developing brains. Potential health risks of ENDS secondhand emissions exposure exist. Using ENDS to facilitate total tobacco cessation is not proven.

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

Interrupting Intergenerational Cycles of Maternal Obesity

PubMed Central

Gillman, Matthew W.

2016-01-01

Factors operating in the preconception and prenatal periods, such as maternal obesity, excessive gestational weight gain, and gestational diabetes, predict a substantial fraction of childhood obesity as well as lifelong adverse health consequences in the mother. These periods may lend themselves to successful intervention to reduce such risk factors because parents may be especially willing to change behavior if it confers health advantages to their children. If effective interventions started before or during pregnancy can be maintained after birth, they have the potential to lower the risk of both maternal obesity in the next pregnancy and obesity in the growing child, thus helping to interrupt maternal and child inter-generational vicious cycles of obesity, diabetes, and related cardiometabolic health consequences. While this paradigm is appealing, challenges include determining the magnitude, causality, and modifiability of these risk factors, and quantifying any adverse consequences of intervention. PMID:27088333

Bezlotoxumab: A Review in Preventing Clostridium difficile Infection Recurrence.

PubMed

Deeks, Emma D

2017-10-01

Bezlotoxumab (Zinplava™) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk. It is the first agent approved for recurrence prevention and is administered as a single intravenous infusion in conjunction with standard-of-care (SoC) antibacterial treatment for CDI. In well-designed, placebo-controlled, phase 3 trials (MODIFY 1 and 2), a single infusion of bezlotoxumab, given in combination with SoC antibacterial therapy for CDI in adults, was effective in reducing CDI recurrence in the 12 weeks post-treatment, with this benefit being seen mainly in the patients at high recurrence risk. Bezlotoxumab did not impact the efficacy of the antibacterials being used to treat the CDI and, consistent with its benefits on CDI recurrence, appeared to reduce the need for subsequent antibacterials, thus minimizing further gut microbiota disruption. Longer term, there were no further CDI recurrences over 12 months' follow-up among patients who had received bezlotoxumab in MODIFY 2 and entered an extension substudy. Bezlotoxumab has low immunogenicity and is generally well tolerated, although the potential for heart failure in some patients requires consideration; cost-effectiveness data for bezlotoxumab are awaited with interest. Thus, a single intravenous infusion of bezlotoxumab during SoC antibacterial treatment for CDI is an emerging option for reducing CDI recurrence in adults at high risk of recurrence.

Speciation of heavy metals Cu, Ni and Zn by modified BCR sequential extraction procedure in sediments from Banten Bay, Banten Province, Indonesia

NASA Astrophysics Data System (ADS)

Lestari; Budiyanto, F.; Hindarti, D.

2018-02-01

Banten Bay is categorized as a marine area that is busy with marine tourism activities, settlements and also industries. One potential impact of the condition is the occurrence of pollution from both industrial and domestic sources, erosion and sedimentation in the coastal environment. Samples were collected from 25 representative stations in April 2016. Chemical speciation of three heavy metals (Cu, Ni, and Zn) was studied using a modified sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM&T) program, formerly the Community Bureau of Reference (BCR). The aims of this study are to determine geochemical speciation of 4 bounds of metal: acid-soluble, reducible, oxidizable and residual, and to assess their impacts in the sediments of Banten Bay, Indonesia. The result shows that the percentage of Copper (45.90-83.75%), Nickel (18.28-65.66%), and Zinc (30.45-79.51%) were mostly accumulated in residual fraction of the total concentrations. The Risk Assessment Code (RAC) reveals that about 0-7.07% of Copper and 1.11-24.35 % of Zinc at sites exist in exchangeable fraction and therefore, they are in low risk category. While 7.34-34.90 of Ni at sites exists in exchangeable fraction and therefore, it is in medium risk category to aquatic environment.

Alcohol consumption and the risk of type 2 diabetes mellitus: effect modification by hypercholesterolemia: the Third Korea National Health and Nutrition Examination Survey (2005).

PubMed

Jang, Hyeongap; Jang, Won-Mo; Park, Jong-Heon; Oh, Juhwan; Oh, Mu-Kyung; Hwang, Soo-Hee; Kim, Yong-Ik; Lee, Jin-Seok

2012-01-01

While the protective nature of moderate alcohol consumption against diabetes mellitus is well known, inconsistent findings continue to be reported. The possibility of different mixes of effect modifiers has been raised as a reason for those inconsistent findings. Our study aim was to examine potential effect modifiers that can change the effect of alcohol consumption on type 2 diabetes. From data in the third Korea National Health and Nutrition Examination Survey, 3,982 individuals over the age of 30 years who had not been diagnosed with diabetes were selected for inclusion in the study population. Breslow and Day's test and the Wald test between hypercholesterolemia and alcohol consumption in a multiple logistic regression model were used to assess effect modification. Odds ratios for diabetes stratified by alcohol consumption strata and assessed using Breslow and Day's tests for homogeneity indicated that hypercholesterolemia was not a significant confounding factor (p=0.01). However, the Wald test for interaction terms, which is a conservative method of effect modification, was significant (p=0.03). The results indicate that moderate alcohol consumption is not necessarily protective for type 2 diabetes mellitus, if a person has hypercholesterolemia. People who have hypercholesterolemia should be aware of the risk associated with alcohol consumption, a risk that contrasts with the reported protective effect of moderate alcohol consumption on diabetes.

Introduction to the Centers for Disease Control and Prevention and Healthcare Infection Control Practices Advisory Committee Guideline for Prevention of Surgical Site Infection: Prosthetic Joint Arthroplasty Section.

PubMed

Segreti, John; Parvizi, Javad; Berbari, Elie; Ricks, Philip; Berríos-Torres, Sandra I

Peri-prosthetic joint infection (PJI) is a severe complication of total joint arthroplasty that appears to be increasing as more of these procedures are performed. Numerous risk factors for incisional (superficial and deep) and organ/space (e.g., PJI) surgical site infections (SSIs) have been identified. A better understanding and reversal of modifiable risk factors may lead to a reduction in the incidence of incisional SSI and PJI. The Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recently updated the national Guideline for Prevention of Surgical Site Infection. The updated guideline applies evidence-based methodology, presents recommendations for potential strategies to reduce the risk of SSI, and includes an arthroplasty-specific section. This article serves to introduce the guideline development process and to complement the Prosthetic Joint Arthroplasty section with background information on PJI-specific economic burden, epidemiology, pathogenesis and microbiology, and risk factor information.

Interventions to modify the progression to type 2 diabetes mellitus in women with gestational diabetes: a systematic review of literature.

PubMed

Morton, Suzanna; Kirkwood, Samantha; Thangaratinam, Shakila

2014-12-01

Gestational diabetes mellitus (GDM) increases the lifetime risk of developing type 2 diabetes mellitus (T2DM) in the mother. We undertook a systematic review to assess the effectiveness of interventions that delay or prevent the onset of T2DM in women with previous gestational diabetes. Diet and lifestyle interventions show differing effects on women with GDM and their long-term risk of T2DM. Pharmacological interventions, such as metformin, appear to have a beneficial role. Breastfeeding may have a protective role by reducing the risk of progression to T2DM. The findings were limited by the small number of heterogeneous studies that varied in their population, intervention, outcome and duration of follow-up. Women with GDM should be informed about the future risk of T2DM and the potential benefit with lifestyle interventions. Further studies are needed prior to routine use of metformin as a preventive strategy for T2DM in women with GDM.

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

PubMed Central

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A.M.; Meijers-Heijboer, Hanne E.J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P.G.; Hoogerbrugge, Nicoline; Ausems, Margreet G.E.M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

2014-01-01

Background BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. PMID:25336561

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

PubMed

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B; Rudolph, Anja; Schmutzler, Rita K; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A; Easton, Douglas F; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A; Schmidt, Marjanka K; van der Baan, Frederieke H; Spurdle, Amanda B; Walker, Logan C; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B; Olopade, Olufunmilayo I; Nussbaum, Robert L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Karlan, Beth Y; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K; Miron, Alex; Southey, Melissa C; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E; Blazer, Kathleen R; Weitzel, Jeffrey N; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D Gareth R; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V; Ellis, Steve; Cole, Trevor; Godwin, Andrew K; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L; Rodriguez, Gustavo C; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A M; Meijers-Heijboer, Hanne E J; van der Hout, Annemarie H; Vreeswijk, Maaike P G; Hoogerbrugge, Nicoline; Ausems, Margreet G E M; van Doorn, Helena C; Collée, J Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R; Olswold, Curtis; Couch, Fergus J; Lindor, Noralane M; Wang, Xianshu; Szabo, Csilla I; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C; Friedman, Eitan

2015-01-01

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. ©2014 American Association for Cancer Research.

Malaria resurgence risk in southern Europe: climate assessment in an historically endemic area of rice fields at the Mediterranean shore of Spain.

PubMed

Sainz-Elipe, Sandra; Latorre, Jose Manuel; Escosa, Raul; Masià, Montserrat; Fuentes, Marius Vicent; Mas-Coma, Santiago; Bargues, Maria Dolores

2010-07-31

International travel and immigration have been related with an increase of imported malaria cases. This fact and climate change, prolonging the period favouring vector development, require an analysis of the malaria transmission resurgence risk in areas of southern Europe. Such a study is made for the first time in Spain. The Ebro Delta historically endemic area was selected due to its rice field landscape, the presence of only one vector, Anopheles atroparvus, with densities similar to those it presented when malaria was present, in a situation which pronouncedly differs from already assessed potential resurgence areas in other Mediterranean countries, such as France and Italy, where many different Anopheles species coexist and a different vector species dominates. The transmission risk was assessed analysing: 1) climate diagrams including the minimum temperature for Plasmodium falciparum and Plasmodium vivax development; 2) monthly evolution of the Gradient Model Risk (GMR) index, specifying transmission risk period and number of potential Plasmodium generations; 3) ecological characteristics using remote sensing images with the Eurasia Land Cover characteristics database and the monthly evolution of the Normalized Difference Vegetation Index (NDVI); 4) evaluation of A. atroparvus population dynamics. Climatological analyses and GMR index show that a transmission risk presently exists, lasting from May until September for P. falciparum, and from May until October for P. vivax. The GMR index shows that the temperature increase does not actually mean a transmission risk increase if accompanied by a precipitation decrease reducing the number of parasite generations and transmission period. Nevertheless, this limitation is offset by the artificial flooding of the rice fields. Maximum NDVI values and A. atroparvus maximum abundance correspond to months with maximum growth of the rice fields. The Ebro Delta presents the ecological characteristics that favour transmission. The temperature increase has favoured a widening of the monthly potential transmission window with respect to when malaria was endemic. The combined application of modified climate diagrams and GMR index, together with spatial characterization conforms a useful tool for assessing potential areas at risk of malaria resurgence. NDVI is a good marker when dealing with a rice field area.

Malaria resurgence risk in southern Europe: climate assessment in an historically endemic area of rice fields at the Mediterranean shore of Spain

PubMed Central

2010-01-01

Background International travel and immigration have been related with an increase of imported malaria cases. This fact and climate change, prolonging the period favouring vector development, require an analysis of the malaria transmission resurgence risk in areas of southern Europe. Such a study is made for the first time in Spain. The Ebro Delta historically endemic area was selected due to its rice field landscape, the presence of only one vector, Anopheles atroparvus, with densities similar to those it presented when malaria was present, in a situation which pronouncedly differs from already assessed potential resurgence areas in other Mediterranean countries, such as France and Italy, where many different Anopheles species coexist and a different vector species dominates. Methods The transmission risk was assessed analysing: 1) climate diagrams including the minimum temperature for Plasmodium falciparum and Plasmodium vivax development; 2) monthly evolution of the Gradient Model Risk (GMR) index, specifying transmission risk period and number of potential Plasmodium generations; 3) ecological characteristics using remote sensing images with the Eurasia Land Cover characteristics database and the monthly evolution of the Normalized Difference Vegetation Index (NDVI); 4) evaluation of A. atroparvus population dynamics. Results Climatological analyses and GMR index show that a transmission risk presently exists, lasting from May until September for P. falciparum, and from May until October for P. vivax. The GMR index shows that the temperature increase does not actually mean a transmission risk increase if accompanied by a precipitation decrease reducing the number of parasite generations and transmission period. Nevertheless, this limitation is offset by the artificial flooding of the rice fields. Maximum NDVI values and A. atroparvus maximum abundance correspond to months with maximum growth of the rice fields. Conclusions The Ebro Delta presents the ecological characteristics that favour transmission. The temperature increase has favoured a widening of the monthly potential transmission window with respect to when malaria was endemic. The combined application of modified climate diagrams and GMR index, together with spatial characterization conforms a useful tool for assessing potential areas at risk of malaria resurgence. NDVI is a good marker when dealing with a rice field area. PMID:20673367

Modifiable Risk Factors for Attempted Suicide in Australian Clinical and Community Samples

ERIC Educational Resources Information Center

Carter, Gregory L.; Page, Andrew; Clover, Kerrie; Taylor, Richard

2007-01-01

Modifiable risk factors for suicide attempt require identification in clinical and community samples. The aim of this study was to determine if similar social and psychiatric factors are associated with suicide attempts in community and clinical settings and whether the magnitude of effect is greater in clinical populations. Two case-control…

Characterizing Stressors and Modifiable Health Risk Factors among Homeless Smokers: An Exploratory Pilot Study

ERIC Educational Resources Information Center

Kendzor, Darla E.; Reitzel, Lorraine R.; Businelle, Michael S.

2015-01-01

This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were…

The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study.

PubMed

Carere, Deanna Alexis; VanderWeele, Tyler; Moreno, Tanya A; Mountain, Joanna L; Roberts, J Scott; Kraft, Peter; Green, Robert C

2015-10-15

Direct access to genomic information has the potential to transform cancer risk counseling. We measured the impact of direct-to-consumer genomic risk information on changes to perceived risk (ΔPR) of breast, prostate, colorectal and lung cancer among personal genomic testing (PGT) customers. We hypothesized that ΔPR would reflect directionality of risk estimates, attenuate with time, and be modified by participant characteristics. Pathway Genomics and 23andMe customers were surveyed prior to receiving PGT results, and 2 weeks and 6 months post-results. For each cancer, PR was measured on a 5-point ordinal scale from "much lower than average" to "much higher than average." PGT results, based on genotyping of common genetic variants, were dichotomized as elevated or average risk. The relationship between risk estimate and ΔPR was evaluated with linear regression; generalized estimating equations modeled this relationship over time. With the exception of lung cancer (for which ΔPR was positive regardless of result), elevated risk results were significantly associated with positive ΔPR, and average risk results with negative ΔPR (e.g., prostate cancer, 2 weeks: least squares-adjusted ΔPR = 0.77 for elevated risk versus -0.21 for average risk; p-valuedifference < 0.0001) among 1154 participants. Large changes were rare: for each cancer, <4 % of participants overall reported a ΔPR of ±3 or more units. Effect modification by age, cancer family history, and baseline interest was observed for breast, colorectal, and lung cancer, respectively. A pattern of decreasing impact on ΔPR over time was consistently observed, but this trend was significant only in the case of colorectal cancer. We have quantified the effect on consumer risk perception of returning genetic-based cancer risk information directly to consumers without clinician mediation. Provided via PGT, this information has a measurable but modest effect on perceived cancer risk, and one that is in some cases modified by consumers' non-genetic risk context. Our observations of modest marginal effect sizes, infrequent extreme changes in perceived risk, and a pattern of diminishing impact with time, suggest that the ability of PGT to effect changes to cancer screening and prevention behaviors may be limited by relatively small changes to perceived risk.

Coagulant plus ballast technique provides a rapid mitigation of cyanobacterial nuisance

PubMed Central

de Magalhães, Leonardo; Miranda, Marcela; Mucci, Maíra; van Oosterhout, Frank; Huszar, Vera L. M.; Marinho, Marcelo M.; Lima, Eduardo R. A.; Lürling, Miquel

2017-01-01

Cyanobacteria blooms are a risk to environmental health and public safety due to the potent toxins certain cyanobacteria can produce. These nuisance organisms can be removed from water bodies by biomass flocculation and sedimentation. Here, we studied the efficacy of combinations of a low dose coagulant (poly-aluminium chloride—PAC—or chitosan) with different ballast compounds (red soil, bauxite, gravel, aluminium modified zeolite and lanthanum modified bentonite) to remove cyanobacterial biomass from water collected in Funil Reservoir (Brazil). We tested the effect of different cyanobacterial biomass concentrations on removal efficiency. We also examined if zeta potential was altered by treatments. Addition of low doses of PAC and chitosan (1–8 mg Al L-1) to the cyanobacterial suspensions caused flock formation, but did not settle the cyanobacteria. When those low dose coagulants were combined with ballast, effective settling in a dose-dependent way up to 99.7% removal of the flocks could be achieved without any effect on the zeta potential and thus without potential membrane damage. Removal efficacy was influenced by the cyanobacterial biomass and at higher biomass more ballast was needed to achieve good removal. The combined coagulant-ballast technique provides a promising alternative to algaecides in lakes, ponds and reservoirs. PMID:28598977

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PubMed

Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

PubMed Central

Fernandez-Prado, Raul; Esteras, Raquel; Perez-Gomez, Maria Vanessa; Gracia-Iguacel, Carolina; Gonzalez-Parra, Emilio; Sanz, Ana B.; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

2017-01-01

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes. PMID:28498348

Stakeholders' attitude to genetically modified foods and medicine.

PubMed

Amin, Latifah; Jahi, Jamaluddin Md; Nor, Abd Rahim Md

2013-01-01

Public acceptance of genetically modified (GM) foods has to be adequately addressed in order for their potential economic and social benefits to be realized. The objective of this paper is to assess the attitude of the Malaysian public toward GM foods (GM soybean and GM palm oil) and GM medicine (GM insulin). A survey was carried out using self-constructed multidimensional instrument measuring attitudes towards GM products. The respondents (n = 1017) were stratified according to stakeholders' groups in the Klang Valley region. Results of the survey show that the overall attitude of the Malaysian stakeholders towards GM products was cautious. Although they acknowledged the presence of moderate perceived benefits associated with GM products surveyed and were moderately encouraging of them, they were also moderately concerned about the risks and moral aspects of the three GM products as well as moderately accepting the risks. Attitudes towards GM products among the stakeholders were found to vary not according to the type of all GM applications but rather depend on the intricate relationships between the attitudinal factors and the type of gene transfers involved. Analyses of variance showed significant differences in the six dimensions of attitude towards GM products across stakeholders' groups.

Stakeholders' Attitude to Genetically Modified Foods and Medicine

PubMed Central

Md Jahi, Jamaluddin; Md Nor, Abd Rahim

2013-01-01

Public acceptance of genetically modified (GM) foods has to be adequately addressed in order for their potential economic and social benefits to be realized. The objective of this paper is to assess the attitude of the Malaysian public toward GM foods (GM soybean and GM palm oil) and GM medicine (GM insulin). A survey was carried out using self-constructed multidimensional instrument measuring attitudes towards GM products. The respondents (n = 1017) were stratified according to stakeholders' groups in the Klang Valley region. Results of the survey show that the overall attitude of the Malaysian stakeholders towards GM products was cautious. Although they acknowledged the presence of moderate perceived benefits associated with GM products surveyed and were moderately encouraging of them, they were also moderately concerned about the risks and moral aspects of the three GM products as well as moderately accepting the risks. Attitudes towards GM products among the stakeholders were found to vary not according to the type of all GM applications but rather depend on the intricate relationships between the attitudinal factors and the type of gene transfers involved. Analyses of variance showed significant differences in the six dimensions of attitude towards GM products across stakeholders' groups. PMID:24381520

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease.

PubMed

Fernandez-Prado, Raul; Esteras, Raquel; Perez-Gomez, Maria Vanessa; Gracia-Iguacel, Carolina; Gonzalez-Parra, Emilio; Sanz, Ana B; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

2017-05-12

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

Prehispanic Functional Foods and Nutraceuticals in the Treatment of Dyslipidemia Associated to Cardiovascular Disease: a Mini-Review.

PubMed

Ríos-Hoyo, Alejandro; Romo-Araiza, Alejandra; Meneses-Mayo, Marcos; Guttiérrez-Salmeán, Gabriela

2017-01-27

Dyslipidemia is an important modifi able risk factor for cardiovascular and metabolic diseases, which are responsible for a large number of mortality and disability cases around the globe. Different strategies have been used within the treatment of dyslipidemia, including lifestyle modifi cations, pharmacologic therapy, as well as functional foods and nutraceuticals. Functional foods have been used worldwide since ancient times, particularly, the prehispanic civilizations utilized several as medicinal foods. In the current pandemic of dyslipidemia as well as the nutritional transition, particularly in Latin America, the use of native functional foods represents an attractive target for the treatment and/ or prevention of these conditions. In this mini-review, evidence regarding different functional foods such as cacao, amaranth, chia, nopal, spirulina, as well as their nutraceutical compounds, including fl avonoids, omega-3 PUFAs, fi ber, prebiotics, lovastatin, c-phycocyanin, among others, and their mechanism of action are presented and discussed. Although such foods certainly are considered as attractive potential agents to target dyslipidemia thus decrease the associated cardiometabolic risk, we conclude that for most of the presented functional foods there is currently not enough evidence to support its recommendation and every-day use.

Factors associated with stress among adolescents in the city of Nawabshah, Pakistan.

PubMed

Parpio, Yasmin; Farooq, Salima; Gulzar, Saleema; Tharani, Ambreen; Javed, Fawad; Ali, Tazeen Saeed

2012-11-01

To identify the risk factors of stress among school-going adolescents in rural Nawabshah, Pakistan. The cross-sectional study was conducted in 2005, comprising 800 school-going children of 10-16 years of age in Nawabshah, through simple random sampling. Data was collected using a structured questionnaire to assess the potential risk factors of stress. A modified version of Perceived stress scale was utilized to measure stress level. SPSS 12 was used for statistical analysis, while multiple linear regression analysis was run to identify the factors associated with stress in the study population. Of the total, 529 (66%) children belonged to state-run schools while 271 (34%) were studying at private facilities. The mean age was 13.7+/-1.3 years. The level of stress was positively associated with the number of siblings, parental conflicts, the age of the mother and the number of rooms in the household. There was decreased level of stress among female adolescents (n=474; 59.3%) who had prior information about pubertal body changes than the boys (n=326; 40.8%). The study showed that stress among adolescents can be reduced by modifying socio-economic and demographic factors.

Influence of Parameters of a Reactive Interatomic Potential on the Properties of Saturated Hydrocarbons

DTIC Science & Technology

2017-01-01

Methodology 3 2.1 Modified Embedded-Atom Method Theory 3 2.1.1 Embedding Energy Function 3 2.1.2 Screening Factor 8 2.1.3 Modified Embedded-Atom...Simulation Methodology 2.1 Modified Embedded-Atom Method Theory In the EAM and MEAM formalisms1,2,5 the total energy of a system of atoms (Etot) is...An interatomic potential for saturated hydrocarbons using the modified embedded-atom method (MEAM), a semiempirical many-body potential based on

Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis.

PubMed

Fogarty, Emer; Schmitz, Susanne; Tubridy, Niall; Walsh, Cathal; Barry, Michael

2016-09-01

Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome. The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk. Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.