Air-mediated pollen flow from genetically modified to conventional crops.

PubMed

Kuparinen, Anna; Schurr, Frank; Tackenberg, Oliver; O'Hara, Robert B

2007-03-01

Tools for estimating pollen dispersal and the resulting gene flow are necessary to assess the risk of gene flow from genetically modified (GM) to conventional fields, and to quantify the effectiveness of measures that may prevent such gene flow. A mechanistic simulation model is presented and used to simulate pollen dispersal by wind in different agricultural scenarios over realistic pollination periods. The relative importance of landscape-related variables such as isolation distance, topography, spatial configuration of the fields, GM field size and barrier, and environmental variation are examined in order to find ways to minimize gene flow and to detect possible risk factors. The simulations demonstrated a large variation in pollen dispersal and in the predicted amount of contamination between different pollination periods. This was largely due to variation in vertical wind. As this variation in wind conditions is difficult to control through management measures, it should be carefully considered when estimating the risk of gene flow from GM crops. On average, the predicted level of gene flow decreased with increasing isolation distance and with increasing depth of the conventional field, and increased with increasing GM field size. Therefore, at a national scale and over the long term these landscape properties should be accounted for when setting regulations for controlling gene flow. However, at the level of an individual field the level of gene flow may be dominated by uncontrollable variation. Due to the sensitivity of pollen dispersal to the wind, we conclude that gene flow cannot be summarized only by the mean contamination; information about the frequency of extreme events should also be considered. The modeling approach described in this paper offers a way to predict and compare pollen dispersal and gene flow in varying environmental conditions, and to assess the effectiveness of different management measures.

Compatibility of breeding for increased wood production and longterm sustainability: the genetic variation of seed orchard seed and associated risks.

Treesearch

R Johnson; S. Lipow

2002-01-01

Because breeding imposes strong artificial selection for a narrow suite of economically important traits, genetic variation is reduced in seedlings derived from operational seed orchards. Both quantitative genetics theory and studies of allozyme variation show that seed orchards contain most of the genetic diversity found in natural populations, although low-frequency...

A Rapidly Prototyped Vegetation Dryness Index Evaluated for Wildfire Risk Assessment at Stennis Space Center

NASA Technical Reports Server (NTRS)

Ross, Kenton; Graham, William; Prados, Don; Spruce, Joseph

2007-01-01

MVDI, which effectively involves the differencing of NDMI and NDVI, appears to display increased noise that is consistent with a differencing technique. This effect masks finer variations in vegetation moisture, preventing MVDI from fulfilling the requirement of giving decision makers insight into spatial variation of fire risk. MVDI shows dependencies on land cover and phenology which also argue against its use as a fire risk proxy in an area of diverse and fragmented land covers. The conclusion of the rapid prototyping effort is that MVDI should not be implemented for SSC decision support.

[Temporal and spatial characteristics of ecological risk in Shunyi, Beijing, China based on landscape structure.

PubMed

Qing, Feng Ting; Peng, Yu

2016-05-01

Based on the remote sensing data in 1997, 2001, 2005, 2009 and 2013, this article classified the landscape types of Shunyi, and the ecological risk index was built based on landscape disturbance index and landscape fragility. The spatial auto-correlation and geostatistical analysis by GS + and ArcGIS was used to study temporal and spatial changes of ecological risk. The results showed that eco-risk degree in the study region had positive spatial correlation which decreased with the increasing grain size. Within a certain grain range (<12 km), the spatial auto-correlation had an obvious dependence on scale. The random variation of spatial heterogeneity was less than spatial auto-correlation variation from 1997 to 2013, which meant the auto-correlation had a dominant role in spatial heterogeneity. The ecological risk of Shunyi was mainly at moderate level during the study period. The area of the district with higher and lower ecological risk increased, while that of mode-rate ecological risk decreased. The area with low ecological risk was mainly located in the airport region and forest of southeast Shunyi, while that with high ecological risk was mainly concentrated in the water landscape, such as the banks of Chaobai River.

Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois: variation within species and relevance to risk communication.

PubMed

Burger, Joanna; Gochfeld, Michael

2013-07-01

There is an emerging consensus that people consuming large amounts of fish with selenium:mercury ratios below 1 are at higher risk from mercury toxicity. As the relative amount of selenium increases compared to mercury, risk may be lowered, but it is unclear how much excess selenium is required. It would be useful if the selenium:mercury ratio was relatively consistent within a species, but this has not been the case in our studies of wild-caught fish. Since most people in developed countries and urban areas obtain their fish and other seafood commercially, we examined selenium:mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago. There was substantial interspecific and intraspecific variation in molar ratios. Across species the selenium:mercury molar ratio decreased with increasing mean mercury levels, but selenium variation also contributed to the ratio. Few samples had selenium:mercury molar ratios below 1, but there was a wide range in ratios, complicating the interpretation for use in risk management and communication. Before ratios can be used in risk management, more information is needed on mercury:selenium interactions and mutual bioavailability, and on the relationship between molar ratios and health outcomes. Further, people who are selenium deficient may be more at risk from mercury toxicity than others. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois: Variation within species and relevance to risk communication

PubMed Central

Burger, Joanna; Gochfeld, Michael

2015-01-01

There is an emerging consensus that people consuming large amounts of fish with selenium:mercury ratios below 1 may be at higher risk from mercury toxicity. As the relative amount of selenium increases compared to mercury, risk may be lowered, but it is unclear how much excess selenium is required. It would be useful if the selenium:mercury ratio was relatively consistent within a species, but this has not been the case in our studies of wild-caught fish. Since most people in developed countries and urban areas obtain their fish and other seafood commercially, we examined selenium:mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago. There was substantial interspecific and intraspecific variation in molar ratios. Across species the selenium:mercury molar ratio decreased with increasing mean mercury levels, but selenium variation also contributed to the ratio. Few samples had selenium:mercury molar ratios below 1, but there was a wide range in ratios, complicating the interpretation for use in risk management and communication. Before ratios can be used in risk management, more information is needed on mercury:selenium interactions and mutual bioavailability, and on the relationship between molar ratios and health outcomes. Further, people who are selenium deficient may be more at risk from mercury toxicity than others. PMID:23541437

Variation in the CYP19A1 gene and risk of colon and rectal cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2011-01-01

CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case–control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16–1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50–0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26–2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism. PMID:21479914

Extinction risks forced by climatic change and intraspecific variation in the thermal physiology of a tropical lizard.

PubMed

Pontes-da-Silva, Emerson; Magnusson, William E; Sinervo, Barry; Caetano, Gabriel H; Miles, Donald B; Colli, Guarino R; Diele-Viegas, Luisa M; Fenker, Jessica; Santos, Juan C; Werneck, Fernanda P

2018-04-01

Temperature increases can impact biodiversity and predicting their effects is one of the main challenges facing global climate-change research. Ectotherms are sensitive to temperature change and, although predictions indicate that tropical species are highly vulnerable to global warming, they remain one of the least studied groups with respect to the extent of physiological variation and local extinction risks. We model the extinction risks for a tropical heliothermic teiid lizard (Kentropyx calcarata) integrating previously obtained information on intraspecific phylogeographic structure, eco-physiological traits and contemporary species distributions in the Amazon rainforest and its ecotone to the Cerrado savannah. We also investigated how thermal-biology traits vary throughout the species' geographic range and the consequences of such variation for lineage vulnerability. We show substantial variation in thermal tolerance of individuals among thermally distinct sites. Thermal critical limits were highly correlated with operative environmental temperatures. Our physiological/climatic model predicted relative extinction risks for local populations within clades of K. calcarata for 2050 ranging between 26.1% and 70.8%, while for 2070, extinction risks ranged from 52.8% to 92.8%. Our results support the hypothesis that tropical-lizard taxa are at high risk of local extinction caused by increasing temperatures. However, the thermo-physiological differences found across the species' distribution suggest that local adaptation may allow persistence of this tropical ectotherm in global warming scenarios. These results will serve as basis to further research to investigate the strength of local adaptation to climate change. Persistence of Kentropyx calcarata also depends on forest preservation, but the Amazon rainforest is currently under high deforestation rates. We argue that higher conservation priority is necessary so the Amazon rainforest can fulfill its capacity to absorb the impacts of temperature increase on tropical ectotherms during climate change. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cost-efficient and storm surge-sensitive bridge design for coastal Maine.

DOT National Transportation Integrated Search

2013-08-01

Climatic variation felt through changing weather patterns is having increasingly acute effects on Maines : transportation infrastructure. Acute risk occurs as a result of events, such as storms and flooding, while chronic risk : surrounds longer r...

Variation in vulnerability to extreme-temperature-related mortality in Japan: A 40-year time-series analysis.

PubMed

Onozuka, Daisuke; Hagihara, Akihito

2015-07-01

Although the impact of extreme heat and cold on mortality has been documented in recent years, few studies have investigated whether variation in susceptibility to extreme temperatures has changed in Japan. We used data on daily total mortality and mean temperatures in Fukuoka, Japan, for 1973-2012. We used time-series analysis to assess the effects of extreme hot and low temperatures on all-cause mortality, stratified by decade, gender, and age, adjusting for time trends. We used a multivariate meta-analysis with a distributed lag non-linear model to estimate pooled non-linear lag-response relationships associated with extreme temperatures on mortality. The relative risk of mortality increased during heat extremes in all decades, with a declining trend over time. The mortality risk was higher during cold extremes for the entire study period, with a dispersed pattern across decades. Meta-analysis showed that both heat and cold extremes increased the risk of mortality. Cold effects were delayed and lasted for several days, whereas heat effects appeared quickly and did not last long. Our study provides quantitative evidence that extreme heat and low temperatures were significantly and non-linearly associated with the increased risk of mortality with substantial variation. Our results suggest that timely preventative measures are important for extreme high temperatures, whereas several days' protection should be provided for extreme low temperatures. Copyright © 2015 Elsevier Inc. All rights reserved.

Breeding phenology of birds: mechanisms underlying seasonal declines in the risk of nest predation.

PubMed

Borgmann, Kathi L; Conway, Courtney J; Morrison, Michael L

2013-01-01

Seasonal declines in avian clutch size are well documented, but seasonal variation in other reproductive parameters has received less attention. For example, the probability of complete brood mortality typically explains much of the variation in reproductive success and often varies seasonally, but we know little about the underlying cause of that variation. This oversight is surprising given that nest predation influences many other life-history traits and varies throughout the breeding season in many songbirds. To determine the underlying causes of observed seasonal decreases in risk of nest predation, we modeled nest predation of Dusky Flycatchers (Empidonax oberholseri) in northern California as a function of foliage phenology, energetic demand, developmental stage, conspecific nest density, food availability for nest predators, and nest predator abundance. Seasonal variation in the risk of nest predation was not associated with seasonal changes in energetic demand, conspecific nest density, or predator abundance. Instead, seasonal variation in the risk of nest predation was associated with foliage density (early, but not late, in the breeding season) and seasonal changes in food available to nest predators. Supplemental food provided to nest predators resulted in a numerical response by nest predators, increasing the risk of nest predation at nests that were near supplemental feeders. Our results suggest that seasonal changes in foliage density and factors associated with changes in food availability for nest predators are important drivers of temporal patterns in risk of avian nest predation.

Breeding Phenology of Birds: Mechanisms Underlying Seasonal Declines in the Risk of Nest Predation

PubMed Central

Borgmann, Kathi L.; Conway, Courtney J.; Morrison, Michael L.

2013-01-01

Seasonal declines in avian clutch size are well documented, but seasonal variation in other reproductive parameters has received less attention. For example, the probability of complete brood mortality typically explains much of the variation in reproductive success and often varies seasonally, but we know little about the underlying cause of that variation. This oversight is surprising given that nest predation influences many other life-history traits and varies throughout the breeding season in many songbirds. To determine the underlying causes of observed seasonal decreases in risk of nest predation, we modeled nest predation of Dusky Flycatchers (Empidonax oberholseri) in northern California as a function of foliage phenology, energetic demand, developmental stage, conspecific nest density, food availability for nest predators, and nest predator abundance. Seasonal variation in the risk of nest predation was not associated with seasonal changes in energetic demand, conspecific nest density, or predator abundance. Instead, seasonal variation in the risk of nest predation was associated with foliage density (early, but not late, in the breeding season) and seasonal changes in food available to nest predators. Supplemental food provided to nest predators resulted in a numerical response by nest predators, increasing the risk of nest predation at nests that were near supplemental feeders. Our results suggest that seasonal changes in foliage density and factors associated with changes in food availability for nest predators are important drivers of temporal patterns in risk of avian nest predation. PMID:23776566

An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

DTIC Science & Technology

2008-10-01

pathway. Within single gene analyses we observed breast cancer risk to be modestly associated with one SNPs in each GSTP1 (rs1695: OR = 1.4 [95% CI...CYP1B1*2 and GSTP1 ), breast cancer risk was 1.6 (95% CI: 1.03-2.4) times higher for carriers of 1 high risk genotype and 2.8 (95% CI: 1.5-5.3) times...breast cancer risk. We observed a that the risk of breast cancer increased as the number of high risk alleles in the combined CYP1B1- GSTP1 increased

Place matters: variation in the black/white very preterm birth rate across U.S. metropolitan areas, 2002-2004.

PubMed

Kramer, Michael R; Hogue, Carol R

2008-01-01

We reported on the distribution of very preterm (VPT) birth rates by race across metropolitan statistical areas (MSAs). Rates of singleton VPT birth for non-Hispanic white, non-Hispanic black, and Hispanic women were calculated with National Center for Health Statistics 2002-2004 natality files for infants in 168 MSAs. Subanalysis included stratification by parity, age, smoking, maternal education, metropolitan size, region, proportion of MSA that was black, proportion of black population living below the poverty line, and indices of residential segregation. The mean metropolitan-level VPT birth rate was 12.3, 34.8, and 15.7 per 1,000 live births for white, black, and Hispanic women, respectively. There was virtually no overlap in the white and black distributions. The variation in mean risk across cities was three times greater for black women compared with white women. The threefold disparity in mean rate, and two- to threefold increased variation as indicated by standard deviation, was maintained in all subanalyses. Compared with white women, black women have three times the mean VPT birth risk, as well as three times the variance in city-level rates. The racial disparity in VPT birth rates was composed of characteristics that were constant across MSAs, as well as factors that varied by MSA. The increased sensitivity to place for black women was unexplained by measured maternal and metropolitan factors. Understanding determinants of differences in both the mean risk and the variation of risk among black and white women may contribute to reducing the disparity in risk between races.

Spatial and temporal variation of heavy metal risk and source in sediments of Dongting Lake wetland, mid-south China.

PubMed

Liang, Jie; Liu, Jiayu; Yuan, Xingzhong; Zeng, Guangming; Lai, Xu; Li, Xiaodong; Wu, Haipeng; Yuan, Yujie; Li, Fei

2015-01-01

Surface sediments of Dongting Lake wetland were collected from ten sites to investigate variation trend, risk and sources of heavy metal distribution in dry seasons of 2011∼2013. The three-year mean concentrations (mg/kg) of Cr, Cu, Pb, Cd, Hg and As were 91.33, 36.27, 54.82, 4.39, 0.19 and 25.67, respectively, which were all higher than the corresponding background values. Sediment quality guidelines (SQGs) and Geo-accumulation index (Igeo) were used for the assessment of pollution level of heavy metals. The pollution risk of Cd, Hg and As were great and that of Cr needed urgent attention because of its obvious increase. Pollution load index (PLI) and geographic information system (GIS) methods were conducted to assess spatial and temporal variation of heavy metal contamination. Results confirmed an increased contamination contribution inflow from Xiang River. Multivariate statistical analyses were applied to identify contribution sources of heavy metal, which showed anthropogenic origin mainly from mining, smelting, chemical industry and agricultural activity.

Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity

PubMed Central

Raj, Prithvi; Rai, Ekta; Song, Ran; Khan, Shaheen; Wakeland, Benjamin E; Viswanathan, Kasthuribai; Arana, Carlos; Liang, Chaoying; Zhang, Bo; Dozmorov, Igor; Carr-Johnson, Ferdicia; Mitrovic, Mitja; Wiley, Graham B; Kelly, Jennifer A; Lauwerys, Bernard R; Olsen, Nancy J; Cotsapas, Chris; Garcia, Christine K; Wise, Carol A; Harley, John B; Nath, Swapan K; James, Judith A; Jacob, Chaim O; Tsao, Betty P; Pasare, Chandrashekhar; Karp, David R; Li, Quan Zhen; Gaffney, Patrick M; Wakeland, Edward K

2016-01-01

Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes. DOI: http://dx.doi.org/10.7554/eLife.12089.001 PMID:26880555

Spatially varying density dependence drives a shifting mosaic of survival in a recovering apex predator (Canis lupus).

PubMed

O'Neil, Shawn T; Bump, Joseph K; Beyer, Dean E

2017-11-01

Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves ( Canis lupus ), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves ( C. lupus ) during a 21-year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time-dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time-dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual-level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long-term change was density-dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long-term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source-sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density-dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.

Risk of Resource Failure and Toolkit Variation in Small-Scale Farmers and Herders

PubMed Central

Collard, Mark; Ruttle, April; Buchanan, Briggs; O’Brien, Michael J.

2012-01-01

Recent work suggests that global variation in toolkit structure among hunter-gatherers is driven by risk of resource failure such that as risk of resource failure increases, toolkits become more diverse and complex. Here we report a study in which we investigated whether the toolkits of small-scale farmers and herders are influenced by risk of resource failure in the same way. In the study, we applied simple linear and multiple regression analysis to data from 45 small-scale food-producing groups to test the risk hypothesis. Our results were not consistent with the hypothesis; none of the risk variables we examined had a significant impact on toolkit diversity or on toolkit complexity. It appears, therefore, that the drivers of toolkit structure differ between hunter-gatherers and small-scale food-producers. PMID:22844421

Mammographic density and breast cancer risk: current understanding and future prospects

PubMed Central

2011-01-01

Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making. PMID:22114898

Season and region of birth as risk factors for coeliac disease a key to the aetiology?

PubMed Central

Namatovu, Fredinah; Lindkvist, Marie; Olsson, Cecilia; Ivarsson, Anneli; Sandström, Olof

2016-01-01

Background Coeliac disease (CD) incidence has increased in recent decades, characterised by variations according to sex, age at diagnosis, year of birth, month of birth and region of birth. Genetic susceptibility and exposure to gluten are the necessary factors in CD aetiology, although several environmental factors are considered. Methods A nationwide prospective cohort longitudinal study was conducted consisting of 1 912 204 children aged 0–14.9 years born in Sweden from 1991 to 2009. A total of 6569 children were diagnosed with biopsy-verified CD from 47 paediatric departments. Using Cox regression, we examined the association between CD diagnosis and season of birth, region of birth and year of birth. Results Overall, CD risk was higher for children born during spring, summer and autumn as compared with children born during winter: adjusted HR for spring 1.08 (95% CI 1.01 to 1.16), summer 1.10 (95% CI 1.03 to 1.18) and autumn 1.10 (95% CI 1.02 to 1.18). Increased CD risk was highest if born in the south, followed by central Sweden when compared with children born in northern Sweden. Children diagnosed at <2 years had an increased CD risk if born in spring while those diagnosed at 2–14.9 years the risk was increased for summer and autumn births. The birth cohort of 1991–1996 had increased CD risk if born during spring, for the 1997–2002 birth cohort the risk increased for summer and autumn births, while for the birth cohort of 2003–2009 the risk was increased if born during autumn. Conclusions Season of birth and region of birth are independently and jointly associated with increased risk of developing CD during the first 15 years of life. Seasonal variation in infectious load is the likely explanation. PMID:27528621

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

Variation in work tasks in relation to pinch grip strength among middle-aged female dentists.

PubMed

Ding, Hebo; Leino-Arjas, Päivi; Murtomaa, Heikki; Takala, Esa-Pekka; Solovieva, Svetlana

2013-11-01

We aimed to investigate the relationship of task variation during dental work history with pinch grip strength among dentists. We measured pinch grip strength among 295 female Finnish dentists aged 45-63 years. Variation in dental work tasks during work history was empirically defined by cluster analysis. Three clusters of task variation emerged: low (most work time in restoration treatment/endodontics), moderate (about 50% in the former and 50% in prosthodontics/periodontics/surgery), and high (variable tasks including administrative duties). Hand radiographs were examined for the presence of OA in the wrist and each joint of the 1-3rd fingers. Information on hand-loading leisure-time activities, and joint pain was obtained by questionnaire. Glove size was used as a proxy for hand size. BMI (kg/m2) was based on measured weight and self-reported height. Dentists with low variation of work task history had an increased risk of low pinch grip strength in the right hand (OR 2.3, 95% CI 1.2-4.3), but not in the left (1.13, 0.62-2.08), compared to dentists with high task variation, independent of age, hand size, hand-loading leisure-time activities, BMI and symptomatic hand OA. The dentists with the most hand-loading tasks were at an increased risk of low pinch grip strength, independent of e.g. symptomatic hand OA. It is advisable among dentists to perform as diverse work tasks as possible to reduce the risk of decreased pinch grip strength. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Low maternal melatonin level increases autism spectrum disorder risk in children.

PubMed

Braam, Wiebe; Ehrhart, Friederike; Maas, Anneke P H M; Smits, Marcel G; Curfs, Leopold

2018-02-28

It is assumed that autism spectrum disorder (ASD) is caused by a combination of de novo inherited variation and common variation as well as environmental factors. It often co-occurs with intellectual disability (ID). Almost eight hundred potential causative genetic variations have been found in ASD patients. However, not one of them is responsible for more than 1% of ASD cases. Low melatonin levels are a frequent finding in ASD patients. Melatonin levels are negatively correlated with severity of autistic impairments, it is important for normal neurodevelopment and is highly effective in protecting DNA from oxidative damage. Melatonin deficiency could be a major factor, and well a common heritable variation, that increases the susceptibility to environmental risk factors for ASD. ASD is already present at birth. As the fetus does not produce melatonin, low maternal melatonin levels may be involved. We measured 6-sulfatoxymelatonin in urine of 60 mothers of a child with ASD and controls. 6-sulfatoxymelatonin levels were significantly lower in mothers with an ASD child than in controls (p = 0.012). Low parental melatonin levels could be one of the contributors to ASD and possibly ID etiology. Our findings need to be duplicated on a larger scale. If our hypothesis is correct, this could lead to policies to detect future parents who are at risk and to treatment strategies to ASD and intellectual disability risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prenatal exposure to ambient temperature variation increases the risk of common cold in children.

PubMed

Lu, Chan; Miao, Yufeng; Zeng, Ji; Jiang, Wei; Shen, Yong-Ming; Deng, Qihong

2018-06-15

Common cold is a frequent upper respiratory tract infection, but the role of ambient temperature in the infection is unclear. We investigated the role of prenatal exposure to diurnal temperature variation (DTV), the difference between the daily maximal and minimal temperatures, in the risk of common cold in children. We conducted a cohort study of 2598 preschool children in Changsha, China. Occurrence of common cold during the past year was surveyed using questionnaire. We then estimated each child's prenatal exposure to DTV during pregnancy. Multivariate logistic regression model was used to examine the association between occurrence of common cold and prenatal exposure to DTV in terms of odds ratios (OR) and 95% confidence interval (CI). About 45% children have common cold (≥3 times) during the past year. We found that common cold in children was associated with maternal DTV exposure during pregnancy, particularly during the first trimester with adjusted OR (95% CI) = 1.27 (1.10-1.46). Male and atopic children were more susceptible to the effect of DTV during pregnancy. The risk of common cold due to DTV is higher in children living in the suburban areas and the bigger houses and in those exposed to environmental tobacco smoke, mold/dampness, new furniture and redecoration. We observed that the risk of common cold in children has been increased in recent years due to increasing DTV. Common cold in children was associated with maternal exposure to temperature variation during pregnancy, suggesting that the risk of common cold may originate in pregnancy. Copyright © 2018 Elsevier Inc. All rights reserved.

Defining micro-epidemiology for malaria elimination: systematic review and meta-analysis.

PubMed

Bannister-Tyrrell, Melanie; Verdonck, Kristien; Hausmann-Muela, Susanna; Gryseels, Charlotte; Muela Ribera, Joan; Peeters Grietens, Koen

2017-04-20

Malaria risk can vary markedly between households in the same village, or between villages, but the determinants of this "micro-epidemiological" variation in malaria risk remain poorly understood. This study aimed to identify factors that explain fine-scale variation in malaria risk across settings and improve definitions and methods for malaria micro-epidemiology. A systematic review of studies that examined risk factors for variation in malaria infection between individuals, households, clusters, hotspots, or villages in any malaria-endemic setting was conducted. Four databases were searched for studies published up until 6th October 2015. Crude and adjusted effect estimates for risk factors for malaria infection were combined in random effects meta-analyses. Bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. From 743 retrieved records, 51 studies were selected, representing populations comprising over 160,000 individuals in 21 countries, in high- and low-endemicity settings. Sixty-five risk factors were identified and meta-analyses were conducted for 11 risk factors. Most studies focused on environmental factors, especially increasing distance from a breeding site (OR 0.89, 95% CI 0.86-0.92, 10 studies). Individual bed net use was protective (OR 0.63, 95% CI 0.52-0.77, 12 studies), but not household bed net ownership. Increasing household size (OR 1.08, 95% CI 1.01-1.15, 4 studies) and household crowding (OR 1.79, 95% CI 1.48-2.16, 4 studies) were associated with malaria infection. Health seeking behaviour, medical history and genetic traits were less frequently studied. Only six studies examined whether individual-level risk factors explained differences in malaria risk at village or hotspot level, and five studies reported different risk factors at different levels of analysis. The risk of bias varied from low to high in individual studies. Insufficient reporting and comparability of measurements limited the number of meta-analyses conducted. Several variables associated with individual-level malaria infection were identified, but there was limited evidence that these factors explain variation in malaria risk at village or hotspot level. Social, population and other factors may confound estimates of environmental risk factors, yet these variables are not included in many studies. A structured framework of malaria risk factors is proposed to improve study design and quality of evidence in future micro-epidemiological studies.

Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: the Breast Cancer Health Disparities Study

PubMed Central

Baumgartner, Kathy B.; Baumgartner, Richard N.; Connor, Avonne E.; Pinkston, Christina M.; Rai, Shesh N.; Riley, Elizabeth C.; Hines, Lisa M.; Giuliano, Anna R.; John, Esther M.; Stern, Mariana C.; Torres-Mejía, Gabriela; Wolff, Roger K.; Slattery, Martha L.

2015-01-01

The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case–control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11–1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05–1.72. A significant interaction was observed for rs2470144 and menopausal status (padj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05–1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64–0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer. PMID:25088806

Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial.

PubMed

Hemilä, Harri

2016-11-01

Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.

Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study.

PubMed

Habibi, Mohsen; Mirfakhraie, Reza; Khani, Maryam; Rakhshan, Azadeh; Azargashb, Eznollah; Pouresmaeili, Farkhondeh

2017-11-15

Glucuronidation is a major pathway for elimination of exogenous and endogenous compounds such as environmental carcinogens and androgens from the body. This biochemical pathway is mediated by enzymes called uridine diphosphoglucuronosyltransferases (UGTs). Null (del/del) genes polymorphisms in UGT2B17, and UGT2B28 and D85Y single-nucleotide polymorphism (SNP) of UGT2B15 have been reported to increase the risk of prostate cancer. The goal of this study was to determine the association of mentioned genetic variants with the risk of prostate cancer. We investigated the copy number variations (CNVs) of UGT2B17 and UGT2B28 loci and the association between rs1902023 polymorphism of UGT2B15 gene in 360 subjects consisted of 120 healthy controls, 120 prostate cancer (PC) patients and 120 benign prostatic hyperplasia (BPH) patients. No association was detected for the mentioned polymorphisms and the risk of PC. However, a significant association was detected between UGT2B17 copy number variation and BPH risk (OR=2.189; 95% CI, 1.303-3.675; p=0.003). Furthermore, we observed that the D85Y polymorphism increases the risk of BPH when analyzed in combination with the copy number variation of UGT2B17 gene (OR=0.135; 95% CI, 0.036-0.512; p=0.003). Our findings suggest that the D85Y polymorphism of UGT2B15 and CNVs in UGT2B28 and UGT2B17 genes is not associated with prostate cancer risk in Iranian patients. To our knowledge, this is the first report that implicates the role of CNV of UGT2B17 gene in BPH. Copyright © 2017 Elsevier B.V. All rights reserved.

Colon cancer: a civilization disorder.

PubMed

Watson, Alastair J M; Collins, Paul D

2011-01-01

Colorectal cancer arises in individuals with acquired or inherited genetic predisposition who are exposed to a range of risk factors. Many of these risk factors are associated with affluent Western societies. More than 95% of colorectal cancers are sporadic, arising in individuals without a significant hereditary risk. Geographic variation in the incidence of colorectal cancer is considerable with a higher incidence observed in the West. Environmental factors contribute substantially to this variation. A number of these risk factors are associated with a Western lifestyle and could be considered a product of 'civilization'. Recently, smoking has been recognized as a risk factor. Energy consumption also influences colorectal cancer risk, with obesity increasing risk and exercise reducing risk. However, the strongest contribution to environmental risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat is associated with an increased risk. Fresh fruit and vegetables and dietary fibre may be protective. Much has been learnt recently about the molecular pathogenesis of colorectal cancer. Colorectal cancer always arises in the context of genomic instability. There is inactivation of the tumour suppressor genes adenomatous polyposis coli, p53, transforming growth factor-β, activation of oncogene pathways including K-ras, and activation of the cyclooxygenase-2, epidermal growth factor receptor and vascular endothelial growth factor pathways. The mechanisms by which some environmental factors modify the mutation risk in these pathways have been described. Copyright © 2011 S. Karger AG, Basel.

Geographic variation in colorectal cancer survival and the role of small-area socioeconomic deprivation: a multilevel survival analysis of the NIH-AARP Diet and Health Study Cohort.

PubMed

Lian, Min; Schootman, Mario; Doubeni, Chyke A; Park, Yikyung; Major, Jacqueline M; Stone, Rosalie A Torres; Laiyemo, Adeyinka O; Hollenbeck, Albert R; Graubard, Barry I; Schatzkin, Arthur

2011-10-01

Adverse socioeconomic conditions, at both the individual and the neighborhood level, increase the risk of colorectal cancer (CRC) death, but little is known regarding whether CRC survival varies geographically and the extent to which area-level socioeconomic deprivation affects this geographic variation. Using data from the National Institutes of Health (NIH)-AARP Diet and Health Study, the authors examined geographic variation and the role of area-level socioeconomic deprivation in CRC survival. CRC cases (n = 7,024), identified during 1995-2003, were followed for their CRC-specific vital status through 2005 and overall vital status through 2006. Bayesian multilevel survival models showed that there was significant geographic variation in overall (variance = 0.2, 95% confidence interval (CI): 0.1, 0.2) and CRC-specific (variance = 0.3, 95% CI: 0.1, 0.4) risk of death. More socioeconomically deprived neighborhoods had a higher overall risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.4) and a higher CRC-specific risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.5). However, neighborhood socioeconomic deprivation did not account for the geographic variation in overall and CRC-specific risks of death. In future studies, investigators should evaluate other neighborhood characteristics to help explain geographic heterogeneity in CRC survival. Such research could facilitate interventions for reducing geographic disparity in CRC survival.

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

PubMed Central

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

2016-01-01

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID:26807442

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

PubMed

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

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10 -4 ]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1 , may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

30 min of treadmill walking at self-selected speed does not increase gait variability in independent elderly.

PubMed

Da Rocha, Emmanuel S; Kunzler, Marcos R; Bobbert, Maarten F; Duysens, Jacques; Carpes, Felipe P

2018-06-01

Walking is one of the preferred exercises among elderly, but could a prolonged walking increase gait variability, a risk factor for a fall in the elderly? Here we determine whether 30 min of treadmill walking increases coefficient of variation of gait in elderly. Because gait responses to exercise depend on fitness level, we included 15 sedentary and 15 active elderly. Sedentary participants preferred a lower gait speed and made smaller steps than the actives. Step length coefficient of variation decreased ~16.9% by the end of the exercise in both the groups. Stride length coefficient of variation decreased ~9% after 10 minutes of walking, and sedentary elderly showed a slightly larger step width coefficient of variation (~2%) at 10 min than active elderly. Active elderly showed higher walk ratio (step length/cadence) than sedentary in all times of walking, but the times did not differ in both the groups. In conclusion, treadmill gait kinematics differ between sedentary and active elderly, but changes over time are similar in sedentary and active elderly. As a practical implication, 30 min of walking might be a good strategy of exercise for elderly, independently of the fitness level, because it did not increase variability in step and stride kinematics, which is considered a risk of fall in this population.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: The Viva La Familia Study

USDA-ARS?s Scientific Manuscript database

Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it...

GPSS/360 computer models to simulate aircraft passenger emergency evacuations.

DOT National Transportation Integrated Search

1972-09-01

Live tests of emergency evacuation of transport aircraft are becoming increasingly expensive as the planes grow to a size seating hundreds of passengers. Repeated tests, to cope with random variations, increase these costs, as well as risks of injuri...

[Ecological risk assessment of rural-urban ecotone based on landscape pattern: A case study in Daiyue District of Tai' an City, Shandong Province of East China].

PubMed

Shi, Hao-Peng; Yu, Kai-Qin; Feng, Yong-jun

2013-03-01

Based on the remote sensing data in 2000, 2005, and 2010, this paper analyzed the variation trends of the land use type and landscape pattern in Daiyue District of Tai' an City from 2000 to 2010. The ecological risk index was built, that of the District was re-sampled and spatially interpolated, and the spatiotemporal pattern of the ecological risk in the rural-urban ecotone of the District was analyzed. In 2000-2010, the main variation trend of the land use type in the District was the shift from natural landscape to artificial landscape. The intensity of human disturbance was larger in cultivated land, garden plot, and forestland than in other landscape types, while the human disturbance in water area was smaller. The ecological loss degree of cultivated land and water area decreased somewhat, while that of the other land use types presented an increasing trend. The ecological risk distribution in the District was discrete in 2000 and 2010, but most centralized in 2005. The ecological risk of each ecological risk sub-area had an increasing trend in 2000-2005, but was in adverse in 2005-2010. In 2000-2010, the ecological risk of the District was mainly at medium level. Spatially, the distribution of the ecological risk in the District had an obvious differentiation, with an overall diffusive increasing from forestland as the center to the surrounding areas. In the District, the ecological risk was mainly at medium and higher levels, the area with lower ecological risk had an obvious dynamic change, while that with the lowest and highest ecological risk had less change.

Placental genetic variations in circadian clock-related genes increase the risk of placental abruption.

PubMed

Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

2016-01-01

The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome.

Moving standard deviation and moving sum of outliers as quality tools for monitoring analytical precision.

PubMed

Liu, Jiakai; Tan, Chin Hon; Badrick, Tony; Loh, Tze Ping

2018-02-01

An increase in analytical imprecision (expressed as CV a ) can introduce additional variability (i.e. noise) to the patient results, which poses a challenge to the optimal management of patients. Relatively little work has been done to address the need for continuous monitoring of analytical imprecision. Through numerical simulations, we describe the use of moving standard deviation (movSD) and a recently described moving sum of outlier (movSO) patient results as means for detecting increased analytical imprecision, and compare their performances against internal quality control (QC) and the average of normal (AoN) approaches. The power of detecting an increase in CV a is suboptimal under routine internal QC procedures. The AoN technique almost always had the highest average number of patient results affected before error detection (ANPed), indicating that it had generally the worst capability for detecting an increased CV a . On the other hand, the movSD and movSO approaches were able to detect an increased CV a at significantly lower ANPed, particularly for measurands that displayed a relatively small ratio of biological variation to CV a. CONCLUSION: The movSD and movSO approaches are effective in detecting an increase in CV a for high-risk measurands with small biological variation. Their performance is relatively poor when the biological variation is large. However, the clinical risks of an increase in analytical imprecision is attenuated for these measurands as an increased analytical imprecision will only add marginally to the total variation and less likely to impact on the clinical care. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Circadian variation in the circulatory responses to exercise: relevance to the morning peaks in strokes and cardiac events

PubMed Central

2009-01-01

Sudden cardiac and cerebral events are most common in the morning. A fundamental question is whether these events are triggered by the increase in physical activity after waking, and/or a result of circadian variation in the responses of circulatory function to exercise. Although signaling pathways from the master circadian clock in the suprachiasmatic nuclei to sites of circulatory control are not yet understood, it is known that cerebral blood flow, autoregulation and cerebrovascular reactivity to changes in CO2 are impaired in the morning and, therefore, could explain the increased risk of cerebrovascular events. Blood pressure (BP) and the rate pressure product (RPP) show marked ‘morning surges’ when people are studied in free-living conditions, making the rupture of a fragile atherosclerotic plaque and sudden cardiac event more likely. Since cerebral autoregulation is reduced in the morning, this surge in BP may also exacerbate the risk of hemorrhagic and ischemic strokes in the presence of other acute and chronic risk factors. Increased sympathetic activity, decreased endothelial function, and increased platelet aggregability could also be important in explaining the morning peak in cardiac and cerebral events but how these factors respond to exercise at different times of day is unclear. Evidence is emerging that the exercise-related responses of BP and RPP are increased in the morning when prior sleep is controlled. We recommend that such ‘semi-constant routine’ protocols are employed to examine the relative influence of the body clock and exogenous factors on the 24-h variation in other circulatory factors. PMID:19826832

Variations of the sciatic nerve anatomy and blood supply in the gluteal region: a review of the literature.

PubMed

Kanawati, Andrew James

2014-11-01

Variations of the sciatic nerve anatomy and blood supply are complex and largely not dealt with in common anatomy texts. Variations of the sciatic nerve anatomy can be divided into the height of division of its branches, relation of the branches to the piriformis muscle, and its blood supply. These variations should be well known to any surgeon operating in this anatomical region. It is unknown whether these variations increase the risk of surgical injury and consequent morbidity. This paper will review the current knowledge regarding anatomical variations of the sciatic nerve and its blood supply. © 2014 Royal Australasian College of Surgeons.

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

PubMed Central

Albert, Dustin; Belsky, Daniel W.; Crowley, D. Max; Latendresse, Shawn J.; Aliev, Fazil; Riley, Brien; Sun, Cuie; Dick, Danielle M.; Dodge, Kenneth R.

2014-01-01

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track Randomized Control Trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era. PMID:26106668

Variations in 5-HTTLPR: relation to familiar risk of affective disorder, life events, neuroticism and cortisol.

PubMed

Vinberg, Maj; Mellerup, Erling; Andersen, Per Kragh; Bennike, Bente; Kessing, Lars Vedel

2010-02-01

Variations in the serotonin transporter gene (5-HTTLPR) and stressful life events are associated with affective disorders. To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol. In a high-risk population study, healthy monozygotic and dizygotic twins with (high-risk twins) and without (low-risk twins) a co-twin history of affective disorder were identified through nationwide registers. When comparing the 81 individuals homozygote for the long allele with the 125 individuals hetero- and homozygote for the short allele no associations between the allele distribution and a genetic predisposition were found. The presence of the short allele of the 5-HTTLPR and the experience of SLE was associated with a higher neuroticism score, but not with depressive symptoms nor awakening or evening salivary cortisol. A combination of variants in 5-HTTLPR and environmental stress seems to increase neuroticism in healthy individuals. Copyright 2009 Elsevier Inc. All rights reserved.

Oxytocin Receptor Genetic and Epigenetic Variations: Association with Child Abuse and Adult Psychiatric Symptoms

ERIC Educational Resources Information Center

Smearman, Erica L.; Almli, Lynn M.; Conneely, Karen N.; Brody, Gene H.; Sales, Jessica M.; Bradley, Bekh; Ressler, Kerry J.; Smith, Alicia K.

2016-01-01

Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date…

Epidemiology and Individual, Household and Geographical Risk Factors of Podoconiosis in Ethiopia: Results from the First Nationwide Mapping

PubMed Central

Deribe, Kebede; Brooker, Simon J.; Pullan, Rachel L.; Sime, Heven; Gebretsadik, Abeba; Assefa, Ashenafi; Kebede, Amha; Hailu, Asrat; Rebollo, Maria P.; Shafi, Oumer; Bockarie, Moses J.; Aseffa, Abraham; Reithinger, Richard; Cano, Jorge; Enquselassie, Fikre; Newport, Melanie J.; Davey, Gail

2015-01-01

Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1–6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9–4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, and being semiskilled or unemployed were significantly associated with increased risk of podoconiosis. Attending formal education and living in a house with a covered floor were associated with decreased risk of podoconiosis. Podoconiosis exhibits marked geographical variation across Ethiopia, with variation in risk associated with variation in rainfall, enhanced vegetation index, and altitude. PMID:25404069

Nest predation risk explains variation in avian clutch size

USGS Publications Warehouse

Dillon, Kristen G.; Conway, Courtney J.

2018-01-01

Questions about the ecological drivers of, and mechanistic constraints on, productivity have driven research on life-history evolution for decades. Resource availability and offspring mortality are considered among the 2 most important influences on the number of offspring per reproductive attempt. We used a factorial experimental design to manipulate food abundance and perceived offspring predation risk in a wild avian population (red-faced warblers; Cardellina rubrifrons) to identify the mechanistic cause of variation in avian clutch size. Additionally, we tested whether female quality helped explain the extant variation in clutch size. We found no support for the Food Limitation or Female Quality Hypotheses, but we did find support for both predictions of the Nest Predation Risk Hypothesis. Females that experienced an experimentally heightened perception of offspring predation risk responded by laying a smaller clutch than females in the control group. Additionally, predation rates at artificial nests were highest where red-faced warbler clutch size was smallest (at high elevations). Life-history theory predicts that an individual should invest less in reproduction when high nest predation risk reduces the likely benefit from that nesting attempt and, indeed, we found that birds exhibit phenotypic plasticity in clutch size by laying fewer eggs in response to increasing nest predation risk.

The effect of price and production risks on optimal farm plans in Swiss dairy production considering 2 different milk quota systems.

PubMed

Briner, S; Finger, R

2013-04-01

The amount of milk produced on Swiss dairy farms is restricted by contracts between the farmers and their marketing agent. In the past, these contracts have been calculated on a yearly base. Due to a switch in agricultural policy, these yearly contracts are currently more and more replaced by contracts calculated on a monthly base. These new contracts are assumed to restrict the flexibility of farmers to react on changes in milk price as well as on changes in fodder availability. Thus, the contract design is expected to influence farmers' ability to cope with risks and, thus, to influence the farm's gross margin variability. Applying a bioeconomic whole-farm model, the effects of price and weather risk as well as different risk-management strategies on the gross margin and the variability of the gross margin in Swiss dairy production are assessed under the 2 contract designs. We consider both risk-neutral and risk-averse behavior of farmers in our study. Results show that gross margin is slightly higher under the yearly than under the monthly contract. Variability of gross margin is also higher under the yearly than under the monthly contract. If the farmer is assumed to be risk averse, under both contracts he can reduce the coefficient of variation of the gross margin by almost 20% at opportunity costs below 1% of the gross margin. To reduce variability of gross margin under both contracts the size of the feedstock needs to be increased. This increase, however, must be considerably higher under the monthly contract than under the yearly contract. An additional risk-management strategy under a monthly contract is an increase in the area used as intensive pasture to ensure fodder availability in years with unfavorable weather. Under the yearly contract, an increase in the area used as extensive pasture is shown to be more favorable because it increases the amount of direct payments the farmer will receive. Additional restrictions in farm management due to a monthly milk contract do not lead to a higher variation in gross margin. However, if a farmer agrees to a monthly contract, he needs to adapt his risk-management strategies. Furthermore, our results show that farmers have to be aware that they will need additional barn capacities to reduce variation in gross margin under a monthly milk contract. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The "PHS Increased Risk" Label Is Associated With Nonutilization of Hundreds of Organs per Year.

PubMed

Volk, Michael L; Wilk, Amber R; Wolfe, Cameron; Kaul, Daniel R

2017-07-01

The Public Health Service "Increased Risk" (PHS IR) designation identifies donors at increased risk of transmitting hepatitis B, C, and human immunodeficiency virus. Although the risk remains very low in the era of nucleic acid testing, we hypothesized that this label may result in decreased organ utilization. Organ Procurement and Transplantation Network data were used to compare utilization rates between PHS-IR and non-PHS-IR donors, as well as to compare export rates and variation in utilization. Among adult standard criteria donors between 2010 and 2013 with a known PHS-IR status, covariate-adjusted utilization rates were lower among PHS-IR donors than non-PHS-IR donors for all organs. For example, 4073 (76.7%) of 5314 PHS-IR kidneys were used, compared with 25 490 (83.7%) of 30 456 non-PHS-IR kidneys-an absolute difference of 7%. Furthermore, all PHS-IR organs had higher export rates than non-PHS-IR organs. For example, 28.7% of PHS-IR kidneys were exported versus 19.7% of non-PHS-IR kidneys. Finally, the utilization rate of PHS-IR organs varied by Donation Service Area; utilization ranged from 20% to 100% among adult kidneys, suggesting significant variation in practices. Similar patterns were seen among pediatric donors. Based on the covariate-adjusted model, if the PHS-IR label did not exist, there could be an additional 313 transplants performed in the United States each year. The PHS "increased risk" label appears to be associated with nonutilization of hundreds of organs per year, despite the very low risk of disease transmission. Better tools are needed to communicate the magnitude of risk to patients and their families.

Variation in the use of active surveillance for low-risk prostate cancer.

PubMed

Löppenberg, Björn; Friedlander, David F; Krasnova, Anna; Tam, Andrew; Leow, Jeffrey J; Nguyen, Paul L; Barry, Hawa; Lipsitz, Stuart R; Menon, Mani; Abdollah, Firas; Sammon, Jesse D; Sun, Maxine; Choueiri, Toni K; Kibel, Adam S; Trinh, Quoc-Dien

2018-01-01

This study assessed the use of active surveillance in men with low-risk prostate cancer and evaluated institutional factors associated with the receipt of active surveillance. A retrospective, hospital-based cohort of 115,208 men with low-risk prostate cancer diagnosed between 2010 and 2014 was used. Multivariate and mixed effects models were used to examine variation and factors associated with active surveillance. During the study period, the use of active surveillance increased from 6.8% in 2010 to 19.9% in 2014 (estimated annual percentage change, +28.8%; 95% confidence interval [CI], + 19.6% to + 38.7%; P = .002). The adjusted probability of active-surveillance receipt by institution was highly variable. Compared with patients treated at comprehensive community cancer centers, patients treated at community cancer programs (odds ratio [OR], 2.00; 95% CI, 1.50-2.67; P < .001) and academic institutions (OR, 2.47; 95%, CI, 1.81-3.37; P < .001) had higher odds of receiving active surveillance. Compared with patients treated at very low-volume facilities, patients treated at very high-volume facilities had higher odds of receiving active surveillance (OR, 3.57; 95% CI, 1.94-6.55; P < .001). Patient and hospital characteristics accounted for 60.2% of the overall variation, whereas the treating institution accounted for 91.5% of the unexplained variability. Within this hospital-based cohort, the use of active surveillance for low-risk prostate cancer increased significantly over time. Significant variation was found in the use of active surveillance. Most of the variation was attributable to facility-related factors such as the facility type, facility volume, and institution. Policies to achieve consistent and higher rates of active surveillance, when appropriate, should be a priority of professional societies and patient advocacy groups. Cancer 2018;124:55-64. © 2017 American Cancer Society. © 2017 American Cancer Society.

Variation in the miRNA-433 Binding Site of FGF20 Confers Risk for Parkinson Disease by Overexpression of α-Synuclein

PubMed Central

Wang, Gaofeng; van der Walt, Joelle M.; Mayhew, Gregory; Li, Yi-Ju; Züchner, Stephan; Scott, William K.; Martin, Eden R.; Vance, Jeffery M.

2008-01-01

Parkinson disease (PD) is a common neurodegenerative disorder caused by environmental and genetic factors. We have previously shown linkage of PD to chromosome 8p. Subsequently, fibroblast growth factor 20 (FGF20) at 8p21.3–22 was identified as a risk factor in several association studies. To identify the risk-conferring polymorphism in FGF20, we performed genetic and functional analysis of single-nucleotide polymorphisms within the gene. In a sample of 729 nuclear families with 1089 affected and 1165 unaffected individuals, the strongest evidence of association came from rs12720208 in the 3′ untranslated region of FGF20. We show in several functional assays that the risk allele for rs12720208 disrupts a binding site for microRNA-433, increasing translation of FGF20 in vitro and in vivo. In a cell-based system and in PD brains, this increase in translation of FGF20 is correlated with increased α-synuclein expression, which has previously been shown to cause PD through both overexpression and point mutations. We suggest a novel mechanism of action for PD risk in which the modulation of the susceptibility gene's translation by common variations interfere with the regulation mechanisms of microRNA. We propose this is likely to be a common mechanism of genetic modulation of individual susceptibility to complex disease. PMID:18252210

Pesticides that inhibit the ubiquitin-proteasome system: effect measure modification by genetic variation in SKP1 in Parkinson׳s disease.

PubMed

Rhodes, Shannon L; Fitzmaurice, Arthur G; Cockburn, Myles; Bronstein, Jeff M; Sinsheimer, Janet S; Ritz, Beate

2013-10-01

Cytoplasmic inclusions known as Lewy bodies, a hallmark of Parkinson's disease (PD) pathology, may protect against cytotoxic proteins. Since the ubiquitin-proteasome system (UPS) degrades cytotoxic proteins, dysfunction in the UPS may contribute to PD etiology. Our goal in this study was to screen pesticides for proteasome inhibition and investigate (i) whether ambient exposures to pesticides that inhibit the UPS increase PD risk and (ii) whether genetic variation in candidate genes of the UPS pathway modify those increased risks. We assessed 26S UPS activity in SK-N-MC(u) cells by fluorescence. We recruited idiopathic PD cases (n=360) and population-based controls (n=816) from three counties in California with considerable commercial agriculture. We determined ambient pesticide exposure by our validated GIS-based model utilizing residential and workplace address histories. We limited effect measure modification assessment to Caucasians (287 cases, 453 controls). Eleven of 28 pesticides we screened inhibited 26S UPS activity at 10 µM. Benomyl, cyanazine, dieldrin, endosulfan, metam, propargite, triflumizole, and ziram were associated with increased PD risk. We estimated an odds ratio of 2.14 (95% CI: 1.42, 3.22) for subjects with ambient exposure to any UPS-inhibiting pesticide at both residential and workplace addresses; this association was modified by genetic variation in the s-phase kinase-associated protein 1 gene (SKP1; interaction p-value=0.005). Our results provide evidence that UPS-inhibiting pesticides play a role in the etiology of PD and suggest that genetic variation in candidate genes involved in the UPS pathway might exacerbate the toxic effects of pesticide exposures. © 2013 Published by Elsevier Inc.

Amygdala Volume in Offspring from Multiplex for Alcohol Dependence Families: The Moderating Influence of Childhood Environment and 5-HTTLPR Variation.

PubMed

Hill, Shirley Y; Wang, Shuhui; Carter, Howard; McDermott, Michael D; Zezza, Nicholas; Stiffler, Scott

2013-12-12

The increased susceptibility for developing alcohol dependence seen in offspring from families with alcohol dependence may be related to structural and functional differences in brain circuits that influence emotional processing. Early childhood environment, genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLCA4 gene and allelic variation in the Brain Derived Neurotrophic Factor (BDNF) gene have each been reported to be related to volumetric differences in the temporal lobe especially the amygdala. Magnetic resonance imaging was used to obtain amygdala volumes for 129 adolescent/young adult individuals who were either High-Risk (HR) offspring from families with multiple cases of alcohol dependence (N=71) or Low-Risk (LR) controls (N=58). Childhood family environment was measured prospectively using age-appropriate versions of the Family Environment Scale during a longitudinal follow-up study. The subjects were genotyped for Brain-Derived Neurotrophic Factor (BDNF) Val66Met and the serotonin transporter polymorphism (5-HTTLPR). Two family environment scale scores (Cohesion and Conflict), genotypic variation, and their interaction were tested for their association with amygdala volumes. Personal and prenatal exposure to alcohol and drugs were considered in statistical analyses in order to more accurately determine the effects of familial risk group differences. Amygdala volume was reduced in offspring from families with multiple alcohol dependent members in comparison to offspring from control families. High-Risk offspring who were carriers of the S variant of the 5-HTTLPR polymorphism had reduced amygdala volume in comparison to those with an LL genotype. Larger amygdala volume was associated with greater family cohesion but only in Low-Risk control offspring. Familial risk for alcohol dependence is an important predictor of amygdala volume even when removing cases with significant personal exposure and covarying for prenatal exposure effects. The present study provides new evidence that amygdala volume is modified by 5-HTTLPR variation in High-Risk families.

Social deprivation, inequality, and the neighborhood-level incidence of psychotic syndromes in East London.

PubMed

Kirkbride, James B; Jones, Peter B; Ullrich, Simone; Coid, Jeremy W

2014-01-01

Although urban birth, upbringing, and living are associated with increased risk of nonaffective psychotic disorders, few studies have used appropriate multilevel techniques accounting for spatial dependency in risk to investigate social, economic, or physical determinants of psychosis incidence. We adopted Bayesian hierarchical modeling to investigate the sociospatial distribution of psychosis risk in East London for DSM-IV nonaffective and affective psychotic disorders, ascertained over a 2-year period in the East London first-episode psychosis study. We included individual and environmental data on 427 subjects experiencing first-episode psychosis to estimate the incidence of disorder across 56 neighborhoods, having standardized for age, sex, ethnicity, and socioeconomic status. A Bayesian model that included spatially structured neighborhood-level random effects identified substantial unexplained variation in nonaffective psychosis risk after controlling for individual-level factors. This variation was independently associated with greater levels of neighborhood income inequality (SD increase in inequality: Bayesian relative risks [RR]: 1.25; 95% CI: 1.04-1.49), absolute deprivation (RR: 1.28; 95% CI: 1.08-1.51) and population density (RR: 1.18; 95% CI: 1.00-1.41). Neighborhood ethnic composition effects were associated with incidence of nonaffective psychosis for people of black Caribbean and black African origin. No variation in the spatial distribution of the affective psychoses was identified, consistent with the possibility of differing etiological origins of affective and nonaffective psychoses. Our data suggest that both absolute and relative measures of neighborhood social composition are associated with the incidence of nonaffective psychosis. We suggest these associations are consistent with a role for social stressors in psychosis risk, particularly when people live in more unequal communities.

Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

PubMed

Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

2012-08-07

The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

Economic impacts of increasing seasonal precipitation variation on southeast Wyoming cow-calf enterprises

USDA-ARS?s Scientific Manuscript database

Economic impacts of predicted increases in precipitation variability on cow-calf enterprises, through influences of precipitation on both forage and cattle productivity, are needed by land managers for risk management strategies. Here we utilize existing forage production and cattle performance data...

Quality of reporting of studies evaluating time to diagnosis: a systematic review in paediatrics.

PubMed

Launay, Elise; Morfouace, Michele; Deneux-Tharaux, Catherine; Gras le-Guen, Christèle; Ravaud, Philippe; Chalumeau, Martin

2014-03-01

An ever-increasing number of studies analyses the distribution, determinants and consequences of time to diagnosis and delays. Weaknesses in their reporting can impede the assessment of the risks of bias and variation and thus create a risk of invalid conclusions and counterproductive clinical and public health efforts. This study sought to assess systematically the quality of reporting of articles about time to diagnosis in paediatrics. Two authors identified and analysed the quality of reporting of 50 consecutive articles assessing these intervals published from 2005 through October 2011, according to a checklist we developed of 35 items potentially associated with risks of bias and variation. Frequency of articles reporting each item. Symptoms that should trigger a diagnostic procedure were reported in 28% of the articles; only two articles reported whether all patients with these symptoms underwent that procedure. Only 44% of the articles defined the beginning of the illness, 46% the date of diagnosis and 60% the distribution of time to diagnosis. Two studies met the criteria for all 11 items considered essential for assessing the risks of bias and variation in this type of study. This study identified many weaknesses in the quality of reporting of studies of time to diagnosis in paediatrics, especially for items potentially related to risks of bias and variation. This finding underlines the need for the development of new (or the refinement of existing) guidelines for reporting this type of study.

Variations in respiratory sounds in relation to fluid accumulation in the upper airways.

PubMed

Yadollahi, Azadeh; Rudzicz, Frank; Montazeri, Aman; Bradley, T Douglas

2013-01-01

Obstructive sleep apnea (OSA) is a common disorder due to recurrent collapse of the upper airway (UA) during sleep that increases the risk for several cardiovascular diseases. Recently, we showed that nocturnal fluid accumulation in the neck can narrow the UA and predispose to OSA. Our goal is to develop non-invasive methods to study the pathogenesis of OSA and the factors that increase the risks of developing it. Respiratory sound analysis is a simple and non-invasive way to study variations in the properties of the UA. In this study we examine whether such analysis can be used to estimate the amount of neck fluid volume and whether fluid accumulation in the neck alters the properties of these sounds. Our acoustic features include estimates of formants, pitch, energy, duration, zero crossing rate, average power, Mel frequency power, Mel cepstral coefficients, skewness, and kurtosis across segments of sleep. Our results show that while all acoustic features vary significantly among subjects, only the variations in respiratory sound energy, power, duration, pitch, and formants varied significantly over time. Decreases in energy and power over time accompany increases in neck fluid volume which may indicate narrowing of UA and consequently an increased risk of OSA. Finally, simple discriminant analysis was used to estimate broad classes of neck fluid volume from acoustic features with an accuracy of 75%. These results suggest that acoustic analysis of respiratory sounds might be used to assess the role of fluid accumulation in the neck on the pathogenesis of OSA.

Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker

PubMed Central

Iasonos, Alexia; Chapman, Paul B.; Satagopan, Jaya M.

2016-01-01

There is an increased interest in finding predictive biomarkers that can guide treatment options for both mutation carriers and non-carriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time to event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a Proportional Hazards regression model is commonly used as a measure of variation in treatment benefit. While this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus non-carriers. We illustrate the use and interpretation of the proposed measures using data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. PMID:27141007

Maternal body condition influences magnitude of anti-predator response in offspring.

PubMed

Bennett, Amanda M; Murray, Dennis L

2014-11-07

Organisms exhibit plasticity in response to their environment, but there is large variation even within populations in the expression and magnitude of response. Maternal influence alters offspring survival through size advantages in growth and development. However, the relationship between maternal influence and variation in plasticity in response to predation risk is unknown. We hypothesized that variation in the magnitude of plastic responses between families is at least partly due to maternal provisioning and examined the relationship between maternal condition, egg provisioning and magnitude of plastic response to perceived predation risk (by dragonfly larvae: Aeshna spp.) in northern leopard frogs (Lithobates pipiens). Females in better body condition tended to lay more (clutch size) larger (egg diameter) eggs. Tadpoles responded to predation risk by increasing relative tail depth (morphology) and decreasing activity (behaviour). We found a positive relationship between morphological effect size and maternal condition, but no relationship between behavioural effect size and maternal condition. These novel findings suggest that limitations imposed by maternal condition can constrain phenotypic variation, ultimately influencing the capacity of populations to respond to environmental change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Greater Fall Risk in Elderly Women Than in Men Is Associated With Increased Gait Variability During Multitasking.

PubMed

Johansson, Jonas; Nordström, Anna; Nordström, Peter

2016-06-01

As 90% of fractures are caused by falls, and as fractures are more common in elderly women than in elderly men, a better understanding of potential sex differences in fall rates and underlying mechanisms is needed. The purpose of this study was to determine whether women are more prone than men to falling, and to evaluate whether the risk of falling is associated with variations in gait patterns. The cohort for this prospective observational study consisted of 1390 community-dwelling men and women aged 70 years, examined in a health survey between July 2012 and November 2014. Gait patterns were measured using a computerized walkway system during normal-speed, fast-speed, and dual-task trials. Triaxial accelerometers were used to collect objective data on physical activity, and self-reported fall data were collected by telephone 6 and 12 months after examination. Incident low-energy falls were defined as unexpected events in which participants came to rest on the ground. During the follow-up period, 148 study participants (88 women, 60 men; P = .01) reported falls. After adjusting for multiple confounders, including objective measures of physical activity, socioeconomic factors, cardiovascular disease, and cognitive function, the odds ratio for falling in women was 1.49 (95% confidence interval [CI] 1.02-2.19). Variations in gait pattern were significantly (20%-40%) increased in fallers compared with nonfallers during the dual-task trial for step width, step length, stride length, step time, stance time, stride velocity, and single support time (all P < .05). Furthermore, women showed 15% to 35% increased variability in all of these gait parameters during the dual-task trial compared with men (all P < .01). In the present cohort, 70-year-old women were at greater risk of falls compared with their male counterparts. This increased risk was associated with increased variation in gait pattern during dual-task activities, and may contribute to women's greater fracture risk compared with men. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

The efficiency of cardiovascular risk assessment: do the right patients get statin treatment?

PubMed Central

van Staa, Tjeerd-Pieter; Smeeth, Liam; Ng, Edmond S-W; Goldacre, Ben; Gulliford, Martin

2013-01-01

Objective To evaluate targeting of statin prescribing for primary prevention to those with high cardiovascular disease (CVD) risk. Design Two cohort studies including the general population and initiators of statins aged 35–74 years. Setting UK primary care records in the Clinical Practice Research Datalink. Patients 3.8 million general population patients and 300 914 statin users. Intervention Statin prescribing. Main outcome measures Statin prescribing by CVD risk; observed 5-year CVD risks; variability between practices. Results Statin prescribing increased substantially over time to patients with high 10-year CVD risk (≥20%): 7.0% of these received a statin prior to 2007, and 30.4% in 2007 onwards. Prescribing to patients with low risk (<15%) also increased (from 1.9% to 5.0%). Only about half the patients initiating statin treatment were high risk according to CVD risk score. The 5-year CVD risks, as observed during statin treatment, reduced over calendar time (from 17.0% to 7.1%). There was a large variation between general practices in the percentage of high-risk patients prescribed a statin in 2007 onwards, ranging from 8.2% to 61.5%. For low-risk patients, these varied from 2.1% to 29.1%. Conclusions There appeared to be substantive overuse in low CVD risk and underuse in high CVD risk (600 000 and 850 000 patients, respectively, in the UK since 2007). There is wide variation between practices in statin prescribing to patients at high CVD risk. There is a clear need for randomised trials for the best strategy to target statin treatment and manage CVD risk for primary prevention. PMID:23735939

Experience during development triggers between-individual variation in behavioural plasticity.

PubMed

Urszán, Tamás János; Garamszegi, László Zsolt; Nagy, Gergely; Hettyey, Attila; Török, János; Herczeg, Gábor

2018-05-12

1.Behavioural consistency within and across behaviours (animal personality and behavioural syndrome, respectively) have been vigorously studied in the last decade, leading to the emergence of 'animal personality' research. It has been proposed recently that not only mean behaviour (behavioural type), but the environmentally induced behavioural change (behavioural plasticity) might also differ between individuals within populations. 2.While case studies presenting between-individual variation in behavioural plasticity have started to accumulate, the mechanisms behind its emergence are virtually unknown. We have recently demonstrated that ecologically relevant environmental stimuli during ontogeny are necessary for the development of animal personality and behavioural syndromes. However, it is unknown whether between-individual variation in behavioural plasticity is hard-wired or induced. 3.Here, we tested whether experience with predation during development affected predator-induced behavioural plasticity in Rana dalmatina tadpoles. We ran a common garden experiment with two ontogenetic predation treatments: tadpoles developed from hatching in either the presence or absence of olfactory predator stimuli. Then, we assayed all tadpoles repeatedly for activity and risk-taking both in the absence and presence of olfactory predator stimuli. 4. We found that (i) between-individual variation in predator-induced behavioural plasticity was present only in the group that developed in the presence of olfactory stimuli from predators and (ii) previous experience with predatory stimuli resulted in lower plastic response at the group-level. The latter pattern resulted from increased between-individual variation and not from universally lower individual responses. We also found that experience with predation during development increased the predictability (i.e. decreased the within-individual variation unrelated to environmental change) of activity, but not risk-taking. In line with this, tadpoles developing under perceived predatory risk expressed their activity with higher repeatability. 5. We suggest that ecologically relevant environmental stimuli are not only fundamental for the development of animal personality and behavioural syndromes, but also for individual variation in behavioural plasticity. Thus, experience is of central importance for the emergence of individual behavioural variation at many levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Can variation in risk of nest predation explain altitudinal migration in tropical birds?

PubMed

Boyle, W Alice

2008-03-01

Migration is among the best studied of animal behaviors, yet few empirical studies have tested hypotheses explaining the ultimate causes of these cyclical annual movements. Fretwell's (1980) hypothesis predicts that if nest predation explains why many tropical birds migrate uphill to breed, then predation risk must be negatively associated with elevation. Data from 385 artificial nests spanning 2,740 m of elevation on the Atlantic slope of Costa Rica show an overall decline in predation with increasing elevation. However, nest predation risk was highest at intermediate elevations (500-650 m), not at lowest elevations. The proportion of nests depredated by different types of predators differed among elevations. These results imply that over half of the altitudinal migrant bird species in this region migrate to safer breeding areas than their non-breeding areas, suggesting that variation in nest predation risk could be an important benefit of uphill migrations of many species.

Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head

PubMed Central

Hong, Jung Min; Kim, Tae-Ho; Kim, Hyun-Ju; Park, Eui-Kyun

2010-01-01

Multiple factors have been implicated in the development of osteonecrosis of the femoral head (ONFH). In particular, non-traumatic ONFH is directly or indirectly related to injury of the vascular supply to the femoral head. Thus, hypoxia in the femoral head caused by impaired blood flow may be an important risk factor for ONFH. In this study, we investigated whether genetic variations of angiogenesis- and hypoxia-related genes contribute to an increased risk for the development of ONFH. Candidate genes were selected based on known hypoxia and angiogenesis pathways. An association study was performed using an Affymetrix Targeted Genotyping 3K Chip array with 460 ONFH patients and 300 control subjects. We showed that single nucleotide polymorphisms (SNPs) in the genes TF, VEGFC, IGFBP3, and ACE were associated with an increased risk of ONFH. On the other hand, SNPs in the KDR and NRP1 genes were associated with protection against ONFH. The most important finding was that one SNP (rs2453839) in the IGFBP3 gene was significantly associated with a higher risk of ONFH (P = 0.0061, OR 7.74). In subgroup analysis, most candidate gene variations that were associated with ONFH occurred in the idiopathic subgroup. Among other SNPs, ACE SNPs were associated with steroid-induced ONFH (P = 0.0018-0.0037, OR > 3). Collectively, our findings suggest that genetic variations in angiogenesis- and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population. PMID:20215856

Seasonal modeling of hand, foot, and mouth disease as a function of meteorological variations in Chongqing, China

NASA Astrophysics Data System (ADS)

Wang, Pin; Zhao, Han; You, Fangxin; Zhou, Hailong; Goggins, William B.

2017-08-01

Hand, foot, and mouth disease (HFMD) is an enterovirus-induced infectious disease, mainly affecting children under 5 years old. Outbreaks of HFMD in recent years indicate the disease interacts with both the weather and season. This study aimed to investigate the seasonal association between HFMD and weather variation in Chongqing, China. Generalized additive models and distributed lag non-linear models based on a maximum lag of 14 days, with negative binomial distribution assumed to account for overdispersion, were constructed to model the association between reporting HFMD cases from 2009 to 2014 and daily mean temperature, relative humidity, total rainfall and sun duration, adjusting for trend, season, and day of the week. The year-round temperature and relative humidity, rainfall in summer, and sun duration in winter were all significantly associated with HFMD. An inverted-U relationship was found between mean temperature and HFMD above 19 °C in summer, with a maximum morbidity at 27 °C, while the risk increased linearly with the temperature in winter. A hockey-stick association was found for relative humidity in summer with increasing risks over 60%. Heavy rainfall, relative to no rain, was found to be associated with reduced HFMD risk in summer and 2 h of sunshine could decrease the risk by 21% in winter. The present study showed meteorological variables were differentially associated with HFMD incidence in two seasons. Short-term weather variation surveillance and forecasting could be employed as an early indicator for potential HFMD outbreaks.

[Effect of intermittent variable intensity exercise on QT variation and risk of sudden cardiac death among Cameroonian school adolescents].

PubMed

Bika Lele, E C; Pepouomi, M N; Temfemo, A; Mekoulou, J; Assomo Ndemba, P; Mandengue, S H

2018-02-01

Several cases of sudden deaths are observed among students practicing sport and physical activity (SPA). Just few studies have been carried out on the variation of the QT (interval) and risk of sudden death during sporting exercises. To determine the effect of variable intermittent stress intensity on the variation of QT and the risk of sudden cardiac death. Form 4, lower sixth and upper sixth students were recruited from a high school in Douala (Cameroon). Each subject was tested; starting with a 2-km walk followed by a sprint race or an endurance race, protocol I (P1) or the reverse; protocol II (P2). Two electrocardiograms were recorded; prior to the beginning of the SPA and 5minutes after the last race. QT was corrected using four formulas. Forty-one subjects (21 women and 20 men), mean age 18±2 years were recruited. At the end of the exercise, corrected QT increased with Bazzet's formula and decreased with Frahmingam's formula. The difference was not significant with Fridericia and Hodges formulas. The frequency of long QT was higher at the end of the exercise with Bazzet's formula (12.2% vs. 24.4%, P=0.009) while the difference was not significant for the other formulas. The risk of sudden cardiac death increases significantly after SPA. More studies on large samples are needed. Copyright © 2017. Published by Elsevier SAS.

Occupation and relative risk of cutaneous squamous cell carcinoma (cSCC): A 45-year follow-up study in 4 Nordic countries.

PubMed

Alfonso, Jose Hernán; Martinsen, Jan Ivar; Pukkala, Eero; Weiderpass, Elisabete; Tryggvadottir, Laufey; Nordby, Karl-Christian; Kjærheim, Kristina

2016-09-01

The age-adjusted incidence of cutaneous squamous cell carcinoma (cSCC) in the Nordic countries has increased during the last 60 years, and the identification of occupational variation in the relative risk of cSCC may have preventive implications. We sought to describe variation in the relative risk of cSCC between occupational categories in Finland, Iceland, Norway, and Sweden. This is a historical prospective cohort study based on record linkages between census data for 12.9 million people and cancer registry data from 1961 to 2005. Standardized incidence ratios for cSCC were estimated for 53 occupational categories with the cSCC incidence rates for the national population of each country used as reference. During follow-up, 87,619 incident cases of cSCC were reported to the national cancer registries. In all countries combined, significant increased standardized incidence ratios were observed among seamen, military personnel, public safety workers, technical workers, teachers, transport workers, physicians, dentists, nurses, other health workers, religious workers, clerical workers, administrators, and sale agents (standardized incidence ratios between 1.08 and 1.77). Information on occupation was based on 1 point in time only. The occupational variation of the relative risk of cSCC might be associated with socioeconomic factors, and to some extent to occupational exposures. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort.

PubMed

Abdullah, N; Abdul Murad, N A; Mohd Haniff, E A; Syafruddin, S E; Attia, J; Oldmeadow, C; Kamaruddin, M A; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

2017-08-01

Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation. This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R 2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. The models including environmental risk factors only had pseudo R 2 values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10 -4 -4.83 × 10 -12 ) and increased the pseudo R 2 by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 < P < 0.05. This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene-environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection. Copyright © 2017 The Royal Society for Public Health. All rights reserved.

Performance of hospitals according to the ESC ACCA quality indicators and 30-day mortality for acute myocardial infarction: national cohort study using the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) register.

PubMed

Bebb, Owen; Hall, Marlous; Fox, Keith A A; Dondo, Tatendashe B; Timmis, Adam; Bueno, Hector; Schiele, François; Gale, Chris P

2017-04-01

To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality. National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was 'fondaparinux received among NSTEMI' (interquartile range 84.7%) and least variation 'centre organisation' (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%). Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction. © The Author 2017. Published on behalf of the European Society of Cardiology

Performance of hospitals according to the ESC ACCA quality indicators and 30-day mortality for acute myocardial infarction: national cohort study using the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) register

PubMed Central

Bebb, Owen; Hall, Marlous; Fox, Keith A. A.; Dondo, Tatendashe B.; Timmis, Adam; Bueno, Hector; Schiele, François; Gale, Chris P.

2017-01-01

Aims To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality. Methods and results National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was ′fondaparinux received among NSTEMI′ (interquartile range 84.7%) and least variation ′centre organisation′ (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%). Conclusions Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction. PMID:28329279

Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS.

PubMed

Sarkar, B; Manikandan, A; Nandy, M; Munshi, A; Sayan, P; Sujatha, N

2016-01-01

The study aimed to investigate the interplay between Monte Carlo Variance (MCV) and fluence smoothing factor (FSF) in volumetric modulated arc therapy treatment planning by using a sample set of complex treatment planning cases and a X-ray Voxel Monte Carlo-based treatment planning system equipped with tools to tune fluence smoothness as well as MCV. The dosimetric (dose to tumor volume, and organ at risk) and physical characteristic (treatment time, number of segments, and so on) of a set 45 treatment plans for all combinations of 1%, 3%, 5% MCV and 1, 3, 5 FSF were evaluated for five carcinoma esophagus cases under the study. Increase in FSF reduce the treatment time. Variation of MCV and FSF gives a highest planning target volume (PTV), heart and lung dose variation of 3.6%, 12.8% and 4.3%, respectively. The heart dose variation was highest among all organs at risk. Highest variation of spinal cord dose was 0.6 Gy. Variation of MCV and FSF influences the organ at risk (OAR) doses significantly but not PTV coverage and dose homogeneity. Variation in FSF causes difference in dosimetric and physical parameters for the treatment plans but variation of MCV does not. MCV 3% or less do not improve the plan quality significantly (physical and clinical) compared with MCV greater than 3%. The use of MCV between 3% and 5% gives similar results as 1% with lesser calculation time. Minimally detected differences in plan quality suggest that the optimum FSF can be set between 3 and 5.

Fuel poverty and the health of older people: the role of local climate.

PubMed

de Vries, R; Blane, D

2013-09-01

Fuel poverty is a risk factor for ill-health, particularly among older people. We hypothesized that both the risk of fuel poverty and the strength of its detrimental effects on health would be increased in areas of colder and wetter climate. Individual data on respiratory health, hypertension, depressive symptoms and self-rated health were derived from the 2008/09 wave of the English Longitudinal Study of Ageing. Climate data for 89 English counties and unitary authorities were obtained from the UK Met Office. Multilevel regression models (n = 7160) were used to test (i) the association between local climate and fuel poverty risk, and (ii) the association between local climate and the effect of fuel poverty on health (adjusted for age, gender, height, smoking status and household income). Individual risk of fuel poverty varied across counties. However, this variation was not explained by differences in climate. Fuel poverty was significantly related to worse health for two of the outcomes (respiratory health and depressive symptoms). However, there was no significant effect of climate on fuel poverty's association with these outcomes. Although there is regional variation in England in both the risk of fuel poverty and its effects on health, this variation is not explained by differences in rainfall and winter temperatures.

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO)

PubMed Central

2012-01-01

Introduction Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. Methods We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model. Results Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3). Conclusions Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC. PMID:22762150

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

PubMed

Lecarpentier, Julie; Noguès, Catherine; Mouret-Fourme, Emmanuelle; Gauthier-Villars, Marion; Lasset, Christine; Fricker, Jean-Pierre; Caron, Olivier; Stoppa-Lyonnet, Dominique; Berthet, Pascaline; Faivre, Laurence; Bonadona, Valérie; Buecher, Bruno; Coupier, Isabelle; Gladieff, Laurence; Gesta, Paul; Eisinger, François; Frénay, Marc; Luporsi, Elisabeth; Lortholary, Alain; Colas, Chrystelle; Dugast, Catherine; Longy, Michel; Pujol, Pascal; Tinat, Julie; Lidereau, Rosette; Andrieu, Nadine

2012-07-03

Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. We assessed variation in BC risk according to factors related to pregnancies by location of mutation in the homogeneous risk region of BRCA1 and BRCA2 in 990 women in the French study GENEPSO by using a weighted Cox regression model. Our results confirm the existence of the protective effect of an increasing number of full-term pregnancies (FTPs) toward BC among BRCA1 and BRCA2 mutation carriers (≥3 versus 0 FTPs: hazard ratio (HR) = 0.51, 95% confidence interval (CI) = 0.33 to 0.81). Additionally, the HR shows an association between incomplete pregnancies and a higher BC risk, which reached 2.39 (95% CI = 1.28 to 4.45) among women who had at least three incomplete pregnancies when compared with women with zero incomplete pregnancies. This increased risk appeared to be restricted to incomplete pregnancies occurring before the first FTP (HR = 1.77, 95% CI = 1.19 to 2.63). We defined the TMAP score (defined as the Time of Breast Mitotic Activity during Pregnancies) to take into account simultaneously the opposite effect of full-term and interrupted pregnancies. Compared with women with a TMAP score of less than 0.35, an increasing TMAP score was associated with a statistically significant increase in the risk of BC (P trend = 0.02) which reached 1.97 (95% CI = 1.19 to 3.29) for a TMAP score >0.5 (versus TMAP ≤0.35). All these results appeared to be similar in BRCA1 and BRCA2. Nevertheless, our results suggest a variation in BC risk associated with parity according to the location of the mutation in BRCA1. Indeed, parity seems to be associated with a significantly decreased risk of BC only among women with a mutation in the central region of BRCA1 (low-risk region) (≥1 versus 0 FTP: HR = 0.27, 95% CI = 0.13 to 0.55) (Pinteraction <10-3). Our findings show that, taking into account environmental and lifestyle modifiers, mutation position might be important for the clinical management of BRCA1 and BRCA2 mutation carriers and could also be helpful in understanding how BRCA1 and BRCA2 genes are involved in BC.

Genetics and risk factors for basal cell carcinoma.

PubMed

Madan, V; Hoban, P; Strange, R C; Fryer, A A; Lear, J T

2006-05-01

Nonmelanoma skin cancer (NMSC) is the commonest cancer in whites and its incidence is increasing worldwide. The prevalence of this cancer is predicted to equal that of all others combined and it was estimated that there were over 2 million cases diagnosed in the U.S.A. in 2004. Patients exhibit marked differences in clinical phenotype with variations in tumour numbers, rate of tumour accrual, site and histological subtype. Furthermore, patients are at increased risk of other cutaneous and noncutaneous cancers. The factors accounting for this variation are complex and still not completely understood. Clearly, ultraviolet light (UV) exposure is a major influence but its relationship to clinical phenotype is not yet clear. In addition, immunosuppression is a significant risk factor. Our group has identified high-risk groups for the development of further basal cell carcinoma (BCC), namely patients with truncal BCC and those presenting with tumour clusters. This presentation will concentrate on these clinical subgroups as well as immunosuppressed patients. These groups represent significant management challenges and are areas where novel, nonsurgical treatment options may make a significant clinical impact in patient care. The risk factors predisposing to these clinical phenotypes will be discussed, including genetic factors and UV exposure. Potential clinical applications, including predictive indices, will be considered.

The epidemiology of anophthalmia and microphthalmia in Sweden.

PubMed

Källén, Bengt; Tornqvist, Kristina

2005-01-01

Infants with a clinical diagnosis of anophthalmia or microphthalmia were identified from four health registers in Sweden, covering different parts of the period 1965-2001. During the observation period, the rate of anophthalmia decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered rate of microphthalmia increased markedly during the observation period to reach a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified children had a chromosome anomaly. There was no geographical variation in prevalence and infants born in urban or rural districts had, if anything, a lower risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non-eye malformations were more common at anophthalmia (63%) than at microphthalmia (30%). Sex ratio was normal and no statistically significant variation between sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye malformations) could be demonstrated. There was a marked risk increase with maternal age but no certain parity effect, no effect of maternal education, but a possible association with subfertility. Maternal smoking in early pregnancy seemed to increase the risk for anophthalmia or microphthalmia in the absence of a coloboma.

Predicting evolutionary rescue via evolving plasticity in stochastic environments

PubMed Central

Baskett, Marissa L.

2016-01-01

Phenotypic plasticity and its evolution may help evolutionary rescue in a novel and stressful environment, especially if environmental novelty reveals cryptic genetic variation that enables the evolution of increased plasticity. However, the environmental stochasticity ubiquitous in natural systems may alter these predictions, because high plasticity may amplify phenotype–environment mismatches. Although previous studies have highlighted this potential detrimental effect of plasticity in stochastic environments, they have not investigated how it affects extinction risk in the context of evolutionary rescue and with evolving plasticity. We investigate this question here by integrating stochastic demography with quantitative genetic theory in a model with simultaneous change in the mean and predictability (temporal autocorrelation) of the environment. We develop an approximate prediction of long-term persistence under the new pattern of environmental fluctuations, and compare it with numerical simulations for short- and long-term extinction risk. We find that reduced predictability increases extinction risk and reduces persistence because it increases stochastic load during rescue. This understanding of how stochastic demography, phenotypic plasticity, and evolution interact when evolution acts on cryptic genetic variation revealed in a novel environment can inform expectations for invasions, extinctions, or the emergence of chemical resistance in pests. PMID:27655762

A new view of avian life-history evolution tested on an incubation paradox.

PubMed

Martin, Thomas E

2002-02-07

Viewing life-history evolution in birds based on an age-specific mortality framework can explain broad life-history patterns, including the long incubation periods in southern latitudes documented here. I show that incubation periods of species that are matched phylogenetically and ecologically between Argentina and Arizona are longer in Argentina. Long incubation periods have mystified scientists because they increase the accumulated risk of time-dependent mortality to young without providing a clear benefit. I hypothesize that parents of species with low adult mortality accept increased risk of mortality to their young from longer incubation if this allows reduced risk of mortality to themselves. During incubation, songbird parents can reduce risk of mortality to themselves by reducing nest attentiveness (percentage of time on the nest). Here I show that parents of species with lower adult mortality exhibit reduced nest attentiveness and that lower attentiveness is associated with longer incubation periods. However, the incubation period is also modified by juvenile mortality. Clutch size variation is also strongly correlated with age-specific mortality. Ultimately, adult and juvenile mortality explain variation in incubation and other life-history traits better than the historical paradigm.

Fourier Transformed Infra-Red Imaging of Femoral Neck Bone: Reduced Heterogeneity of Mineral-to-Matrix and Carbonate-to-Phosphate and more Variable Crystallinity in Treatment-Naïve Fracture Cases compared to Fracture-Free Controls

PubMed Central

Gourion-Arsiquaud, Samuel; Lukashova, Lyudmilla; Power, Jon; Loveridge, Nigel; Reeve, Jonathan; Boskey, Adele L.

2012-01-01

After age 60 hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier Transform Infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and non-fractured bones. Whole femoral neck cross sections, divided into quadrants along the neck’s axis, from 10 women with hip fracture and 10 cadaveric controls were studied using FTIRI and micro-computed Tomography. Although 3-dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix ratio was reduced in the cases of hip fracture, confirming previous reports. New findings were that the FTIRI microscopic variation (heterogeneity) of the mineral-to-matrix ratio was substantially reduced in the fracture group as was the heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity of crystallinity was increased. Increased variation of crystallinity was statistically associated with reduced variation of the carbonate-to-phosphate ratio. Anatomical variation in these properties between the different femoral neck quadrants was reduced in the fracture group compared to controls. While our treatment-naïve patients had reduced rather than increased bending resistance, these changes in heterogeneity associated with hip fracture are in another way comparable to the effects of experimental bisphosphonate therapy, which decreases heterogeneity and other indicators of bone’s toughness as a material. PMID:22865771

Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls.

PubMed

Gourion-Arsiquaud, Samuel; Lukashova, Lyudmilla; Power, Jon; Loveridge, Nigel; Reeve, Jonathan; Boskey, Adele L

2013-01-01

After the age of 60 years, hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced bone mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier transform infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and nonfractured bones. Whole femoral neck cross sections, divided into quadrants along the neck's axis, from 10 women with hip fracture and 10 cadaveric controls were studied using FTIRI and micro-computed tomography. Although 3-dimensional micro-CT bone mineral densities were similar, the mineral-to-matrix ratio was reduced in the cases of hip fracture, confirming previous reports. New findings were that the FTIRI microscopic variation (heterogeneity) of the mineral-to-matrix ratio was substantially reduced in the fracture group as was the heterogeneity of the carbonate-to-phosphate ratio. Conversely, the heterogeneity of crystallinity was increased. Increased variation of crystallinity was statistically associated with reduced variation of the carbonate-to-phosphate ratio. Anatomical variation in these properties between the different femoral neck quadrants was reduced in the fracture group compared with controls. Although our treatment-naive patients had reduced rather than increased bending resistance, these changes in heterogeneity associated with hip fracture are in another way comparable to the effects of experimental bisphosphonate therapy, which decreases heterogeneity and other indicators of bone's toughness as a material. Copyright © 2013 American Society for Bone and Mineral Research.

Occupational variation in incidence of bladder cancer: a comparison of population-representative cohorts from Nordic countries and Canada.

PubMed

Hadkhale, Kishor; MacLeod, Jill; Demers, Paul A; Martinsen, Jan Ivar; Weiderpass, Elisabete; Kjaerheim, Kristina; Lynge, Elsebeth; Sparen, Pär; Tryggvadottir, Laufey; Anne Harris, M; Tjepkema, Michael; Peters, Paul A; Pukkala, Eero

2017-08-04

The objective of this study was to compare occupational variation of the risk of bladder cancer in the Nordic countries and Canada. In the Nordic Occupational Cancer study (NOCCA), 73 653 bladder cancer cases were observed during follow-up of 141.6 million person-years. In the Canadian Census Health and Environment Cohort (CanCHEC), 8170 cases were observed during the follow-up of 36.7 million person-years. Standardised incidence ratios with 95% CI were estimated for 53 occupations in the NOCCA cohort and HR with 95% CIs were estimated for 42 occupations in the CanCHEC. Elevated risks of bladder cancer were observed among hairdressers, printers, sales workers, plumbers, painters, miners and laundry workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Chimney-sweeps, tobacco workers and waiters had about 1.5-fold risk in the Nordic countries; no risk estimates for these categories were given from the CanCHEC cohort. We observed different occupational patterns in risk of bladder cancer in Nordic countries and Canada. The only occupation with similarly increased risk was observed among sales workers. Differences in smoking across occupational groups may explain some, but not all, of this variation. © 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.

Risk factors associated with incidence and persistence of signs and symptoms of temporomandibular disorders.

PubMed

Marklund, Susanna; Wänman, Anders

2010-09-01

To analyze whether gender, self-reported bruxism, and variations in dental occlusion predicted incidence and persistence of temporomandibular disorder (TMD) during a 2-year period. The study population comprised 280 dental students at Umeå University in Sweden. The study design was that of a case-control study within a 2-year prospective cohort. The investigation comprised a questionnaire and a clinical examination at enrolment and at 12 and 24 months. Cases (incidence) and controls (no incidence) were identified among those without signs and symptoms of TMD at the start of the study. Cases with 2-year persistence of signs and symptoms of TMD were those with such signs and symptoms at all three examinations. Clinical registrations of baseline variables were used as independent variables. Odds ratio estimates and 95% confidence intervals of the relative risks of being a case or control in relation to baseline registrations were calculated using logistic regression analyses. The analyses revealed that self-reported bruxism and crossbite, respectively increased the risk of the 2-year cumulative incidence and duration of temporomandibular joint (TMJ) signs or symptoms. Female gender was related to an increased risk of developing and maintaining myofascial pain. Signs of mandibular instability increased the risk of maintained TMD signs and symptoms during the observation period. This 2-year prospective observational study indicated that self-reported bruxism and variations in dental occlusion were linked to the incidence and persistence of TMJ signs and symptoms to a higher extent than to myofascial pain.

Influence of vectors' risk-spreading strategies and environmental stochasticity on the epidemiology and evolution of vector-borne diseases: the example of Chagas' disease.

PubMed

Pelosse, Perrine; Kribs-Zaleta, Christopher M; Ginoux, Marine; Rabinovich, Jorge E; Gourbière, Sébastien; Menu, Frédéric

2013-01-01

Insects are known to display strategies that spread the risk of encountering unfavorable conditions, thereby decreasing the extinction probability of genetic lineages in unpredictable environments. To what extent these strategies influence the epidemiology and evolution of vector-borne diseases in stochastic environments is largely unknown. In triatomines, the vectors of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, juvenile development time varies between individuals and such variation most likely decreases the extinction risk of vector populations in stochastic environments. We developed a simplified multi-stage vector-borne SI epidemiological model to investigate how vector risk-spreading strategies and environmental stochasticity influence the prevalence and evolution of a parasite. This model is based on available knowledge on triatomine biodemography, but its conceptual outcomes apply, to a certain extent, to other vector-borne diseases. Model comparisons between deterministic and stochastic settings led to the conclusion that environmental stochasticity, vector risk-spreading strategies (in particular an increase in the length and variability of development time) and their interaction have drastic consequences on vector population dynamics, disease prevalence, and the relative short-term evolution of parasite virulence. Our work shows that stochastic environments and associated risk-spreading strategies can increase the prevalence of vector-borne diseases and favor the invasion of more virulent parasite strains on relatively short evolutionary timescales. This study raises new questions and challenges in a context of increasingly unpredictable environmental variations as a result of global climate change and human interventions such as habitat destruction or vector control.

Influence of Vectors’ Risk-Spreading Strategies and Environmental Stochasticity on the Epidemiology and Evolution of Vector-Borne Diseases: The Example of Chagas’ Disease

PubMed Central

Pelosse, Perrine; Kribs-Zaleta, Christopher M.; Ginoux, Marine; Rabinovich, Jorge E.; Gourbière, Sébastien; Menu, Frédéric

2013-01-01

Insects are known to display strategies that spread the risk of encountering unfavorable conditions, thereby decreasing the extinction probability of genetic lineages in unpredictable environments. To what extent these strategies influence the epidemiology and evolution of vector-borne diseases in stochastic environments is largely unknown. In triatomines, the vectors of the parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, juvenile development time varies between individuals and such variation most likely decreases the extinction risk of vector populations in stochastic environments. We developed a simplified multi-stage vector-borne SI epidemiological model to investigate how vector risk-spreading strategies and environmental stochasticity influence the prevalence and evolution of a parasite. This model is based on available knowledge on triatomine biodemography, but its conceptual outcomes apply, to a certain extent, to other vector-borne diseases. Model comparisons between deterministic and stochastic settings led to the conclusion that environmental stochasticity, vector risk-spreading strategies (in particular an increase in the length and variability of development time) and their interaction have drastic consequences on vector population dynamics, disease prevalence, and the relative short-term evolution of parasite virulence. Our work shows that stochastic environments and associated risk-spreading strategies can increase the prevalence of vector-borne diseases and favor the invasion of more virulent parasite strains on relatively short evolutionary timescales. This study raises new questions and challenges in a context of increasingly unpredictable environmental variations as a result of global climate change and human interventions such as habitat destruction or vector control. PMID:23951018

Weekly variations in feelings of trust predict incident STI within a prospective cohort of adolescent women from a US city.

PubMed

Matson, Pamela A; Fortenberry, J Dennis; Chung, Shang-En; Gaydos, Charlotte A; Ellen, Jonathan M

2018-03-24

Feelings of intimacy, perceptions of partner concurrency (PPC) and perceptions of risk for an STD (PRSTD) are meaningful and dynamic attributes of adolescent sexual relationships. Our objective was to examine whether variations in these STI-associated feelings and perceptions predicted incident Chlamydia trachomatis and/or Neisseriagonorrhoeae infection within a prospective cohort of urban adolescent women. A cohort of clinic-recruited women aged 16-19 completed daily surveys on feelings and risk perceptions about each current sex partner on a smartphone continuously for up to 18 months. Urine was tested for C. trachomatis and N. gonorrhoeae every 3 months. Daily responses were averaged across the week. As overall means for trust, closeness and commitment were high, data were coded to indicate any decrease in feelings from the previous week. PRSTD and PPC were reverse coded to indicate any increase from the previous week. An index was created to examine the cumulative effect of variation in these feelings and perceptions. Generalised linear models were used to account for correlation among repeated measures within relationships. For each week that there was a decrease in trust, there was a 45% increase in the risk of being infected with an STI at follow-up (relative risk (RR) 1.45, 95% CI 1.18 to 1.78, P=0.004). Neither a decrease in closeness or commitment, nor an increase in PRSTD or PPC was associated with an STI outcome. Cumulatively, the index measure indicated that a change in an additional feeling or perception over the week increased the odds of an STI by 14% (RR 1.14, 95% CI 1.02 to 1.29, P=0.026). A decrease in feelings of trust towards a main partner may be a more sensitive indicator of STI risk than PRSTD, PPC or commitment. The next generation of behavioural interventions for youth will need strategies to address feelings of intimacy within adolescent romantic relationships. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Future probabilities of coastal floods in Finland

NASA Astrophysics Data System (ADS)

Pellikka, Havu; Leijala, Ulpu; Johansson, Milla M.; Leinonen, Katri; Kahma, Kimmo K.

2018-04-01

Coastal planning requires detailed knowledge of future flooding risks, and effective planning must consider both short-term sea level variations and the long-term trend. We calculate distributions that combine short- and long-term effects to provide estimates of flood probabilities in 2050 and 2100 on the Finnish coast in the Baltic Sea. Our distributions of short-term sea level variations are based on 46 years (1971-2016) of observations from the 13 Finnish tide gauges. The long-term scenarios of mean sea level combine postglacial land uplift, regionally adjusted scenarios of global sea level rise, and the effect of changes in the wind climate. The results predict that flooding risks will clearly increase by 2100 in the Gulf of Finland and the Bothnian Sea, while only a small increase or no change compared to present-day conditions is expected in the Bothnian Bay, where the land uplift is stronger.

Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

PubMed Central

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2012-01-01

Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

Variability in sperm form and function in the context of sperm competition risk in two Tupinambis lizards

PubMed Central

Blengini, Cecilia S; Sergio, Naretto; Gabriela, Cardozo; Giojalas, Laura C; Margarita, Chiaraviglio

2014-01-01

In polyandrous species, sperm morphometry and sperm velocity are under strong sexual selection. Although several hypotheses have been proposed to explain the role of sperm competition in sperm trait variation, this aspect is still poorly understood. It has been suggested that an increase in sperm competition pressure could reduce sperm size variation or produce a diversity of sperm to maximize male fertilization success. We aim at elucidating the variability of sperm morphometric traits and velocity in two Tupinambis lizards in the context of sperm competition risk. Sperm traits showed substantial variation at all levels examined: between species, among males within species, and within the ejaculate of individual males. Sperm velocity was found to be positively correlated with flagellum: midpiece ratio, with relatively longer flagella associated with faster sperm. Our results document high variability in sperm form and function in lizards. PMID:25505535

Blood type gene locus has no influence on ACE association with Alzheimer's disease.

PubMed

Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

2015-04-01

The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Trends and Regional Variation in Hospital Mortality, Length of Stay and Cost in Hospital of Ischemic Stroke Patients in Alberta Accompanying the Provincial Reorganization of Stroke Care.

PubMed

Ohinmaa, Arto; Zheng, Yufei; Jeerakathil, Thomas; Klarenbach, Scott; Häkkinen, Unto; Nguyen, Thanh; Friesen, Dan; Ruseski, Jane; Kaul, Padma; Ariste, Ruolz; Jacobs, Philip

2016-12-01

This study aimed to evaluate the trends and regional variation of stroke hospital care in 30-day in-hospital mortality, hospital length of stay (LOS), and 1-year total hospitalization cost after implementation of the Alberta Provincial Stroke Strategy. New ischemic stroke patients (N = 7632) admitted to Alberta acute care hospitals between 2006 and 2011 were followed for 1 year. We analyzed in-hospital mortality with logistic regression, LOS with negative binomial regression, and the hospital costs with generalized gamma model (log link). The risk-adjusted results were compared over years and between zones using observed/expected results. The risk-adjusted mortality rates decreased from 12.6% in 2006/2007 to 9.9% in 2010/2011. The regional variations in mortality decreased from 8.3% units in 2008/2009 to 5.6 in 2010/2011. The LOS of the first episode dropped significantly in 2010/2011 after a 4-year slight increase. The regional variation in LOS was 15.5 days in 2006/2007 and decreased to 10.9 days in 2010/2011. The 1-year hospitalization cost increased initially, and then kept on declining during the last 3 years. The South and Calgary zones had the lowest costs over the study period. However, this gap was diminishing. After implementation of the Alberta Provincial Stroke Strategy, both mortality and hospital costs demonstrated a decreasing trend during the later years of study. The LOS increased slightly during the first 4 years but had a significant drop at the last year. In general, the regional variations in all 3 indicators had a diminishing trend. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker.

PubMed

Iasonos, Alexia; Chapman, Paul B; Satagopan, Jaya M

2016-05-01

An increased interest has been expressed in finding predictive biomarkers that can guide treatment options for both mutation carriers and noncarriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time-to-event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a proportional hazards regression model is commonly used as a measure of variation in TB. Although this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus noncarriers. We illustrate the use and interpretation of the proposed measures with data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. Clin Cancer Res; 22(9); 2114-20. ©2016 AACR. ©2016 American Association for Cancer Research.

Using a Virtual Environment to Examine How Children Cross Streets: Advancing Our Understanding of How Injury Risk Arises

PubMed Central

Corbett, Michael; Milanovic, Melissa; Beer, Jonathan

2016-01-01

Purpose To examine how risk of injury can arise for child pedestrians. Methods Using a highly immersive virtual reality system interfaced with a 3-D movement measurement system, younger (M = 8 years) and older (M = 10 years) children’s crossing behaviors were measured under conditions that introduced variation in vehicle speed, distance, and intervehicle gaps. Results Children used distance cues in deciding when to cross; there were no age or sex differences. This increased risk of injury in larger intervehicle gaps because they started late and did not monitor traffic or adjust walking speed as they crossed. In contrast, injury risk in smaller intervehicle gaps of equal risk (i.e., same time to contact) occurred because crossing behavioral adjustments (starting early, increasing walking speed while crossing) were not sufficient. Conclusions Dependence on distance cues increases children’s risk of injury as pedestrians when crossing in a variety of traffic situations. PMID:26338980

Risk Factors for Dementia in People with Down Syndrome: Issues in Assessment and Diagnosis

ERIC Educational Resources Information Center

Bush, Alick; Beail, Nigel

2004-01-01

It has been clearly established that there is an increased incidence of early onset dementia of the Alzheimer type (DAT) in people who have Down syndrome. There are variations in the age of onset of the clinical signs of DAT, which may be accounted for by different risk factors. In this review we examined the evidence that different biological and…

A General Econometric Model of the Determinants of Library Subscription Prices of Scholarly Journals: The Role of Exchange Rate Risk and Other Factors.

ERIC Educational Resources Information Center

Chressanthis, George A.; Chressanthis, June D.

1994-01-01

Provides regression-based empirical evidence of the effects of variations in exchange rate risk on 1985 library prices of the top-ranked 99 journals in economics. The relationship between individual journal prices and library prices is shown, and other factors associated with increases and decreases in library journal prices are given. (Contains…

Seasonal variation in surface fuel moisture between unthinned and thinned mixed conifer forest, northern California, USA

Treesearch

Becky L. Estes; Eric E. Knapp; Carl N. Skinner; Fabian C. C. Uzoh

2012-01-01

Reducing stand density is often used as a tool for mitigating the risk of high-intensity crown fires. However, concern has been expressed that opening stands might lead to greater drying of surface fuels, contributing to increased fire risk. The objective of this study was to determine whether woody fuel moisture differed between unthinned and thinned mixed-conifer...

Testicular cancer in twins: a meta-analysis.

PubMed

Neale, R E; Carrière, P; Murphy, M F G; Baade, P D

2008-01-15

In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same sex twins 1.4 (1.2-1.8).

Variations in risk and protective factors for life satisfaction and mental wellbeing with deprivation: a cross-sectional study.

PubMed

Bellis, Mark A; Lowey, Helen; Hughes, Karen; Deacon, Lynn; Stansfield, Jude; Perkins, Clare

2012-07-02

Improving life satisfaction (LS) and mental wellbeing (MWB) is important for better public health. Like other health issues, LS and MWB are closely related to deprivation (i.e. lack of resources). Developing public health measures that reduce inequalities in wellbeing requires an understanding of how factors associated with high and low LS and MWB vary with deprivation. Here, we examine such variations and explore which public health measures are likely to improve wellbeing while reducing related inequalities. A self-administered questionnaire measuring LS and MWB was used with a cross-sectional sample of adults from the North West of England (n = 15,228). Within deprivation tertiles, analyses examined how demographics, health status, employment, relationships and behaviours (alcohol, tobacco, physical exercise) were associated with LS and MWB. Deprivation was strongly related to low LS and MWB with, for instance, 17.1% of the most deprived tertile having low LS compared to 8.9% in the most affluent. After controlling for confounders, across all deprivation tertiles, better self-assessed health status and being in a relationship were protective against low LS and MWB. Unemployment increased risks of low LS across all tertiles but only risks of low MWB in the deprived tertile. For this tertile, South Asian ethnicity and higher levels of exercise were protective against low MWB. In the middle tertile retired individuals had a reduced risk of low MWB and an increased chance of high LS even in comparison to those in employment. Alcohol's impact on LS was limited to the most deprived tertile where heavy drinkers were at most risk of poor outcomes. In this study, positive outcomes for LS and MWB were strongly associated with lower deprivation and good health status. Public health measures already developed to promote these issues are likely to improve LS and MWB. Efforts to increase engagement in exercise are also likely to have positive impacts, particularly in deprived communities. The development of future initiatives that address LS and MWB must take account of variations in their risk and protective factors at different levels of deprivation.

Selective Pressure along a Latitudinal Gradient Affects Subindividual Variation in Plants

PubMed Central

Sobral, Mar; Guitián, José; Guitián, Pablo; Larrinaga, Asier R.

2013-01-01

Individual plants produce repeated structures such as leaves, flowers or fruits, which, although belonging to the same genotype, are not phenotypically identical. Such subindividual variation reflects the potential of individual genotypes to vary with micro-environmental conditions. Furthermore, variation in organ traits imposes costs to foraging animals such as time, energy and increased predation risk. Therefore, animals that interact with plants may respond to this variation and affect plant fitness. Thus, phenotypic variation within an individual plant could be, in part, an adaptive trait. Here we investigated this idea and we found that subindividual variation of fruit size of Crataegus monogyna, in different populations throughout the latitudinal gradient in Europe, was explained at some extent by the selective pressures exerted by seed-dispersing birds. These findings support the hypothesis that within-individual variation in plants is an adaptive trait selected by interacting animals which may have important implications for plant evolution. PMID:24069297

Land cover variation and West Nile virus prevalence: Patterns, processes, and implications for disease control

USGS Publications Warehouse

Ezenwa, V.O.; Milheim, L.E.; Coffey, M.F.; Godsey, M.S.; King, R.J.; Guptill, S.C.

2007-01-01

Identifying links between environmental variables and infectious disease risk is essential to understanding how human-induced environmental changes will effect the dynamics of human and wildlife diseases. Although land cover change has often been tied to spatial variation in disease occurrence, the underlying factors driving the correlations are often unknown, limiting the applicability of these results for disease prevention and control. In this study, we described associations between land cover composition and West Nile virus (WNV) infection prevalence, and investigated three potential processes accounting for observed patterns: (1) variation in vector density; (2) variation in amplification host abundance; and (3) variation in host community composition. Interestingly, we found that WNV infection rates among Culex mosquitoes declined with increasing wetland cover, but wetland area was not significantly associated with either vector density or amplification host abundance. By contrast, wetland area was strongly correlated with host community composition, and model comparisons suggested that this factor accounted, at least partially, for the observed effect of wetland area on WNV infection risk. Our results suggest that preserving large wetland areas, and by extension, intact wetland bird communities, may represent a valuable ecosystem-based approach for controlling WNV outbreaks. ?? Mary Ann Liebert, Inc.

Maladaptive decision making and substance use outcomes in high-risk individuals: preliminary evidence for the role of 5-HTTLPR variation.

PubMed

O'Brien, Jessica W; Lichenstein, Sarah D; Hill, Shirley Y

2014-07-01

Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes. Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86). HR offspring showed poorer performance overall on the IGT and especially poor performance on the final trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no significant COMT by Risk interaction. Significantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was significantly associated with an earlier age at SUD onset. This is the first study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefits during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood.

ITKids part II: variation of postures and muscle activity in children using different information and communication technologies.

PubMed

Ciccarelli, Marina; Straker, Leon; Mathiassen, Svend Erik; Pollock, Clare

2011-01-01

There are concerns that insufficient variation in postural and muscle activity associated with use of modern information and communication technology (ICT) presents a risk for musculoskeletal ill-health among school children. However, scientific knowledge on physical exposure variation in this group is limited. The purpose of this study was to quantify postures and muscle activity of school children using different types of ICT. Postures of the head, upper back and upper arm, and muscle activity of the right and left upper trapezius and right forearm extensors were measured over 10-12 hours in nine school children using different types of ICT at school and away-from-school. Variation in postures and muscle activity was quantified using two indices, EVA{sd} and APDF₉₀-₁₀. Paper-based (Old) ICT tasks produced postures that were less neutral but more variable than electronics-based (New ICT) and Non-ICT tasks. Non-ICT tasks involved mean postures similar to New ICT tasks, but with greater variation. Variation of muscle activity was similar between ICT types in the right and left upper trapezius muscles. Non-ICT tasks produced more muscle activity variation in the right forearm extensor group compared to New and Old ICT tasks. Different ICT tasks produce different degrees of variation in posture and muscle activity. Combining tasks that use different ICT may increase overall exposure variation. More research is needed to determine what degree of postural and muscle activity variation is associated with reduced risk of musculoskeletal ill-health.

Mapping child maltreatment risk: a 12-year spatio-temporal analysis of neighborhood influences.

PubMed

Gracia, Enrique; López-Quílez, Antonio; Marco, Miriam; Lila, Marisol

2017-10-18

'Place' matters in understanding prevalence variations and inequalities in child maltreatment risk. However, most studies examining ecological variations in child maltreatment risk fail to take into account the implications of the spatial and temporal dimensions of neighborhoods. In this study, we conduct a high-resolution small-area study to analyze the influence of neighborhood characteristics on the spatio-temporal epidemiology of child maltreatment risk. We conducted a 12-year (2004-2015) small-area Bayesian spatio-temporal epidemiological study with all families with child maltreatment protection measures in the city of Valencia, Spain. As neighborhood units, we used 552 census block groups. Cases were geocoded using the family address. Neighborhood-level characteristics analyzed included three indicators of neighborhood disadvantage-neighborhood economic status, neighborhood education level, and levels of policing activity-, immigrant concentration, and residential instability. Bayesian spatio-temporal modelling and disease mapping methods were used to provide area-specific risk estimations. Results from a spatio-temporal autoregressive model showed that neighborhoods with low levels of economic and educational status, with high levels of policing activity, and high immigrant concentration had higher levels of substantiated child maltreatment risk. Disease mapping methods were used to analyze areas of excess risk. Results showed chronic spatial patterns of high child maltreatment risk during the years analyzed, as well as stability over time in areas of low risk. Areas with increased or decreased child maltreatment risk over the years were also observed. A spatio-temporal epidemiological approach to study the geographical patterns, trends over time, and the contextual determinants of child maltreatment risk can provide a useful method to inform policy and action. This method can offer a more accurate description of the problem, and help to inform more localized prevention and intervention strategies. This new approach can also contribute to an improved epidemiological surveillance system to detect ecological variations in risk, and to assess the effectiveness of the initiatives to reduce this risk.

Complex Adaptive System Models and the Genetic Analysis of Plasma HDL-Cholesterol Concentration

PubMed Central

Rea, Thomas J.; Brown, Christine M.; Sing, Charles F.

2006-01-01

Despite remarkable advances in diagnosis and therapy, ischemic heart disease (IHD) remains a leading cause of morbidity and mortality in industrialized countries. Recent efforts to estimate the influence of genetic variation on IHD risk have focused on predicting individual plasma high-density lipoprotein cholesterol (HDL-C) concentration. Plasma HDL-C concentration (mg/dl), a quantitative risk factor for IHD, has a complex multifactorial etiology that involves the actions of many genes. Single gene variations may be necessary but are not individually sufficient to predict a statistically significant increase in risk of disease. The complexity of phenotype-genotype-environment relationships involved in determining plasma HDL-C concentration has challenged commonly held assumptions about genetic causation and has led to the question of which combination of variations, in which subset of genes, in which environmental strata of a particular population significantly improves our ability to predict high or low risk phenotypes. We document the limitations of inferences from genetic research based on commonly accepted biological models, consider how evidence for real-world dynamical interactions between HDL-C determinants challenges the simplifying assumptions implicit in traditional linear statistical genetic models, and conclude by considering research options for evaluating the utility of genetic information in predicting traits with complex etiologies. PMID:17146134

An expected utility maximizer walks into a bar…

PubMed

Burghart, Daniel R; Glimcher, Paul W; Lazzaro, Stephanie C

2013-06-01

We conducted field experiments at a bar to test whether blood alcohol concentration (BAC) correlates with violations of the generalized axiom of revealed preference (GARP) and the independence axiom. We found that individuals with BACs well above the legal limit for driving adhere to GARP and independence at rates similar to those who are sober. This finding led to the fielding of a third experiment to explore how risk preferences might vary as a function of BAC. We found gender-specific effects: Men did not exhibit variations in risk preferences across BACs. In contrast, women were more risk averse than men at low BACs but exhibited increasing tolerance towards risks as BAC increased. Based on our estimates, men and women's risk preferences are predicted to be identical at BACs nearly twice the legal limit for driving. We discuss the implications for policy-makers.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Geographical variation of diabetic emergencies attended by prehospital Emergency Medical Services is associated with measures of ethnicity and socioeconomic status.

PubMed

Villani, Melanie; Earnest, Arul; Smith, Karen; de Courten, Barbora; Zoungas, Sophia

2018-03-23

Geographical variation of diabetic emergencies attended by prehospital emergency medical services (EMS) and the relationship between area-level social and demographic factors and risk of a diabetic emergency were examined. All cases of hypoglycaemia and hyperglycaemia attended by Ambulance Victoria between 1/01/2009 and 31/12/2015 were tabulated by Local Government Area (LGA). Conditional autoregressive models were used to create smoothed maps of age and gender standardised incidence ratio (SIR) of prehospital EMS attendance for a diabetic emergency. Spatial regression models were used to examine the relationship between risk of a diabetic emergency and area-level factors. The areas with the greatest risk of prehospital EMS attendance for a diabetic emergency were disperse. Area-level factors associated with risk of a prehospital EMS-attended diabetic emergency were socioeconomic status (SIR 0.70 95% CrI [0.51, 0.96]), proportion of overseas-born residents (SIR 2.02 95% CrI [1.37, 2.91]) and motor vehicle access (SIR 1.47 95% CrI [1.08, 1.99]). Recognition of areas of increased risk of prehospital EMS-attended diabetic emergencies may be used to assist prehospital EMS resource planning to meet increased need. In addition, identification of associated factors can be used to target preventative interventions tailored to individual regions to reduce demand.

The mathematical limits of genetic prediction for complex chronic disease.

PubMed

Keyes, Katherine M; Smith, George Davey; Koenen, Karestan C; Galea, Sandro

2015-06-01

Attempts at predicting individual risk of disease based on common germline genetic variation have largely been disappointing. The present paper formalises why genetic prediction at the individual level is and will continue to have limited utility given the aetiological architecture of most common complex diseases. Data were simulated on one million populations with 10 000 individuals in each populations with varying prevalences of a genetic risk factor, an interacting environmental factor and the background rate of disease. The determinant risk ratio and risk difference magnitude for the association between a gene variant and disease is a function of the prevalence of the interacting factors that activate the gene, and the background rate of disease. The risk ratio and total excess cases due to the genetic factor increase as the prevalence of interacting factors increase, and decrease as the background rate of disease increases. Germline genetic variations have high predictive capacity for individual disease only under conditions of high heritability of particular genetic sequences, plausible only under rare variant hypotheses. Under a model of common germline genetic variants that interact with other genes and/or environmental factors in order to cause disease, the predictive capacity of common genetic variants is determined by the prevalence of the factors that interact with the variant and the background rate. A focus on estimating genetic associations for the purpose of prediction without explicitly grounding such work in an understanding of modifiable (including environmentally influenced) factors will be limited in its ability to yield important insights about the risk of disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models

EPA Science Inventory

Underlying cardiovascular disease (CVD) has been considered a risk factor for exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Pulmonary complications and altered iron homeost...

Does conurbation affect the risk of poor mental health? A population based record linkage study.

PubMed

Maguire, A; O'Reilly, D

2015-07-01

To determine if urban residence is associated with an increased risk of anxiety/depression independent of psychosocial stressors, concentrated disadvantage or selective migration between urban and rural areas, this population wide record-linkage study utilised data on receipt of prescription medication linked to area level indicators of conurbation and disadvantage. An urban/rural gradient in anxiolytic and antidepressant use was evident that was independent of variation in population composition. This gradient was most pronounced amongst disadvantaged areas. Migration into increasingly urban areas increased the likelihood of medication. These results suggest increasing conurbation is deleterious to mental health, especially amongst residents of deprived areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Risk-adjusted antibiotic consumption in 34 public acute hospitals in Ireland, 2006 to 2014

PubMed Central

Oza, Ajay; Donohue, Fionnuala; Johnson, Howard; Cunney, Robert

2016-01-01

As antibiotic consumption rates between hospitals can vary depending on the characteristics of the patients treated, risk-adjustment that compensates for the patient-based variation is required to assess the impact of any stewardship measures. The aim of this study was to investigate the usefulness of patient-based administrative data variables for adjusting aggregate hospital antibiotic consumption rates. Data on total inpatient antibiotics and six broad subclasses were sourced from 34 acute hospitals from 2006 to 2014. Aggregate annual patient administration data were divided into explanatory variables, including major diagnostic categories, for each hospital. Multivariable regression models were used to identify factors affecting antibiotic consumption. Coefficient of variation of the root mean squared errors (CV-RMSE) for the total antibiotic usage model was very good (11%), however, the value for two of the models was poor (> 30%). The overall inpatient antibiotic consumption increased from 82.5 defined daily doses (DDD)/100 bed-days used in 2006 to 89.2 DDD/100 bed-days used in 2014; the increase was not significant after risk-adjustment. During the same period, consumption of carbapenems increased significantly, while usage of fluoroquinolones decreased. In conclusion, patient-based administrative data variables are useful for adjusting hospital antibiotic consumption rates, although additional variables should also be employed. PMID:27541730

Testicular cancer in twins: a meta-analysis

PubMed Central

Neale, R E; Carrière, P; Murphy, M F G; Baade, P D

2007-01-01

In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1–1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0–1.7) and for monozygotic or same sex twins 1.4 (1.2–1.8). PMID:18071360

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

PubMed

Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G; Tromp, Gerard; Jones, Gregory T; Kuivaniemi, Helena; Elmore, James R; Johansson, Mattias; Mckay, James; Scelo, Ghislaine; Carreras-Torres, Robert; Gaborieau, Valerie; Brennan, Paul; Bracci, Paige M; Neale, Rachel E; Olson, Sara H; Gallinger, Steven; Li, Donghui; Petersen, Gloria M; Risch, Harvey A; Klein, Alison P; Han, Jiali; Abnet, Christian C; Freedman, Neal D; Taylor, Philip R; Maris, John M; Aben, Katja K; Kiemeney, Lambertus A; Vermeulen, Sita H; Wiencke, John K; Walsh, Kyle M; Wrensch, Margaret; Rice, Terri; Turnbull, Clare; Litchfield, Kevin; Paternoster, Lavinia; Standl, Marie; Abecasis, Gonçalo R; SanGiovanni, John Paul; Li, Yong; Mijatovic, Vladan; Sapkota, Yadav; Low, Siew-Kee; Zondervan, Krina T; Montgomery, Grant W; Nyholt, Dale R; van Heel, David A; Hunt, Karen; Arking, Dan E; Ashar, Foram N; Sotoodehnia, Nona; Woo, Daniel; Rosand, Jonathan; Comeau, Mary E; Brown, W Mark; Silverman, Edwin K; Hokanson, John E; Cho, Michael H; Hui, Jennie; Ferreira, Manuel A; Thompson, Philip J; Morrison, Alanna C; Felix, Janine F; Smith, Nicholas L; Christiano, Angela M; Petukhova, Lynn; Betz, Regina C; Fan, Xing; Zhang, Xuejun; Zhu, Caihong; Langefeld, Carl D; Thompson, Susan D; Wang, Feijie; Lin, Xu; Schwartz, David A; Fingerlin, Tasha; Rotter, Jerome I; Cotch, Mary Frances; Jensen, Richard A; Munz, Matthias; Dommisch, Henrik; Schaefer, Arne S; Han, Fang; Ollila, Hanna M; Hillary, Ryan P; Albagha, Omar; Ralston, Stuart H; Zeng, Chenjie; Zheng, Wei; Shu, Xiao-Ou; Reis, Andre; Uebe, Steffen; Hüffmeier, Ulrike; Kawamura, Yoshiya; Otowa, Takeshi; Sasaki, Tsukasa; Hibberd, Martin Lloyd; Davila, Sonia; Xie, Gang; Siminovitch, Katherine; Bei, Jin-Xin; Zeng, Yi-Xin; Försti, Asta; Chen, Bowang; Landi, Stefano; Franke, Andre; Fischer, Annegret; Ellinghaus, David; Flores, Carlos; Noth, Imre; Ma, Shwu-Fan; Foo, Jia Nee; Liu, Jianjun; Kim, Jong-Won; Cox, David G; Delattre, Olivier; Mirabeau, Olivier; Skibola, Christine F; Tang, Clara S; Garcia-Barcelo, Merce; Chang, Kai-Ping; Su, Wen-Hui; Chang, Yu-Sun; Martin, Nicholas G; Gordon, Scott; Wade, Tracey D; Lee, Chaeyoung; Kubo, Michiaki; Cha, Pei-Chieng; Nakamura, Yusuke; Levy, Daniel; Kimura, Masayuki; Hwang, Shih-Jen; Hunt, Steven; Spector, Tim; Soranzo, Nicole; Manichaikul, Ani W; Barr, R Graham; Kahali, Bratati; Speliotes, Elizabeth; Yerges-Armstrong, Laura M; Cheng, Ching-Yu; Jonas, Jost B; Wong, Tien Yin; Fogh, Isabella; Lin, Kuang; Powell, John F; Rice, Kenneth; Relton, Caroline L; Martin, Richard M; Davey Smith, George

2017-05-01

The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Genomewide association studies (GWAS) published up to January 15, 2015. GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

Age-Specific Injury Risk Curves for Distributed, Anterior Thoracic Loading of Various Sizes of Adults Based on Sternal Deflections.

PubMed

Mertz, Harold J; Prasad, Priya; Dalmotas, Dainius J; Irwin, Annette L

2016-11-01

Injury Risk Curves are developed from cadaver data for sternal deflections produced by anterior, distributed chest loads for a 25, 45, 55, 65 and 75 year-old Small Female, Mid-Size Male and Large Male based on the variations of bone strengths with age. These curves show that the risk of AIS ≥ 3 thoracic injury increases with the age of the person. This observation is consistent with NASS data of frontal accidents which shows that older unbelted drivers have a higher risk of AIS ≥ 3 chest injury than younger drivers.

Genetic variation associated with cardiovascular risk in autoimmune diseases

PubMed Central

Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio

2017-01-01

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122

Interaction between APC and Fen1 during breast carcinogenesis

PubMed Central

Narayan, Satya; Jaiswal, Aruna S.; Law, Brian K.; Mohammed, Kamal A.; Sharma, Arun K.; Hromas, Robert A.

2016-01-01

Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER – adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) – promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents. PMID:27088617

Interaction between APC and Fen1 during breast carcinogenesis.

PubMed

Narayan, Satya; Jaiswal, Aruna S; Law, Brian K; Kamal, Mohammad A; Sharma, Arun K; Hromas, Robert A

2016-05-01

Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER - adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) - promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents. Published by Elsevier B.V.

Regional variations in pedal cyclist injuries in New Zealand: safety in numbers or risk in scarcity?

PubMed

Tin, Sandar Tin; Woodward, Alistair; Thornley, Simon; Ameratunga, Shanthi

2011-08-01

To assess regional variations in rates of traffic injuries to pedal cyclists resulting in death or hospital inpatient treatment, in relation to time spent cycling and time spent travelling in a car. Cycling injuries were identified from the Mortality Collection and the National Minimum Dataset. Time spent cycling and time spent travelling as a driver or passenger in a car/van/ute/SUV were computed from National Household Travel Surveys. There are 16 census regions in New Zealand, some of which were combined for this analysis to ensure an adequate sample size, resulting in eight regional groups. Analyses were undertaken for 1996-99 and 2003-07. Injury rates, per million hours spent cycling, varied widely across regions (11 to 33 injuries during 1996-99 and 12 to 78 injuries during 2003-07). The injury rate increased with decreasing per capita time spent cycling. The rate also increased with increasing per capita time spent travelling in a car. There was an inverse association between the injury rate and the ratio of time spent cycling to time spent travelling in a car. The expected number of cycling injuries increased with increasing total time spent cycling but at a decreasing rate particularly after adjusting for total time spent travelling in a car. The findings indicate a 'risk in scarcity' effect for New Zealand cyclists such that risk profiles of cyclists are likely to deteriorate if fewer people use a bicycle and more use a car. Cooperative efforts to promote cycling and its safety and to restrict car use may reverse the risk in scarcity effect. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

Risk prediction for early-onset gastric carcinoma: a case-control study of polygenic gastric cancer in Han Chinese with hereditary background.

PubMed

Yuan, Jiajia; Li, Yanyan; Tian, Tiantian; Li, Na; Zhu, Yan; Zou, Jianling; Gao, Jing; Shen, Lin

2016-06-07

Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk. Of the 116 patients diagnosed with cancer, 65 had at least 1 direct lineal relative with carcinoma of the digestive system or breast/ovarian cancer. These 65 had another 4 SNPs associated with gastric cancer susceptibility: PSCA (prostate stem cell antigen) rs2294008, PLCE1 (phospholipase C epsilon 1) rs2274223, PTGER4/PRKAA1 (prostaglandin E receptor 4/ protein kinase AMP-activated catalytic subunit alpha 1) rs13361707, and TYMS (thymidylate synthetase) rs2790. However, each of these low-penetrance susceptibility polymorphisms alone is not considered influential enough to predict the absolute risk of early-onset gastric cancer. Thus we decided to study different combinations of polygenes as they affected for our population. Those subjects with both the risk alleles MUC1 rs9841504 and ZBTB20 rs4072037 had a greater than 3-fold increased risk of gastric cancer. Also those with a hereditary background including the risk alleles PLCE1 rs2274223 and PTGER4/PRKAA1 rs13361707 were 3 times more susceptible to cardia cancer than those without. These findings show that the study of combined polymorphisms, instead of single low-penetrance variations in susceptibility, may lead to a high-risk classification for a specific population.

Risk prediction for early-onset gastric carcinoma: a case-control study of polygenic gastric cancer in Han Chinese with hereditary background

PubMed Central

Yuan, Jiajia; Li, Yanyan; Tian, Tiantian; Li, Na; Zhu, Yan; Zou, Jianling; Gao, Jing; Shen, Lin

2016-01-01

Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk. Of the 116 patients diagnosed with cancer, 65 had at least 1 direct lineal relative with carcinoma of the digestive system or breast/ovarian cancer. These 65 had another 4 SNPs associated with gastric cancer susceptibility: PSCA (prostate stem cell antigen) rs2294008, PLCE1 (phospholipase C epsilon 1) rs2274223, PTGER4/PRKAA1 (prostaglandin E receptor 4/protein kinase AMP-activated catalytic subunit alpha 1) rs13361707, and TYMS (thymidylate synthetase) rs2790. However, each of these low-penetrance susceptibility polymorphisms alone is not considered influential enough to predict the absolute risk of early-onset gastric cancer. Thus we decided to study different combinations of polygenes as they affected for our population. Those subjects with both the risk alleles MUC1 rs9841504 and ZBTB20 rs4072037 had a greater than 3-fold increased risk of gastric cancer. Also those with a hereditary background including the risk alleles PLCE1 rs2274223 and PTGER4/PRKAA1 rs13361707 were 3 times more susceptible to cardia cancer than those without. These findings show that the study of combined polymorphisms, instead of single low-penetrance variations in susceptibility, may lead to a high-risk classification for a specific population. PMID:27127881

The contribution of gestational age, area deprivation and mother’s country of birth to ethnic variations in infant mortality in England and Wales: A national cohort study using routinely collected data

PubMed Central

Quigley, Maria A.; Dattani, Nirupa; Gray, Ron; Jayaweera, Hiranthi; Kurinczuk, Jennifer J.; Macfarlane, Alison; Hollowell, Jennifer

2018-01-01

Objectives We aimed to describe ethnic variations in infant mortality and explore the contribution of area deprivation, mother’s country of birth, and prematurity to these variations. Methods We analyzed routine birth and death data on singleton live births (gestational age≥22 weeks) in England and Wales, 2006–2012. Infant mortality by ethnic group was analyzed using logistic regression with adjustment for sociodemographic characteristics and gestational age. Results In the 4,634,932 births analyzed, crude infant mortality rates were higher in Pakistani, Black Caribbean, Black African, and Bangladeshi infants (6.92, 6.00, 5.17 and 4.40 per 1,000 live births, respectively vs. 2.87 in White British infants). Adjustment for maternal sociodemographic characteristics changed the results little. Further adjustment for gestational age strongly attenuated the risk in Black Caribbean (OR 1.02, 95% CI 0.89–1.17) and Black African infants (1.17, 1.06–1.29) but not in Pakistani (2.32, 2.15–2.50), Bangladeshi (1.47, 1.28–1.69), and Indian infants (1.24, 1.11–1.38). Ethnic variations in infant mortality differed significantly between term and preterm infants. At term, South Asian groups had higher risks which cannot be explained by sociodemographic characteristics. In preterm infants, adjustment for degree of prematurity (<28, 28–31, 32–33, 34–36 weeks) fully explained increased risks in Black but not Pakistani and Bangladeshi infants. Sensitivity analyses with further adjustment for small for gestational age, or excluding deaths due to congenital anomalies did not fully explain the excess risk in South Asian groups. Conclusions Higher infant mortality in South Asian and Black infants does not appear to be explained by sociodemographic characteristics. Higher proportions of very premature infants appear to explain increased risks in Black infants but not in South Asian groups. Strategies targeting the prevention and management of preterm birth in Black groups and suboptimal birthweight and modifiable risk factors for congenital anomalies in South Asian groups might help reduce ethnic inequalities in infant mortality. PMID:29649290

Ethnic variations in incidence of asthma episodes in England & Wales: national study of 502,482 patients in primary care.

PubMed

Netuveli, Gopalakrishnan; Hurwitz, Brian; Sheikh, Aziz

2005-10-21

Recent studies have demonstrated marked international variations in the prevalence of asthma, but less is known about ethnic variations in asthma epidemiology within individual countries and in particular the impact of migration on risk of developing asthma. Recent within country comparisons have however revealed that despite originating from areas of the world with a low risk for developing asthma, South Asian and Afro-Caribbean people in the UK are significantly (3x and 2x respectively) more likely to be admitted to hospital for asthma related problems than Whites. Using data from the Fourth National Study of Morbidity Statistics in General Practice, a one-percent broadly representative prospective cohort study of consultations in general practice, we investigated ethnic variations in incident asthma consultations (defined as new or first consultations), and compared consultation rates between those born inside and outside the UK (migrant status). Logistic regression models were used to examine the combined effects of ethnicity and migration on asthma incident consultations. Results showed significantly lower new/first asthma consultation rates for Whites than for each of the ethnic minority groups studied (mean age-adjusted consultation rates per 1000 patient-years: Whites 26.4 (95%CI 26.4, 26.4); South Asians 30.4 (95%CI 30.3, 30.5); Afro-Caribbeans 35.1 (95%CI 34.9, 35.3); and Others 27.8 (27.7, 28.0). Within each of these ethnic groups, those born outside of the UK showed consistently lower rates of incident asthma consultations. Modelling the combined effects of ethnic and migrant status revealed that UK-born South Asians and Afro-Caribbeans experienced comparable risks for incident GP consultations for asthma to UK-born Whites. Non-UK born Whites however experienced reduced risks (adjusted OR 0.82, 95%CI 0.69, 0.97) whilst non-UK born South Asians experienced increased risks (adjusted OR 1.33, 95%CI 1.04, 1.70) compared to UK-born Whites. These findings strongly suggest that ethnicity and migration have significant and independent effects on asthma incidence. The known poorer asthma outcomes in UK South Asians and Afro-Caribbeans may in part be explained by the offspring of migrants experiencing an increased risk of developing asthma when compared to UK-born Whites. This is the first study to find heterogeneity for incident asthma consultations in Whites by migrant status.

Reliability Coupled Sensitivity Based Design Approach for Gravity Retaining Walls

NASA Astrophysics Data System (ADS)

Guha Ray, A.; Baidya, D. K.

2012-09-01

Sensitivity analysis involving different random variables and different potential failure modes of a gravity retaining wall focuses on the fact that high sensitivity of a particular variable on a particular mode of failure does not necessarily imply a remarkable contribution to the overall failure probability. The present paper aims at identifying a probabilistic risk factor ( R f ) for each random variable based on the combined effects of failure probability ( P f ) of each mode of failure of a gravity retaining wall and sensitivity of each of the random variables on these failure modes. P f is calculated by Monte Carlo simulation and sensitivity analysis of each random variable is carried out by F-test analysis. The structure, redesigned by modifying the original random variables with the risk factors, is safe against all the variations of random variables. It is observed that R f for friction angle of backfill soil ( φ 1 ) increases and cohesion of foundation soil ( c 2 ) decreases with an increase of variation of φ 1 , while R f for unit weights ( γ 1 and γ 2 ) for both soil and friction angle of foundation soil ( φ 2 ) remains almost constant for variation of soil properties. The results compared well with some of the existing deterministic and probabilistic methods and found to be cost-effective. It is seen that if variation of φ 1 remains within 5 %, significant reduction in cross-sectional area can be achieved. But if the variation is more than 7-8 %, the structure needs to be modified. Finally design guidelines for different wall dimensions, based on the present approach, are proposed.

Exercise systolic blood pressure variability is associated with increased risk for new-onset hypertension among normotensive adults.

PubMed

Berger, Assaf; Grossman, Ehud; Katz, Moshe; Kivity, Shaye; Klempfner, Robert; Segev, Shlomo; Goldenberg, Ilan; Sidi, Yehezkel; Maor, Elad

2016-06-01

Both resting blood pressure (BP) variability and exercise BP previously showed association with incident hypertension. The aim of the present study was to examine whether visit-to-visit variability in exercise systolic blood pressure (SBP) can predict the risk for new-onset hypertension among normotensive adults. We investigated 6546 normotensive men and women who were annually screened in a tertiary medical center and completed treadmill exercise tests at each visit. Based on the initial three baseline annual visits, long-term intervisit variability of exercise SBP among the three tests was measured using standard deviation (SD) and coefficient of variation for each participant. The rate of newly diagnosed hypertension was measured in different variability levels during 6 ± 3 years of follow-up. Multivariate analysis adjusted for various clinical factors, including resting BP, showed that each 5 mm Hg rise in the SD of exercise SBP resulted in a significant 5% increase in the risk for the development of future hypertension (P = .015). Subjects in the upper exercise SBP SD variability tertile had a 28% (P = .007) increased risk for hypertension during follow-up, as compared with those in the lowest tertile. Similar results were achieved for the assessment of coefficient of variation of exercise SBP. In conclusion, visit-to-visit variability in exercise SBP can predict the development of future hypertension among normotensive individuals. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Temporal variations in volumetric magma eruption rates of Quaternary volcanoes in Japan

NASA Astrophysics Data System (ADS)

Yamamoto, Takahiro; Kudo, Takashi; Isizuka, Osamu

2018-04-01

Long-term evaluations of hazard and risk related to volcanoes rely on extrapolations from volcano histories, including the uniformity of their eruption rates. We calculated volumetric magma eruption rates, compiled from quantitative eruption histories of 29 Japanese Quaternary volcanoes, and analyzed them with respect to durations spanning 101-105 years. Calculated eruption rates vary greatly (101-10-4 km3 dense-rock equivalent/1000 years) between individual volcanoes. Although large basaltic stratovolcanoes tend to have high eruption rates and relatively constant repose intervals, these cases are not representative of the various types of volcanoes in Japan. At many Japanese volcanoes, eruption rates are not constant through time, but increase, decrease, or fluctuate. Therefore, it is important to predict whether eruption rates will increase or decrease for long-term risk assessment. Several temporal co-variations of eruption rate and magmatic evolution suggest that there are connections between them. In some cases, magma supply rates increased in response to changing magma-generation processes. On the other hand, stable plumbing systems without marked changes in magma composition show decreasing eruption rates through time.[Figure not available: see fulltext.

Design-corrected variation by centre in mortality reduction in the ERSPC randomised prostate cancer screening trial.

PubMed

Hakama, Matti; Moss, Sue M; Stenman, Ulf-Hakan; Roobol, Monique J; Zappa, Marco; Carlsson, Sigrid; Randazzo, Marco; Nelen, Vera; Hugosson, Jonas

2017-06-01

Objectives To calculate design-corrected estimates of the effect of screening on prostate cancer mortality by centre in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Setting The ERSPC has shown a 21% reduction in prostate cancer mortality in men invited to screening with follow-up truncated at 13 years. Centres either used pre-consent randomisation (effectiveness design) or post-consent randomisation (efficacy design). Methods In six centres (three effectiveness design, three efficacy design) with follow-up until the end of 2010, or maximum 13 years, the effect of screening was estimated as both effectiveness (mortality reduction in the target population) and efficacy (reduction in those actually screened). Results The overall crude prostate cancer mortality risk ratio in the intervention arm vs control arm for the six centres was 0.79 ranging from a 14% increase to a 38% reduction. The risk ratio was 0.85 in centres with effectiveness design and 0.73 in those with efficacy design. After correcting for design, overall efficacy was 27%, 24% in pre-consent and 29% in post-consent centres, ranging between a 12% increase and a 52% reduction. Conclusion The estimated overall effect of screening in attenders (efficacy) was a 27% reduction in prostate cancer mortality at 13 years' follow-up. The variation in efficacy between centres was greater than the range in risk ratio without correction for design. The centre-specific variation in the mortality reduction could not be accounted for by the randomisation method.

Genome scan of clot lysis time and its association with thrombosis in a protein C deficient kindred

PubMed Central

Meltzer, M.E.; Hasstedt, S.J.; Vossen, C.Y.; Callas, P.W.; de Groot, Ph.G.; Rosendaal, F.R.; Lisman, T.; Bovill, E.G.

2011-01-01

Summary Background Previously we found increased clot lysis time (CLT), as measured with a plasma-based assay, to increase the risk of venous thrombosis in two population-based case-control studies. Genes influencing CLT are yet unknown. Objectives and Patients/Methods We tested CLT as risk factor for venous thrombosis in Kindred Vermont II (n=346), a pedigree suffering from a high thrombosis risk, partially attributable to a type I protein C deficiency. Furthermore we tested for quantitative trait loci (QTL) for CLT using variance component linkage analysis. Results Protein C deficient family members had shorter CLT than non-deficient members (median CLT 67 versus 75 minutes). One standard deviation increase in CLT increased risk of venous thrombosis 2.4-fold in non-deficient family members. Protein C deficiency without elevated CLT increased risk 6.9-fold. Combining both risk factors yielded a 27.8-fold increased risk. Heritability of CLT was 42-52%. We found suggestive evidence of linkage on chromosome 11 (62 cM), partly explained by the prothrombin 20210A mutation, and on chromosome 13 (52 cM). Thrombin Activatable Fibrinolysis Inhibitor genotypes did not explain the variation in CLT. Conclusion Hypofibrinolysis appears to increase thrombosis risk in this family especially in combination with protein C deficiency. Protein C deficiency is associated with short CLT. CLT is partly genetically regulated. Suggestive QTL were found on chromosome 11 and 13. PMID:21575129

Genome scan of clot lysis time and its association with thrombosis in a protein C-deficient kindred.

PubMed

Meltzer, M E; Hasstedt, S J; Vossen, C Y; Callas, P W; DE Groot, Ph G; Rosendaal, F R; Lisman, T; Bovill, E G

2011-07-01

 Previously, we found increased clot-lysis time (CLT), as measured with a plasma-based assay, to increase the risk of venous thrombosis in two population-based case-control studies. The genes influencing CLT are as yet unknown.  We tested CLT as risk factor for venous thrombosis in Kindred Vermont II (n = 346), a pedigree suffering from a high thrombosis risk, partially attributable to a type I protein C deficiency. Furthermore, we tested for quantitative trait loci (QTLs) for CLT, using variance component linkage analysis.  Protein C-deficient family members had shorter CLTs than non-deficient members (median CLT 67 min vs. 75 min). One standard deviation increase in CLT increased the risk of venous thrombosis 2.4-fold in non-deficient family members. Protein C deficiency without elevated CLT increased the risk 6.9-fold. Combining both risk factors yielded a 27.8-fold increased risk. The heritability of CLT was 42-52%. We found suggestive evidence of linkage on chromosome 11 (62 cM), partly explained by the prothrombin 20210A mutation, and on chromosome 13 (52 cM). Thrombin-activatable fibrinolysis inhibitor genotypes did not explain the variation in CLT. Hypofibrinolysis appears to increase thrombosis risk in this family, especially in combination with protein C deficiency. Protein C deficiency is associated with short CLT. CLT is partly genetically regulated. Suggestive QTLs were found on chromosomes 11 and 13. © 2011 International Society on Thrombosis and Haemostasis.

The "Nursing Home Compare" measure of urinary/fecal incontinence: cross-sectional variation, stability over time, and the impact of case mix.

PubMed

Li, Yue; Schnelle, John; Spector, William D; Glance, Laurent G; Mukamel, Dana B

2010-02-01

To assess the impact of facility case mix on cross-sectional variations and short-term stability of the "Nursing Home Compare" incontinence quality measure (QM) and to determine whether multivariate risk adjustment can minimize such impacts. Retrospective analyses of the 2005 national minimum data set (MDS) that included approximately 600,000 long-term care residents in over 10,000 facilities in each quarterly sample. Mixed logistic regression was used to construct the risk-adjusted QM (nonshrinkage estimator). Facility-level ordinary least-squares models and adjusted R(2) were used to estimate the impact of case mix on cross-sectional and short-term longitudinal variations of currently published and risk-adjusted QMs. At least 50 percent of the cross-sectional variation and 25 percent of the short-term longitudinal variation of the published QM are explained by facility case mix. In contrast, the cross-sectional and short-term longitudinal variations of the risk-adjusted QM are much less susceptible to case-mix variations (adjusted R(2)<0.10), even for facilities with more extreme or more unstable outcome. Current "Nursing Home Compare" incontinence QM reflects considerable case-mix variations across facilities and over time, and therefore it may be biased. This issue can be largely addressed by multivariate risk adjustment using risk factors available in the MDS.

Variation in Management of Fever and Neutropenia Among Pediatric Patients With Cancer: A Survey of Providers in Michigan.

PubMed

Mueller, Emily L; Walkovich, Kelly J; Yanik, Gregory A; Clark, Sarah J

2015-01-01

Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended "Decreased" and "Increased" patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC <500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management.

Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

PubMed

Bogdan, Ryan; Pagliaccio, David; Baranger, David Aa; Hariri, Ahmad R

2016-01-01

Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, known as imaging gene x environment interaction (iGxE), is beginning to contribute to our understanding of the neural mechanisms through which genetic variation and stress increase psychopathology risk. Although awaiting replication, evidence suggests that genetic variation within the canonical neuroendocrine stress hormone system, the hypothalamic-pituitary-adrenal axis, contributes to variability in stress-related corticolimbic structure and function, which, in turn, confers risk for psychopathology. For iGxE research to reach its full potential it will have to address many challenges, of which we discuss: (i) small effects, (ii) measuring the environment and neural phenotypes, (iii) the absence of detailed mechanisms, and (iv) incorporating development. By actively addressing these challenges, iGxE research is poised to help identify the neural mechanisms underlying genetic and environmental associations with psychopathology.

Outdoor temperature, blood pressure, and cardiovascular disease mortality among 23 000 individuals with diagnosed cardiovascular diseases from China.

PubMed

Yang, Ling; Li, Liming; Lewington, Sarah; Guo, Yu; Sherliker, Paul; Bian, Zheng; Collins, Rory; Peto, Richard; Liu, Yun; Yang, Rong; Zhang, Yongrui; Li, Guangchun; Liu, Shumei; Chen, Zhengming

2015-05-14

Blood pressure is a major cause of cardiovascular disease (CVD) and both may increase as outdoor temperatures fall. However, there are still limited data about seasonal variation in blood pressure and CVD mortality among patients with prior-CVD. We analysed data on 23 000 individuals with prior-CVD who were recruited from 10 diverse regions into the China Kadoorie Biobank during 2004-8. After 7 years of follow-up, 1484 CVD deaths were recorded. Baseline survey data were used to assess seasonal variation in systolic blood pressure (SBP) and its association with outdoor temperature. Cox regression was used to examine the association of usual SBP with subsequent CVD mortality, and seasonal variation in CVD mortality was assessed by Poisson regression. All analyses were adjusted for age, sex, and region. Mean SBP was significantly higher in winter than in summer (145 vs. 136 mmHg, P < 0.001), especially among those without central heating. Above 5°C, each 10°C lower outdoor temperature was associated with 6.2 mmHg higher SBP. Systolic blood pressure predicted subsequent CVD mortality, with each 10 mmHg higher usual SBP associated with 21% (95% confidence interval: 16-27%) increased risk. Cardiovascular disease mortality varied by season, with 41% (21-63%) higher risk in winter compared with summer. Among adult Chinese with prior-CVD, there is both increased blood pressure and CVD mortality in winter. Careful monitoring and more aggressive blood pressure lowering treatment in the cold months are needed to help reduce the winter excess CVD mortality in high-risk individuals. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas

PubMed Central

Flores-Ferrer, Alheli; Blanchet, Denis; Gourbière, Sébastien

2016-01-01

The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French-Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID:26867025

Customized vs INTERGROWTH-21st standards for the assessment of birthweight and stillbirth risk at term.

PubMed

Francis, Andre; Hugh, Oliver; Gardosi, Jason

2018-02-01

Fetal growth abnormalities are linked to stillbirth and other adverse pregnancy outcomes, and use of the correct birthweight standard is essential for accurate assessment of growth status and perinatal risk. Two competing, conceptually opposite birthweight standards are currently being implemented internationally: customized gestation-related optimal weight (GROW) and INTERGROWTH-21 st . We wanted to compare their performance when applied to a multiethnic international cohort, and evaluate their usefulness in the assessment of stillbirth risk at term. We analyzed routinely collected maternity data from 10 countries with a total of 1.25 million term pregnancies in their respective main ethnic groups. The 2 standards were applied to determine small for gestational age (SGA) and large for gestational age (LGA) rates, with associated relative risk and population-attributable risk of stillbirth. The customized standard (GROW) was based on the term optimal weight adjusted for maternal height, weight, parity, and ethnic origin, while INTERGROWTH-21 st was a fixed standard derived from a multiethnic cohort of low-risk pregnancies. The customized standard showed an average SGA rate of 10.5% (range 10.1-12.7) and LGA rate of 9.5% (range 7.3-9.9) for the set of cohorts. In contrast, there was a wide variation in SGA and LGA rates with INTERGROWTH-21 st , with an average SGA rate of 4.4% (range 3.1-16.8) and LGA rate of 20.6% (range 5.1-27.5). This variation in INTERGROWTH-21 st SGA and LGA rates was correlated closely (R = ±0.98) to the birthweights predicted for the 10 country cohorts by the customized method to derive term optimal weight, suggesting that they were mostly due to physiological variation in birthweight. Of the 10.5% of cases defined as SGA according to the customized standard, 4.3% were also SGA by INTERGROWTH-21 st and had a relative risk of 3.5 (95% confidence interval, 3.1-4.1) for stillbirth. A further 6.3% (60% of the whole customized SGA) were not SGA by INTERGROWTH-21 st , and had a relative risk of 1.9 (95% confidence interval, 3.1-4.1) for stillbirth. An additional 0.2% of cases were SGA by INTERGROWTH-21 st only, and had no increased risk of stillbirth. At the other end, customized assessment classified 9.5% of births as large for gestational age, most of which (9.0%) were also LGA by the INTERGROWTH-21 st standard. INTERGROWTH-21 st identified a further 11.6% as LGA, which, however, had a reduced risk of stillbirth (relative risk, 0.6; 95% confidence interval, 0.5-0.7). Customized assessment resulted in increased identification of small for gestational age and stillbirth risk, while the wide variation in SGA rates using the INTERGROWTH-21 st standard appeared to mostly reflect differences in physiological pregnancy characteristics in the 10 maternity populations. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

PubMed

Ekenberg, C; Lodding, I P; Wareham, N E; Sørensen, S S; Sengeløv, H; Gustafsson, F; Rasmussen, A; Perch, M; Lundgren, J D; Helleberg, M

2017-12-01

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12-36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.

Implementing a hybrid approach to select patients for care management: variations across practices.

PubMed

Vogeli, Christine; Spirt, Jenna; Brand, Richard; Hsu, John; Mohta, Namita; Hong, Clemens; Weil, Eric; Ferris, Timothy G

2016-05-01

Appropriate selection of patients is key to the success of care management programs (CMPs). Hybrid patient selection approaches, in which large data assets are culled to develop a list of patients for more targeted clinical review, are increasingly common. We sought to describe the patient and practice characteristics associated with high-risk patient identification and selection for a CMP during clinical review, and to explore variation across primary care practices. Retrospective cohort study. Standardized estimates of Medicare beneficiaries identified as high risk for poor outcomes and high medical expense, and appropriate for a CMP within a large Pioneer Accountable Care Organization, were developed using mixed effects logistic models. Study subjects were 2685 Medicare beneficiaries aged over 18 (includes individuals eligible for Medicare due to a disability) aligned to 35 primary care practices in 2013. Independent predictors of patient identification as high risk include older age; higher risk score; recent increases in medical conditions; higher numbers of medical hospitalizations, skilled nursing facility days, and primary care physician visits; and shorter relationships with the primary care physician. Older age, and lower income, but no prior hospice use were independently associated with patient selection for a CMP among the subset of patients identified as being high risk. Adjusted predicted percents of high-risk patients varied significantly across practices overall and for 5 of the 6 patient characteristics that were independently associated with identification as high risk. Inconsistency in high-risk patient identification and selection for a CMP may reflect differences in practice resources, but also highlight the need for continual training and feedback in order to protect against unintentional biases.

From event analysis to global lessons: disaster forensics for building resilience

NASA Astrophysics Data System (ADS)

Keating, Adriana; Venkateswaran, Kanmani; Szoenyi, Michael; MacClune, Karen; Mechler, Reinhard

2016-04-01

With unprecedented growth in disaster risk, there is an urgent need for enhanced learning about and understanding disasters, particularly in relation to the trends in the drivers of increasing risk. Building on the disaster forensics field, we introduce the Post Event Review Capability (PERC) methodology for systematically and holistically analyzing disaster events, and identifying actionable recommendations. PERC responds to a need for learning about the successes and failures in disaster risk management and resilience, and uncovers the underlying drivers of increasing risk. We draw generalizable insights identified from seven applications of the methodology to date, where we find that across the globe policy makers and practitioners in disaster risk management face strikingly similar challenges despite variations in context, indicating encouraging potential for mutual learning. These lessons highlight the importance of integrated risk reduction strategies. We invite others to utilize the freely available PERC approach and contribute to building a repository of learnings on disaster risk management and resilience.

From event analysis to global lessons: disaster forensics for building resilience

NASA Astrophysics Data System (ADS)

Keating, Adriana; Venkateswaran, Kanmani; Szoenyi, Michael; MacClune, Karen; Mechler, Reinhard

2016-07-01

With unprecedented growth in disaster risk, there is an urgent need for enhanced learning and understanding of disasters, particularly in relation to the trends in drivers of increasing risk. Building on the disaster forensics field, we introduce the post-event review capability (PERC) methodology for systematically and holistically analysing disaster events, and identifying actionable recommendations. PERC responds to a need for learning about the successes and failures in disaster risk management and resilience, and uncovers the underlying drivers of increasing risk. We draw generalisable insights identified from seven applications of the methodology to date, where we find that across the globe policy makers and practitioners in disaster risk management face strikingly similar challenges despite variations in context, indicating encouraging potential for mutual learning. These lessons highlight the importance of integrated risk reduction strategies. We invite others to utilise the freely available PERC approach and contribute to building a repository of learning on disaster risk management and resilience.

The Life-Long Mortality Risks Of World War II Experiences

PubMed Central

Elder, Glen H.; Brown, James Scott; Martin, Leslie R.; Friedman, Howard W.

2009-01-01

Objective This longitudinal study of American veterans investigated the mortality risks of five World War II military experiences (i.e., combat exposure) and their variation among veterans in the post-war years. Methods The male subjects (N=854) are members of the Stanford-Terman study, and 38 percent served in World War II. Cox models (proportional hazards regressions) compared the relative mortality risk associated with each military experience. Results Overseas duty, service in the Pacific and exposure to combat significantly increased the mortality risks of veterans in the study. Individual differences in education, mental health in 1950, and age at entry into the military, as well as personality factors made no difference in these results. Conclusions A gradient is observable such that active duty on the home front, followed by overseas duty, service in the Pacific, and combat exposure markedly increased the risk of relatively early mortality. Potential linking mechanisms include heavy drinking. PMID:20161074

An expected utility maximizer walks into a bar…

PubMed Central

Glimcher, Paul W.; Lazzaro, Stephanie C.

2013-01-01

We conducted field experiments at a bar to test whether blood alcohol concentration (BAC) correlates with violations of the generalized axiom of revealed preference (GARP) and the independence axiom. We found that individuals with BACs well above the legal limit for driving adhere to GARP and independence at rates similar to those who are sober. This finding led to the fielding of a third experiment to explore how risk preferences might vary as a function of BAC. We found gender-specific effects: Men did not exhibit variations in risk preferences across BACs. In contrast, women were more risk averse than men at low BACs but exhibited increasing tolerance towards risks as BAC increased. Based on our estimates, men and women’s risk preferences are predicted to be identical at BACs nearly twice the legal limit for driving. We discuss the implications for policy-makers. PMID:24244072

Geography of current and future global mammal extinction risk

PubMed Central

Shoemaker, Kevin T.; Weinstein, Ben; Costa, Gabriel C.; Brooks, Thomas M.; Ceballos, Gerardo; Radeloff, Volker C.; Rondinini, Carlo; Graham, Catherine H.

2017-01-01

Identifying which species are at greatest risk, what makes them vulnerable, and where they are distributed are central goals for conservation science. While knowledge of which factors influence extinction risk is increasingly available for some taxonomic groups, a deeper understanding of extinction correlates and the geography of risk remains lacking. Here, we develop a predictive random forest model using both geospatial and mammalian species’ trait data to uncover the statistical and geographic distributions of extinction correlates. We also explore how this geography of risk may change under a rapidly warming climate. We found distinctive macroecological relationships between species-level risk and extinction correlates, including the intrinsic biological traits of geographic range size, body size and taxonomy, and extrinsic geographic settings such as seasonality, habitat type, land use and human population density. Each extinction correlate exhibited ranges of values that were especially associated with risk, and the importance of different risk factors was not geographically uniform across the globe. We also found that about 10% of mammals not currently recognized as at-risk have biological traits and occur in environments that predispose them towards extinction. Southeast Asia had the most actually and potentially threatened species, underscoring the urgent need for conservation in this region. Additionally, nearly 40% of currently threatened species were predicted to experience rapid climate change at 0.5 km/year or more. Biological and environmental correlates of mammalian extinction risk exhibit distinct statistical and geographic distributions. These results provide insight into species-level patterns and processes underlying geographic variation in extinction risk. They also offer guidance for future conservation research focused on specific geographic regions, or evaluating the degree to which species-level patterns mirror spatial variation in the pressures faced by populations within the ranges of individual species. The added impacts from climate change may increase the susceptibility of at-risk species to extinction and expand the regions where mammals are most vulnerable globally. PMID:29145486

Geography of current and future global mammal extinction risk.

PubMed

Davidson, Ana D; Shoemaker, Kevin T; Weinstein, Ben; Costa, Gabriel C; Brooks, Thomas M; Ceballos, Gerardo; Radeloff, Volker C; Rondinini, Carlo; Graham, Catherine H

2017-01-01

Identifying which species are at greatest risk, what makes them vulnerable, and where they are distributed are central goals for conservation science. While knowledge of which factors influence extinction risk is increasingly available for some taxonomic groups, a deeper understanding of extinction correlates and the geography of risk remains lacking. Here, we develop a predictive random forest model using both geospatial and mammalian species' trait data to uncover the statistical and geographic distributions of extinction correlates. We also explore how this geography of risk may change under a rapidly warming climate. We found distinctive macroecological relationships between species-level risk and extinction correlates, including the intrinsic biological traits of geographic range size, body size and taxonomy, and extrinsic geographic settings such as seasonality, habitat type, land use and human population density. Each extinction correlate exhibited ranges of values that were especially associated with risk, and the importance of different risk factors was not geographically uniform across the globe. We also found that about 10% of mammals not currently recognized as at-risk have biological traits and occur in environments that predispose them towards extinction. Southeast Asia had the most actually and potentially threatened species, underscoring the urgent need for conservation in this region. Additionally, nearly 40% of currently threatened species were predicted to experience rapid climate change at 0.5 km/year or more. Biological and environmental correlates of mammalian extinction risk exhibit distinct statistical and geographic distributions. These results provide insight into species-level patterns and processes underlying geographic variation in extinction risk. They also offer guidance for future conservation research focused on specific geographic regions, or evaluating the degree to which species-level patterns mirror spatial variation in the pressures faced by populations within the ranges of individual species. The added impacts from climate change may increase the susceptibility of at-risk species to extinction and expand the regions where mammals are most vulnerable globally.

Using a Virtual Environment to Examine How Children Cross Streets: Advancing Our Understanding of How Injury Risk Arises.

PubMed

Morrongiello, Barbara A; Corbett, Michael; Milanovic, Melissa; Beer, Jonathan

2016-03-01

To examine how risk of injury can arise for child pedestrians. Using a highly immersive virtual reality system interfaced with a 3-D movement measurement system, younger (M = 8 years) and older (M = 10 years) children's crossing behaviors were measured under conditions that introduced variation in vehicle speed, distance, and intervehicle gaps. Children used distance cues in deciding when to cross; there were no age or sex differences. This increased risk of injury in larger intervehicle gaps because they started late and did not monitor traffic or adjust walking speed as they crossed. In contrast, injury risk in smaller intervehicle gaps of equal risk (i.e., same time to contact) occurred because crossing behavioral adjustments (starting early, increasing walking speed while crossing) were not sufficient. Dependence on distance cues increases children's risk of injury as pedestrians when crossing in a variety of traffic situations. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The cancer awareness assessment project: A small-scale survey across people with different levels of education in Mysore, India.

PubMed

Sheshachalam, A; Chakravarthy, A R

2015-01-01

To assess the cancer awareness in respondents, their knowledge about the nature of cancer as a disease, its diagnosis and treatment, warning signs, environmental risk factors and conceptions of how risk factors work, as well as willingness to participate in screening programs if available. Cancer awareness is an increasingly important issue in light of increasing incidence and associated healthcare costs, as well as the presence of risk management strategies. In this study, 453 people, drawn from several educational institutes/workplaces, were surveyed with respect to cancer awareness. The test sample included pre university students, undergraduates, and postgraduate students/workers. We checked for variations in cancer awareness across multiple educational levels to determine whether there was variation in levels of cancer awareness across educational classes. We found that confidence in perception of cancer awareness, and awareness itself, was not very high, and only postgraduates had a nuanced appreciation of some of the complexities of cancer epidemiology, and even then only moderately. The conclusions of the study point towards the need for optimal policymaking in the development of cancer awareness in the population.

Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.

PubMed

Barnes, Jammie; Mayes, Maureen D

2012-03-01

To identify the recent data regarding prevalence, incidence, survival, and risk factors for systemic sclerosis (SSc) and to compare these data to previously published findings. SSc disease occurrence data are now available for Argentina, Taiwan, and India and continue to show wide variation across geographic regions. The survival rate is negatively impacted by older age of onset, male sex, scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer, and antitopoisomerase and anti-U1 antibodies. It appears that silica exposure confers an increased risk for developing scleroderma, but this exposure accounts for a very small proportion of male patients. Smoking is not associated with increased SSc susceptibility. Malignancies are reported in scleroderma at an increased rate, but the magnitude of this risk and the type of cancer vary among reports. Prevalence and incidence of SSc appears to be greater in populations of European ancestry and lower in Asian groups. Exposure to silica dust appears to be an environmental trigger, but this only accounts for a small proportion of male cases. Evidence for increased risk of neoplasia is suggestive, but the magnitude of the risk and the types of malignancies vary among reports.

Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women.

PubMed

McTigue, Kathleen M; Chang, Yue-Fang; Eaton, Charles; Garcia, Lorena; Johnson, Karen C; Lewis, Cora E; Liu, Simin; Mackey, Rachel H; Robinson, Jennifer; Rosal, Milagros C; Snetselaar, Linda; Valoski, Alice; Kuller, Lewis H

2014-03-01

To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk. Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF). Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for. Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity. Copyright © 2012 The Obesity Society.

Mortality risk and social network position in resident killer whales: sex differences and the importance of resource abundance.

PubMed

Ellis, S; Franks, D W; Nattrass, S; Cant, M A; Weiss, M N; Giles, D; Balcomb, K C; Croft, D P

2017-10-25

An individual's ecological environment affects their mortality risk, which in turn has fundamental consequences for life-history evolution. In many species, social relationships are likely to be an important component of an individual's environment, and therefore their mortality risk. Here, we examine the relationship between social position and mortality risk in resident killer whales ( Orcinus orca ) using over three decades of social and demographic data. We find that the social position of male, but not female, killer whales in their social unit predicts their mortality risk. More socially integrated males have a significantly lower risk of mortality than socially peripheral males, particularly in years of low prey abundance, suggesting that social position mediates access to resources. Male killer whales are larger and require more resources than females, increasing their vulnerability to starvation in years of low salmon abundance. More socially integrated males are likely to have better access to social information and food-sharing opportunities which may enhance their survival in years of low salmon abundance. Our results show that observable variation in the social environment is linked to variation in mortality risk, and highlight how sex differences in social effects on survival may be linked to sex differences in life-history evolution. © 2017 The Authors.

Mortality risk and social network position in resident killer whales: sex differences and the importance of resource abundance

PubMed Central

Franks, D. W.; Nattrass, S.; Weiss, M. N.; Giles, D.; Balcomb, K. C.; Croft, D. P.

2017-01-01

An individual's ecological environment affects their mortality risk, which in turn has fundamental consequences for life-history evolution. In many species, social relationships are likely to be an important component of an individual's environment, and therefore their mortality risk. Here, we examine the relationship between social position and mortality risk in resident killer whales (Orcinus orca) using over three decades of social and demographic data. We find that the social position of male, but not female, killer whales in their social unit predicts their mortality risk. More socially integrated males have a significantly lower risk of mortality than socially peripheral males, particularly in years of low prey abundance, suggesting that social position mediates access to resources. Male killer whales are larger and require more resources than females, increasing their vulnerability to starvation in years of low salmon abundance. More socially integrated males are likely to have better access to social information and food-sharing opportunities which may enhance their survival in years of low salmon abundance. Our results show that observable variation in the social environment is linked to variation in mortality risk, and highlight how sex differences in social effects on survival may be linked to sex differences in life-history evolution. PMID:29070720

Racial differences in venous thromboembolism.

PubMed

Zakai, N A; McClure, L A

2011-10-01

The incidence of venous thrombosis (VTE) varies by race, with African-Americans having over 5-fold greater incidence than Asian-ancestry populations, and an intermediate risk for European and Hispanic populations. Known racial differences in genetic polymorphisms associated with thrombosis do not account for this gradient of risk, nor do known racial variations in environmental risk factors. Data on the incidence of and risk factors for VTE outside of Europe and North America and in non-European ancestry populations are sparse. Common genetic polymorphisms in European-Ancestry populations, such as factor V Leiden and prothrombin G20210A, and environmental risk factors, such as obesity, may account for some of the increased risk in European populations, and high factor VIII, high von Willebrand factor and low protein C levels and increased prevalence of obesity may explain some of the increased risk in African-Americans. The low rates in Asian populations may be partially explained by low clinical suspicion in a perceived low-risk population and lack of access to healthcare in other populations. As risk factors for thrombosis, such as surgery and treatment for cancer, are applicable to more people, as obesity increases in prevalence in the developing world, and as surveillance systems for VTE improve, VTE may increase in previously low-risk populations. While differences in VTE by race due to genetic predisposition will probably always be present, understanding the reasons for racial differences in VTE will help providers develop strategies to minimize VTE in all populations. © 2011 International Society on Thrombosis and Haemostasis.

Seasonal Variations in the Risk of Reoperation for Surgical Site Infection Following Elective Spinal Fusion Surgery: A Retrospective Study Using the Japanese Diagnosis Procedure Combination Database.

PubMed

Ohya, Junichi; Chikuda, Hirotaka; Oichi, Takeshi; Kato, So; Matsui, Hiroki; Horiguchi, Hiromasa; Tanaka, Sakae; Yasunaga, Hideo

2017-07-15

A retrospective study of data abstracted from the Diagnosis Procedure Combination (DPC) database, a national representative database in Japan. The aim of this study was to examine seasonal variations in the risk of reoperation for surgical site infection (SSI) following spinal fusion surgery. Although higher rates of infection in the summer than in other seasons were thought to be caused by increasing inexperience of new staff, high temperature, and high humidity, no studies have examined seasonal variations in the risk of SSI following spinal fusion surgery in the country where medical staff rotation timing is not in summer season. In Japan, medical staff rotation starts in April. We retrospectively extracted the data of patients who were admitted between July 2010 and March 2013 from the DPC database. Patients were included if they were aged 20 years or older and underwent elective spinal fusion surgery. The primary outcome was reoperation for SSI during hospitalization. We performed multivariate analysis to clarify the risk factors of primary outcome with adjustment for patient background characteristics. We identified 47,252 eligible patients (23,659 male, 23,593 female). The mean age of the patients was 65.4 years (range, 20-101 yrs). Overall, reoperation for SSI occurred in 0.93% of the patients during hospitalization. The risk of reoperation for SSI was significantly higher in April (vs. February; odds ratio, 1.93; 95% confidence interval, 1.09-3.43, P = 0.03) as well as other known risk factors. In subgroup analysis with stratification for type of hospital, month of surgery was identified as an independent risk factor of reoperation for SSI among cases in an academic hospital, although there was no seasonal variation among those in a nonacademic hospital. This study showed that month of surgery is a risk factor of reoperation for SSI following elective spinal fusion surgery, nevertheless, in the country where medical staff rotation timing is not in summer season. 3.

Associations between residence at birth and mental health disorders: a spatial analysis of retrospective cohort data.

PubMed

Hoffman, Kate; Aschengrau, Ann; Webster, Thomas F; Bartell, Scott M; Vieira, Verónica M

2015-07-21

Mental health disorders impact approximately one in four US adults. While their causes are likely multifactorial, prior research has linked the risk of certain mental health disorders to prenatal and early childhood environmental exposures, motivating a spatial analysis to determine whether risk varies by birth location. We investigated the spatial associations between residence at birth and odds of depression, bipolar disorder, and post-traumatic stress disorder (PTSD) in a retrospective cohort (Cape Cod, Massachusetts, 1969-1983) using generalized additive models to simultaneously smooth location and adjust for confounders. Birth location served as a surrogate for prenatal exposure to the combination of social and environmental factors related to the development of mental illness. We predicted crude and adjusted odds ratios (aOR) for each outcome across the study area. The results were mapped to identify areas of increased risk. We observed spatial variation in the crude odds ratios of depression that was still present even after accounting for spatial confounding due to geographic differences in the distribution of known risk factors (aOR range: 0.61-3.07, P = 0.03). Similar geographic patterns were seen for the crude odds of PTSD; however, these patterns were no longer present in the adjusted analysis (aOR range: 0.49-1.36, P = 0.79), with family history of mental illness most notably influencing the geographic patterns. Analyses of the odds of bipolar disorder did not show any meaningful spatial variation (aOR range: 0.58-1.17, P = 0.82). Spatial associations exist between residence at birth and odds of PTSD and depression, but much of this variation can be explained by the geographic distributions of available risk factors. However, these risk factors did not account for all the variation observed with depression, suggesting that other social and environmental factors within our study area need further investigation.

The serotonin transporter 5-HTTPR polymorphism is associated with current and lifetime depression in persons with chronic psychotic disorders.

PubMed

Contreras, J; Hare, L; Camarena, B; Glahn, D; Dassori, A; Medina, R; Contreras, S; Ramirez, M; Armas, R; Munoz, R; Mendoza, R; Raventos, H; Ontiveros, A; Nicolini, H; Palmer, R; Escamilla, M

2009-02-01

Variation in the serotonin transporter gene (SLC6A4) promoter region has been shown to influence depression in persons who have been exposed to a number of stressful life events. We evaluated whether genetic variation in 5-HTTLPR, influences current depression, lifetime history of depression and quantitative measures of depression in persons with chronic psychotic disorders. This is an association study of a genetic variant with quantitative and categorical definitions of depression conducted in the southwest US, Mexico and Costa Rica. We analyzed 260 subjects with a history of psychosis, from a sample of 129 families. We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (P < 0.02, odds ratio 2.18, 95% CI 1.10-4.20). The 'ss' or 'sl' genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of psychotic individuals to develop major depression during the course of their illness.

Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: A prospective imaging gene × environment analysis.

PubMed

Little, Keriann; Olsson, Craig A; Youssef, George J; Whittle, Sarah; Simmons, Julian G; Yücel, Murat; Sheeber, Lisa B; Foley, Debra L; Allen, Nicholas B

2015-11-01

A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume. (c) 2015 APA, all rights reserved).

Identifying increased risk of post-infarct people with diabetes using multi-lag Tone-Entropy analysis.

PubMed

Karmakar, Chandan; Jelinek, Herbert; Khandoker, Ahsan; Tulppo, Mikko; Makikallio, Timo; Kiviniemi, Antti; Huikuri, Heikki; Palaniswami, Marimuthu

2012-01-01

Diabetes mellitus is associated with multi-organ system dysfunction. One of the key causative factors is the increased blood sugar level that leads to an increase in free radical activity and organ damage including the cardiovascular and nervous system. Heart rhythm is extrinsically modulated by the autonomic nervous system and cardiac autonomic neuropathy or dysautonomia has been shown to lead to sudden cardiac death in people with diabetes due to the decrease in heart rate variability (HRV). Current algorithms for determining HRV describe only beat-to-beat variation and therefore do not consider the ability of a heart beat to influence a train of succeeding beats. Therefore mortality risk analysis based on HRV has often not been able to discern the presence of an increased risk. This study used a novel innovation of the tone-entropy algorithm by incorporating increased lag intervals and found that both the sympatho-vagal balance and total activity changed at larger lag intervals. Tone-Entropy was found to be better risk identifier of cardiac mortality in people with diabetes at lags higher than one and best at lag seven.

CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression.

PubMed

Rogers, J; Raveendran, M; Fawcett, G L; Fox, A S; Shelton, S E; Oler, J A; Cheverud, J; Muzny, D M; Gibbs, R A; Davidson, R J; Kalin, N H

2013-06-01

The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.

Ethnoracial Variations in Acute PTSD Symptoms Among Hospitalized Survivors of Traumatic Injury

PubMed Central

Stephens, Kari A.; Sue, Stanley; Roy-Byrne, Peter; Unützer, Jürgen; Wang, Jin; Rivara, Frederick P.; Jurkovich, Gregory J.; Zatzick, Douglas F.

2011-01-01

Ethnoracial minority status contributes to an increased risk for posttraumatic stress disorder (PTSD) after trauma exposure, beyond other risk factors. A population-based sampling frame was used to examine the associations between ethnoracial groups and early PTSD symptoms while adjusting for relevant clinical and demographic characteristics. Acutely injured trauma center inpatients (N = 623) were screened with the PTSD Checklist. American Indian and African American patients reported the highest levels of posttraumatic stress and preinjury cumulative trauma burden. African American heritage was independently associated with an increased risk of higher acute PTSD symptom levels. Disparities in trauma history, PTSD symptoms, and event related factors emphasize the need for acute care services to incorporate culturally competent approaches for treating these diverse populations. PMID:20564368

Associations Between a Dopamine D4 Receptor Gene, Alcohol Use, and Sexual Behaviors among Female Adolescent African Americans

PubMed Central

Sales, Jessica M.; Smearman, Erica; Brown, Jennifer L.; Brody, Gene H.; Philibert, Robert A.; Rose, Eve; DiClemente, Ralph J.

2016-01-01

Adolescent African-American females are disproportionately impacted by HIV, thus there is a clear need to understand factors associated with increased HIV-risk behaviors among this vulnerable population. We sought to explore the association between a dopamine D4 receptor gene (DRD4), a genetic marker associated with natural variations in rewarding behaviors, and self-reported alcohol-use and sexual risk-behaviors, while controlling for other known correlates of risk-taking such as impulsivity, sensation seeking, and peer norms among a group of high-risk African American female adolescents to evaluate whether this biological factor enhances our understanding of patterns of risk in this vulnerable group. PMID:27087792

Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

ERIC Educational Resources Information Center

Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

2004-01-01

This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

Climate change risk to forests in China associated with warming.

PubMed

Yin, Yunhe; Ma, Danyang; Wu, Shaohong

2018-01-11

Variations in forest net primary productivity (NPP) reflects the combined effects of key climate variables on ecosystem structure and function, especially on the carbon cycle. We performed risk analysis indicated by the magnitude of future negative anomalies in NPP in comparison with the natural interannual variability to investigate the impact of future climatic projections on forests in China. Results from the multi-model ensemble showed that climate change risk of decreases in forest NPP would be more significant in higher emission scenario in China. Under relatively low emission scenarios, the total area of risk was predicted to decline, while for RCP8.5, it was predicted to first decrease and then increase after the middle of 21st century. The rapid temperature increases predicted under the RCP8.5 scenario would be probably unfavorable for forest vegetation growth in the long term. High-level risk area was likely to increase except RCP2.6. The percentage area at high risk was predicted to increase from 5.39% (2021-2050) to 27.62% (2071-2099) under RCP8.5. Climate change risk to forests was mostly concentrated in southern subtropical and tropical regions, generally significant under high emission scenario of RCP8.5, which was mainly attributed to the intensified dryness in south China.

Meteor Shower Forecasting for Spacecraft Operations

NASA Technical Reports Server (NTRS)

Moorhead, Althea V.; Cooke, William J.; Campbell-Brown, Margaret D.

2017-01-01

Although sporadic meteoroids generally pose a much greater hazard to spacecraft than shower meteoroids, meteor showers can significantly increase the risk of damage over short time periods. Because showers are brief, it is sometimes possible to mitigate the risk operationally, which requires accurate predictions of shower activity. NASA's Meteoroid Environment Office (MEO) generates an annual meteor shower forecast that describes the variations in the near-Earth meteoroid flux produced by meteor showers, and presents the shower flux both in absolute terms and relative to the sporadic flux. The shower forecast incorporates model predictions of annual variations in shower activity and quotes fluxes to several limiting particle kinetic energies. In this work, we describe our forecasting methods and present recent improvements to the temporal profiles based on flux measurements from the Canadian Meteor Orbit Radar (CMOR).

The joint effect of air pollution exposure and copy number variation on risk for autism.

PubMed

Kim, Dokyoon; Volk, Heather; Girirajan, Santhosh; Pendergrass, Sarah; Hall, Molly A; Verma, Shefali S; Schmidt, Rebecca J; Hansen, Robin L; Ghosh, Debashis; Ludena-Rodriguez, Yunin; Kim, Kyoungmi; Ritchie, Marylyn D; Hertz-Picciotto, Irva; Selleck, Scott B

2017-09-01

Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P < 0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25-2.73) or ozone (OR 1.20, 95% CI 0.93-1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. Autism Res 2017, 10: 1470-1480. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

PubMed

Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

2017-03-01

Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

Risk as Social Context: Immigration Policy and Autism in California*

PubMed Central

Fountain, Christine; Bearman, Peter

2010-01-01

Motivated by the dramatic increase in autism diagnoses in recent years, research into risk factors has uncovered substantial variation in autism prevalence by race/ethnicity, SES, and geography. Less studied is the connection between autism diagnosis rates and the social and political context. In this article, we link the temporal pattern of autism diagnosis for Hispanic children in California to state and federal anti-immigrant policy, particularly ballot initiative Proposition 187, limiting access to public services for undocumented immigrants and their families. Using a population-level dataset of 1992–2003 California births linked to 1992–2006 autism case records, we show that the effects of state and federal policies toward immigrants are visible in the rise and fall of autism risk over time. The common epidemiological practice of estimating risk on pooled samples is thereby shown to obscure patterns and mis-estimate effect sizes. Finally, we illustrate how spatial variation in Hispanic autism rates reflects differential vulnerability to these policies. This study reveals not only the spillover effects of immigration policy on children’s health, but also the hazards of treating individual attributes like ethnicity as risk factors without regard to the social and political environments that give them salience. PMID:21643443

Perils and pitfalls of reporting sex differences

PubMed Central

Maney, Donna L.

2016-01-01

The idea of sex differences in the brain both fascinates and inflames the public. As a result, the communication and public discussion of new findings is particularly vulnerable to logical leaps and pseudoscience. A new US National Institutes of Health policy to consider both sexes in almost all preclinical research will increase the number of reported sex differences and thus the risk that research in this important area will be misinterpreted and misrepresented. In this article, I consider ways in which we might reduce that risk, for example, by (i) employing statistical tests that reveal the extent to which sex explains variation, rather than whether or not the sexes ‘differ’, (ii) properly characterizing the frequency distributions of scores or dependent measures, which nearly always overlap, and (iii) avoiding speculative functional or evolutionary explanations for sex-based variation, which usually invoke logical fallacies and perpetuate sex stereotypes. Ultimately, the factor of sex should be viewed as an imperfect, temporary proxy for yet-unknown factors, such as hormones or sex-linked genes, that explain variation better than sex. As scientists, we should be interested in discovering and understanding the true sources of variation, which will be more informative in the development of clinical treatments. PMID:26833839

The impact of obesity on US mortality levels: the importance of age and cohort factors in population estimates.

PubMed

Masters, Ryan K; Reither, Eric N; Powers, Daniel A; Yang, Y Claire; Burger, Andrew E; Link, Bruce G

2013-10-01

To estimate the percentage of excess death for US Black and White men and women associated with high body mass, we examined the combined effects of age variation in the obesity-mortality relationship and cohort variation in age-specific obesity prevalence. We examined 19 National Health Interview Survey waves linked to individual National Death Index mortality records, 1986-2006, for age and cohort patterns in the population-level association between obesity and US adult mortality. The estimated percentage of adult deaths between 1986 and 2006 associated with overweight and obesity was 5.0% and 15.6% for Black and White men, and 26.8% and 21.7% for Black and White women, respectively. We found a substantially stronger association than previous research between obesity and mortality risk at older ages, and an increasing percentage of mortality attributable to obesity across birth cohorts. Previous research has likely underestimated obesity's impact on US mortality. Methods attentive to cohort variation in obesity prevalence and age variation in obesity's effect on mortality risk suggest that obesity significantly shapes US mortality levels, placing it at the forefront of concern for public health action.

Comparative analyses of fungicide sensitivity and SSR marker variations indicate a low risk of developing azoxystrobin resistance in Phytophthora infestans

PubMed Central

Qin, Chun-Fang; He, Meng-Han; Chen, Feng-Ping; Zhu, Wen; Yang, Li-Na; Wu, E-Jiao; Guo, Zheng-Liang; Shang, Li-Ping; Zhan, Jiasui

2016-01-01

Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight. PMID:26853908

Comparative analyses of fungicide sensitivity and SSR marker variations indicate a low risk of developing azoxystrobin resistance in Phytophthora infestans.

PubMed

Qin, Chun-Fang; He, Meng-Han; Chen, Feng-Ping; Zhu, Wen; Yang, Li-Na; Wu, E-Jiao; Guo, Zheng-Liang; Shang, Li-Ping; Zhan, Jiasui

2016-02-08

Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight.

Analysis of exogenous components of mortality risks.

PubMed

Blinkin, V L

1998-04-01

A new technique for deriving exogenous components of mortality risks from national vital statistics has been developed. Each observed death rate Dij (where i corresponds to calendar time (year or interval of years) and j denotes the number of corresponding age group) was represented as Dij = Aj + BiCj, and unknown quantities Aj, Bi, and Cj were estimated by a special procedure using the least-squares principle. The coefficients of variation do not exceed 10%. It is shown that the term Aj can be interpreted as the endogenous and the second term BiCj as the exogenous components of the death rate. The aggregate of endogenous components Aj can be described by a regression function, corresponding to the Gompertz-Makeham law, A(tau) = gamma + beta x e alpha tau, where gamma, beta, and alpha are constants, tau is age, A(tau) [symbol: see text] tau = tau j identical to A(tau j) identical to Aj and tau j is the value of age tau in jth age group. The coefficients of variation for such a representation does not exceed 4%. An analysis of exogenous risk levels in the Moscow and Russian populations during 1980-1995 shows that since 1992 all components of exogenous risk in the Moscow population had been increasing up to 1994. The greatest contribution to the total level of exogenous risk was lethal diseases, and their death rate was 387 deaths per 100,000 persons in 1994, i.e., 61.9% of all deaths. The dynamics of exogenous mortality risk change during 1990-1994 in the Moscow population and in the Russian population without Moscow had been identical: the risk had been increasing and its value in the Russian population had been higher than that in the Moscow population.

Nest predation risk and growth strategies of passerine species: grow fast or develop traits to escape risk?

USGS Publications Warehouse

Cheng, Yi-Ru; Martin, Thomas E.

2012-01-01

Different body components are thought to trade off in their growth and development rates, but the causes for relative prioritization of any trait remains a critical question. Offspring of species at higher risk of predation might prioritize development of locomotor traits that facilitate escaping risky environments over growth of mass. We tested this possibility in 12 altricial passerine species that differed in their risk of nest predation. We found that rates of growth and development of mass, wings, and endothermy increased with nest predation risk across species. In particular, species with higher nest predation risk exhibited relatively faster growth of wings than of mass, fledged with relatively larger wing sizes and smaller mass, and developed endothermy earlier at relatively smaller mass. This differential development can facilitate both escape from predators and survival outside of the nest environment. Tarsus growth was not differentially prioritized with respect to nest predation risk, and instead all species achieved adult tarsus size by age of fledging. We also tested whether different foraging modes (aerial, arboreal, and ground foragers) might explain the variation of differential growth of locomotor modules, but we found that little residual variation was explained. Our results suggest that differences in nest predation risk among species are associated with relative prioritization of body components to facilitate escape from the risky nest environment.

[Comparative quality measurements part 3: funnel plots].

PubMed

Kottner, Jan; Lahmann, Nils

2014-02-01

Comparative quality measurements between organisations or institutions are common. Quality measures need to be standardised and risk adjusted. Random error must also be taken adequately into account. Rankings without consideration of the precision lead to flawed interpretations and enhances "gaming". Application of confidence intervals is one possibility to take chance variation into account. Funnel plots are modified control charts based on Statistical Process Control (SPC) theory. The quality measures are plotted against their sample size. Warning and control limits that are 2 or 3 standard deviations from the center line are added. With increasing group size the precision increases and so the control limits are forming a funnel. Data points within the control limits are considered to show common cause variation; data points outside special cause variation without the focus of spurious rankings. Funnel plots offer data based information about how to evaluate institutional performance within quality management contexts.

Discrimination and mental health among Latinos: variation by place of origin.

PubMed

Held, Mary L; Lee, Sungkyu

2017-10-01

The US Latino population experiences high rates of discrimination, which may contribute to psychiatric disorders. Yet, little is known about the distinctions in this relationship for Latino subgroups. Using data from the National Latino and Asian American study, we examined the association between discrimination and mental health for 2503 Latinos. Logistic regression analyses were used to examine variation in the relationship by place of origin (Cuba, Puerto Rico, Mexico, or Other). Results suggest that perceived discrimination increased the probability of having a psychiatric disorder. The effect of discrimination on having a psychiatric disorder was greater for Mexicans than Puerto Ricans. The findings of this study suggest that variation exists in the relationship between discrimination and mental health by origin. Implications for practice include increasing awareness of place of origin, in addition to discrimination, as a risk factor for mental illness. Future research should examine this relationship longitudinally and consider immigration status.

Decision-making under risk in children, adolescents, and young adults.

PubMed

Paulsen, David J; Platt, Michael L; Huettel, Scott A; Brannon, Elizabeth M

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk-return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk.

Multilevel Analysis of Trachomatous Trichiasis and Corneal Opacity in Nigeria: The Role of Environmental and Climatic Risk Factors on the Distribution of Disease.

PubMed

Smith, Jennifer L; Sivasubramaniam, Selvaraj; Rabiu, Mansur M; Kyari, Fatima; Solomon, Anthony W; Gilbert, Clare

2015-01-01

The distribution of trachoma in Nigeria is spatially heterogeneous, with large-scale trends observed across the country and more local variation within areas. Relative contributions of individual and cluster-level risk factors to the geographic distribution of disease remain largely unknown. The primary aim of this analysis is to assess the relationship between climatic factors and trachomatous trichiasis (TT) and/or corneal opacity (CO) due to trachoma in Nigeria, while accounting for the effects of individual risk factors and spatial correlation. In addition, we explore the relative importance of variation in the risk of trichiasis and/or corneal opacity (TT/CO) at different levels. Data from the 2007 National Blindness and Visual Impairment Survey were used for this analysis, which included a nationally representative sample of adults aged 40 years and above. Complete data were available from 304 clusters selected using a multi-stage stratified cluster-random sampling strategy. All participants (13,543 individuals) were interviewed and examined by an ophthalmologist for the presence or absence of TT and CO. In addition to field-collected data, remotely sensed climatic data were extracted for each cluster and used to fit Bayesian hierarchical logistic models to disease outcome. The risk of TT/CO was associated with factors at both the individual and cluster levels, with approximately 14% of the total variation attributed to the cluster level. Beyond established individual risk factors (age, gender and occupation), there was strong evidence that environmental/climatic factors at the cluster-level (lower precipitation, higher land surface temperature, higher mean annual temperature and rural classification) were also associated with a greater risk of TT/CO. This study establishes the importance of large-scale risk factors in the geographical distribution of TT/CO in Nigeria, supporting anecdotal evidence that environmental conditions are associated with increased risk in this context and highlighting their potential use in improving estimates of disease burden at large scales.

Melanocytic nevi, nevus genes and melanoma risk in a large case-control study in the United Kingdom

PubMed Central

Newton-Bishop, Julia A; Chang, Yu-Mei; Iles, Mark M; Taylor, John C; Bakker, Bert; Chan, May; Leake, Susan; Karpavicius, Birute; Haynes, Sue; Fitzgibbon, Elaine; Elliott, Faye; Kanetsky, Peter A.; Harland, Mark; Barrett, Jennifer H; Bishop, D Timothy

2010-01-01

Background Increased number of melanocytic nevi is a potent melanoma risk factor. We have carried out a large population-based case-control study to explore the environmental and genetic determinants of nevi and the relationship with melanoma risk. Methods We report nevus phenotype in relation to differing patterns of sun exposure, inherited variation at loci shown in recent genome-wide association studies to be nevus genes, and risk. Results Increased numbers of nevi were associated with holiday sun exposure, particularly on intermittently sun-exposed body sites (test for trend p<0.0001). Large nevi were also associated with holiday sun exposure (p=0.002). Single nucleotide polymorphisms (SNPs) on chromosomes 9 and 22 were associated with increased numbers of nevi (p=0.04 and p=0.002 respectively) and larger nevi (p=0.03 and p=0.002), whereas that on chromosome 6 was associated only with large nevi (p=0.01). Melanoma risk was associated with increased nevus count, large nevi and atypical nevi for tumors in all body sites (including rare sites) irrespective of age. The risk persisted when adjusted for inheritance of nevus SNPs. Conclusions The at-risk nevus phenotype is associated with behaviors known to increase melanoma risk (holiday sun exposure). Although SNPs on chromosomes 6, 9 and 22 were shown to be nevus genes they explained only a small proportion of melanoma risk and nevus phenotype; therefore a number of nevus genes likely remain to be identified. Impact This paper confirms the importance of nevi in melanoma pathogenesis and increases understanding of their genetic determinants. PMID:20647408

General Practice Clinical Data Help Identify Dementia Hotspots: A Novel Geospatial Analysis Approach.

PubMed

Bagheri, Nasser; Wangdi, Kinley; Cherbuin, Nicolas; Anstey, Kaarin J

2018-01-01

We have a poor understanding of whether dementia clusters geographically, how this occurs, and how dementia may relate to socio-demographic factors. To shed light on these important questions, this study aimed to compute a dementia risk score for individuals to assess spatial variation of dementia risk, identify significant clusters (hotspots), and explore their association with socioeconomic status. We used clinical records from 16 general practices (468 Statistical Area level 1 s, N = 14,746) from the city of west Adelaide, Australia for the duration of 1 January 2012 to 31 December 2014. Dementia risk was estimated using The Australian National University-Alzheimer's Disease Risk Index. Hotspot analyses were applied to examine potential clusters in dementia risk at small area level. Significant hotspots were observed in eastern and southern areas while coldspots were observed in the western area within the study perimeter. Additionally, significant hotspots were observed in low socio-economic communities. We found dementia risk scores increased with age, sex (female), high cholesterol, no physical activity, living alone (widow, divorced, separated, or never married), and co-morbidities such as diabetes and depression. Similarly, smoking was associated with a lower dementia risk score. The identification of dementia risk clusters may provide insight into possible geographical variations in risk factors for dementia and quantify these risks at the community level. As such, this research may enable policy makers to tailor early prevention strategies to the correct individuals within their precise locations.

Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China.

PubMed

Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

2013-11-21

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

SU-F-T-394: Impact of PTV Margins With Taking Into Account Shape Variation On IMRT Plans For Prostate Cancer

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

Hirose, T; Arimura, H; Oga, S

2016-06-15

Purpose: The purpose of this study was to investigate the impact of planning target volume (PTV) margins with taking into consideration clinical target volume (CTV) shape variations on treatment plans of intensity modulated radiation therapy (IMRT) for prostate cancer. Methods: The systematic errors and the random errors for patient setup errors in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions were obtained from data of 20 patients, and those for CTV shape variations were calculated from 10 patients, who were weekly scanned using cone beam computed tomography (CBCT). The setup error was defined as the difference in prostate centers betweenmore » planning CT and CBCT images after bone-based registrations. CTV shape variations of high, intermediate and low risk CTVs were calculated for each patient from variances of interfractional shape variations on each vertex of three-dimensional CTV point distributions, which were manually obtained from CTV contours on the CBCT images. PTV margins were calculated using the setup errors with and without CTV shape variations for each risk CTV. Six treatment plans were retrospectively made by using the PTV margins with and without CTV shape variations for the three risk CTVs of 5 test patients. Furthermore, the treatment plans were applied to CBCT images for investigating the impact of shape variations on PTV margins. Results: The percentages of population to cover with the PTV, which satisfies the CTV D98 of 95%, with and without the shape variations were 89.7% and 74.4% for high risk, 89.7% and 76.9% for intermediate risk, 84.6% and 76.9% for low risk, respectively. Conclusion: PTV margins taking into account CTV shape variation provide significant improvement of applicable percentage of population (P < 0.05). This study suggested that CTV shape variation should be taken consideration into determination of the PTV margins.« less

Childhood Exposure to Adversity and Risk of Substance-Use Disorder in Two American Indian Populations: The Meditational Role of Early Substance-Use Initiation*

PubMed Central

Whitesell, Nancy Rumbaugh; Beals, Janette; Mitchell, Christina M.; Manson, Spero M.; Turner, R. Jay

2009-01-01

Objective: We examined the relationship of childhood exposure to adversity and risk of substance-use disorder in two culturally distinct American Indian reservation communities, exploring both the role of early initiation of substance use in mediating this relationship and variation in risk across types of adversity exposure. Method: The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project provided data from 2,927 American Indians on the occurrence and age at onset of adversities, substance use, and substance-use-disorder symptoms. Results: The risk of substance-use disorder associated with early adversity was explained partially by early initiation of substance use. Three types of adversity (major childhood events, traumas, and witnessed violence) were associated with early onset of substance use and increased risk of substance-use disorder. Gender and tribe were also related to variation in both early substance use and substance-use disorder. Conclusions: Early exposure to adverse events was associated with early substance use and the subsequent development of substance-use disorders among American Indians. Public health initiatives targeting substance use and substance-use disorders in American Indian communities should include efforts to help children in these communities cope with adversities they encounter. PMID:19895776

Radiation dose and cancer risk estimates in helical CT for pulmonary tuberculosis infections

NASA Astrophysics Data System (ADS)

Adeleye, Bamise; Chetty, Naven

2017-12-01

The preference for computed tomography (CT) for the clinical assessment of pulmonary tuberculosis (PTB) infections has increased the concern about the potential risk of cancer in exposed patients. In this study, we investigated the correlation between cancer risk and radiation doses from different CT scanners, assuming an equivalent scan protocol. Radiation doses from three 16-slice units were estimated using the CT-Expo dosimetry software version 2.4 and standard CT scan protocol for patients with suspected PTB infections. The lifetime risk of cancer for each scanner was determined using the methodology outlined in the BEIR VII report. Organ doses were significantly different (P < 0.05) between the scanners. The calculated effective dose for scanner H2 is 34% and 37% higher than scanners H3 and H1 respectively. A high and statistically significant correlation was observed between estimated lifetime cancer risk for both male (r2 = 0.943, P < 0.05) and female patients (r2 = 0.989, P < 0.05). The risk variation between the scanners was slightly higher than 2% for all ages but was much smaller for specific ages for male and female patients (0.2% and 0.7%, respectively). These variations provide an indication that the use of a scanner optimizing protocol is imperative.

Childhood Malnutrition and Its Determinants among Under-Five Children in Ghana.

PubMed

Aheto, Justice Moses K; Keegan, Thomas J; Taylor, Benjamin M; Diggle, Peter J

2015-11-01

Childhood malnutrition adversely affects short- and long-term health and economic well-being of children. Malnutrition is a global challenge and accounts for around 40% of under-five mortality in Ghana. Limited studies are available indicating determinants of malnutrition among children. This study investigates prevalence and determinants of malnutrition among children under-five with the aim of providing advice to policymakers and other stakeholders responsible for the health and nutrition of children. The study used data from the 2008 Ghana Demographic and Health Survey (GDHS). Analyses were conducted on 2083 children under 5 years old nested within 1641 households with eligible anthropometric measurements, using multilevel regression analysis. Results from the multilevel models were used to compute probabilities of malnutrition. This study observed that 588 (28%), 276 (13%), and 176 (8%) of the children were moderately 'stunted', moderately 'underweight', and moderately 'wasted' respectively. Older ages are associated with increased risk of stunting and underweight. Longer breast-feeding duration, multiple births, experience of diarrhoeal episodes, small size at birth, absence of toilet facilities in households, poor households, and mothers who are not covered by national health insurance are associated with increased risk of malnutrition. Increase in mother's years of education and body mass index are associated with decreased malnutrition. Strong residual household-level variations in childhood nutritional outcomes were found. Policies and intervention strategies aimed at improving childhood nutrition and health should address the risk factors identified and the need to search for additional risk factors that might account for the unexplained household-level variations. © 2015 John Wiley & Sons Ltd.

Trends and regional variations in provision of contraception methods in a commercially insured population in the United States based on nationally proposed measures.

PubMed

Law, A; Yu, J S; Wang, W; Lin, J; Lynen, R

2017-09-01

Three measures to assess the provision of effective contraception methods among reproductive-aged women have recently been endorsed for national public reporting. Based on these measures, this study examined real-world trends and regional variations of contraceptive provision in a commercially insured population in the United States. Women 15-44years old with continuous enrollment in each year from 2005 to 2014 were identified from a commercial claims database. In accordance with the proposed measures, percentages of women (a) provided most effective or moderately effective (MEME) methods of contraception and (b) provided a long-acting reversible contraceptive (LARC) method were calculated in two populations: women at risk for unintended pregnancy and women who had a live birth within 3 and 60days of delivery. During the 10-year period, the percentages of women at risk for unintended pregnancy provided MEME contraceptive methods increased among 15-20-year-olds (24.5%-35.9%) and 21-44-year-olds (26.2%-31.5%), and those provided a LARC method also increased among 15-20-year-olds (0.1%-2.4%) and 21-44-year-olds (0.8%-3.9%). Provision of LARC methods increased most in the North Central and West among both age groups of women. Provision of MEME contraceptives and LARC methods to women who had a live birth within 60days postpartum also increased across age groups and regions. This assessment indicates an overall trend of increasing provision of MEME contraceptive methods in the commercial sector, albeit with age group and regional variations. If implemented, these proposed measures may have impacts on health plan contraceptive access policy. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress Reactivity and Corticolimbic Response to Emotional Faces in Adolescents

ERIC Educational Resources Information Center

Liu, Jie; Chaplin, Tara M.; Wang, Fei; Sinha, Rajita; Mayes, Linda C.; Blumberg, Hilary P.

2012-01-01

Objective: Adolescence is a critical period in the development of lifelong patterns of responding to stress. Understanding underpinnings of variations in stress reactivity in adolescents is important, as adolescents with altered stress reactivity are vulnerable to negative risk-taking behaviors including substance use, and have increased lifelong…

Within-summer variation in out-of-hospital cardiac arrest due to extremely long sunshine duration.

PubMed

Onozuka, Daisuke; Hagihara, Akihito

2017-03-15

Although several studies have reported the impacts of extremely high temperatures on cardiovascular diseases, no studies have examined whether variation in out-of-hospital cardiac arrest (OHCA) due to extremely long sunshine duration changes during the summer. We obtained daily data on all cases of OHCA and weather variations for all 47 prefectures of Japan during the summer (June to September) between 2005 and 2014. A distributed lag non-linear model combined with a quasi-Poisson regression model was used to estimate within-summer variation in OHCA due to extremely long sunshine duration for each prefecture. Then, multivariate random-effects meta-analysis was performed to derive overall effect estimates of sunshine duration at the national level. A total of 166,496 OHCAs of presumed cardiac origin met the inclusion criteria. The minimum morbidity percentile (MMP) was the 0th percentile of sunshine duration at the national level. The overall cumulative relative risk (RR) at the 99th percentile vs. the MMP was 1.15 (95% CI: 1.05-1.27) during the summer. The effect of extremely long sunshine duration on OHCA in early summer was acute and did not persist, whereas an identical effect was observed in late summer, but it was delayed and lasted for several days. During summer periods, excessive sunshine duration could increase the risk of OHCA. Timely preventive measures to reduce the OHCA risk due to extremely long sunshine duration are important in early summer, whereas these measures could include a wider time window of several days to reduce the risk in late summer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantifying Geographic Variation in Health Care Outcomes in the United States before and after Risk-Adjustment.

PubMed

Rosenberg, Barry L; Kellar, Joshua A; Labno, Anna; Matheson, David H M; Ringel, Michael; VonAchen, Paige; Lesser, Richard I; Li, Yue; Dimick, Justin B; Gawande, Atul A; Larsson, Stefan H; Moses, Hamilton

2016-01-01

Despite numerous studies of geographic variation in healthcare cost and utilization at the local, regional, and state levels across the U.S., a comprehensive characterization of geographic variation in outcomes has not been published. Our objective was to quantify variation in US health outcomes in an all-payer population before and after risk-adjustment. We used information from 16 independent data sources, including 22 million all-payer inpatient admissions from the Healthcare Cost and Utilization Project (which covers regions where 50% of the U.S. population lives) to analyze 24 inpatient mortality, inpatient safety, and prevention outcomes. We compared outcome variation at state, hospital referral region, hospital service area, county, and hospital levels. Risk-adjusted outcomes were calculated after adjusting for population factors, co-morbidities, and health system factors. Even after risk-adjustment, there exists large geographical variation in outcomes. The variation in healthcare outcomes exceeds the well publicized variation in US healthcare costs. On average, we observed a 2.1-fold difference in risk-adjusted mortality outcomes between top- and bottom-decile hospitals. For example, we observed a 2.3-fold difference for risk-adjusted acute myocardial infarction inpatient mortality. On average a 10.2-fold difference in risk-adjusted patient safety outcomes exists between top and bottom-decile hospitals, including an 18.3-fold difference for risk-adjusted Central Venous Catheter Bloodstream Infection rates. A 3.0-fold difference in prevention outcomes exists between top- and bottom-decile counties on average; including a 2.2-fold difference for risk-adjusted congestive heart failure admission rates. The population, co-morbidity, and health system factors accounted for a range of R2 between 18-64% of variability in mortality outcomes, 3-39% of variability in patient safety outcomes, and 22-70% of variability in prevention outcomes. The amount of variability in health outcomes in the U.S. is large even after accounting for differences in population, co-morbidities, and health system factors. These findings suggest that: 1) additional examination of regional and local variation in risk-adjusted outcomes should be a priority; 2) assumptions of uniform hospital quality that underpin rationale for policy choices (such as narrow insurance networks or antitrust enforcement) should be challenged; and 3) there exists substantial opportunity for outcomes improvement in the US healthcare system.

Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer's Disease: A Pilot Study.

PubMed

Patten, Ryan Van; Fagan, Anne M; Kaufman, David A S

2018-04-04

There exists a need for more sensitive measures, capable of detecting subtle cognitive decline due to Alzheimer's disease. To advance the literature in Alzheimer's disease by demonstrating that performance on a cued-Stroop task is impacted by preclinical Alzheimer's disease neuropathology. Twenty-nine cognitively asymptomatic older adults completed a computerized, cued-Stroop task in which accuracy rates and intraindividual variability in reaction times were the outcomes of interest. Cerebrospinal fluid biomarkers of Aβ42 and tau were measured and participants were then grouped according to a published p-tau/Aβ42 cutoff reflecting risk for Alzheimer's disease (preclinical Alzheimer's disease = 14; control = 15). ANOVAs indicated that accuracy rates did not differ between the groups but 4-second delay incongruent color-naming Stroop coefficient of variation reaction times were higher in the preclinical Alzheimer's disease group compared to the control group, reflecting increased within-person variability. Moreover, partial correlations showed no relationships between cerebrospinal fluid biomarkers and accuracy rates. However, increases in coefficient of variation reaction times correlated with decreased Aβ42 and increases in p-tau and the p-tau/Aβ42 ratio. Results supported the ability of the computerized, cued-Stroop task to detect subtle Alzheimer's disease neuropathology using a small cohort of cognitively asymptomatic older adults. The ongoing measurement of cued-Stroop coefficient of variation reaction times has both scientific and clinical utility in preclinical Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Decision-Making Under Risk in Children, Adolescents, and Young Adults

PubMed Central

Paulsen, David J.; Platt, Michael L.; Huettel, Scott A.; Brannon, Elizabeth M.

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk–return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk. PMID:21687443

Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: A nationwide population-based cohort study.

PubMed

Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K

2016-11-01

Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype-specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Advancing the Hypothesis that Geographic Variations in Risk Factors Contribute Relatively Little to Observed Geographic Variations in Heart Disease and Stroke Mortality

PubMed Central

Howard, George; Cushman, Mary; Prineas, Ronald J.; Howard, Virginia J.; Moy, Claudia S.; Sullivan, Lisa M.; D’Agostino, Ralph B.; McClure, Leslie A.; Pulley, Lea Vonne; Safford, Monika M.

2009-01-01

Purpose Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality. Methods Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates. Results There was no relationship between CHD and stroke mortality rates (r = 0.04; p = 0.78), but there was between CHD and stroke risk scores at the individual (r = 0.68; p < 0.0001) and state (r = 0.64, p < 0.0001) level. There was a stronger (p < 0.0001) association between state-level FCRS and state-level CHD mortality (r = 0.28, p = 0.18), than between FSRS and stroke mortality (r = 0.12, p = 0.56). Conclusions Weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest geographic variation in risk factors may not underlie geographic variations in stroke and CHD mortality. The relationship between risk factor scores and mortality was stronger for CHD than stroke. PMID:19285103

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

PubMed Central

Li, James J.; Savage, Jeanne E.; Kendler, Kenneth S.; Hickman, Matthew; Mahedy, Liam; Macleod, John; Kaprio, Jaakko; Rose, Richard J.; Dick, Danielle M.

2017-01-01

Objective: Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality. Method: We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality. Results: PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence. Conclusions: These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems. PMID:28499112

A prospective study on the variation in falling and fall risk among community-dwelling older citizens in 12 European countries

PubMed Central

Franse, Carmen B; Rietjens, Judith AC; Burdorf, Alex; van Grieken, Amy; Korfage, Ida J; van der Heide, Agnes; Mattace Raso, Francesco; van Beeck, Ed; Raat, Hein

2017-01-01

Objectives The rate of falling among older citizens appears to vary across different countries, but the underlying aspects causing this variation are unexplained. We aim to describe between-country variation in falling and explore whether intrinsic fall risk factors can explain possible variation. Design Prospective study on data from the cross-national Survey of Health, Ageing and Retirement in Europe (SHARE). Setting Twelve European countries (Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland). Participants Community-dwelling persons aged ≥65 years (n=18 596). Measurements Socio-demographic factors (age, gender, education level and living situation) and intrinsic fall risk factors (less than good self-rated health (SRH), mobility limitations, limitations with activities of daily living (ADL), dizziness, impaired vision, depression and impaired cognition) were assessed in a baseline interview. Falling was assessed 2 years later by asking whether the participant had fallen within the 6 months prior to the follow-up interview. Results There was significant between-country variation in the rate of falling (varying from 7.9% in Switzerland to 16.2% in the Czech Republic). The prevalence of intrinsic fall risk factors varied twofold to fourfold between countries. Associations between factors age ≥80 years, less than good SRH, mobility limitations, ADL limitations, dizziness and depression, and falling were different between countries (p<0.05). Between-country differences in falling largely persisted after adjusting for socio-demographic differences but strongly attenuated after adjusting for differences in intrinsic fall risk factors. Conclusion There is considerable variation in the rate of falling between European countries, which can largely be explained by between-country variation in the prevalence of intrinsic fall risk factors. There are also country-specific variations in the association between these intrinsic risk factors and falling. These findings emphasise the importance of addressing intrinsic fall risk in (inter)national fall-prevention strategies, while highlighting country-specific priorities. PMID:28667220

A flexed posture in elderly patients is associated with impairments in postural control during walking.

PubMed

de Groot, Maartje H; van der Jagt-Willems, Hanna C; van Campen, Jos P C M; Lems, Willem F; Beijnen, Jos H; Lamoth, Claudine J C

2014-02-01

A flexed posture (FP) is characterized by protrusion of the head and an increased thoracic kyphosis (TK), which may be caused by osteoporotic vertebral fractures (VFs). These impairments may affect motor function, and consequently increase the risk of falling and fractures. The aim of the current study was therefore to examine postural control during walking in elderly patients with FP, and to investigate the relationship with geriatric phenomena that may cause FP, such as increased TK, VFs, frailty, polypharmacy and cognitive impairments. Fifty-six elderly patients (aged 80 ± 5.2 years; 70% female) walked 160 m at self-selected speed while trunk accelerations were recorded. Walking speed, mean stride time and coefficient of variation (CV) of stride time were recorded. In addition, postural control during walking was quantified by time-dependent variability measures derived from the theory of stochastic dynamics, indicating smoothness, degree of predictability, and local stability of trunk acceleration patterns. Twenty-five patients (45%) had FP and demonstrated a more variable and less structured gait pattern, and a more irregular trunk acceleration pattern than patients with normal posture. FP was significantly associated with an increased TK, but not with other geriatric phenomena. An increased TK may bring the body's centre of mass forward, which requires correcting responses, and reduces the ability to respond on perturbation, which was reflected by higher variation in the gait pattern in FP-patients. Impairments in postural control during walking are a major risk factor for falling: the results indicate that patients with FP have impaired postural control during walking and might therefore be at increased risk of falling. Copyright © 2013 Elsevier B.V. All rights reserved.

Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis.

PubMed

Ogden, Nicholas H; Radojevic, Milka; Wu, Xiaotian; Duvvuri, Venkata R; Leighton, Patrick A; Wu, Jianhong

2014-06-01

The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. We quantified potential effects of future climate change on the basic reproduction number (R0) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R0. Modeled R0 increases were compared with R0 ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. R0 for I. scapularis in North America increased during the years 1971-2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R0 by factors (2-5 times in Canada and 1.5-2 times in the United States), comparable to observed ranges of R0 for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects.

A clustering approach to segmenting users of internet-based risk calculators.

PubMed

Harle, C A; Downs, J S; Padman, R

2011-01-01

Risk calculators are widely available Internet applications that deliver quantitative health risk estimates to consumers. Although these tools are known to have varying effects on risk perceptions, little is known about who will be more likely to accept objective risk estimates. To identify clusters of online health consumers that help explain variation in individual improvement in risk perceptions from web-based quantitative disease risk information. A secondary analysis was performed on data collected in a field experiment that measured people's pre-diabetes risk perceptions before and after visiting a realistic health promotion website that provided quantitative risk information. K-means clustering was performed on numerous candidate variable sets, and the different segmentations were evaluated based on between-cluster variation in risk perception improvement. Variation in responses to risk information was best explained by clustering on pre-intervention absolute pre-diabetes risk perceptions and an objective estimate of personal risk. Members of a high-risk overestimater cluster showed large improvements in their risk perceptions, but clusters of both moderate-risk and high-risk underestimaters were much more muted in improving their optimistically biased perceptions. Cluster analysis provided a unique approach for segmenting health consumers and predicting their acceptance of quantitative disease risk information. These clusters suggest that health consumers were very responsive to good news, but tended not to incorporate bad news into their self-perceptions much. These findings help to quantify variation among online health consumers and may inform the targeted marketing of and improvements to risk communication tools on the Internet.

Environmental Risk Factors influencing Bicycle Theft: A Spatial Analysis in London, UK.

PubMed

Mburu, Lucy Waruguru; Helbich, Marco

2016-01-01

Urban authorities are continuously drawing up policies to promote cycling among commuters. However, these initiatives are counterproductive for the targeted objectives because they increase opportunities for bicycle theft. This paper explores Inner London as a case study to address place-specific risk factors for bicycle theft at the street-segment level while controlling for seasonal variation. The presence of certain public amenities (e.g., bicycle stands, railway stations, pawnshops) was evaluated against locations of bicycle theft between 2013 and 2016 and risk effects were estimated using negative binomial regression models. Results showed that a greater level of risk stemmed from land-use facilities than from area-based socioeconomic status. The presence of facilities such as train stations, vacant houses, pawnbrokers and payday lenders increased bicycle theft, but no evidence was found that linked police stations with crime levels. The findings have significant implications for urban crime prevention with respect to non-residential land use.

[Spatiotemporal dynamic fuzzy evaluation of wetland environmental pollution risk in Dayang estuary of Liaoning Province, Northeast China based on remote sensing].

PubMed

Sun, Yong-Guang; Zhao, Dong-Zhi; Zhang, Feng-Shou; Wei, Bao-Quan; Chu, Jia-Lan; Su, Xiu

2012-11-01

Based on the aerial image data of Dayang estuary in 2008, and by virtue of Analytic Hierarchy Process (AHP) , remote sensing technology, and GIS spatial analysis, a spatiotemporal evaluation was made on the comprehensive level of wetland environmental pollution risk in Dayang estuary, with the impacts of typical human activities on the dynamic variation of this comprehensive level discussed. From 1958 to 2008, the comprehensive level of the environmental pollution risk in study area presented an increasing trend. Spatially, this comprehensive level declined from land to ocean, and showed a zonal distribution. Tourism development activities unlikely led to the increase of the comprehensive level, while human inhabitation, transportation, and aquaculture would exacerbate the risk of environmental pollution. This study could provide reference for the sea area use planning, ecological function planning, and pollutants control of estuary region.

Exposures in the painting trades and paint manufacturing industry and risk of cancer among men and women in Sweden.

PubMed

Brown, Linda Morris; Moradi, Tahereh; Gridley, Gloria; Plato, Nils; Dosemeci, Mustafa; Fraumeni, Joseph F

2002-03-01

Using data from the 1960 and 1970 Swedish censuses and the Swedish Cancer Register for 1971 to 1989, this study investigated variations in cancer risk by gender associated with employment in painting trades and paint manufacturing. Among men, standardized incidence ratios were significantly increased for lung cancer among painters and lacquerers; bladder cancer among artists; and pancreas cancer, lung cancer, and nonlymphocytic leukemia among paint and varnish plant workers. Risks for women were elevated for cancers of the esophagus, larynx, and oral cavity among lacquerers and for oral cancer among glaziers. These findings are consistent with the report of the International Agency for Research on Cancer that classified painting as an occupationally related cause of cancer and provide further evidence that the risk of certain cancers is increased by exposures in the paint manufacturing process.

Plasticity in thermal tolerance has limited potential to buffer ectotherms from global warming.

PubMed

Gunderson, Alex R; Stillman, Jonathon H

2015-06-07

Global warming is increasing the overheating risk for many organisms, though the potential for plasticity in thermal tolerance to mitigate this risk is largely unknown. In part, this shortcoming stems from a lack of knowledge about global and taxonomic patterns of variation in tolerance plasticity. To address this critical issue, we test leading hypotheses for broad-scale variation in ectotherm tolerance plasticity using a dataset that includes vertebrate and invertebrate taxa from terrestrial, freshwater and marine habitats. Contrary to expectation, plasticity in heat tolerance was unrelated to latitude or thermal seasonality. However, plasticity in cold tolerance is associated with thermal seasonality in some habitat types. In addition, aquatic taxa have approximately twice the plasticity of terrestrial taxa. Based on the observed patterns of variation in tolerance plasticity, we propose that limited potential for behavioural plasticity (i.e. behavioural thermoregulation) favours the evolution of greater plasticity in physiological traits, consistent with the 'Bogert effect'. Finally, we find that all ectotherms have relatively low acclimation in thermal tolerance and demonstrate that overheating risk will be minimally reduced by acclimation in even the most plastic groups. Our analysis indicates that behavioural and evolutionary mechanisms will be critical in allowing ectotherms to buffer themselves from extreme temperatures. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Daily variation in natural disaster casualties: information flows, safety, and opportunity costs in tornado versus hurricane strikes.

PubMed

Zahran, Sammy; Tavani, Daniele; Weiler, Stephan

2013-07-01

Casualties from natural disasters may depend on the day of the week they strike. With data from the Spatial Hazard Events and Losses Database for the United States (SHELDUS), daily variation in hurricane and tornado casualties from 5,043 tornado and 2,455 hurricane time/place events is analyzed. Hurricane forecasts provide at-risk populations with considerable lead time. Such lead time allows strategic behavior in choosing protective measures under hurricane threat; opportunity costs in terms of lost income are higher during weekdays than during weekends. On the other hand, the lead time provided by tornadoes is near zero; hence tornados generate no opportunity costs. Tornado casualties are related to risk information flows, which are higher during workdays than during leisure periods, and are related to sheltering-in-place opportunities, which are better in permanent buildings like businesses and schools. Consistent with theoretical expectations, random effects negative binomial regression results indicate that tornado events occurring on the workdays of Monday through Thursday are significantly less lethal than tornados that occur on weekends. In direct contrast, and also consistent with theory, the expected count of hurricane casualties increases significantly with weekday occurrences. The policy implications of observed daily variation in tornado and hurricane events are considered. © 2012 Society for Risk Analysis.

Plasticity in thermal tolerance has limited potential to buffer ectotherms from global warming

PubMed Central

Gunderson, Alex R.; Stillman, Jonathon H.

2015-01-01

Global warming is increasing the overheating risk for many organisms, though the potential for plasticity in thermal tolerance to mitigate this risk is largely unknown. In part, this shortcoming stems from a lack of knowledge about global and taxonomic patterns of variation in tolerance plasticity. To address this critical issue, we test leading hypotheses for broad-scale variation in ectotherm tolerance plasticity using a dataset that includes vertebrate and invertebrate taxa from terrestrial, freshwater and marine habitats. Contrary to expectation, plasticity in heat tolerance was unrelated to latitude or thermal seasonality. However, plasticity in cold tolerance is associated with thermal seasonality in some habitat types. In addition, aquatic taxa have approximately twice the plasticity of terrestrial taxa. Based on the observed patterns of variation in tolerance plasticity, we propose that limited potential for behavioural plasticity (i.e. behavioural thermoregulation) favours the evolution of greater plasticity in physiological traits, consistent with the ‘Bogert effect’. Finally, we find that all ectotherms have relatively low acclimation in thermal tolerance and demonstrate that overheating risk will be minimally reduced by acclimation in even the most plastic groups. Our analysis indicates that behavioural and evolutionary mechanisms will be critical in allowing ectotherms to buffer themselves from extreme temperatures. PMID:25994676

Nutrigenomics, Vitamin D and Cancer Prevention

PubMed Central

Davis, Cindy D.; Milner, John A.

2011-01-01

Although there is growing epidemiological, preclinical and clinical evidence suggesting that low vitamin D intake, exposure and/or status is associated with an increased risk of various types of cancer, the optimum amount needed remains controversial. Furthermore, there is evidence that a U- or J-shaped response curve exist between 25(OH)D and certain cancers. Increasing information about the impact of genetic variation, especially polymorphisms that influence absorption, transport, metabolism and associated molecular targets, should help clarify inconsistencies in the data regarding vitamin D's effect on cancer risk. Rather than focusing on the main effects of a few variants of these genes alone, future studies need to consider gene-nutrient or environmental interactions. Nutrigenomics should clarify who might benefit and be placed at risk because of vitamin D exposure. PMID:21430387

Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

PubMed

Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

2014-09-01

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

Host contact and shedding patterns clarify variation in pathogen exposure and transmission in threatened tortoise Gopherus agassizii: implications for disease modelling and management

USGS Publications Warehouse

Aiello, Christina M.; Nussear, Kenneth E.; Esque, Todd C.; Emblidge, Patrick G.; Sah, Pratha; Bansal, Shweta; Hudson, Peter J.

2016-01-01

Mean field models may misrepresent natural transmission patterns in this and other populations depending on the distribution of high-risk contact and shedding events. Rapid outbreaks in generally solitary species may result from changes to their naturally low-risk contact patterns or due to increases in the frequency of severe infections or super-shedding events – population characteristics that should be further investigated to develop effective management strategies.

Wildfires and post-fire erosion risk in a coastal area under severe anthropic pressure associated with the touristic fluxes

NASA Astrophysics Data System (ADS)

Canu, Annalisa; Arca, Bachisio; Pellizzaro, Grazia; Valeriano Pintus, Gian; Ferrara, Roberto; Duce, Pierpaolo

2017-04-01

In the last decades a rapid and intense development of the tourism industry led to an increasing of anthropic pressure on several coastal areas of Sardinia. This fact not only modified the coastal aesthetics, but has also generated an increase of risk for the environment. This phenomenon affected also the ancient structure of the landscape with a negative impact mainly caused by the following factors: land abandonment, wildfire occurrence, post-fire erosion, urbanization. These regional changes can be analyzed in detail by considering the geo-diachronic dynamics. The main objectives of this work were i) to perform a diachronic analysis of land use and land cover dynamics, ii) to analyse the recent dynamics of wildfires, and iii) to predict the soil erosion risk in relation to land use change occurred between the 1950s and the 2000s. The study was realized in a coastal area located in North-East Sardinia where the geo-historical processes were summarized and organized in a geographic information system that has been employed to examine the landscape variations at three different time steps: 1954, 1977 and 2000. In addition, different scenarios of wildfire propagation were simulated by FlamMap in order to estimate the spatial pattern of fire danger factors in the study area. Afterwards, maps of post-fire soil erosion were produced to identify the temporal and spatial variations of the erosion risk. The results show how the changes in land use and the significant and rapid increase of the residential areas affect the risk of both wildfires and post-fire soil erosion. The study reveals the capabilities of this type of approach and can be used by management agencies and policy makers e in sustainable landscape management planning. This approach can be extended to other regions of the Mediterranean basin characterized by complex interactions among landscape and anthropic factors affecting the environmental risk.

Defining payments associated with the treatment of colorectal cancer.

PubMed

Gani, Faiz; Cerullo, Marcelo; Canner, Joseph K; Conca-Cheng, Alison; Harzman, Alan E; Husain, Syed G; Cirocco, William C; Arnold, Mark W; Traugott, Amber; Johnston, Fabian M; Pawlik, Timothy M

2017-12-01

While bundled payments aim to reduce variations in health care spending across the continuum of care, data reporting on variations in payments for privately insured patients undergoing treatment for colon cancer (CC) are lacking. The current study sought to characterize variations in payments received for the treatment of CC using a cohort of commercially insured patients. Patients who underwent a colectomy for CC were identified using the MarketScan Database for 2010-2014. Multivariable regression analysis was used to calculate and compare risk-adjusted payments between patients. A total of 18,337 patients were identified who met inclusion criteria. The median risk-adjusted payment for surgery was $26,408 (IQR: $19,193-$38,037) ranging from $19,762 (IQR: $15,595-$25,636) among patients in the lowest quartile of payments to $33,809 (IQR: $24,783-$48,254) for patients in the highest (+△71.1%). The median risk-adjusted payment for chemotherapy was $70,090 (IQR: $57,813-$83,216); compared with patients in the lowest quartile of payments, payments associated with chemotherapy were 40.4% higher among patients in the highest quartile of payments (Q1 versus Q4: $56,827 [IQR: 49,173-65,353] versus $79,801 [IQR: 67,270-90,999]). When stratified by treatment type, patients in the highest two quartiles of risk-adjusted payments accounted for a total of 58.5% of all payments, whereas patients in the lower two quartiles of risk-adjusted payments accounted for only 41.5% of all payments. A younger patient age, increasing patient comorbidity and undergoing an open operation were associated with higher overall payments. Wide variations in payments exist for the treatment for colon cancer. Episode-based bundle payments for surgery and chemotherapy may differentially impact reimbursement for CC. Copyright © 2017 Elsevier Inc. All rights reserved.

Quality of Care in Chinese Hospitals: Processes and Outcomes After ST-segment Elevation Myocardial Infarction.

PubMed

Downing, Nicholas S; Wang, Yongfei; Dharmarajan, Kumar; Nuti, Sudhakar V; Murugiah, Karthik; Du, Xue; Zheng, Xin; Li, Xi; Li, Jing; Masoudi, Frederick A; Spertus, John A; Jiang, Lixin; Krumholz, Harlan M

2017-06-23

China has gaps in the quality of care provided to patients with ST-elevation myocardial infarction, but little is known about how quality varies between hospitals. Using nationally representative data from the China PEACE-Retrospective AMI Study, we characterized the quality of care for ST-elevation myocardial infarction at the hospital level and examined variation between hospitals. Two summary measures were used to describe the overall quality of care at each hospital and to characterize variations in quality between hospitals in 2001, 2006, and 2011. The composite rate measured the proportion of opportunities a hospital had to deliver 6 guideline-recommended treatments for ST-elevation myocardial infarction that were successfully met, while the defect-free rate measured the proportion of patients at each hospital receiving all guideline-recommended treatments for which they were eligible. Risk-standardized mortality rates were calculated. Our analysis included 12 108 patients treated for ST-elevation myocardial infarction at 162 hospitals. The median composite rate increased from 56.8% (interquartile range [IQR], 45.9-72.0) in 2001 to 80.5% (IQR, 74.7-84.8) in 2011; however, substantial variation remained in 2011 with defect-free rates ranging from 0.0% to 76.9%. The median risk-standardized mortality rate increased from 9.9% (IQR, 9.1-11.7) in 2001 to 12.6% (IQR, 10.9-14.6) in 2006 before falling to 10.4% (IQR, 9.1-12.4) in 2011. Higher rates of guideline-recommended care and a decline in variation between hospitals are indicative of an improvement in quality. Although some variation persisted in 2011, very top-performing hospitals missed few opportunities to provide guideline-recommended care. Quality improvement initiatives should focus on eliminating residual variation as well as measuring and improving outcomes. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Ecological correlates of group-size variation in a resource-defense ungulate, the sedentary guanaco.

PubMed

Marino, Andrea; Baldi, Ricardo

2014-01-01

For large herbivores, predation-risk, habitat structure and population density are often reported as major determinants of group size variation within and between species. However, whether the underlying causes of these relationships imply an ecological adaptation or are the result of a purely mechanistic process in which fusion and fragmentation events only depend on the rate of group meeting, is still under debate. The aim of this study was to model guanaco family and bachelor group sizes in contrasting ecological settings in order to test hypotheses regarding the adaptive significance of group-size variation. We surveyed guanaco group sizes within three wildlife reserves located in eastern Patagonia where guanacos occupy a mosaic of grasslands and shrublands. Two of these reserves have been free from predators for decades while in the third, pumas often prey on guanacos. All locations have experienced important changes in guanaco abundance throughout the study offering the opportunity to test for density effects. We found that bachelor group size increased with increasing density, as expected by the mechanistic approach, but was independent of habitat structure or predation risk. In contrast, the smaller and territorial family groups were larger in the predator-exposed than in the predator-free locations, and were larger in open grasslands than in shrublands. However, the influence of population density on these social units was very weak. Therefore, family group data supported the adaptive significance of group-size variation but did not support the mechanistic idea. Yet, the magnitude of the effects was small and between-population variation in family group size after controlling for habitat and predation was negligible, suggesting that plasticity of these social units is considerably low. Our results showed that different social units might respond differentially to local ecological conditions, supporting two contrasting hypotheses in a single species, and highlight the importance of taking into account the proximate interests and constraints to which group members may be exposed to when deriving predictions about group-size variation.

Seasonal variations in urinary risk factors among patients with nephrolithiasis

NASA Technical Reports Server (NTRS)

Hill, K.; Poindexter, J.; Pak, C. Y.

1991-01-01

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.

Annual variations and effects of temperature on Legionella spp. and other potential opportunistic pathogens in a bathroom.

PubMed

Lu, Jingrang; Buse, Helen; Struewing, Ian; Zhao, Amy; Lytle, Darren; Ashbolt, Nicholas

2017-01-01

Opportunistic pathogens (OPs) in drinking water, like Legionella spp., mycobacteria, Pseudomonas aeruginosa, and free-living amobae (FLA) are a risk to human health, due to their post-treatment growth in water systems. To assess and manage these risks, it is necessary to understand their variations and environmental conditions for the water routinely used. We sampled premise tap (N cold  = 26, N hot  = 26) and shower (N shower  = 26) waters in a bathroom and compared water temperatures to levels of OPs via qPCR and identified Legionella spp. by 16S ribosomal RNA (rRNA) gene sequencing. The overall occurrence and cell equivalent quantities (CE L -1 ) of Mycobacterium spp. were highest (100 %, 1.4 × 10 5 ), followed by Vermamoeba vermiformis (91 %, 493), Legionella spp. (59 %, 146), P. aeruginosa (14 %, 10), and Acanthamoeba spp. (5 %, 6). There were significant variations of OP's occurrence and quantities, and water temperatures were associated with their variations, especially for Mycobacterium spp., Legionella spp., and V. vermiformis. The peaks observed for Legionella, mainly consisted of Legionella pneumophila sg1 or Legionella anisa, occurred in the temperature ranged from 19 to 49 °C, while Mycobacterium spp. and V. vermiformis not only co-occurred with Legionella spp. but also trended to increase with increasing temperatures. There were higher densities of Mycobacterium in first than second draw water samples, indicating their release from faucet/showerhead biofilm. Legionella spp. were mostly at detectable levels and mainly consisted of L. pneumophila, L. anisa, Legionella donaldsonii, Legionella tunisiensis, and an unknown drinking water isolate based on sequence analysis. Results from this study suggested potential health risks caused by opportunistic pathogens when exposed to warm shower water with low chlorine residue and the use of Mycobacterium spp. as an indicator of premise pipe biofilm and the control management of those potential pathogens.

Testing the effect of risk on intertemporal choice in the Chinese cultural context.

PubMed

Sun, Yan; Li, Shu

2011-01-01

Previous studies using Western samples have found that introducing uncertainty to an intertemporal choice decreases the degree of discounting future rewards. The authors of this article examined the effect of risk on intertemporal choice using Chinese participants and found that respondents preferred the smaller but sooner (SS) outcome to the larger but later (LL) one in the presence of risk, which indicates that risk increases rather than decreases the degree of discounting future rewards. Thus, variations in response patterns between different cultural groups suggest that culture may play an important role in intertemporal choice and researchers should delve into this topic from an emic rather than an etic perspective.

Experimental evidence for adaptive personalities in a wild passerine bird

PubMed Central

Nicolaus, Marion; Tinbergen, Joost M.; Bouwman, Karen M.; Michler, Stephanie P. M.; Ubels, Richard; Both, Christiaan; Kempenaers, Bart; Dingemanse, Niels J.

2012-01-01

Individuals of the same species differ consistently in risky actions. Such ‘animal personality’ variation is intriguing because behavioural flexibility is often assumed to be the norm. Recent theory predicts that between-individual differences in propensity to take risks should evolve if individuals differ in future fitness expectations: individuals with high long-term fitness expectations (i.e. that have much to lose) should behave consistently more cautious than individuals with lower expectations. Consequently, any manipulation of future fitness expectations should result in within-individual changes in risky behaviour in the direction predicted by this adaptive theory. We tested this prediction and confirmed experimentally that individuals indeed adjust their ‘exploration behaviour’, a proxy for risk-taking behaviour, to their future fitness expectations. We show for wild great tits (Parus major) that individuals with experimentally decreased survival probability become faster explorers (i.e. increase risk-taking behaviour) compared to individuals with increased survival probability. We also show, using quantitative genetics approaches, that non-genetic effects (i.e. permanent environment effects) underpin adaptive personality variation in this species. This study thereby confirms a key prediction of adaptive personality theory based on life-history trade-offs, and implies that selection may indeed favour the evolution of personalities in situations where individuals differ in future fitness expectations. PMID:23097506

Elastic scattering spectroscopy for detection of cancer risk in Barrett's esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy

NASA Astrophysics Data System (ADS)

Zhu, Ying; Fearn, Tom; MacKenzie, Gary; Clark, Ben; Dunn, Jason M.; Bigio, Irving J.; Bown, Stephen G.; Lovat, Laurence B.

2009-07-01

Elastic scattering spectroscopy (ESS) may be used to detect high-grade dysplasia (HGD) or cancer in Barrett's esophagus (BE). When spectra are measured in vivo by a hand-held optical probe, variability among replicated spectra from the same site can hinder the development of a diagnostic model for cancer risk. An experiment was carried out on excised tissue to investigate how two potential sources of this variability, pressure and angle, influence spectral variability, and the results were compared with the variations observed in spectra collected in vivo from patients with Barrett's esophagus. A statistical method called error removal by orthogonal subtraction (EROS) was applied to model and remove this measurement variability, which accounted for 96.6% of the variation in the spectra, from the in vivo data. Its removal allowed the construction of a diagnostic model with specificity improved from 67% to 82% (with sensitivity fixed at 90%). The improvement was maintained in predictions on an independent in vivo data set. EROS works well as an effective pretreatment for Barrett's in vivo data by identifying measurement variability and ameliorating its effect. The procedure reduces the complexity and increases the accuracy and interpretability of the model for classification and detection of cancer risk in Barrett's esophagus.

Characterization and source apportionment of health risks from ambient PM10 in Hong Kong over 2000-2011

NASA Astrophysics Data System (ADS)

Li, Zhiyuan; Yuan, Zibing; Li, Ying; Lau, Alexis K. H.; Louie, Peter K. K.

2015-12-01

Atmospheric particulate matter (PM) pollution is a major public health concern in Hong Kong. In this study, the spatiotemporal variations of health risks from ambient PM10 from seven air quality monitoring stations between 2000 and 2011 were analyzed. Positive matrix factorization (PMF) was adopted to identify major source categories of ambient PM10 and quantify their contributions. Afterwards, a point-estimated risk model was used to identify the inhalation cancer and non-cancer risks of PM10 sources. The long-term trends of the health risks from classified local and non-local sources were explored. Furthermore, the reason for the increase of health risks during high PM10 days was discussed. Results show that vehicle exhaust source was the dominant inhalation cancer risk (ICR) contributor (72%), whereas trace metals and vehicle exhaust sources contributed approximately 27% and 21% of PM10 inhalation non-cancer risk (INCR), respectively. The identified local sources accounted for approximately 80% of the ICR in Hong Kong, while contribution percentages of the non-local and local sources for INCR are comparable. The clear increase of ICR at high PM days was mainly attributed to the increase of contributions from coal combustion/biomass burning and secondary sulfate, while the increase of INCR at high PM days was attributed to the increase of contributions from the sources coal combustion/biomass burning, secondary nitrate, and trace metals. This study highlights the importance of health risk-based source apportionment in air quality management with protecting human health as the ultimate target.

Prevalence and risk factors for self-reported diabetes among adult men and women in India: findings from a national cross-sectional survey.

PubMed

Agrawal, Sutapa; Ebrahim, Shah

2012-06-01

We examined the distribution of diabetes and modifiable risk factors to provide data to aid diabetes prevention programmes in India. Population-based cross-sectional survey of men and women included in India's third National Family Health Survey (NFHS-3, 2005-2006). The sample is a multistage cluster sample with an overall response rate of 98 %. All states of India are represented in the sample (except the small Union Territories), covering more than 99 % of the country's population. Women (n 99 574) and men (n 56 742) aged 20-49 years residing in the sample households. Prevalence of diabetes was 1598/100 000 (95 % CI 1462, 1735) among men and 1054/100 000 (95 % CI 974, 1134) among women in India. Rural-urban and marked geographic variation were found with higher rates in south and north-eastern India. Weekly and daily fish intake contributed to a significantly higher risk of diabetes among both women and men. Risks of diabetes increased with increased BMI, age and wealth status of both women and men, but no effects of the consumption of milk/curd, vegetables, eggs, television watching, alcohol consumption or smoking were found. Daily consumption of pulse/beans or fruits was associated with a significantly reduced risk of diabetes among women, whereas non-significant inverse associations were observed in the case of men. Prevalence was underestimated using self-reports. The wide variation in self-reported diabetes is unlikely to be due entirely to reporting biases or access to health care, and indicates that modifiable risk factors exist. Prevention of diabetes should focus on obesity and target specific socio-economic groups in India.

Geographic Variation in Opioid Prescribing in the U.S.

PubMed Central

McDonald, Douglas C.; Carlson, Kenneth; Izrael, David

2012-01-01

Estimates of geographic variation among states and counties in the prevalence of opioid prescribing are developed using data from a large (135M) representative national sample of opioid prescriptions dispensed during 2008 by 37,000 retail pharmacies. Statistical analyses are used to estimate the extent to which county variation is explained by characteristics of resident populations, their healthcare utilization, proxy measures of morbidity, availability of healthcare resources, and prescription monitoring laws. Geographic variation in prevalence of prescribed opioids is large, greater than variation observed for other healthcare services. Counties having the highest prescribing rates for opioids were disproportionately located in Appalachia and in Southern and Western states. The number of available physicians was by far the strongest predictor of amounts prescribed, but only one-third of county variation is explained by the combination of all measured factors. Wide variation in prescribing opioids reflects weak consensus regarding the appropriate use of opioids for treating pain, especially chronic non-cancer pain. Patients’ demands for treatment have increased, more potent opioids have become available, an epidemic of abuse has emerged, and calls for increased government regulation are growing. Greater guidance, education and training in opioid prescribing are needed for clinicians to support appropriate prescribing practices. Perspective Wide geographic variation that does not reflect differences in the prevalence of injuries, surgeries, or conditions requiring analgesics raises questions about opioid prescribing practices. Low prescription rates may indicate under-treatment, while high rates may indicate overprescribing and insufficient attention to risks of misuse. PMID:23031398

NONDRINKER MORTALITY RISK IN THE UNITED STATES

PubMed Central

Rogers, Richard G.; Krueger, Patrick M.; Miech, Richard; Lawrence, Elizabeth M.; Kemp, Robert

2014-01-01

The literature has shown that people who do not drink alcohol are at greater risk for death than light to moderate drinkers, yet the reasons for this remain largely unexplained. We examine whether variation in people's reasons for nondrinking explains the increased mortality. Our data come from the 1988-2006 National Health Interview Survey Linked Mortality File (N= 41,076 individuals age 21 and above, of whom 10,421 died over the follow-up period). The results indicate that nondrinkers include several different groups that have unique mortality risks. Among abstainers and light drinkers the risk of mortality is the same as light drinkers for a subgroup who report that they do not drink because of their family upbringing, and moral/religious reasons. In contrast, the risk of mortality is higher than light drinkers for former drinkers who cite health problems or who report problematic drinking behaviors. Our findings address a notable gap in the literature and may inform social policies to reduce or prevent alcohol abuse, increase health, and lengthen life. PMID:25045194

Long-term cortisol measures predict Alzheimer disease risk.

PubMed

Ennis, Gilda E; An, Yang; Resnick, Susan M; Ferrucci, Luigi; O'Brien, Richard J; Moffat, Scott D

2017-01-24

To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD. © 2016 American Academy of Neurology.

Trends and characteristics of animal-vehicle collisions in the United States.

PubMed

Sullivan, John M

2011-02-01

Since 1990, fatal animal-vehicle collisions (AVCs) in the United States have more than doubled. This paper examines annual AVC trends in the United States over a 19-year period, seasonal and diurnal patterns of AVC risk, the geographic distribution of crash risk by state, and the association between posted speed limit and AVC crash risk in darkness. AVCs were compiled from the Fatality Analysis Reporting System (FARS) and the General Estimates System (GES) for the years 1990-2008 to examine annual crash trends for fatal and nonfatal crashes. Seasonal trends for fatal AVCs were examined with the aggregated FARS dataset; seasonal trends for fatal and nonfatal AVCs were also examined by aggregating four years of Michigan crash data. State-by-state distributions of fatal AVCs were also described with the aggregated FARS dataset. Finally, the relationship between posted speed limit and the odds that a fatal or nonfatal AVC occurred in darkness were examined with logistic regressions using the aggregated FARS and Michigan datasets. Between 1990 and 2008, fatal AVCs increased by 104% and by 1.3 crashes per trillion vehicle miles travelled per year. Although not all AVCs involve deer, daily and seasonal AVC crash trends follow the general activity pattern of deer populations, consistent with prior reports. The odds that a fatal AVC occurred in darkness were also found to increase by 2.3% for each mile-per-hour increase in speed; a similar, albeit smaller, effect was also observed in the aggregated Michigan dataset, among nonfatal crashes. AVCs represent a small but increasing share of crashes in the United States. Seasonal and daily variation in the pattern of AVCs seem to follow variation in deer exposure and ambient light level. Finally, the relative risk that a fatal and nonfatal AVC occurred in darkness is influenced by posted speed limit, suggesting that a driver's limited forward vision at night plays a role in AVCs, as it does in pedestrian collisions. The association between speed limit and crash risk in darkness suggests that AVC risk might be reduced with countermeasures that improve a driver's forward view of the road. Copyright © 2010 Elsevier Ltd. All rights reserved.

Trends in colorectal cancer incidence: a period and birth-cohort analysis in a well-defined French population.

PubMed

Chauvenet, Marion; Cottet, Vanessa; Lepage, Côme; Jooste, Valérie; Faivre, Jean; Bouvier, Anne-Marie

2011-06-30

France stands among high-risk areas for colorectal cancer. Different trends in CRC incidence are reported around the world. The aim of this study was to provide temporal trends in CRC incidence over a 30-year period in a French well-defined population. Between 1976 and 2005, 17,028 new cases were registered by the Burgundy digestive cancer registry. The mean variations in age-standardized incidence rates were estimated using a Poisson regression adjusted for age for each gender and location. The cumulative risk by birth cohort of developing a cancer over the age range 0-74 years was estimated using an age-cohort model. Incidence rates for right and left colon cancers increased more rapidly in males (respectively +11.7% and +10.3% on average by 5-year period) than in females (respectively +5.9% and +6.1%). It remained stable for sigmoid cancers in males (-0.1%) and decreased in females (-5.2%). It also decreased for rectal cancers both in males (-2.7%) and in females (-2.0%). The cumulative risk increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased (4.5% among those born around 1950). It remained at the same level for females born around 1900 (2.7%) as for those born around 1930 (2.7%) and then slightly increased (2.9%) for those born around 1950. For right colon cancers, the cumulative risk increased strikingly in successive birth cohorts from 0.53% to 1.2% in males and 0.55% to 0.77% in females. The corresponding cumulative risks for the left colon were 0.24% and 0.42% in males and 0.14% and 0.29% in females. For sigmoid cancer, they decreased from 1.59% to 1.08% in males, and 0.88% to 0.80% in females. Temporal variations in incidence rates of colorectal cancers differed according to subsite, suggesting different aetiological factors and implications for diagnosis and screening strategies. Total colonoscopy must be the preferred strategy in high-risk groups or after a positive faecal occult blood test.

Auditing Practice Style Variation in Pediatric Inpatient Asthma Care.

PubMed

Silber, Jeffrey H; Rosenbaum, Paul R; Wang, Wei; Ludwig, Justin M; Calhoun, Shawna; Guevara, James P; Zorc, Joseph J; Zeigler, Ashley; Even-Shoshan, Orit

2016-09-01

Asthma is the most prevalent chronic illness among children, remaining a leading cause of pediatric hospitalizations and representing a major financial burden to many health care systems. To implement a new auditing process examining whether differences in hospital practice style may be associated with potential resource savings or inefficiencies in treating pediatric asthma admissions. A retrospective matched-cohort design study, matched for asthma severity, compared practice patterns for patients admitted to Children's Hospital Association hospitals contributing data to the Pediatric Hospital Information System (PHIS) database. With 3 years of PHIS data on 48 887 children, an asthma template was constructed consisting of representative children hospitalized for asthma between April 1, 2011, and March 31, 2014. The template was matched with either a 1:1, 2:1, or 3:1 ratio at each of 37 tertiary care children's hospitals, depending on available sample size. Treatment at each PHIS hospital. Cost, length of stay, and intensive care unit (ICU) utilization. After matching patients (n = 9100; mean [SD] age, 7.1 [3.6] years; 3418 [37.6%] females) to the template (n = 100, mean [SD] age, 7.2 [3.7] years; 37 [37.0%] females), there was no significant difference in observable patient characteristics at the 37 hospitals meeting the matching criteria. Despite similar characteristics of the patients, we observed large and significant variation in use of the ICUs as well as in length of stay and cost. For the same template-matched populations, comparing utilization between the 12.5th percentile (lower eighth) and 87.5th percentile (upper eighth) of hospitals, median cost varied by 87% ($3157 vs $5912 per patient; P < .001); total hospital length of stay varied by 47% (1.5 vs 2.2 days; P < .001); and ICU utilization was 254% higher (6.5% vs 23.0%; P < .001). Furthermore, the patterns of resource utilization by patient risk differed significantly across hospitals. For example, as patient risk increased one hospital displayed significantly increasing costs compared with their matched controls (comparative cost difference: lowest risk, -34.21%; highest risk, 53.27%; P < .001). In contrast, another hospital displayed significantly decreasing costs relative to their matched controls as patient risk increased (comparative cost difference: lowest risk, -10.12%; highest risk, -16.85%; P = .01). For children with asthma who had similar characteristics, we observed different hospital resource utilization; some values differed greatly, with important differences by initial patient risk. Through the template matching audit, hospitals and stakeholders can better understand where this excess variation occurs and can help to pinpoint practice styles that should be emulated or avoided.

A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

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

Little, Mark P., E-mail: mark.little@nih.gov; Stovall, Marilyn; Smith, Susan A.

Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018,more » 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.« less

Increased Attention to Human Sexuality Can Improve HIV-AIDS Prevention Efforts: Key Research Issues and Directions.

ERIC Educational Resources Information Center

Kelly, Jeffrey A.; Kalichman, Seth C.

1995-01-01

Discusses curtailing the human immunodeficiency virus (HIV) by helping people reduce high-risk sexual behavior. Reviews research in the relationship contexts of sexuality, including variations in monogamy, condom use in affectionate versus casual relationships, sexual communication, and coercion. Notes policy and training issues related to human…

The Serotonin Transporter 5-HTTPR Polymorphism is associated with Current and Lifetime Depression in Persons with Chronic Psychotic Disorders

PubMed Central

Contreras, Javier; Hare, Liz; Camarena, Beatriz; Glahn, David; Dassori, Albana; Medina, Rolando; Contrerasa, Salvador; Ramirez, Mercedes; Armas, Regina; Munoz, Rodrigo; Mendoza, Rick; Raventos, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Palmer, Raymond; Escamilla, Michael

2013-01-01

Objective Variation in the serotonin transporter gene (SLC6A4) promoter region has been shown to influence depression in persons who have been exposed to a number of stressful life events. Method We evaluated whether genetic variation in 5-HTTLPR, influences current depression, lifetime history of depression and quantitative measures of depression in persons with chronic psychotic disorders. This is an association study of a genetic variant with quantitative and categorical definitions of depression conducted in the Southwest United States, Mexico, and Costa Rica. We analyzed 260 subjects with a history of psychosis, from a sample of 129 families. Results We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (p<.02, Odds Ratio=2.18, 95% CI=1.10–4.20). Conclusion The “ss” or “sl” genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of psychotic individuals to develop major depression during the course of their illness. PMID:19016667

Is social deprivation an independent predictor of outcomes following cardiac surgery? An analysis of 240,221 patients from a national registry.

PubMed

Barnard, James; Grant, Stuart W; Hickey, Graeme L; Bridgewater, Ben

2015-06-29

Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac surgery risk prediction models. The objective was to investigate geographical variations in social deprivation of patients undergoing cardiac surgery and identify whether social deprivation is an independent predictor of outcomes. National Adult Cardiac Surgery Audit data for coronary artery bypass graft (CABG), or valve surgery performed in England between April 2003 and March 2013, were analysed. Base hospitals in England were divided into geographical regions. Social deprivation was measured by quintile groups of the index of multiple deprivation (IMD) score with the first quintile group (Q1) being the least, and the last quintile group (Q5) the most deprived group. In-hospital mortality and midterm survival were analysed using mixed effects logistic, and stratified Cox proportional hazards regression models respectively. 240,221 operations were analysed. There was substantial regional variation in social deprivation with the proportion of patients in IMD Q5 ranging from 34.5% in the North East to 6.5% in the East of England. Following adjustment for preoperative risk factors, patients undergoing all cardiac surgery in IMD Q5 were found to have an increased risk of in-hospital mortality relative to IMD Q1 (OR=1.13; 95%CI 1.03 to 1.24), as were patients undergoing isolated CABG (OR=1.19; 95%CI 1.03 to 1.37). For midterm survival, patients in IMD Q5 had an increased hazard in all groups (HRs ranged between 1.10 (valve+CABG) and 1.26 (isolated CABG)). For isolated CABG, the median postoperative length of stay was 6 and 7 days, respectively, for IMD Q1-Q4 and Q5. Significant regional variation exists in the social deprivation of patients undergoing cardiac surgery in England. Social deprivation is associated with an increased risk of in-hospital mortality and reduced midterm survival. These findings have implications for health service provision, risk prediction models and analyses of surgical outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

An Online Tool for Global Benchmarking of Risk-Adjusted Surgical Outcomes.

PubMed

Spence, Richard T; Chang, David C; Chu, Kathryn; Panieri, Eugenio; Mueller, Jessica L; Hutter, Matthew M

2017-01-01

Increasing evidence demonstrates significant variation in adverse outcomes following surgery between countries. In order to better quantify these variations, we hypothesize that freely available online risk calculators can be used as a tool to generate global benchmarking of risk-adjusted surgical outcomes. This is a prospective cohort study conducted at an academic teaching hospital in South Africa (GSH). Consecutive adult patients undergoing major general or vascular surgery who met the ACS-NSQIP inclusion criteria for a 3-month period were included. Data variables required by the ACS risk calculator were prospectively collected, and patients were followed for 30 days post-surgery for the occurrence of endpoints. Calculating observed-to-expected ratios for ten outcome measures of interest generated risk-adjusted outcomes benchmarked against the ACS-NSQIP consortium. A total of 373 major general and vascular surgery procedures met the inclusion criteria. The GSH operative cohort varied significantly compared to the 2012 ACS-NSQIP database. The risk-adjusted O/E ratios were significant for any complication O/E 1.91 (95 % CI 1.57-2.31), surgical site infections O/E 4.76 (95 % CI 3.71-6.01), renal failure O/E 3.29 (95 % CI 1.50-6.24), death O/E 3.43 (95 % CI 2.19-5.11), and total length of stay (LOS) O/E 3.43 (95 % CI 2.19-5.11). Freely available online risk calculators can be utilized as tools for global benchmarking of risk-adjusted surgical outcomes.

Fine scale spatial and temporal variation in temperature and arrhythmia episodes in the VA Normative Aging Study

PubMed Central

Zanobetti, Antonella; Coull, Brent A.; Kloog, Itai; Sparrow, David; Vokonas, Pantel S.; Gold, Diane R.; Schwartz, Joel D.

2017-01-01

Many studies have demonstrated that cold and hot temperatures are associated with increased deaths and hospitalization rates; new findings indicate also an association with more specific cardiac risk factors. Most of these existing studies have relied on few weather stations to characterize exposures; few have used residence-specific estimates of temperature, or examined the exposure-response function. We investigated the association of arrhythmia episodes with spatial and temporal variation in temperature. We also evaluated the association between monitored ambient temperature (central) and the same outcome. This longitudinal analysis included 701 older men participating in the VA Normative Aging Study. Arrhythmia episodes were measured as ventricular ectopy (VE) (bigeminy, trigemini or couplets episodes) by 4min electrocardiogram (ECG) monitoring in repeated visits during 2000–2010. The outcome was defined as having or not VE episodes during a study visit. We applied a mixed effect logistic regression model with a random intercept for subject, controlling for seasonality, weekday, medication use, smoking, diabetes status, body mass index and age. We also examined effect modification by personal characteristics, confounding by air pollution, and the exposure-response function. For 1° C increase in the same day residence-specific temperature, the odds of having VE episodes was 1.10 (95%CI: 1.04–1.17). The odds associated with 1° C increase in central temperature was 1.05 (95%CI: 1.02–1.09). The exposure-response function was non-linear for averages of temperature, presenting a J-shaped pattern, suggesting greater risk at lower and higher temperatures. Increased warm temperature and decreased cold temperature may increase the risk of ventricular arrhythmias. PMID:28001123

Increasing incidence of testicular cancer--birth cohort effects.

PubMed

Ekbom, A; Akre, O

1998-01-01

The incidence of testicular cancer is rising in most Western populations. A collaborative study between nine population-based cancer registries in countries around the Baltic Sea was utilized in order to analyze in detail geographic variations and temporal trends in the occurrence of testicular cancer. There were 34,309 cases registered up until 1989 starting in Denmark in 1942 and most recently in Latvia in 1977. From the descriptive epidemiology it was obvious that there was a substantial variation in the age-standardized incidence amounting to about a 10-fold difference between the different countries ranging from 0.8 per 100,000 person-years in Lithuania to 7.6 per 100,000 person-years in Denmark. Previous studies have indicated that this increase is due to birth cohort effects. A more detailed analysis was therefore performed in those six countries with a sufficiently long period of cancer registration; Poland, former East Germany, Norway, Finland, Denmark and Sweden. This analysis showed that birth cohort is a more important determinant of testicular cancer risk than year of diagnosis. In Poland, former East Germany and Finland, there was an increasing risk for all birth cohorts. Among men born in Denmark, Norway or Sweden between 1930 and 1945, this increasing trend in risk was interrupted in these birth cohorts but followed thereafter by an uninterrupted increase by birth cohort. In conclusion, life time exposure to environmental factors which are associated with the incidence of testicular cancer appear to be more related to birth cohort than to year of diagnosis. Because testicular cancer typically occurs at an early age, major etiological factors therefore need to operate early in life, perhaps even in utero.

Is coxa valga a predictor for the severity of knee osteoarthritis? A cross-sectional study.

PubMed

Coskun Benlidayi, Ilke; Guzel, Rengin; Basaran, Sibel; Aksungur, Erol H; Seydaoglu, Gulsah

2015-05-01

In the present study, we aimed to evaluate the affect of the variations in hip anatomy and pelvic geometry on the severity of knee OA. Idiopathic knee OA patients fulfilling the clinical criteria of American College of Rheumatology for OA were enrolled in the study. Several measurements regarding the hip and pelvis were performed on pelvic radiographs. Each knee was graded according to the Kellgren and Lawrence (KL) radiographic system (0-4) along with a categorization in accordance with the medial tibiofemoral joint space widths (JSW). The study group consisted of 111 subjects. The inner and outer pelvic diameters were getting wider as the JSW grade increased. Likewise, among the hip measurements, femoral head, neck and shaft diameters and hip axis lengths were linked with KL grade. There were significant differences in neck-shaft angle (NSA) between groups of JSW with a highest NSA in JSW grade 3. The optimal cut-off value for NSA in predicting the severity of knee OA was 134.4°. Furthermore, NSA beyond 134.4° was found to increase the risk of severe knee OA eightfold. Variations in pelvic geometry and hip anatomy are associated with the severity of knee OA. People with NSA of above 134.4° have eightfold increased risk of developing severe knee OA. Pelvic radiographies could be evaluated at younger ages-particularly in people with high genetic predispositions-to identify the individuals at high risk and in turn, to tailor the preventive measures to these subjects.

Seasonal Variation of Chemical Species Associated With Short-Term Mortality Effects of PM2.5 in Xi’an, a Central City in China

PubMed Central

Huang, Wei; Cao, Junji; Tao, Yebin; Dai, Lingzhen; Lu, Shou-En; Hou, Bin; Wang, Zheng; Zhu, Tong

2012-01-01

The authors conducted a time-series analysis to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) and chemical species in Xi’an, China, using daily air pollution and all-cause and cause-specific mortality data (2004–2008). Poisson regression incorporating natural splines was used to estimate mortality risks of PM2.5 and its chemical components, adjusting for day of the week, time trend, and meteorologic effects. Increases of 2.29% (95% confidence interval: 0.83, 3.76) for all-cause mortality and 3.08% (95% confidence interval: 0.94, 5.26) for cardiovascular mortality were associated with an interquartile range increase of 103.0 μg/m3 in lagged 1–2 day PM2.5 exposure. Stronger effects were observed for the elderly (≥65 years), males, and cardiovascular diseases groups. Secondary components (sulfate and ammonium), combustion species (elemental carbon, sulfur, chlorine), and transition metals (chromium, lead, nickel, and zinc) appeared most responsible for increased risk, particularly in the cold months. The authors concluded that differential association patterns observed across species and seasons indicated that PM2.5-related effects might not be sufficiently explained by PM2.5 mass alone. Future research is needed to examine spatial and temporal varying factors that might play important roles in modifying the PM2.5–mortality association. PMID:22323403

Growth rate variation among passerine species in tropical and temperate sites: an antagonistic interaction between parental food provisioning and nest predation risk

USGS Publications Warehouse

Martin, Thomas E.; Llyod, Penn; Bosque, Carlos; Barton, Daniel C.; Biancucci, Atilio L.; Cheng, Yi-Ru; Ton, Riccardo

2011-01-01

Causes of interspecific variation in growth rates within and among geographic regions remain poorly understood. Passerine birds represent an intriguing case because differing theories yield the possibility of an antagonistic interaction between nest predation risk and food delivery rates on evolution of growth rates. We test this possibility among 64 Passerine species studied on three continents, including tropical and north and south temperate latitudes. Growth rates increased strongly with nestling predation rates within, but not between, sites. The importance of nest predation was further emphasized by revealing hidden allometric scaling effects. Nestling predation risk also was associated with reduced total feeding rates and per-nestling feeding rates within each site. Consequently, faster growth rates were associated with decreased per-nestling food delivery rates across species, both within and among regions. These relationships suggest that Passerines can evolve growth strategies in response to predation risk whereby food resources are not the primary limit on growth rate differences among species. In contrast, reaction norms of growth rate relative to brood size suggest that food may limit growth rates within species in temperate, but not tropical, regions. Results here provide new insight into evolution of growth strategies relative to predation risk and food within and among species.

Disease-Specific Trends of Comorbidity Coding and Implications for Risk Adjustment in Hospital Administrative Data.

PubMed

Nimptsch, Ulrike

2016-06-01

To investigate changes in comorbidity coding after the introduction of diagnosis related groups (DRGs) based prospective payment and whether trends differ regarding specific comorbidities. Nationwide administrative data (DRG statistics) from German acute care hospitals from 2005 to 2012. Observational study to analyze trends in comorbidity coding in patients hospitalized for common primary diseases and the effects on comorbidity-related risk of in-hospital death. Comorbidity coding was operationalized by Elixhauser diagnosis groups. The analyses focused on adult patients hospitalized for the primary diseases of heart failure, stroke, and pneumonia, as well as hip fracture. When focusing the total frequency of diagnosis groups per record, an increase in depth of coding was observed. Between-hospital variations in depth of coding were present throughout the observation period. Specific comorbidity increases were observed in 15 of the 31 diagnosis groups, and decreases in comorbidity were observed for 11 groups. In patients hospitalized for heart failure, shifts of comorbidity-related risk of in-hospital death occurred in nine diagnosis groups, in which eight groups were directed toward the null. Comorbidity-adjusted outcomes in longitudinal administrative data analyses may be biased by nonconstant risk over time, changes in completeness of coding, and between-hospital variations in coding. Accounting for such issues is important when the respective observation period coincides with changes in the reimbursement system or other conditions that are likely to alter clinical coding practice. © Health Research and Educational Trust.

Risks of developing breast and colorectal cancer in association with incomes and geographic locations in Texas: a retrospective cohort study.

PubMed

Liu, Zheyu; Zhang, Kai; Du, Xianglin L

2016-04-26

No study has been conducted to investigate the spatial pattern and association of socioeconomic status (such as income) with breast and colorectal cancer incidence in Texas, United States. This study aimed to determine whether median household income was associated with the risk of developing breast and colorectal cancer in Texas and to identify higher cancer risks by race/ethnicity and geographic areas. This was a retrospective cohort study with an ecological component in using aggregated measures at the county level. We identified 243,677 women with breast cancer and 155,534 men and women with colorectal cancer residing in 254 counties in Texas in 1995-2011 from the public-use dataset of Texas Cancer Registry. The denominator population and median household income at the county level was obtained from the U.S. Bureau of the Census. Cancer incidence rates were calculated as number of cases per 100,000 persons and age-adjusted using the 2000 US population data. We used the ArcGIS v10.1 (geographic information system software) to identify multiple clustered counties with high and low cancer incidences in Texas. Age-adjusted breast cancer incidence rate in the highest median income quintile group was 151.51 cases per 100,000 in 2008-2011 as compared to 98.95 cases per 100,000 in the lowest median income quintile group. The risk of colorectal cancer appeared to decrease with increasing median income in racial/ethnic population. Spatial analysis revealed the significant low breast cancer incidence cluster regions located in southwest US-Mexico border counties in Texas. This study demonstrated that higher income was associated with an increased risk of breast cancer and a decreased risk of colorectal cancer in Texas. There were geographic variations with cancer incidence clustered in high risk areas in Texas. Future studies may need to explore more factors that might explain income and cancer risk associations and their geographic variations.

Elevated stress hormone diminishes the strength of female preferences for acoustic signals in the green treefrog.

PubMed

Davis, A Gabriell; Leary, Christopher J

2015-03-01

Mate selection can be stressful; time spent searching for mates can increase predation risk and/or decrease food consumption, resulting in elevated stress hormone levels. Both high predation risk and low food availability are often associated with increased variation in mate choice by females, but it is not clear whether stress hormone levels contribute to such variation in female behavior. We examined how the stress hormone corticosterone (CORT) affects female preferences for acoustic signals in the green treefrog, Hyla cinerea. Specifically, we assessed whether CORT administration affects female preferences for call rate - an acoustic feature that is typically under directional selection via mate choice by females in most anurans and other species that communicate using acoustic signals. Using a dual speaker playback paradigm, we show that females that were administered higher doses of CORT were less likely to choose male advertisement calls broadcast at high rates. Neither CORT dose nor level was related to the latency of female phonotactic responses, suggesting that elevated CORT does not influence the motivation to mate. Results were also not related to circulating sex steroids (i.e., progesterone, androgens or estradiol) that have traditionally been the focus of studies examining the hormonal basis for variation in female mate choice. Our results thus indicate that elevated CORT levels decrease the strength of female preferences for acoustic signals. Copyright © 2015 Elsevier Inc. All rights reserved.

Individual variation in behavioural plasticity: direct and indirect effects of boldness, exploration and sociability on habituation to predators in lizards.

PubMed

Rodríguez-Prieto, Iñaki; Martín, José; Fernández-Juricic, Esteban

2011-01-22

Little is known about the factors causing variation in behavioural plasticity and the interplay between personality and plasticity. Habituation to predators is a special case of behavioural plasticity. We investigated the direct and indirect effects of boldness, exploration and sociability traits on the habituation ability of Iberian wall lizards, considering exposure and sex effects. Individual boldness was consistent across several non-habituation contexts, but it did not significantly affect habituation. Exploration had a strong direct effect on habituation, with more exploratory individuals being able to habituate faster than less exploratory ones, probably because of their ability to assess risk better. Individual variation in habituation was also affected by sociability, but this was an indirect effect mediated by exposure to the predator. Less social individuals avoided refuges with conspecific cues, increasing exposure to the predator and eventually habituation. Finally, the direct effects of sex (females habituated faster than males) were opposite to its indirect effects through exposure. We conclude that risk assessment, instead of the proactivity-reactivity gradient usually considered in the literature, can affect behavioural plasticity through complex interactions between direct and indirect effects, including exploratory behaviour, degree of exposure to the predator and sex, which represent novel mechanisms generating inter-individual variation in plasticity.

DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

PubMed Central

BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

2017-01-01

The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

Improving prediction of conditions that modulate dengue fever risks in Yucatán, México.

NASA Astrophysics Data System (ADS)

Laureano-Rosario, A. E.; Garcia-Rejon, J. E.; Gomez-Carro, S.; Farfan-Ale, J.; Muller-Karger, F. E.

2015-12-01

Accurately predicting vector-borne diseases is essential for communities everywhere around the world. Yet this is a difficult task, even in areas where annual epidemics occur. The primary vector for dengue virus disease (DENV) is Aedes aegypti. This is a tropical-subtropical mosquito that proliferates in urban areas. Precipitation and increased temperatures are known to promote growth, reproduction and transmission of DENV. This study assesses potential health risks on coastal communities in the northwest Yucatan Peninsula, Mexico. We studied the relation between DENV incidences and environmental data. We hypothesized that environmental parameters such as rainfall, sea surface temperature (SST), air temperature, humidity, and past DENV cases are the primary drivers of DENV incidences. We collected DENV data from the National Health Information System and demographic data from the National Institute of Statistics and Geography. Precipitation and air temperature were obtained from the National Water Commission. SST was derived from the NOAA Advanced Very High Resolution Radiometer (AVHRR) satellite sensor. In addition, incidence of DENV cases per year was calculated. Multiple regression analyses show that previous DENV cases, minimum air temperature, humidity, and precipitation are positively related to DENV cases and explain 82% of the variation, with 77% explained by previous DENV cases (cases that took place 2-weeks before the target). A second regression model without the previous DENV cases showed 30% of the variation explained by humidity and precipitation (p<0.05). Satellite-derived SST was also included to test whether the percent variation of DENV explained increased. These results imply that if these environmental variables continue to increase with time, the trend of DENV cases will also increase. This study suggests that it is possible to significantly improve DENV prevention and prediction of potential outcomes in Yucatan using remote sensing data.

Tick-borne disease risk in a forest food web.

PubMed

Ostfeld, Richard S; Levi, Taal; Keesing, Felicia; Oggenfuss, Kelly; Canham, Charles D

2018-05-08

Changes to the community ecology of hosts for zoonotic pathogens, particularly rodents, are likely to influence the emergence and prevalence of zoonotic diseases worldwide. However, the complex interactions between abiotic factors, pathogens, vectors, hosts, and both food resources and predators of hosts are difficult to disentangle. Here we (1) use 19 years of data from six large field plots in southeastern New York to compare the effects of hypothesized drivers of interannual variation in Lyme disease risk, including the abundance of acorns, rodents, and deer, as well as a series of climate variables; and (2) employ landscape epidemiology to explore how variation in predator community structure and forest cover influences spatial variation in the infection prevalence of ticks for the Lyme disease bacterium, Borrelia burgdorferi, and two other important tick-borne pathogens, Anaplasma phagocytophilum and Babesia microti. Acorn-driven increases in the abundance of mice were correlated with a lagged increase in the abundance of questing nymph-stage Ixodes scapularis ticks infected with Lyme disease bacteria. Abundance of white-tailed deer two years prior also correlated with increased density of infected nymphal ticks, although the effect was weak. Density of rodents in the current year was a strong negative predictor of nymph density, apparently because high current abundance of these hosts can remove nymphs from the host-seeking population. Warm, dry spring or winter weather was associated with reduced density of infected nymphs. At the landscape scale, the presence of functionally diverse predator communities or of bobcats, the only obligate carnivore, was associated with reduced infection prevalence of I. scapularis nymphs with all three zoonotic pathogens. In the case of Lyme disease, infection prevalence increased where coyotes were present but smaller predators were displaced or otherwise absent. For all pathogens, infection prevalence was lowest when forest cover within a 1km radius was high. Taken together, our results suggest that a food web perspective including bottom-up and top-down forcing is needed to understand drivers of tick-borne disease risk, a result that may also apply to other rodent-borne zoonoses. Prevention of exposure based on ecological indicators of heightened risk should help protect public health. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Polymorphisms in Telomere Length Associated TERC and TERT predispose for Ischemic Stroke in a Chinese Han population.

PubMed

Zhang, Shuo; Ji, Guofa; Liang, Yiqian; Zhang, Rui; Shi, Puyu; Guo, Dangshe; Li, Chunqi; Feng, Jing; Liu, Feng; Peng, Rong; Chen, Mingwei

2017-01-06

The role of telomere in genomic stability is an established fact. Variation in leukocyte telomere length (LTL) has been considered a crucial factor that associated with age-associated diseases. To elucidate the association between LTL variation and ischemic stroke (IS) risk, we selected ten single nucleotide polymorphisms (SNPs) in three genes (TERC, TERT and RTEL1) that previously reported link to LTL, and genotyped SNPs of these genes in a case-control study. The association between polymorphisms and IS risk were tested by Chi squared test and haplotype analysis. In allele association analysis, allele "C" in rs10936599 of TERC gene and allele "G" in rs2853677 of TERT gene were found to have an increased risk of IS when compared with allele "T" and "A", respectively. Model association analysis showed that genotype "G/A" in the overdominant model and genotypes "G/A" and "A/A" in the dominant model of rs2242652 presented a more likelihood to have IS. Another TERT locus (rs2853677) with genotype "G" was also found IS-related risky in the log-additive model. Taken together, our results suggest a potential association between LTL related TERC, TERT gene variants and ischemic stroke risk.

Quantifying Neonatal Sucking Performance: Promise of New Methods

PubMed Central

Capilouto, Gilson J.; Cunningham, Tommy J.; Mullineaux, David R.; Tamilia, Eleonora; Papadelis, Christos; Giannone, Peter J.

2017-01-01

Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge. PMID:28324904

Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease.

PubMed

Brambilla, Donald J; Miller, Scott T; Adams, Robert J

2007-09-01

Children with sickle cell disease (SCD) are at elevated risk of stroke. Risk increases with blood flow velocity in selected cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, and use of TCD to screen these patients is widely recommended. Interpretation of TCD results should be based on knowledge of intra-individual variation in blood flow velocity, information not currently available for sickle cell patients. Between 1995 and 2002, 4,141 subjects, 2-16 years old, with homozygous SCD or Sbeta0-thalasemmia and no history of stroke were screened with TCD, including 2,018 subjects screened in one clinical trial (STOP), 1,816 screened in another (STOP 2), and 307 screened in an interim ancillary prospective study. The 812 subjects with >or=2 examinations<6 months apart were selected for analysis, including 242 (29.8%) subjects with normal average velocities (i.e., <170 cm/sec), 350 (43.1%) subjects with conditional velocities (i.e., 170-199 cm/sec), and 220 (27.1%) subjects with abnormal velocities (i.e., >or=200 cm/sec). The intra-subject standard deviation of TCD velocity was estimated from the difference between velocities at the first two interpretable examinations on each subject. An intra-subject standard deviation of 14.9 cm/sec was obtained. Seven (0.9%) subjects had unusually large and unexplained differences between velocities at the two examinations (range of absolute differences: 69-112 cm/sec). While stroke risk is well demonstrated to increase with increasingly abnormal TCD velocity, given the relatively large intra-subject variability, one TCD examination is generally not sufficient to characterize stroke risk in this patient population. Copyright (c) 2007 Wiley-Liss, Inc.

Expression of SLCO transport genes in castration resistant prostate cancer and impact of genetic variation in SCLO1B3 and SLCO2B1 on prostate cancer outcomes

PubMed Central

Wright, Jonathan L; Kwon, Erika M; Ostrander, Elaine A; Montgomery, R Bruce; Lin, Daniel W; Vessella, Robert; Stanford, Janet L; Mostaghel, Elahe A

2011-01-01

Background Metastases from men with castration resistant prostate cancer (CRPC) harbor increased tumoral androgens vs. untreated prostate cancers (PCa). This may reflect steroid uptake by OATP/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether PCa outcomes are associated with single nucleotide polymorphisms (SNPs) in SLCO2B1 and SLCO1B3, transporters previously demonstrated to mediate androgen uptake. Methods Transcripts encoding 11 SLCO genes were analyzed in untreated PCa, and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian PCa patients. Median survival follow-up was 7.0 years (0.77–16.4). The risk of PCa recurrence/progression and PCa-specific mortality (PCSM) was estimated with Cox proportional hazards analysis. Results Six SLCO genes were highly expressed in CRPC metastases vs. untreated PCa, including SLCO1B3 (3.6 fold, p=0.0517) and SLCO2B1 (5.5 fold, p=0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR 1.99, 95% CI 1.11 – 3.55) or SLCO1B3 SNP rs4149117 (HR 1.76, 95% CI 1.00 – 3.08) had an increased risk of PCSM. Conclusions CRPC metastases demonstrate increased expression of SLCO genes vs. primary PCa. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in PCa outcomes. Impact OATP/SLCO genes may be potential biomarkers for assessing risk of prostate cancer-specific mortality. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of non-hormonal based treatment strategies. PMID:21266523

Interleukin genes and associations with colon and rectal cancer risk and overall survival

PubMed Central

Bondurant, Kristina L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Wolff, Roger K.; Slattery, Martha L.

2012-01-01

Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In this study we examined genetic variation in genes from various anti-inflammatory and pro-inflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1555 cases and 1956 controls) and rectal cancer (754 cases and 954 controls) were utilized. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk and CXCR1, and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1, and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/NSAID, cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% CI 1.18–2.56) and 1.96 (95% CI 1.28–2.99) for rectal cancer. These data suggest interleukin genes play a role in risk and overall survival for colon and rectal cancer. PMID:22674296

Integrating Affect and Impulsivity: The Role of Positive and Negative Urgency in Substance Use Risk

PubMed Central

Smith, Gregory T.; Cyders, Melissa A.

2016-01-01

Background The personality traits of positive and negative urgency refer to the tendencies to act rashly when experiencing unusually positive or negative emotions, respectively. Methods The authors review recent empirical work testing urgency theory (Cyders and Smith, 2008a) and consider advances in theory related to these traits. Results Empirical findings indicate that (a) the urgency traits are particularly important predictors of the onset of, and increases in, substance use in both children and young adults; (b) they appear to operate in part by biasing psychosocial learning; (c) pubertal onset is associated with increases in negative urgency, which in turn predict increases in adolescent drinking behavior; (d) variation in negative urgency trait levels are associated with variations in the functioning of an identified brain system; and (e) variations in the serotonin transporter gene, known to influence the relevant brain system, relate to variations in the urgency traits. Conclusion A recent model (Carver, et al., 2008) proposes the urgency traits to be markers of a tendency to respond reflexively to emotion, whether through impulsive action or ill-advised inaction (the latter leading to depressive symptoms); this model has received empirical support. The authors discuss new directions for research on the urgency traits. PMID:27306729

Integrating affect and impulsivity: The role of positive and negative urgency in substance use risk.

PubMed

Smith, Gregory T; Cyders, Melissa A

2016-06-01

The personality traits of positive and negative urgency refer to the tendencies to act rashly when experiencing unusually positive or negative emotions, respectively. The authors review recent empirical work testing urgency theory (Cyders and Smith, 2008a) and consider advances in theory related to these traits. Empirical findings indicate that (a) the urgency traits are particularly important predictors of the onset of, and increases in, substance use in both children and young adults; (b) they appear to operate in part by biasing psychosocial learning; (c) pubertal onset is associated with increases in negative urgency, which in turn predict increases in adolescent drinking behavior; (d) variation in negative urgency trait levels are associated with variations in the functioning of an identified brain system; and (e) variations in the serotonin transporter gene, known to influence the relevant brain system, relate to variations in the urgency traits. A recent model (Carver et al., 2008) proposes the urgency traits to be markers of a tendency to respond reflexively to emotion, whether through impulsive action or ill-advised inaction (the latter leading to depressive symptoms); this model has received empirical support. The authors discuss new directions for research on the urgency traits. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Enterobius vermicularis and risk factors in healthy Norwegian children.

PubMed

Bøås, Håkon; Tapia, German; Sødahl, John A; Rasmussen, Trond; Rønningen, Kjersti S

2012-09-01

The prevalence of Enterobius vermicularis in neighboring countries of Norway show large variation. The goal of this study was to investigate the prevalence among Norwegian children and possible risk factors. The children were participants in "Environmental Triggers of Type 1 Diabetes: the MIDIA study." The study involved 2 groups with different genetic risks of type 1 diabetes: A high-risk group carries the Human Leukocyte Antigen genotype conferring the highest risk for type 1 diabetes and a nonhigh-risk group consisting of children without this genotype. Scotch tape samples were collected on 3 consecutive days and examined by light microscopy. A total of 18% (72/395) of children were positive for E. vermicularis. The highest prevalence (34%) was in children 6-11 years of age. Only 2 children were prior known positives. Increased number of siblings was linked to more infections, and there were fewer infections in the children with the high-risk genotype. E. vermicularis is a common parasite in Norwegian children. The likelihood of E. vermicularis infection depends on family size and prevalence increases with age. The reduced number of infections in the children carrying the high-risk genotype for type 1 diabetes is intriguing and should be investigated further.

Childhood socioeconomic status and longitudinal patterns of alcohol problems: Variation across etiological pathways in genetic risk.

PubMed

Barr, Peter B; Silberg, Judy; Dick, Danielle M; Maes, Hermine H

2018-05-14

Childhood socioeconomic status (SES) is an important aspect of early life environment associated with later life health/health behaviors, including alcohol misuse. However, alcohol misuse is modestly heritable and involves differing etiological pathways. Externalizing disorders show significant genetic overlap with substance use, suggesting an impulsivity pathway to alcohol misuse. Alcohol misuse also overlaps with internalizing disorders, suggesting alcohol is used to cope. These differing pathways could lead to different patterns over time and/or differential susceptibility to environmental conditions, such as childhood SES. We examine whether: 1) genetic risk for externalizing and internalizing disorders influence trajectories of alcohol problems across adolescence to adulthood, 2) childhood SES alters genetic risk these disorders on trajectories of alcohol problems, and 3) these patterns are consistent across sex. We find modest evidence of gene-environment interaction. Higher childhood SES increases the risk of alcohol problems in late adolescence/early adulthood, while lower childhood SES increases the risk of alcohol problems in later adulthood, but only among males at greater genetic risk of externalizing disorders. Females from lower SES families with higher genetic risk of internalizing or externalizing disorders have greater risk of developing alcohol problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

A prospective study on the variation in falling and fall risk among community-dwelling older citizens in 12 European countries.

PubMed

Franse, Carmen B; Rietjens, Judith Ac; Burdorf, Alex; van Grieken, Amy; Korfage, Ida J; van der Heide, Agnes; Mattace Raso, Francesco; van Beeck, Ed; Raat, Hein

2017-06-30

The rate of falling among older citizens appears to vary across different countries, but the underlying aspects causing this variation are unexplained. We aim to describe between-country variation in falling and explore whether intrinsic fall risk factors can explain possible variation. Prospective study on data from the cross-national Survey of Health, Ageing and Retirement in Europe (SHARE). Twelve European countries (Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland). Community-dwelling persons aged ≥65 years (n=18 596). Socio-demographic factors (age, gender, education level and living situation) and intrinsic fall risk factors (less than good self-rated health (SRH), mobility limitations, limitations with activities of daily living (ADL), dizziness, impaired vision, depression and impaired cognition) were assessed in a baseline interview. Falling was assessed 2 years later by asking whether the participant had fallen within the 6 months prior to the follow-up interview. There was significant between-country variation in the rate of falling (varying from 7.9% in Switzerland to 16.2% in the Czech Republic). The prevalence of intrinsic fall risk factors varied twofold to fourfold between countries. Associations between factors age ≥80 years, less than good SRH, mobility limitations, ADL limitations, dizziness and depression, and falling were different between countries (p<0.05). Between-country differences in falling largely persisted after adjusting for socio-demographic differences but strongly attenuated after adjusting for differences in intrinsic fall risk factors. There is considerable variation in the rate of falling between European countries, which can largely be explained by between-country variation in the prevalence of intrinsic fall risk factors. There are also country-specific variations in the association between these intrinsic risk factors and falling. These findings emphasise the importance of addressing intrinsic fall risk in (inter)national fall-prevention strategies, while highlighting country-specific priorities. © 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.

Ethnic variations in chest pain and angina in men and women: Scottish Ethnicity and Health Linkage Study of 4.65 million people.

PubMed

Bhopal, Raj S; Bansal, Narinder; Fischbacher, Colin; Brown, Helen; Capewell, Simon

2012-12-01

European research on ethnic variations in cardiovascular disease has mostly examined mortality endpoints using country of birth as a proxy for ethnicity. We report on chest pain and angina by ethnic group. Retrospective cohort linking the Census 2001 for Scotland (providing 14 ethnic group categories) and hospital discharge/community and hospital deaths data. Directly age-standardized rates and rate ratios were calculated. Risk ratios were adjusted for age and then highest educational qualification of the individual using Poisson regression. Ratios were multiplied by 100 and 95% confidence intervals (CI) were calculated. The reference was the White Scottish population (100). In the results below, the 95% CI excludes 100. There was raised chest pain mortality/hospital discharge risk in Indian men (rate ratio 141.2), Other South Asian women (rate ratio 140.9), and Pakistanis (rate ratio 216.2 in men, 243.0 in women). Rate ratios were lowest in other White British (rate ratio 76.1 in men, 73.7 in women) and Chinese (rate ratio 67.6 in men, 76.7 in women). Adjustment for age and education attenuated, but did not abolish, differences in other White British (risk ratio from 73.5 to 83.5) and Pakistani (risk ratio from 209.0 to 198.2) male populations and increased them in most others, e.g. other South Asian men (from risk ratio of 128.9 to 140.1). Pakistani populations had the highest risk of angina (rate ratio 189.3 in men, 159.7 in women). Other White British (rate ratio 81.4 for men, 78.0 for women), Other White (rate ratio 89.6 men, 85.2 women), and Chinese (rate ratio 60.5 men, 67.4 women) had the lowest risk. Adjustment for education did not greatly alter these patterns. There were important ethnic variations. The results call for replication elsewhere in Europe and targeted prevention programmes and vigilant diagnosis and management by clinicians.

Has the economic crisis widened the intraurban socioeconomic inequalities in mortality? The case of Barcelona, Spain.

PubMed

Maynou, Laia; Saez, Marc; Lopez-Casasnovas, Guillem

2016-02-01

There is considerable evidence demonstrating socioeconomic inequalities in mortality, some of which focuses on intraurban inequalities. However, all the studies assume that the spatial variation of inequalities is stable over the time. We challenge this assumption and propose two hypotheses: (i) have spatial variations in socioeconomic inequalities in mortality at an intraurban level changed over time? and (ii) as a result of the economic crisis, has the gap between such disparities widened? In this paper, our objective is to assess the effect of the economic recession on the spatio-temporal variation of socioeconomic inequalities in mortality in Barcelona (Catalonia, Spain). We used a spatio-temporal ecological design to analyse mortality inequalities at small area level in Barcelona. Mortality data and socioeconomic indicators correspond to the years 2005 and 2008-2011. We specified spatio-temporal ecological mixed regressions for both men and women using two indicators, neighbourhood and year. We allowed the coefficients of the socioeconomic variables to differ according to the levels and explicitly took into account spatio-temporal adjustment. For men and women both absolute and, above all, relative risks for mortality have increased since 2009. In relative terms, this means that the risk of dying has increased much more in the most economically deprived neighbourhoods than in the more affluent ones. Although the geographical pattern in relative risks for mortality in neighbourhoods in Barcelona remained very stable between 2005 and 2011, socioeconomic inequalities in mortality at an intraurban level have surged since 2009. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The benefits of ω-3 supplementation depend on adiponectin basal level and adiponectin increase after the supplementation: A randomized clinical trial.

PubMed

Barbosa, Milena Maria de Araújo Lima; Melo, Alexandra Lorenzzi Trinanes Raposo de; Damasceno, Nágila Raquel Teixeira

2017-02-01

The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes. In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin). After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both). Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Surface water quality assessment in Miyun reservoir watershed, Beijing in the period 1980-2003].

PubMed

Zhang, Wei-wei; Sun, Dan-feng; Li, Hong; Zhou, Lian-di

2010-07-01

Single factor water quality identification index was adopted to assess the surface water quality of Miyun reservoir watershed in Beijing using nearly 20 years monitoring data of 4 sites, also the surface water quality pollution sources were analyzed. The results indicated TP had the largest temporal variation at every monitoring site, coefficients of variation were 93.86%, 86.08%, 50.56% and 139.47%, respectively. The following element was Hg, the coefficients of its variation were 86.08%, 25.75%, 56.52% and 47.01%, respectively. While TN, permanganate index, BOD5, Pb and Cr were relatively stable with small coefficient of temporal variation. The permanganate index, BOD5, Pb and Cr did not exceed to the Chinese surface drinking water standard limit in the study period, while Hg had high pollution risk in several years, such as monitoring sites S1 and S3 in 1992, monitoring sites S4 in 1996. The major pollutants of Miyun reservoir watershed in Beijing were TN and TP, and TN had larger pollution risk compared with TP in most years. Comparing to that before the 1990s, the decade average fertilizer, pesticide and agricultural plastic mulch inputs after the 1990s had increased by 46%, 173% and 359%, respectively. The husbandry proportion in agriculture rose from 24.4% to 39.8%, and the average gross industrial production by 424%. The upstream of Miyun reservoir had larger pollution risk than its downstream. In addition, Chaohe watershed contributed more TN and TP to the reservoir than Baihe watershed.

Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau

PubMed Central

Leng, Shuguang; Picchi, Maria A.; Liu, Yushi; Thomas, Cynthia L.; Willis, Derall G.; Bernauer, Amanda M.; Carr, Teara G.; Mabel, Padilla T.; Han, Younghun; Amos, Christopher I.; Lin, Yong; Stidley, Christine A.; Gilliland, Frank D.; Jacobson, Marty R.; Belinsky, Steven A.

2013-01-01

Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2×10−5) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

Serotonin transporter genotype modulates functional connectivity between amygdala and PCC/PCu during mood recovery

PubMed Central

Fang, Zhuo; Zhu, Senhua; Gillihan, Seth J.; Korczykowski, Marc; Detre, John A.; Rao, Hengyi

2013-01-01

The short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with increased susceptibility to depression. Previous neuroimaging studies have consistently showed increased amygdala activity during the presentation of negative stimuli or regulation of negative emotion in the homozygous short allele carriers, suggesting the key role of amygdala response in mediating increased risk for depression. The brain default mode network (DMN) has also been shown to modulate amygdala activity. However, it remains unclear whether 5-HTTLPR genetic variation modulates functional connectivity (FC) between the amygdala and regions of DMN. In this study, we re-analyzed our previous imaging dataset and examined the effects of 5-HTTLPR genetic variation on amygdala connectivity. A total of 15 homozygous short (S/S) and 15 homozygous long individuals (L/L) were scanned in functional magnetic resonance imaging (fMRI) during four blocks: baseline, sad mood, mood recovery, and return to baseline. The S/S and L/L groups showed a similar pattern of FC and no differences were found between the two groups during baseline and sad mood scans. However, during mood recovery, the S/S group showed significantly reduced anti-correlation between amygdala and posterior cingulate cortex/precuneus (PCC/PCu) compared to the L/L group. Moreover, PCC/PCu-amygdala connectivity correlated with amygdala activity in the S/S group but not the L/L group. These results suggest that 5-HTTLPR genetic variation modulates amygdala connectivity which subsequently affects its activity during mood regulation, providing an additional mechanism by which the S allele confers depression risk. PMID:24198772

ABC Transporter Genes and Risk of Type 2 Diabetes

PubMed Central

Schou, Jesper; Tybjærg-Hansen, Anne; Møller, Holger J.; Nordestgaard, Børge G.; Frikke-Schmidt, Ruth

2012-01-01

OBJECTIVE Alterations of pancreatic β-cell cholesterol content may contribute to β-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown. RESEARCH DESIGN AND METHODS We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C>T) (n = 322) and a common variant (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415). RESULTS Only one of the variants examined, ABCG1 g.-530A>G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C>T) nor ABCG1 g.-530A>G were associated with type 2 diabetes (P values >0.57 and >0.30, respectively). CONCLUSIONS Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1. PMID:23139370

Introduced mammalian predators induce behavioural changes in parental care in an endemic New Zealand bird

USGS Publications Warehouse

Massaro, M.; Starling-Windhof, A.; Briskie, J.V.; Martin, T.E.

2008-01-01

The introduction of predatory mammals to oceanic islands has led to the extension of many birds. Although introduced predators should favour changes that reduce predation risk in surviving bird species, the ability of island birds to respond to such novel changes remains unstudied. We tested whether novel predation risk imposed by introduced mammalian predators has altered the parental behaviour of the endemic New Zealand bellbird (Anthomis melanura). We examined parental behaviour of billbnirds at three woodlands sites in New Zealand that differed in predation risk: 1) a mainland site with exotic predators present (high predation risk), 2) a mainland site with exotic predators experimentally removed (low risk recently) and, 3) an off-shore island where exotic predators were never introduced (low risk always). We also compared parental behavior of bellbirds with two closely related Tasmanian honeyeaters (Phylidonyris spp) that evolved with native nest predators (high risk always). Increased nest predation risk has been postulated to favour reduced parental activity, and we tested whether island bellbirds responded to variation in predation risk. We found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest during incubation. Parental activity during the nestling period, measured as number of feeding visits/hr, also decreased with increasing nest predation risk across sites, and was lowest among the honeyeaters in Tasmania that evolved with native predators. These results demonstrates that some island birds are able to respond to increased risk of predation by novel predators in ways that appear adaptive. We suggest that conservation efforts may be more effective if they take advantage of the ability of island birds to respond to novel predators, especially when the elimination of exotic predators is not possible.

Cesarean Delivery Rates Vary 10-Fold Among US Hospitals; Reducing Variation May Address Quality, Cost Issues

PubMed Central

Kozhimannil, Katy Backes; Law, Michael R.; Virnig, Beth A.

2013-01-01

Cesarean delivery is the most commonly performed surgical procedure in the United States, and cesarean rates are increasing. Working with 2009 data from 593 US hospitals nationwide, we found that cesarean rates varied tenfold across hospitals, from 7.1 percent to 69.9 percent. Even for women with lower-risk pregnancies, in which more limited variation might be expected, cesarean rates varied fifteen-fold, from 2.4 percent to 36.5 percent. Thus, vast differences in practice patterns are likely to be driving the costly overuse of cesarean delivery in many US hospitals. Because Medicaid pays for nearly half of US births, government efforts to decrease variation are warranted. We focus on four promising directions for reducing these variations, including better coordination of maternity care, more data collection and measurement, tying Medicaid payment to quality improvement, and enhancing patient-centered decision making through public reporting. PMID:23459732

Analyte variations in consecutive 24-hour urine collections in children.

PubMed

Ellison, Jonathan S; Hollingsworth, John M; Langman, Craig B; Asplin, John R; Schwaderer, Andrew L; Yan, Phyllis; Bierlein, Maggie; Barraza, Mark A; Defoor, William R; Figueroa, T Ernesto; Jackson, Elizabeth C; Jayanthi, Venkata R; Johnson, Emilie K; Joseph, David B; Shnorhavorian, Margarett

2017-12-01

The metabolic evaluation of children with nephrolithiasis begins with a 24-h urine collection. For adults, the diagnostic yield increases with consecutive collections; however, little is known regarding the variability of multiple 24-h studies in the pediatric population. We sought to evaluate the variability of consecutive 24-h urine collection in children through a multi-institutional study hypothesizing that compared with a single collection, consecutive 24-h urine collections would reveal a greater degree of clinically useful information in the evaluation of children at risk for nephrolithiasis. Including data from six institutions, we identified children less than 18 years of age considered at risk for recurrent nephrolithiasis, undergoing metabolic evaluation. We evaluated a subset of patients performing two collections with urine creatinine varying by 10% or less during a 7-day period. Discordance between repeat collections based on normative urine chemistry values was evaluated. A total of 733 children met inclusion criteria, and in over a third both urine calcium and urine volume differed by 30% or more between samples. Urine oxalate demonstrated greater variation between collections in children <5 years than among older children (p = 0.030) while variation in other parameters did not differ by age. Discordance between repeat samples based on normative values was most common for urine oxalate (22.5%) and the derived relative supersaturation ratios for both calcium phosphate (25.1%) and calcium oxalate (20.5%). The proportion of discordant samples, based on normative thresholds, as well as variability greater ≥30% and 50%, respectively, are shown in the table. Our analysis indicates that stone risk in as many as one in four children may be misclassified if normative values of only a single 24-h urine are used. In light of these findings, repeat 24-h urine collections prior to targeted intervention to modify stone risk are advised to increase diagnostic yield in children at risk for nephrolithiasis. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Baseline assessment of prevalence and geographical distribution of HPV types in Chile using self-collected vaginal samples

PubMed Central

Ferreccio, Catterina; Corvalán, Alejandro; Margozzini, Paula; Viviani, Paola; González, Claudia; Aguilera, Ximena; Gravitt, Patti E

2008-01-01

Background Chile has broad variations in weather, economics and population from the far desert north (Region 1) to the cold, icy south (Region 12). A home-based self-collected vaginal sampling was nested in the 2003 Chilean population-based health survey in order to explore the possibility of a type-specific geographical variation for human papillomavirus Methods The population was a national probability sample of people 17 years of age and over. Consenting women provided self-collected cervicovaginal swabs in universal collection media (UCM). DNA was extracted and typed to 37 HPV genotypes using PGMY consensus PCR and line blot assay. Weighted prevalence rates and adjusted OR were calculated. Results Of the 1,883 women participating in the health survey, 1,219 (64.7%) provided a cervicovaginal sample and in 1,110 (56.2% of participants and 66.5% of those eligible) the samples were adequate for analysis. Refusal rate was 16.9%. HPV prevalence was 29.2% (15.1% high-risk HPV and 14.1% low-risk HPV). Predominant high-risk types were HPV 16, 52, 51, 56 and 58. Predominant low-risk HPVs were HPV 84, CP6108, 62, 53 and 61. High-risk and low-risk HPV rates were inversely correlated between the regions. High-risk HPV prevalence was highest among the youngest women, whereas low-risk HPV increased slightly with age. Conclusion Self-obtained vaginal sampling is adequate for monitoring HPV in the community, for identifying high-risk areas, and for surveying the long term impact of interventions. PMID:18304362

Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China

PubMed Central

Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

2013-01-01

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was −0.21% (95% CI: −0.34% to −0.08%), and the ER for 1 mm increase in rainfall was −0.23% (95% CI: −0.37% to −0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations. PMID:24257434

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.

Population- and individual-specific regulatory variation in Sardinia.

PubMed

Pala, Mauro; Zappala, Zachary; Marongiu, Mara; Li, Xin; Davis, Joe R; Cusano, Roberto; Crobu, Francesca; Kukurba, Kimberly R; Gloudemans, Michael J; Reinier, Frederic; Berutti, Riccardo; Piras, Maria G; Mulas, Antonella; Zoledziewska, Magdalena; Marongiu, Michele; Sorokin, Elena P; Hess, Gaelen T; Smith, Kevin S; Busonero, Fabio; Maschio, Andrea; Steri, Maristella; Sidore, Carlo; Sanna, Serena; Fiorillo, Edoardo; Bassik, Michael C; Sawcer, Stephen J; Battle, Alexis; Novembre, John; Jones, Chris; Angius, Andrea; Abecasis, Gonçalo R; Schlessinger, David; Cucca, Francesco; Montgomery, Stephen B

2017-05-01

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.

The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders

PubMed Central

Spence, Sarah J; Schneider, Mark T

2009-01-01

Autism is a neurodevelopmental disorder of unknown etiology characterized by social and communication deficits and the presence of restricted interests/repetitive behaviors. Higher rates of epilepsy have long been reported, but prevalence estimates vary from as little as 5% to as much as 46%. This variation is probably the result of sample characteristics that increase epilepsy risk such as sample ascertainment, lower IQ, the inclusion of patients with non-idiopathic autism, age, and gender. However, critical review of the literature reveals that the rate in idiopathic cases with normal IQ is still significantly above the population risk suggesting that autism itself is associated with an increased risk of epilepsy. Recently there has been interest in the occurrence of epileptiform electroencephalograms (EEGs) even in the absence of epilepsy. Rates as high as 60% have been reported and some investigators propose that these abnormalities may play a causal role in the autism phenotype. While this phenomenon is still not well understood and risk factors have yet to be determined, the treatment implications are increasingly important. We review the recent literature to elucidate possible risk factors for both epilepsy and epileptiform EEGs. We then review existing data and discuss controversies surrounding treatment of EEG abnormalities. PMID:19454962

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals

PubMed Central

Rich, Alisa L.; Phipps, Laura M.; Tiwari, Sweta; Rudraraju, Hemanth; Dokpesi, Philip O.

2016-01-01

An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID:27660460

Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition.

PubMed

Rohrmann, Sabine; Linseisen, Jakob; Nöthlings, Ute; Overvad, Kim; Egeberg, Rikke; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Cottet, Vanessa; Pala, Valeria; Tumino, Rosario; Palli, Domenico; Panico, Salvatore; Vineis, Paolo; Boeing, Heiner; Pischon, Tobias; Grote, Verena; Teucher, Birigit; Khaw, Kay-Tee; Wareham, Nicholas J; Crowe, Francesca L; Goufa, Ioulia; Orfanos, Philippos; Trichopoulou, Antonia; Jeurnink, Suzanne M; Siersema, Peter D; Peeters, Petra H M; Brustad, Magritt; Engeset, Dagrun; Skeie, Guri; Duell, Eric J; Amiano, Pilar; Barricarte, Aurelio; Molina-Montes, Esther; Rodríguez, Laudina; Tormo, María-José; Sund, Malin; Ye, Weimin; Lindkvist, Björn; Johansen, Dorthe; Ferrari, Pietro; Jenab, Mazda; Slimani, Nadia; Ward, Heather; Riboli, Elio; Norat, Teresa; Bueno-de-Mesquita, H Bas

2013-02-01

Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings. Copyright © 2012 UICC.

Premium variation in the individual health insurance market.

PubMed

Herring, B; Pauly, M V

2001-03-01

Recent proposals to decrease the number of uninsured in the U.S. indicate that the individual health insurance market's role may increase. Amid fears of possible risk-segmentation in individual insurance, there exists limited information of the functioning of such markets. This paper examines the relationship between expected medical expense and actual paid premiums for households with individual insurance in the 1996-1997 Community Tracking Study's Household Survey. We find that premiums vary less than proportionately with expected expense and vary only with certain risk characteristics. We also explore how the relationship between risk and premiums is affected by local regulations and market characteristics. We find that premiums vary significantly less strongly with risk for persons insured by HMOs and in markets dominated by managed care insurers.

Intellectual Disability, Mild Cognitive Impairment, and Risk for Dementia

PubMed Central

Silverman, Wayne P.; Zigman, Warren B.; Krinsky-McHale, Sharon J.; Ryan, Robert; Schupf, Nicole

2013-01-01

People with intellectual disability (ID) are living longer than ever before, raising concerns about old-age associated disorders. Dementia is among the most serious of these disorders, and theories relating cognitive reserve to risk predict that older adults with ID should be particularly vulnerable. Previous estimates of relative risk for dementia associated with ID have been inconsistent, and the present analyses examined the possible influence of variation in diagnostic criteria on findings. As expected, relaxation in the stringency of case definition for adults with ID increased relative risk, underscoring the importance of developing valid criteria for defining mild cognitive impairment, early dementia, and distinguishing between the two in adults with ID. Once available, these standards will contribute to more effective evidence-based planning. PMID:24273589

Variation in Bariatric Surgery Episode Costs in the Commercially Insured: Implications for Bundled Payments in the Private Sector.

PubMed

Kelsall, Alexander C; Cassidy, Ruth; Ghaferi, Amir A

2017-08-01

To describe hospital-level variation in roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in Michigan. Bariatric surgery is an increasingly prevalent elective surgical procedure that will likely be considered for future bundled payment programs, both public and private. Past research in the Medicare population found that the index hospitalization is responsible for the majority of payment variation among hospitals. However, this research largely excluded SG, now the most commonly performed bariatric surgery procedure nationally. We used data from a state-wide quality collaborative to calculate the average risk and price-adjusted 30-day episode payment for patients undergoing RYGB and SG procedures at Michigan hospitals between January 2009 and October 2014. We organized hospitals into quintiles and compared the variation in payments between highest and lowest-cost quintiles, and also the payment categories that drove this variation. We identified 9035 patients undergoing RYGB (n = 4194) or SG (n = 4841) procedures at 31 hospitals. The average price and risk-adjusted episode payment ranged from $11,874 in the lowest hospital quintile to $13,394 in the highest quintile, representing a difference of $1519 (12.8%). Payments for the index hospitalization accounted for the largest share of total episode costs for both procedure types. Despite representing 2.7% to 6.0% of payments across quintiles, postdischarge payments explained 22.6% of hospital variation in SG. Similarly, readmissions explained 24.5% of payment variation for SG episodes, despite representing between 1.2% and 4.4% of payments. Collectively, our findings suggest that there are previously underappreciated differences in episode payment variation between bariatric surgery procedures. SG may be more amenable to cost containment under bundled payment initiatives by virtue of the greater share of variation explained by readmission and postdischarge payments, components of episode payment more likely to be influenced by provider discretion.

Mexican-Origin Youth's Risk Behavior from Adolescence to Young Adulthood: The Role of Familism Values

PubMed Central

Wheeler, Lorey A.; Zeiders, Katharine H.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.; Rodríguez de Jesús, Sue A.; Perez-Brena, Norma J.

2016-01-01

Engagement in risk behavior has implications for individuals' academic achievement, health, and well-being, yet there is a paucity of developmental research on the role of culturally-relevant strengths in individual and family differences in risk behavior involvement among ethnic minority youth. In this study, we used a longitudinal cohort-sequential design to chart intraindividual trajectories of risk behavior and test variation by gender and familism values in 492 youth from 12 to 22 years of age. Participants were older and younger siblings from 246 Mexican-origin families who reported on their risk behaviors in interviews spaced over eight years. Multilevel cohort-sequential growth models revealed that youth reported an increase in risk behavior from 12 to 18 years of age, and then a decline to age 22. Male youth reported greater overall levels and a steeper increase in risk behavior from ages 12 to 18, compared to female youth. For familism values, on occasions when youth reported higher levels, they also reported lower levels of risk behavior (i.e., within-person effect). For sibling dyads characterized by higher average levels of familism values, youth reported lower average levels of risk behavior (i.e., between-family effect). Findings provide unique insights into risk behavior from adolescence to young adulthood among Mexican-origin youth. PMID:28026193

The effect of differences in time to detection of circulating microbubbles on the risk of decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Gilbert, J. H.; Powell, M. R.; Waligora, J. M.

1992-01-01

Circulating microbubbles (CMB) are frequently detected prior to the appearance of symptoms of Decompression Sickness (DCS). It is difficult to analyze the effect of CMB on symptoms due to differences in the time to detection of CMB. This paper uses survival analysis models to evaluate the risk of symptoms in the presence of CMB. Methods: Information on 81 exposures to an altitude of 6,400 m (6.5 psi) for a period of three hours, with simulated extravehicular activities, was examined. The presence or absence of CMB was included as a time dependent covariate of the Cox proportional hazards regression model. Using this technique, the subgroup of exposures with CMB was analyzed further. Mean (S.D.) time in minutes to onset of CMB and symptoms were 125 (63) and 165 (33) respectively, following the three hours exposure. The risk of symptoms (17/81) increased 14 times in the presence of CMB, after controlling for variations in time to detection of CMB. Further, the risk was lower when time to detection of CMB was greater than 60 minutes (risk ratio = 0.96; 95 percent confidence intervals = 0.94 - 0.99 0.99 P less than 0.01) compared to CMB before 60 minutes at altitude. Conclusions: Survival analysis showed that individual risk of DCS changes significantly due to variations in time to detection of CMB. This information is important in evaluating the risk of DCS in the presence of CMB.

Prevalence of hypertension and circadian blood pressure variations in patients with obstructive sleep apnoea-hypopnoea syndrome.

PubMed

Wang, Yan; Li, Caili; Feng, Liting; Feng, Jing; Cao, Jie; Chen, Baoyuan

2014-06-01

To investigate the prevalence of hypertension and circadian blood pressure (BP) variations in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Patients referred to a sleep clinic underwent polysomnography with measurement of BP at four time points. They were classified into four groups (control, and mild, moderate or severe sleep apnoea) using the apnoea-hypopnoea index (AHI). Circadian variation was assessed using night-time to daytime mean BP (R(N/D)) and morning to evening mean BP (R(M/E)) ratios. Hypertension was significantly more common in patients with OSAHS (50.5%) than in controls (30.4%). AHI was positively correlated with hypertension after controlling for related confounders. Mean BP values at all four time points rose with increasing AHI. The increase in night-time and morning values was more pronounced than the increase in daytime and evening values in patients with OSAHS, resulting in loss of the normal BP diurnal rhythm. The R(N/D) and R(M/E) ratios increased with increasing AHI. Daytime BP was significantly correlated with AHI and the lowest oxygen saturation value. OSAHS was shown to be an independent risk factor for hypertension. It was also associated with loss of the normal BP diurnal rhythm. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Spatial variation in mortality risk for haematological malignancies near a petrochemical refinery: a population-based case-control study

PubMed Central

Di Salvo, Francesca; Meneghini, Elisabetta; Vieira, Veronica; Baili, Paolo; Mariottini, Mauro; Baldini, Marco; Micheli, Andrea; Sant, Milena

2015-01-01

Introduction The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. Material and methods A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied. We mapped (1) adptive kernel density relative risk estimation (KDE) for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls’ densities, and (2) estimated odds ratios for case-control study data using generalized additive models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. Results No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2–6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. Conclusion Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling. PMID:26073202

Multilocus genetic profile in dopaminergic pathway modulates the striatum and working memory.

PubMed

Wang, Chao; Liu, Bing; Zhang, Xiaolong; Cui, Yue; Yu, Chunshui; Jiang, Tianzi

2018-03-29

Dopamine is critical in pathophysiology and therapy of schizophrenia. Many studies have reported altered dopaminergic activity in the dorsal but not ventral striatum in schizophrenia. Based on the largest genome-wide association study of schizophrenia to date, we calculated the polygenic risk score (PGRS) of each subject in a healthy general group, including all variations in the set of functionally related genes involved in dopamine neurotransmitter system. We aimed to test whether the genetic variations in the dopaminergic pathway that have been identified as associated with schizophrenia are related to the function of the striatum and to working memory. We found that a higher PGRS was significantly associated with impairment in working memory. Moreover, resting-state functional connectivity analysis revealed that as the polygenic risk score increased, the connections between left putamen and caudate and the default mode network grew stronger, while the connections with the fronto-parietal network grew weaker. Our findings may shed light on the biological mechanism underlying the "dopamine hypothesis" of schizophrenia and provide some implications regarding the polygenic effects on the dopaminergic activity in the risk for schizophrenia.

Usage of mitochondrial D-loop variation to predict risk for Huntington disease.

PubMed

Mousavizadeh, Kazem; Rajabi, Peyman; Alaee, Mahsa; Dadgar, Sepideh; Houshmand, Massoud

2015-08-01

Huntington's disease (HD) is an inherited autosomal neurodegenerative disease caused by the abnormal expansion of the CAG repeats in the Huntingtin (Htt) gene. It has been proven that mitochondrial dysfunction is contributed to the pathogenesis of Huntington's disease. The mitochondrial displacement loop (D-loop) is proven to accumulate mutations at a higher rate than other regions of mtDNA. Thus, we hypothesized that specific SNPs in the D-loop may contribute to the pathogenesis of Huntington's disease. In the present study, 30 patients with Huntington's disease and 463 healthy controls were evaluated for mitochondrial mutation sites within the D-loop region using PCR-sequencing method. Sequence analysis revealed 35 variations in HD group from Cambridge Mitochondrial Sequences. A significant difference (p < 0.05) was seen between patients and control group in eight SNPs. Polymorphisms at C16069T, T16126C, T16189C, T16519C and C16223T were correlated with an increased risk of HD while SNPs at C16150T, T16086C and T16195C were associated with a decreased risk of Huntington's disease.

Exploring the factors that influence the perception of risk: The case of Volcán de Colima, Mexico

NASA Astrophysics Data System (ADS)

Gavilanes-Ruiz, Juan Carlos; Cuevas-Muñiz, Alicia; Varley, Nick; Gwynne, Gemma; Stevenson, John; Saucedo-Girón, Ricardo; Pérez-Pérez, Anaid; Aboukhalil, Mary; Cortés-Cortés, Abel

2009-10-01

Volcán de Colima has increased its activity considerably since 1998 with four periods of effusion and since 2003, daily Vulcanian explosions. During 2005 the magnitude of the explosivity increased, producing many pyroclastic flows, two of which reached over 5 km from the volcano, making them the largest events since the last Plinian eruption in 1913. A significant risk is also presented by the lahar hazard, with various examples of damage to infrastructure during the last few years and 23 people killed in 1955. Nearly 5000 people live in small settlements within 15 km of the volcano. Since 1997 six studies have been carried out in the region in an attempt to define the relationship that exists between the population and its neighbour. Although the methodologies used were different, each study considered the results of the previous and attempted to contribute further data to define geographical variation in the perception of risk. The results of the studies highlight the minor role of increasing activity on risk perception, and distance from the volcano was shown to not directly influence risk perception. In most cases it is the combination of various socio-cultural, historical and political factors that defines the perception of volcanic risk within these villages. By studying the social representation of the risk, such complexity could be better understood. The 1997-2000 information campaign evidently improved risk perception; however, it is clear that this type of program needs to be continued to achieve a long lasting impact. Increased knowledge, however, does not guarantee willing participation in official risk mitigation strategies.

Mapping the Risk of Soil-Transmitted Helminthic Infections in the Philippines

PubMed Central

Leonardo, Lydia; Gray, Darren J.; Carabin, Hélène; Halton, Kate; McManus, Donald P.; Williams, Gail M.; Rivera, Pilarita; Saniel, Ofelia; Hernandez, Leda; Yakob, Laith; McGarvey, Stephen T.; Clements, Archie C. A.

2015-01-01

Background In order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection. Methodology/Principal Findings Data on STH infection from 35,573 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was stratified geographically in two major regions: 1) Luzon and the Visayas and 2) Mindanao. Bayesian geostatistical models of STH prevalence were developed, including age and sex of individuals and environmental variables (rainfall, land surface temperature and distance to inland water bodies) as predictors, and diagnostic uncertainty was incorporated. The role of environmental variables was different between regions of the Philippines. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. Conclusions/Significance This analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon. PMID:26368819

Genetic variation in the folate metabolic pathway and risk of childhood leukemia

PubMed Central

Johnston, W. Thomas; Painter, Dan; Simpson, Jill; Roman, Eve; Skibola, Chris F.; Smith, Martyn T.; Allan, James M.; Taylor, G. Malcolm

2010-01-01

Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C>T, MTHFR 1298 A>C, SHMT1 1420 C>T, MTR 2756 A>G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development. PMID:20101025

Applying Self-Determination Theory to Adolescent Sexual-Risk Behavior and Knowledge: A Structural Equation Model [Formula: see text].

PubMed

Riley, Bettina H; McDermott, Ryon C

2018-05-01

National health priorities identify adolescent sexual-risk behavior outcomes as research and intervention targets for mental health. Reduce sexual-risk behavioral outcomes by applying self-determination theory to focus on decision-making autonomy. This study examined late adolescents' recollections of parental autonomy support/sexual-risk communication experiences and autonomy motivation as predictors of sexual-risk behaviors/knowledge. A convenience sample ( N = 249) of 19- and 20-year-old university students completed self-report questionnaires. Structural equation modeling with latent variables examined direct/indirect effects in the hypothesized model. Parents contributed uniquely through sexual-risk communication and/or autonomy support to late adolescents' autonomous motivation. The final model evidenced acceptable fit and explained 12% of the variation in adolescent sexual-risk behavior, 7% in adolescent autonomous motivation, and 2% in adolescent sexual-risk knowledge. Psychiatric mental health nurses should conduct further research and design interventions promoting parent autonomy support and adolescent autonomous motivation to reduce sexual risk-behavior and increase sexual-risk knowledge.

Porosity, Mineralization, Tissue Type and Morphology Interactions at the Human Tibial Cortex

NASA Astrophysics Data System (ADS)

Hampson, Naomi A.

Prior research has shown a relationship between tibia robustness (ratio of cross-sectional area to bone length) and stress fracture risk, with less robust bones having a higher risk, which may indicate a compensatory increase in elastic modulus to increase bending strength. Previous studies of human tibiae have shown higher ash content in slender bones. In this study, the relationships between variations in volumetric porosity, ash content, tissue mineral density, secondary bone tissue, and cross sectional geometry, were investigated in order to better understand the tissue level adaptations that may occur in the establishment of cross-sectional properties. In this research, significant differences were found between porosity, ash content, and tissue type around the cortex between robust and slender bones, suggesting that there was a level of co-adaption occurring. Variation in porosity correlated with robustness, and explained large parts of the variation in tissue mineral density. The nonlinear relationship between porosity and ash content may support that slender bones compensate for poor geometry by increasing ash content through reduced remodeling, while robust individuals increase porosity to decrease mass, but only to a point. These results suggest that tissue level organization plays a compensatory role in the establishment of adult bone mass, and may contribute to differences in bone aging between different bone phenotypes. The results suggest that slender individuals have significantly less remodeled bone, however the proportion of remodeled bone was not uniform around the tibia. In the complex results of the study of 38% vs. 66% sites the distal site was subject to higher strains than the 66% site, indicating both local and global regulators may be affecting overall remodeling rates and need to be teased apart in future studies. This research has broad clinical implications on the diagnosis and treatment of fragility fractures. The relationships that were found between local variables and global geometry indicate that there was a fundamental difference between robust and slender bones, which affect the overall properties of the bone. This could allow for simple testing of bone geometry to predict an individual's fracture risk.

Suicidal Ideation in College Students Varies across Semesters: The Mediating Role of Belongingness

ERIC Educational Resources Information Center

Van Orden, Kimberly A.; Witte, Tracy K.; James, Lisa M.; Castro, Yessenia; Gordon, Kathryn H.; Braithwaite, Scott R.; Hollar, Daniel L.; Joiner, Thomas E., Jr.

2008-01-01

The interpersonal-psychological theory of suicidal behavior (Joiner, 2005) proposes that the need to belong is fundamental; when met it can prevent suicide and when thwarted it can substantially increase the risk for suicide. We investigate one source of group-wide variation in belongingness among college students--changes in the social…

The Impact of Federal Preemption of State Antipredatory Lending Laws on the Foreclosure Crisis

ERIC Educational Resources Information Center

Ding, Lei; Quercia, Roberto G.; Reid, Carolina K.; White, Alan M.

2012-01-01

State antipredatory lending laws (APLs) are designed to protect borrowers against predatory lending that can increase the risk of default and deplete the home equity held by borrowers. Federal regulators instituted preemption that limited the scope and reach of state antipredatory lending regulations for certain lenders. Based on the variation in…

APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population

USDA-ARS?s Scientific Manuscript database

APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the c...

The effect of atmospheric temperature and pressure on the occurrence of acute myocardial infarction in Kaunas.

PubMed

Radišauskas, Ričardas; Vaičiulis, Vidmantas; Ustinavičienė, Rūta; Bernotienė, Gailutė

2013-01-01

OBJECTIVE. The aim of the study was to evaluate the impact of meteorological variables (atmospheric temperature and pressure) on the daily occurrence of acute myocardial infarction (AMI). MATERIAL AND METHODS. The study used the daily values of atmospheric temperature and pressure in 2000-2007. The meteorological data were obtained from the Lithuanian Hydrometeorological Service for Kaunas. The relative risks of event occurrence were computed for 5°C atmospheric temperature and for 10-hPa atmospheric pressure variations by means of the Poisson regression model. RESULTS. The occurrence of AMI and atmospheric temperature showed an inverse linear relationship, while the occurrence of AMI and atmospheric pressure, a positive linear relationship. Among the youngest subjects (25-44 years old), no relationships were detected. Contrary, among the subjects aged 45-64 years and those aged 65 years and older, the occurrence of AMI significantly decreased with higher temperature (P=0.001 and P=0.002, respectively). A decrease in atmospheric temperature by 10ºC reduced the risk of AMI by 8.7% in the age groups of 45-64 and 65 years and older and by 19% in the age group of 25 years and older. Among the first AMI cases, the risk increased by 7.5% in the age group of 45-64-year olds and by 6.4% in the age group of 25-64-year olds. The relationship between atmospheric temperature and pressure, and AMI occurrence was found to be linear but inverse. An increase in atmospheric pressure by 10 hPa resulted in an increase in risk by 4% among the subjects aged 65 years and more and by 3% among the subjects aged 25 years and more. CONCLUSIONS. Atmospheric temperature and pressure variations had the greatest effect on middle-aged and aging subjects (starting from 45 years). At younger age, the effect of such factors on the AMI risk was considerably lower.

The worldwide airline network and the dispersal of exotic species: 2007–2010

PubMed Central

Tatem, Andrew J

2009-01-01

International air travel has played a significant role in driving recent increases in the rates of biological invasion and spread of infectious diseases. By providing high speed, busy transport links between spatially distant, but climatically similar regions of the world, the worldwide airline network (WAN) increases the risks of deliberate or accidental movements and establishment of climatically sensitive exotic organisms. With traffic levels continuing to rise and climates changing regionally, these risks will vary, both seasonally and year-by-year. Here, detailed estimates of air traffic trends and climate changes for the period 2007–2010 are used to examine the likely directions and magnitudes of changes in climatically sensitive organism invasion risk across the WAN. Analysis of over 144 million flights from 2007–2010 shows that by 2010, the WAN is likely to change little overall in terms of connecting regions with similar climates, but anticipated increases in traffic and local variations in climatic changes should increase the risks of exotic species movement on the WAN and establishment in new areas. These overall shifts mask spatially and temporally heterogenous changes across the WAN, where, for example, traffic increases and climatic convergence by July 2010 between parts of China and northern Europe and North America raise the likelihood of exotic species invasions, whereas anticipated climatic shifts may actually reduce invasion risks into much of eastern Europe. PMID:20300170

Sociodemographic and cultural determinants of sleep deficiency: implications for cardiometabolic disease risk.

PubMed

Knutson, Kristen L

2013-02-01

Sleep is a biological imperative associated with cardiometabolic disease risk. As such, a thorough discussion of the sociocultural and demographic determinants of sleep is warranted, if not overdue. This paper begins with a brief review of the laboratory and epidemiologic evidence linking sleep deficiency, which includes insufficient sleep and poor sleep quality, with increased risk of chronic cardiometabolic diseases such as obesity, diabetes and hypertension. Identification of the determinants of sleep deficiency is the critical next step to understanding the role sleep plays in human variation in health and disease. Therefore, the majority of this paper describes the different biopsychosocial determinants of sleep, including age, gender, psychosocial factors (depression, stress and loneliness), socioeconomic position and race/ethnicity. In addition, because sleep duration is partly determined by behavior, it will be shaped by cultural values, beliefs and practices. Therefore, possible cultural differences that may impact sleep are discussed. If certain cultural, ethnic or social groups are more likely to experience sleep deficiency, then these differences in sleep could increase their risk of cardiometabolic diseases. Furthermore, if the mechanisms underlying the increased risk of sleep deficiency in certain populations can be identified, interventions could be developed to target these mechanisms, reduce sleep differences and potentially reduce cardiometabolic disease risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

NO2 and Cancer Incidence in Saudi Arabia

PubMed Central

Al-Ahmadi, Khalid; Al-Zahrani, Ali

2013-01-01

Air pollution exposure has been shown to be associated with an increased risk of specific cancers. This study investigated whether the number and incidence of the most common cancers in Saudi Arabia were associated with urban air pollution exposure, specifically NO2. Overall, high model goodness of fit (GOF) was observed in the Eastern, Riyadh and Makkah regions. The significant coefficients of determination (r2) were higher at the regional level (r2 = 0.32–0.71), weaker at the governorate level (r2 = 0.03–0.43), and declined slightly at the city level (r2 = 0.17–0.33), suggesting that an increased aggregated spatial level increased the explained variability and the model GOF. However, the low GOF at the lowest spatial level suggests that additional variation remains unexplained. At different spatial levels, associations between NO2 concentration and the most common cancers were marginally improved in geographically weighted regression (GWR) analysis, which explained both global and local heterogeneity and variations in cancer incidence. High coefficients of determination were observed between NO2 concentration and lung and breast cancer incidences, followed by prostate, bladder, cervical and ovarian cancers, confirming results from other studies. These results could be improved using individual explanatory variables such as environmental, demographic, behavioral, socio-economic, and genetic risk factors. PMID:24192792

Soy isoflavone intake is associated with risk of Kawasaki disease

PubMed Central

Portman, Michael A.; Navarro, Sandi L.; Bruce, Margaret E.; Lampe, Johanna W.

2016-01-01

Kawasaki disease (KD) is an acute vasculitis affecting children. Incidence of KD varies according to ethnicity and is highest in Asian populations. Although genetic differences may explain this variation, dietary or environmental factors could also be responsible. The objectives of this study were to determine dietary soy and isoflavone consumption in a cohort of KD children just before disease onset and their mothers' intake during pregnancy and nursing. We tested the hypothesis that soy isoflavone consumption is associated with risk of KD in US children, potentially explaining some of the ethnic-cultural variation in incidence. We evaluated soy food intake and isoflavone consumption in nearly 200 US KD cases and 200 age-matched controls using a food frequency questionnaire for children and in their mothers. We used a logistic regression model to test the association of isoflavones and KD. Maternal surveys on soy intake during pregnancy and nursing showed no significant differences in isoflavone consumption between groups. However, we identified significantly increased KD risk in children for total isoflavone (odds ratio [OR], 2.33; 95%confidence interval [CI], 1.37–3.96) and genistein (OR, 2.46; 95% CI, 1.46–4.16) intakes, when comparing high soy consumers vs nonconsumers. In addition, significantly increased KD risk occurred in Asian-American children with the highest consumption (total isoflavones: OR, 7.29; 95% CI, 1.73–30.75; genistein: OR, 8.33; 95% CI, 1.92–36.24) compared to whites. These findings indicate that childhood dietary isoflavone consumption, but not maternal isoflavone intake during pregnancy and nursing, relates to KD risk in an ethnically diverse US population. PMID:27440537

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

PubMed Central

Springelkamp, Henriët; Iglesias, Adriana I.; Mishra, Aniket; Höhn, René; Wojciechowski, Robert; Khawaja, Anthony P.; Nag, Abhishek; Wang, Ya Xing; Wang, Jie Jin; Cuellar-Partida, Gabriel; Gibson, Jane; Bailey, Jessica N. Cooke; Vithana, Eranga N.; Gharahkhani, Puya; Boutin, Thibaud; Ramdas, Wishal D.; Zeller, Tanja; Luben, Robert N.; Yonova-Doing, Ekaterina; Viswanathan, Ananth C.; Yazar, Seyhan; Cree, Angela J.; Haines, Jonathan L.; Koh, Jia Yu; Souzeau, Emmanuelle; Wilson, James F.; Amin, Najaf; Müller, Christian; Venturini, Cristina; Kearns, Lisa S.; Kang, Jae Hee; Tham, Yih Chung; Zhou, Tiger; van Leeuwen, Elisabeth M.; Nickels, Stefan; Sanfilippo, Paul; Liao, Jiemin; van der Linde, Herma; Zhao, Wanting; van Koolwijk, Leonieke M.E.; Zheng, Li; Rivadeneira, Fernando; Baskaran, Mani; van der Lee, Sven J.; Perera, Shamira; de Jong, Paulus T.V.M.; Oostra, Ben A.; Uitterlinden, André G.; Fan, Qiao; Hofman, Albert; Tai, E-Shyong; Vingerling, Johannes R.; Sim, Xueling; Wolfs, Roger C.W.; Teo, Yik Ying; Lemij, Hans G.; Khor, Chiea Chuen; Willemsen, Rob; Lackner, Karl J.; Aung, Tin; Jansonius, Nomdo M.; Montgomery, Grant; Wild, Philipp S.; Young, Terri L.; Burdon, Kathryn P.; Hysi, Pirro G.; Pasquale, Louis R.; Wong, Tien Yin; Klaver, Caroline C.W.; Hewitt, Alex W.; Jonas, Jost B.; Mitchell, Paul; Lotery, Andrew J.; Foster, Paul J.; Vitart, Veronique; Pfeiffer, Norbert; Craig, Jamie E.; Mackey, David A.; Hammond, Christopher J.; Wiggs, Janey L.; Cheng, Ching-Yu; van Duijn, Cornelia M.; MacGregor, Stuart

2017-01-01

Abstract Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk. PMID:28073927

Nationwide data on municipal drinking water and hip fracture: could calcium and magnesium be protective? A NOREPOS study.

PubMed

Dahl, Cecilie; Søgaard, Anne Johanne; Tell, Grethe S; Flaten, Trond Peder; Hongve, Dag; Omsland, Tone Kristin; Holvik, Kristin; Meyer, Haakon E; Aamodt, Geir

2013-11-01

Norway has a high incidence of hip fractures, and the incidence varies by degree of urbanization. This variation may reflect a difference in underlying environmental factors, perhaps variations in the concentration of calcium and magnesium in municipal drinking water. A trace metal survey (1986-1991) in 556 waterworks (supplying 64% of the Norwegian population) was linked geographically to hip fractures from hospitals throughout the country (1994-2000). In all, 5472 men and 13,604 women aged 50-85years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, urbanization degree, region of residence, type of water source, and pH. The concentrations of calcium and magnesium in drinking water were generally low. An inverse association was found between concentration of magnesium and risk of hip fracture in both genders (IRR men highest vs. lowest tertile=0.80, 95% CI: 0.74, 0.87; IRR women highest vs. lowest tertile=0.90, 95% CI: 0.85, 0.95), but no consistent association between calcium and hip fracture risk was observed. The highest tertile of urbanization degree (city), compared to the lowest (rural), was related to a 23 and 24% increase in hip fracture risk in men and women, respectively. The association between magnesium and hip fracture did not explain the variation in hip fracture risk between city and rural areas. Magnesium in drinking water may have a protective role against hip fractures; however this association should be further investigated. © 2013 Elsevier Inc. All rights reserved.

Association between genetic variation within vitamin D receptor-DNA binding sites and risk of basal cell carcinoma.

PubMed

Lin, Yuan; Chahal, Harvind S; Wu, Wenting; Cho, Hyunje G; Ransohoff, Katherine J; Dai, Hongji; Tang, Jean Y; Sarin, Kavita Y; Han, Jiali

2017-05-01

An increasing number of studies have reported a protective association between vitamin D and cancer risk. The vitamin D endocrine system regulates transcriptional programs involved in inflammation, cell growth and differentiation through the binding of vitamin D receptor (VDR) to specific VDR elements. However, limited attention has been given to the role of variation within VDR binding sites in the development of basal cell carcinoma (BCC). Across 2,776 previously identified VDR binding sites, we identified 2,540 independent single-nucleotide polymorphisms (SNPs) and examined their associations with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified two SNPs at new loci (rs16917546 at 10q21.1: odds ratio (OR) = 1.06, p = 3.16 × 10 -7 and rs79824801 at 12q13.3: OR = 1.10, p = 1.88 × 10 -5 ) for the first time as independently related to BCC risk in meta-analysis; and both SNPs were nominally significant in two data sets. In addition, the SNP rs3769823 within VDR binding site at a previously reported BCC susceptibility locus (2q33.1, rs13014235) also exhibited a significant association (OR = 1.12, p = 3.99 × 10 -18 ). A mutually adjusted model suggested that rs3769823 explained the signal in this region. Our findings support the hypothesis that inherited common variation in VDR binding sites affects the development of BCC. © 2017 UICC.

On the association between outdoor PM2.5 concentration and the seasonality of tuberculosis for Beijing and Hong Kong.

PubMed

You, Siming; Tong, Yen Wah; Neoh, Koon Gee; Dai, Yanjun; Wang, Chi-Hwa

2016-11-01

Tuberculosis (TB) is still a serious public health problem in various countries. One of the long-elusive but critical questions about TB is what the risk factors are and how they contribute for its seasonality. An ecologic study was conducted to examine the association between the variation of outdoor PM 2.5 concentration and the TB seasonality based on the monthly TB notification and PM 2.5 concentration data of Hong Kong and Beijing. Both descriptive analysis and Poisson regression analysis suggested that the outdoor PM 2.5 concentration could be a potential risk factor for the seasonality of TB disease. The significant relationship between the number of TB cases and PM 2.5 concentration was not changed when regression models were adjusted by sunshine duration, a potential confounder. The regression analysis showed that a 10 μg/m 3 increase in PM 2.5 concentrations during winter is significantly associated with a 3% (i.e. 18 and 14 cases for Beijing and Hong Kong, respectively) increase in the number of TB cases notified during the coming spring or summer for both Beijing and Hong Kong. Three potential mechanisms were proposed to explain the significant relationship: (1) increased PM 2.5 exposure increases host's susceptibility to TB disease by impairing or modifying the immunology of the human respiratory system; (2) increased indoor activities during high outdoor PM 2.5 episodes leads to an increase in human contact and thus the risk of TB transmission; (3) the seasonal change of PM 2.5 concentration is correlated with the variation of other potential risk factors of TB seasonality. Preliminary evidence from the analysis of this work favors the first mechanism about the PM 2.5 exposure-induced immunity impairment. This work adds new horizons to the explanation of the TB seasonality and improves our understanding of the potential mechanisms affecting TB incidence, which benefits the prevention and control of TB disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-E-T-287: Dose Verification On the Variation of Target Volume and Organ at Risk in Preradiation Chemotherapy IMRT for Nasopharyngeal Cancer

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

Zhang, X; Kong, L; Wang, J

2015-06-15

Purpose: To quantify the target volume and organ at risk of nasopharyngeal carcinoma (NPC) patients with preradiation chemotherapy based on CT scanned during intensity-modulated radiotherapy (IMRT), and recalculate the dose distribution. Methods: Seven patients with NPC and preradiation chemotherapy, treated with IMRT (35 to 37 fractions) were reviewed. Repeat CT scanning was required to all of the patients during the radiotherapy, and the number of repeat CTs varies from 2 to 6. The plan CT and repeat CT were generated by different CT scanner. To ensure crespectively on the same IMPT plan. The real dose distribution was calculated by deformablemore » registration and weighted method in Raystation (v 4.5.1). The fraction of each dose is based on radiotherapy record. The volumetric and dose differences among these images were calculated for nascIpharyngeal tumor and retro-pharyngeal lymph nodes (GTV-NX), neck lymph nodes(GTV-ND), and parotid glands. Results: The volume variation in GTV-NX from CT1 to CT2 was 1.15±3.79%, and in GTV-LN −0.23±4.93%. The volume variation in left parotid from CT1 to CT2 was −6.79±11.91%, and in right parotid −3.92±8.80%. In patient 2, the left parotid volume were decreased remarkably, as a Result, the V30 and V40 of it were increased as well. Conclusion: The target volume of patients with NPC varied lightly during IMRT. It shows that preradiation chemotherapy can control the target volume variation and perform a good dose repeatability. Also, the decreasing volume of parotid in some patient might increase the dose of it, which might course potential complications.« less

Geographical variation in dementia: systematic review with meta-analysis

PubMed Central

Russ, Tom C; Batty, G David; Hearnshaw, Gena F; Fenton, Candida; Starr, John M

2012-01-01

Background Geographical variation in dementia prevalence and incidence may indicate important socio-environmental contributions to dementia aetiology. However, previous comparisons have been hampered by combining studies with different methodologies. This review systematically collates and synthesizes studies examining geographical variation in the prevalence and incidence of dementia based on comparisons of studies using identical methodologies. Methods Papers were identified by a comprehensive electronic search of relevant databases, scrutinising the reference sections of identified publications, contacting experts in the field and re-examining papers already known to us. Identified articles were independently reviewed against inclusion/exclusion criteria and considered according to geographical scale. Rural/urban comparisons were meta-analysed. Results Twelve thousand five hundred and eighty records were reviewed and 51 articles were included. Dementia prevalence and incidence varies at a number of scales from the national down to small areas, including some evidence of an effect of rural living [prevalence odds ratio (OR) = 1.11, 90% confidence interval (CI) 0.79–1.57; incidence OR = 1.20, 90% CI 0.84–1.71]. However, this association of rurality was stronger for Alzheimer disease, particularly when early life rural living was captured (prevalence OR = 2.22, 90% CI 1.19–4.16; incidence OR = 1.64, 90% CI 1.08–2.50). Conclusions There is evidence of geographical variation in rates of dementia in affluent countries at a variety of geographical scales. Rural living is associated with an increased risk of Alzheimer disease, and there is a suggestion that early life rural living further increases this risk. However, the fact that few studies have been conducted in resource-poor countries limits conclusions. PMID:22798662

Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea

PubMed Central

Choi, Youn Jin; Ki, Eun Young; Zhang, Chuqing; Ho, Wendy C. S.; Lee, Sung-Jong; Jeong, Min Jin

2016-01-01

Introduction Human papillomavirus (HPV) 52 is a carcinogenic, high-risk genotype frequently detected in cervical cancer cases from East Asia, including Korea. Materials and Methods Sequences of HPV52 detected in 91 cervical samples collected from women attending Seoul St. Mary’s Hospital were analyzed. HPV52 genomic sequences were obtained by polymerase chain reaction (PCR)-based sequencing and analyzed using Seq-Scape software, and phylogenetic trees were constructed using MEGA6 software. Results Of the 91 cervical samples, 40 were normal, 22 were low-grade lesions, 21 were high-grade lesions and 7 were squamous cell carcinomas. Four HPV52 variant lineages (A, B, C and D) were identified. Lineage B was the most frequently detected lineage, followed by lineage C. By analyzing the two most frequently detected lineages (B and C), we found that distinct variations existed in each lineage. We also found that a lineage B-specific mutation K93R (A379G) was associated with an increased risk of cervical neoplasia. Conclusions To our knowledge, we are the first to reveal the predominance of the HPV52 lineages, B and C, in Korea. We also found these lineages harbored distinct genetic alterations that may affect oncogenicity. Our findings increase our understanding on the heterogeneity of HPV52 variants, and may be useful for the development of new diagnostic assays and therapeutic vaccines. PMID:27977741

Diagnosis, management and treatment of glucometabolic disorders emerging after kidney transplantation: a position statement from the Nordic Transplantation Societies.

PubMed

Hornum, Mads; Lindahl, Jørn P; von Zur-Mühlen, Bengt; Jenssen, Trond; Feldt-Rasmussen, Bo

2013-11-01

After successful solid organ transplantation, new-onset diabetes (NODAT) is reported to develop in about 15-40% of the patients. The variation in incidence may partly depend on differences in the populations that have been studied and partly depend on the different definitions of NODAT that have been used. The diagnosis was often based on 'the use of insulin postoperatively', 'oral agents used', random glucose monitoring and a fasting glucose value between 7 and 13 mmol/l (126-234 mg/dl). Only few have used a 2-h glucose tolerance test performed before transplantation. There is a huge variation in the literature regarding risk factors for developing NODAT. They can be divided into factors related to glucose metabolism or to patient demographics and the latter into modifiable and nonmodifiable. Screening for risk factors should start early and be re-evaluated while being on the waitlist. Patients on the waiting list for renal transplantation and transplanted patients share many characteristics in having hyperglycaemia, disturbed insulin secretion and increased insulin resistance. We present guidelines for early risk factor assessment and a screening/treatment strategy for disturbed glucose metabolism, both before and after transplantation. The aim was to avoid the increased cardiovascular disease and mortality rates associated with NODAT. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.

PubMed

Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-06-30

Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

PubMed Central

Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-01-01

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

Environmental Risk Factors influencing Bicycle Theft: A Spatial Analysis in London, UK

PubMed Central

Helbich, Marco

2016-01-01

Urban authorities are continuously drawing up policies to promote cycling among commuters. However, these initiatives are counterproductive for the targeted objectives because they increase opportunities for bicycle theft. This paper explores Inner London as a case study to address place-specific risk factors for bicycle theft at the street-segment level while controlling for seasonal variation. The presence of certain public amenities (e.g., bicycle stands, railway stations, pawnshops) was evaluated against locations of bicycle theft between 2013 and 2016 and risk effects were estimated using negative binomial regression models. Results showed that a greater level of risk stemmed from land-use facilities than from area-based socioeconomic status. The presence of facilities such as train stations, vacant houses, pawnbrokers and payday lenders increased bicycle theft, but no evidence was found that linked police stations with crime levels. The findings have significant implications for urban crime prevention with respect to non-residential land use. PMID:27643788

[Post-partum blues and depression].

PubMed

Jalenques, Isabelle; Legrand, Guillaume

2009-04-20

Post-partum time is an eventful period with modifications of somatic but also biological and psychological status of women, leading to increased risk of anxious and depressive disorders. Diagnosis of post-partum blues (PPB) or post-partum depression (PPD) is sometimes difficult. PPB is usually benign; thus a punctual help is usually sufficient. A severe or long duration PPB is associated with an increased risk of PPD which has to be taken into account. PPD can be difficult to diagnose because of multiple clinical forms and specially variations in intensity. During prenatal period, the aim is to look for women who are at risk for PPB or PPD. So it is necessary that the different practitioners can exchange informations. A treatment of PPD is essential because it has an important impact on mother and child's health. General practitioner involves from prenatal period (deflection of risk factors) to the diagnosis, the look out and the following of mothers and children in collaboration with obstetric, pediatric and psychiatric teams.

Changes in erosion and flooding risk due to long-term and cyclic oceanographic trends

USGS Publications Warehouse

Wahl, Thomas; Plant, Nathaniel G.

2015-01-01

We assess temporal variations in waves and sea level, which are driving factors for beach 23 erosion and coastal flooding in the northern Gulf of Mexico. We find that long-term trends in 24 the relevant variables have caused an increase of ~30% in the erosion/flooding risk since the 25 1980s. Changes in the wave climate-which have often been ignored in earlier assessments-26 were at least as important as sea-level rise (SLR). In the next decades, SLR will likely become 27 the dominating driver and may in combination with ongoing changes in the wave climate (and 28 depending on the emission scenario) escalate the erosion/flooding risk by up to 300% over the 29 next 30 years. We also find significant changes in the seasonal cycles of sea level and 30 significant wave height, which have in combination caused a considerable increase of the 31 erosion/flooding risk in summer and decrease in winter (superimposed onto the long-term 32 trends)

Conservation of genetic uniqueness of populations may increase extinction likelihood of endangered species: the case of Australian mammals.

PubMed

Weeks, Andrew R; Stoklosa, Jakub; Hoffmann, Ary A

2016-01-01

As increasingly fragmented and isolated populations of threatened species become subjected to climate change, invasive species and other stressors, there is an urgent need to consider adaptive potential when making conservation decisions rather than focussing on past processes. In many cases, populations identified as unique and currently managed separately suffer increased risk of extinction through demographic and genetic processes. Other populations currently not at risk are likely to be on a trajectory where declines in population size and fitness soon appear inevitable. Using datasets from natural Australian mammal populations, we show that drift processes are likely to be driving uniqueness in populations of many threatened species as a result of small population size and fragmentation. Conserving and managing such remnant populations separately will therefore often decrease their adaptive potential and increase species extinction risk. These results highlight the need for a paradigm shift in conservation biology practise; strategies need to focus on the preservation of genetic diversity at the species level, rather than population, subspecies or evolutionary significant unit. The introduction of new genetic variants into populations through in situ translocation needs to be considered more broadly in conservation programs as a way of decreasing extinction risk by increasing neutral genetic diversity which may increase the adaptive potential of populations if adaptive variation is also increased.

Geographic variations of the bird-borne structural risk of West Nile virus circulation in Europe

PubMed Central

Durand, Benoit; Tran, Annelise; Balança, Gilles

2017-01-01

The structural risk of West Nile Disease results from the usual functioning of the socio-ecological system, which may favour the introduction of the pathogen, its circulation and the occurrence of disease cases. Its geographic variations result from the local interactions between three components: (i) reservoir hosts, (ii) vectors, both characterized by their diversity, abundance and competence, (iii) and the socio-economic context that impacts the exposure of human to infectious bites. We developed a model of bird-borne structural risk of West Nile Virus (WNV) circulation in Europe, and analysed the association between the geographic variations of this risk and the occurrence of WND human cases between 2002 and 2014. A meta-analysis of WNV serosurveys conducted in wild bird populations was performed to elaborate a model of WNV seropositivity in European bird species, considered a proxy for bird exposure to WNV. Several eco-ethological traits of bird species were linked to seropositivity and the statistical model adequately fitted species-specific seropositivity data (area under the ROC curve: 0.85). Combined with species distribution maps, this model allowed deriving geographic variations of the bird-borne structural risk of WNV circulation. The association between this risk, and the occurrence of WND human cases across the European Union was assessed. Geographic risk variations of bird-borne structural risk allowed predicting WND case occurrence in administrative districts of the EU with a sensitivity of 86% (95% CI: 0.79–0.92), and a specificity of 68% (95% CI: 0.66–0.71). Disentangling structural and conjectural health risks is important for public health managers as risk mitigation procedures differ according to risk type. The results obtained show promise for the prevention of WND in Europe. Combined with analyses of vector-borne structural risk, they should allow designing efficient and targeted prevention measures. PMID:29023472

Parental investment decisions in response to ambient nest-predation risk versus actual predation on the prior nest

USGS Publications Warehouse

Chalfoun, A.D.; Martin, T.E.

2010-01-01

Theory predicts that parents should invest less in dependent offspring with lower reproductive value, such as those with a high risk of predation. Moreover, high predation risk can favor reduced parental activity when such activity attracts nest predators. Yet, the ability of parents to assess ambient nest-predation risk and respond adaptively remains unclear, especially where nest-predator assemblages are diverse and potentially difficult to assess. We tested whether variation in parental investment by a multi-brooded songbird (Brewer's Sparrow, Spizella breweri) in an environment (sagebrush steppe) with diverse predators was predicted by ambient nest-predation risk or direct experience with nest predation. Variation among eight sites in ambient nest-predation risk, assayed by daily probabilities of nest predation, was largely uncorrelated across four years. In this system risk may therefore be unpredictable, and aspects of parental investment (clutch size, egg mass, incubation rhythms, nestling-feeding rates) were not related to ambient risk. Moreover, investment at first nests that were successful did not differ from that at nests that were depredated, suggesting parents could not assess and respond to territorylevel nest-predation risk. However, parents whose nests were depredated reduced clutch sizes and activity at nests attempted later in the season by increasing the length of incubation shifts (on-bouts) and recesses (off-bouts) and decreasing trips to feed nestlings. In this unpredictable environment parent birds may therefore lack sufficient cues of ambient risk on which to base their investment decisions and instead rely on direct experience with nest predation to inform at least some of their decisions. ?? 2010 The Cooper Ornithological Society.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features.

PubMed

Marques, Diego; Ferreira-Costa, Layse Raynara; Ferreira-Costa, Lorenna Larissa; Correa, Romualdo da Silva; Borges, Aline Maciel Pinheiro; Ito, Fernanda Ribeiro; Ramos, Carlos Cesar de Oliveira; Bortolin, Raul Hernandes; Luchessi, André Ducati; Ribeiro-Dos-Santos, Ândrea; Santos, Sidney; Silbiger, Vivian Nogueira

2017-10-07

To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring. Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE , HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE , HLAG , and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS . Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. The INDEL variations in ACE , UCP2 , TYMS , IL4 , NFKB1 , CASP8 , TP53 , HLAG , UGT1A1 , and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

PubMed

Jing, Lijun; Su, Li; Ring, Brian Z

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.

Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China

PubMed Central

Xiao, Hong; Huang, Ru; Gao, Li-Dong; Huang, Cun-Rui; Lin, Xiao-Ling; Li, Na; Liu, Hai-Ning; Tong, Shi-Lu; Tian, Huai-Yu

2016-01-01

Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS. PMID:26711521

Regional Differences in Diabetes as a Possible Contributor to the Geographic Disparity in Stroke Mortality

PubMed Central

Voeks, Jenifer H.; McClure, Leslie A.; Go, Rodney C.; Prineas, Ronald J.; Cushman, Mary; Kissela, Brett M.; Roseman, Jeffrey M.

2013-01-01

Background and Purpose Diabetes and hypertension impart approximately the same increased relative risk for stroke, although hypertension has a larger population-attributable risk because of its higher population prevalence. With a growing epidemic of obesity and associated increasing prevalence of diabetes that disproportionately impacts the southeastern Stroke Belt states, any potential contribution of diabetes to the geographic disparity in stroke mortality will only increase. Methods Racial and geographic differences in diabetes prevalence and diabetes awareness, treatment, and control were assessed in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants older than 45 years of age. At the time of this report, 21 959 had been enrolled. Results The odds of diabetes were significantly increased in both white and black residents of the stroke buckle (OR, 1.26; [1.10, 1.44]; OR, 1.45 [1.26, 1.66], respectively) and Stroke Belt (OR, 1.22; [1.09, 1.36]; OR, 1.13 [1.02, 1.26]) compared to the rest of the United States. In the buckle, regional differences were not fully mediated and remained significant when controlling for socioeconomic status and risk factors. Addition of hypertension to the models did not reduce the magnitude of the associations. There were no significant differences by region with regard to awareness, treatment, or control for either race. Conclusions These analyses support a possible role of regional variation in the prevalence of diabetes as, in part, an explanation for the regional variation in stroke mortality but fail to support the potential for a contribution of regional differences in diabetes management. PMID:18388336

Assessing HIV risk in workplaces for prioritizing HIV preventive interventions in Karnataka State, India.

PubMed

Halli, Shiva S; Buzdugan, Raluca; Ramesh, B M; Gurnani, Vandana; Sharma, Vivek; Moses, Stephen; Blanchard, James F

2009-09-01

To develop a model for prioritizing economic sectors for HIV preventive intervention programs in the workplace. This study was undertaken in Karnataka state, India. A 3-stage survey process was undertaken. In the first stage, we reviewed secondary data available from various government departments, identified industries in the private sector with large workforces, and mapped their geographical distribution. In the second stage, an initial rapid risk assessment of industrial sectors was undertaken, using key-informant interviews conducted in relation to a number of enterprises, and in consultation with stakeholders. In the third stage, we used both quantitative (polling booth survey) and qualitative methods (key informant interviews, in-depth interviews, focus group discussions) to study high-risk sectors in-depth, and assessed the need and feasibility of HIV workplace intervention programs. The highest risk sectors were found to be mining, garment/textile, sugar, construction/infrastructure, and fishing industries. Workers in all sectors had at best partial knowledge about HIV/AIDS, coupled with common misconceptions about HIV transmission. There were intersector and intrasector variations in risk and vulnerability across different geographical locations and across different categories of workers. This has implications for the design and implementation of workplace intervention programs. There is tremendous scope for HIV preventive interventions in workplaces in India. Given the variation in HIV risk across economic sectors and limited available resources, there will be increased pressure to prioritize intervention efforts towards high-risk sectors. This study offers a model for rapidly assessing the risk level of economic sectors for HIV intervention programs.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

PubMed

Kristiansen, W; Andreassen, K E; Karlsson, R; Aschim, E L; Bremnes, R M; Dahl, O; Fosså, S D; Klepp, O; Langberg, C W; Solberg, A; Tretli, S; Adami, H-O; Wiklund, F; Grotmol, T; Haugen, T B

2012-05-01

Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERβ)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. Our findings provide support for ERβ and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

GENETIC VARIATION AND DECREASED RISK FOR OBESITY IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

USDA-ARS?s Scientific Manuscript database

Our objective was to investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We tested the association...

Posture variation among office workers when using different information and communication technologies at work and away from work.

PubMed

Ciccarelli, Marina; Straker, Leon; Mathiassen, Svend Erik; Pollock, Clare

2014-01-01

Office workers perform tasks using different information and communication technologies (ICT) involving various postures. Adequate variation in postures and muscle activity is generally believed to protect against musculoskeletal complaints, but insufficient information exists regarding the effect on postural variation of using different ICT. Thus, this study among office workers aimed to determine and compare postures and postural variation associated with using distinct types of ICT. Upper arm, head and trunk postures of 24 office workers were measured with the Physiometer over a whole day in their natural work and away-from-work environments. Postural variation was quantified using two indices: APDF(90-10) and EVA(sd). Various ICT had different postural means and variation. Paper-based tasks had more non-neutral, yet also more variable postures. Electronics-based tasks had more neutral postures, with less postural variability. Tasks simultaneously using paper- and electronics-based ICT had least neutral and least variable postures. Tasks without ICT usually had the most posture variability. Interspersing tasks involving different ICT could increase overall exposure variation among office workers and may thus contribute to musculoskeletal risk reduction.

Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure

PubMed Central

Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

2014-01-01

Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose–response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59–2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure PMID:22847218

Guidelines for Adolescent Preventive Services: the GAPS in practice.

PubMed

Gadomski, Anne; Bennett, Shannon; Young, Margaret; Wissow, Lawrence S

2003-05-01

Pre- and post-Guidelines for Adolescent Preventive Services (GAPS) comparison of outcomes gathered via chart audit. A rural hospital-based general pediatric clinic. Adolescents who underwent annual examinations between April 1, 1998, and March 31, 2001. A random sample of 441 medical records was reviewed. Training in the GAPS model and use of the questionnaire began in April 1998. Detection of, discussion of, and referrals for GAPS-related risk behavior. The medical records of 162 younger adolescents (aged 11-15 years) and 279 older adolescents (aged 16-19 years) were audited. Detection of risk behaviors increased from 19% at baseline to 95% with the initial GAPS and 87% with the periodic GAPS. The most prevalent risk factor was having a rifle or gun in the home (younger adolescents, 47% and older adolescents, 39%). The mean number of risk behaviors and health concerns documented was higher in the initial GAPS (4.8 and 1.3, respectively) than in the periodic GAPS (3.8 and 0.7) (P =.01 and.006). The GAPS questionnaires detected lower levels of risk behavior compared with a local Youth Risk Behavior Survey. Controlling for sex, age, and clinician, discussion of psychosocial topics increased during the study period; however, there was considerable variation among clinicians regarding the topics addressed. The GAPS-related referral rate did not change significantly. The GAPS model increases clinicians' detection and discussion of risk behaviors.

The influence of vegetation, mesoclimate and meteorology on urban atmospheric microclimates across a coastal to desert climate gradient.

PubMed

Crum, Steven M; Shiflett, Sheri A; Jenerette, G Darrel

2017-09-15

Many cities are increasing vegetation in part due to the potential for microclimate cooling. However, the magnitude of vegetation cooling and sensitivity to mesoclimate and meteorology are uncertain. To improve understanding of the variation in vegetation's influence on urban microclimates we asked: how do meso- and regional-scale drivers influence the magnitude and timing of vegetation-based moderation on summertime air temperature (T a ), relative humidity (RH) and heat index (HI) across dryland cities? To answer this question we deployed a network of 180 temperature sensors in summer 2015 over 30 high- and 30 low-vegetated plots in three cities across a coastal to inland to desert climate gradient in southern California, USA. In a followup study, we deployed a network of temperature and humidity sensors in the inland city. We found negative T a and HI and positive RH correlations with vegetation intensity. Furthermore, vegetation effects were highest in evening hours, increasing across the climate gradient, with reductions in T a and increases in RH in low-vegetated plots. Vegetation increased temporal variability of T a , which corresponds with increased nighttime cooling. Increasing mean T a was associated with higher spatial variation in T a in coastal cities and lower variation in inland and desert cities, suggesting a climate dependent switch in vegetation sensitivity. These results show that urban vegetation increases spatiotemporal patterns of microclimate with greater cooling in warmer environments and during nighttime hours. Understanding urban microclimate variation will help city planners identify potential risk reductions associated with vegetation and develop effective strategies ameliorating urban microclimate. Published by Elsevier Ltd.

Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.

PubMed

Sandberg, S; Järvenpää, S; Penttinen, A; Paton, J Y; McCann, D C

2004-12-01

A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress. Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events. An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children. The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.

US Vulnerability to Natural Disasters

NASA Astrophysics Data System (ADS)

van der Vink, G.; Apgar, S.; Batchelor, A.; Carter, C.; Gail, D.; Jarrett, A.; Levine, N.; Morgan, W.; Orlikowski, M.; Pray, T.; Raymar, M.; Siebert, A.; Shawa, T. W.; Wallace, C.

2002-05-01

Natural disasters result from the coincidence of natural events with the built environment. Our nation's infrastructure is growing at an exponential rate in many areas of high risk, and the Federal government's liability is increasing proportionally. By superimposing population density with predicted ground motion from earthquakes, historical hurricane tracks, historical tornado locations, and areas within the flood plain, we are able to identify locations of high vulnerability within the United States. We present a comprehensive map of disaster risk for the United States that is being produced for the Senate Natural Hazards Caucus. The map allows for the geographic comparison of natural disaster risk with past disaster declarations, the expenditure of Federal dollars for disaster relief, population increase, and variations of GDP. Every state is vulnerable to natural disasters. Although their frequency varies considerably, the annualized losses for disaster relief from hurricanes, earthquakes, and floods are approximately equivalent. While fast-growing states such as California and Florida remain highly vulnerable, changes in the occurrence of natural events combined with population increases are making areas such as Texas, North Carolina, and the East Coast increasingly vulnerable.

Serum magnesium and the risk of prediabetes: a population-based cohort study.

PubMed

Kieboom, Brenda C T; Ligthart, Symen; Dehghan, Abbas; Kurstjens, Steef; de Baaij, Jeroen H F; Franco, Oscar H; Hofman, Albert; Zietse, Robert; Stricker, Bruno H; Hoorn, Ewout J

2017-05-01

Previous studies have found an association between serum magnesium and incident diabetes; however, this association may be due to reverse causation, whereby diabetes may induce urinary magnesium loss. In contrast, in prediabetes (defined as impaired fasting glucose), serum glucose levels are below the threshold for urinary magnesium wasting and, hence, unlikely to influence serum magnesium levels. Thus, to study the directionality of the association between serum magnesium levels and diabetes, we investigated its association with prediabetes. We also investigated whether magnesium-regulating genes influence diabetes risk through serum magnesium levels. Additionally, we quantified the effect of insulin resistance in the association between serum magnesium levels and diabetes risk. Within the population-based Rotterdam Study, we used Cox models, adjusted for age, sex, lifestyle factors, comorbidities, kidney function, serum levels of electrolytes and diuretic use, to study the association between serum magnesium and prediabetes/diabetes. In addition, we performed two mediation analyses: (1) to study if common genetic variation in eight magnesium-regulating genes influence diabetes risk through serum magnesium levels; and (2) to quantify the proportion of the effect of serum magnesium levels on diabetes that is mediated through insulin resistance (quantified by HOMA-IR). A total of 8555 participants (mean age, 64.7 years; median follow-up, 5.7 years) with normal glucose levels (mean ± SD: 5.46 ± 0.58 mmol/l) at baseline were included. A 0.1 mmol/l decrease in serum magnesium level was associated with an increase in diabetes risk (HR 1.18 [95% CI 1.04, 1.33]), confirming findings from previous studies. Of interest, a similar association was found between serum magnesium levels and prediabetes risk (HR 1.12 [95% CI 1.01, 1.25]). Genetic variation in CLDN19, CNNM2, FXYD2, SLC41A2, and TRPM6 significantly influenced diabetes risk (p < 0.05), and for CNNM2, FXYD2, SLC41A2 and TRPM6 this risk was completely mediated by serum magnesium levels. We found that 29.1% of the effect of serum magnesium levels on diabetes was mediated through insulin resistance, whereas for prediabetes 13.4% was mediated through insulin resistance. Low serum magnesium levels are associated with an increased risk of prediabetes and this increased risk is similar to that of diabetes. Furthermore, common variants in magnesium-regulating genes modify diabetes risk through serum magnesium levels. Both findings support a potential causal role of magnesium in the development of diabetes, where the hypothesised pathway is partly mediated through insulin resistance.

Mobile phone use and risk of brain tumours: a systematic review of association between study quality, source of funding, and research outcomes.

PubMed

Prasad, Manya; Kathuria, Prachi; Nair, Pallavi; Kumar, Amit; Prasad, Kameshwar

2017-05-01

Mobile phones emit electromagnetic radiations that are classified as possibly carcinogenic to humans. Evidence for increased risk for brain tumours accumulated in parallel by epidemiologic investigations remains controversial. This paper aims to investigate whether methodological quality of studies and source of funding can explain the variation in results. PubMed and Cochrane CENTRAL searches were conducted from 1966 to December 2016, which was supplemented with relevant articles identified in the references. Twenty-two case control studies were included for systematic review. Meta-analysis of 14 case-control studies showed practically no increase in risk of brain tumour [OR 1.03 (95% CI 0.92-1.14)]. However, for mobile phone use of 10 years or longer (or >1640 h), the overall result of the meta-analysis showed a significant 1.33 times increase in risk. The summary estimate of government funded as well as phone industry funded studies showed 1.07 times increase in odds which was not significant, while mixed funded studies did not show any increase in risk of brain tumour. Metaregression analysis indicated that the association was significantly associated with methodological study quality (p < 0.019, 95% CI 0.009-0.09). Relationship between source of funding and log OR for each study was not statistically significant (p < 0.32, 95% CI 0.036-0.010). We found evidence linking mobile phone use and risk of brain tumours especially in long-term users (≥10 years). Studies with higher quality showed a trend towards high risk of brain tumour, while lower quality showed a trend towards lower risk/protection.

Urbanicity and lifestyle risk factors for cardiometabolic diseases in rural Uganda: a cross-sectional study.

PubMed

Riha, Johanna; Karabarinde, Alex; Ssenyomo, Gerald; Allender, Steven; Asiki, Gershim; Kamali, Anatoli; Young, Elizabeth H; Sandhu, Manjinder S; Seeley, Janet

2014-07-01

Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases. Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77). This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA. Please see later in the article for the Editors' Summary.

Co-variations and Clustering of Chronic Disease Behavioral Risk Factors in China: China Chronic Disease and Risk Factor Surveillance, 2007

PubMed Central

Li, Yichong; Zhang, Mei; Jiang, Yong; Wu, Fan

2012-01-01

Background Chronic diseases have become the leading causes of mortality in China and related behavioral risk factors (BRFs) changed dramatically in past decades. We aimed to examine the prevalence, co-variations, clustering and the independent correlates of five BRFs at the national level. Methodology/Principal Findings We used data from the 2007 China Chronic Disease and Risk Factor Surveillance, in which multistage clustering sampling was adopted to collect a nationally representative sample of 49,247 Chinese aged 15 to 69 years. We estimated the prevalence and clustering (mean number of BRFs) of five BRFs: tobacco use, excessive alcohol drinking, insufficient intake of vegetable and fruit, physical inactivity, and overweight or obesity. We conducted binary logistic regression models to examine the co-variations among five BRFs with adjustment of demographic and socioeconomic factors, chronic conditions and other BRFs. Ordinal logistic regression was constructed to investigate the independent associations between each covariate and the clustering of BRFs within individuals. Overall, 57.0% of Chinese population had at least two BRFs and the mean number of BRFs is 1.80 (95% confidence interval: 1.78–1.83). Eight of the ten pairs of bivariate associations between the five BRFs were found statistically significant. Chinese with older age, being a male, living in rural areas, having lower education level and lower yearly household income experienced increased likelihood of having more BRFs. Conclusions/Significance Current BRFs place the majority of Chinese aged 15 to 69 years at risk for the future development of chronic disease, which calls for urgent public health programs to reduce these risk factors. Prominent correlations between BRFs imply that a combined package of interventions targeting multiple BRFs might be appropriate. These interventions should target elder population, men, and rural residents, especially those with lower SES. PMID:22439010

Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.

PubMed

Mejía-Benítez, Aurora; Klünder-Klünder, Miguel; Yengo, Loic; Meyre, David; Aradillas, Celia; Cruz, Esperanza; Pérez-Luque, Elva; Malacara, Juan Manuel; Garay, Maria Eugenia; Peralta-Romero, Jesús; Flores-Huerta, Samuel; García-Mena, Jaime; Froguel, Philippe; Cruz, Miguel; Bonnefond, Amélie

2013-02-01

Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children. The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children. We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (β = -0.10 μU/mL; P = 1.21 × 10(-3)), respectively. Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.

The influence of climate variables on dengue in Singapore.

PubMed

Pinto, Edna; Coelho, Micheline; Oliver, Leuda; Massad, Eduardo

2011-12-01

In this work we correlated dengue cases with climatic variables for the city of Singapore. This was done through a Poisson Regression Model (PRM) that considers dengue cases as the dependent variable and the climatic variables (rainfall, maximum and minimum temperature and relative humidity) as independent variables. We also used Principal Components Analysis (PCA) to choose the variables that influence in the increase of the number of dengue cases in Singapore, where PC₁ (Principal component 1) is represented by temperature and rainfall and PC₂ (Principal component 2) is represented by relative humidity. We calculated the probability of occurrence of new cases of dengue and the relative risk of occurrence of dengue cases influenced by climatic variable. The months from July to September showed the highest probabilities of the occurrence of new cases of the disease throughout the year. This was based on an analysis of time series of maximum and minimum temperature. An interesting result was that for every 2-10°C of variation of the maximum temperature, there was an average increase of 22.2-184.6% in the number of dengue cases. For the minimum temperature, we observed that for the same variation, there was an average increase of 26.1-230.3% in the number of the dengue cases from April to August. The precipitation and the relative humidity, after analysis of correlation, were discarded in the use of Poisson Regression Model because they did not present good correlation with the dengue cases. Additionally, the relative risk of the occurrence of the cases of the disease under the influence of the variation of temperature was from 1.2-2.8 for maximum temperature and increased from 1.3-3.3 for minimum temperature. Therefore, the variable temperature (maximum and minimum) was the best predictor for the increased number of dengue cases in Singapore.

Precipitation Effects on Microbial Pollution in a River: Lag Structures and Seasonal Effect Modification

PubMed Central

Tornevi, Andreas; Bergstedt, Olof; Forsberg, Bertil

2014-01-01

Background The river Göta Älv is a source of freshwater for 0.7 million swedes. The river is subject to contamination from sewer systems discharge and runoff from agricultural lands. Climate models projects an increase in precipitation and heavy rainfall in this region. This study aimed to determine how daily rainfall causes variation in indicators of pathogen loads, to increase knowledge of variations in river water quality and discuss implications for risk management. Methods Data covering 7 years of daily monitoring of river water turbidity and concentrations of E. coli, Clostridium and coliforms were obtained, and their short-term variations in relation with precipitation were analyzed with time series regression and non-linear distributed lag models. We studied how precipitation effects varied with season and compared different weather stations for predictive ability. Results Generally, the lowest raw water quality occurs 2 days after rainfall, with poor raw water quality continuing for several more days. A rainfall event of >15 mm/24-h (local 95 percentile) was associated with a three-fold higher concentration of E. coli and 30% higher turbidity levels (lag 2). Rainfall was associated with exponential increases in concentrations of indicator bacteria while the effect on turbidity attenuated with very heavy rainfall. Clear associations were also observed between consecutive days of wet weather and decreased water quality. The precipitation effect on increased levels of indicator bacteria was significant in all seasons. Conclusions Rainfall elevates microbial risks year-round in this river and freshwater source and acts as the main driver of varying water quality. Heavy rainfall appears to be a better predictor of fecal pollution than water turbidity. An increase of wet weather and extreme events with climate change will lower river water quality even more, indicating greater challenges for drinking water producers, and suggesting better control of sources of pollution. PMID:24874010

Study of landscape patterns of variation and optimization based on non-point source pollution control in an estuary.

PubMed

Jiang, Mengzhen; Chen, Haiying; Chen, Qinghui; Wu, Haiyan

2014-10-15

Appropriate increases in the "sink" of a landscape can reduce the risk of non-point source pollution (NPSP) to the sea at relatively lower costs and at a higher efficiency. Based on high-resolution remote sensing image data taken between 2003 and 2008, we analyzed the "source" and "sink" landscape pattern variations of nitrogen and phosphorus pollutants in the Jiulongjiang estuary region. The contribution to the sea and distribution of each pollutant in the region was calculated using the LCI and mGLCI models. The results indicated that an increased amount of pollutants was contributed to the sea, and the "source" area of the nitrogen NPSP in the study area increased by 32.75 km(2). We also propose a landscape pattern optimization to reduce pollution in the Jiulongjiang estuary in 2008 through the conversion of cultivated land with slopes greater than 15° and paddy fields near rivers, and an increase in mangrove areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.

PubMed

Viana, Joana; Hannon, Eilis; Dempster, Emma; Pidsley, Ruth; Macdonald, Ruby; Knox, Olivia; Spiers, Helen; Troakes, Claire; Al-Saraj, Safa; Turecki, Gustavo; Schalkwyk, Leonard C; Mill, Jonathan

2017-01-01

Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease. © The Author 2016. Published by Oxford University Press.

Biological variation in tPA-induced plasma clot lysis time.

PubMed

Talens, Simone; Malfliet, Joyce J M C; Rudež, Goran; Spronk, Henri M H; Janssen, Nicole A H; Meijer, Piet; Kluft, Cornelis; de Maat, Moniek P M; Rijken, Dingeman C

2012-10-01

Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.

Ambient Temperature and Stroke Occurrence: A Systematic Review and Meta-Analysis.

PubMed

Wang, Xia; Cao, Yongjun; Hong, Daqing; Zheng, Danni; Richtering, Sarah; Sandset, Else Charlotte; Leong, Tzen Hugh; Arima, Hisatomi; Islam, Shariful; Salam, Abdul; Anderson, Craig; Robinson, Thompson; Hackett, Maree L

2016-07-12

Biologically plausible associations exist between climatic conditions and stroke risk, but study results are inconsistent. We aimed to summarize current evidence on ambient temperature and overall stroke occurrence, and by age, sex, and variation of temperature. We performed a systematic literature search across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 16 October 2015 to identify all population-based observational studies. Where possible, data were pooled for meta-analysis with Odds ratios (OR) and corresponding 95% confidence intervals (CI) by means of the random effects meta-analysis. We included 21 studies with a total of 476,511 patients. The data were varied as indicated by significant heterogeneity across studies for both ischemic stroke (IS) and intracerebral hemorrhage (ICH). Pooled OR (95% CI) in every 1 degree Celsius increase in ambient temperature was significant for ICH 0.97 (0.94-1.00), but not for IS 1.00 (0.99-1.01) and subarachnoid hemorrhage (SAH) 1.00 (0.98-1.01). Meta-analysis was not possible for the pre-specified subgroup analyses by age, sex, and variation of temperature. Change in temperature over the previous 24 h appeared to be more important than absolute temperature in relation to the risk of stroke, especially in relation to the risk of ICH. Older age appeared to increase vulnerability to low temperature for both IS and ICH. To conclude, this review shows that lower mean ambient temperature is significantly associated with the risk of ICH, but not with IS and SAH. Larger temperature changes were associated with higher stroke rates in the elderly.

Epidemiology of pituitary pars intermedia dysfunction: A systematic literature review of clinical presentation, disease prevalence and risk factors.

PubMed

Ireland, J L; McGowan, C M

2018-05-01

Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed screened papers for inclusion, extracted data, and assessed the quality of reporting using predefined criteria. Data were extracted using modified critically appraised topic data collection forms. Meta-analysis was not undertaken due to marked between-study variations. Following removal of duplicate records, of 358 published papers yielded by the search, 97 abstracts were screened for eligibility and 29 publications meeting inclusion criteria were included in the review. Most studies reviewed were case series or cross-sectional studies, with considerable variation in study populations and PPID case definition. Hypertrichosis and/or other hair coat abnormalities, laminitis and epaxial muscle wastage or muscle atrophy are the most frequently reported clinical signs, with prevalence of these signs increasing with increasing horse age. The most robust prevalence estimates for PPID were 21.2% in horses and ponies aged ≥15 years and 2.9% amongst the general equine population. Findings regarding breed and sex predispositions were equivocal and only increasing age has been identified as a significant risk factor for PPID. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester.

PubMed

Bagot, C N; Leishman, E; Onyiaodike, C C; Jordan, F; Freeman, D J

2017-09-01

Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001) with the mean increase from baseline persisting to Day 59 gestation. Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a woman's pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test. Copyright © 2017 Elsevier Ltd. All rights reserved.

Geographic variations in cervical cancer risk in San Luis Potosí state, Mexico: A spatial statistical approach.

PubMed

Terán-Hernández, Mónica; Ramis-Prieto, Rebeca; Calderón-Hernández, Jaqueline; Garrocho-Rangel, Carlos Félix; Campos-Alanís, Juan; Ávalos-Lozano, José Antonio; Aguilar-Robledo, Miguel

2016-09-29

Worldwide, Cervical Cancer (CC) is the fourth most common type of cancer and cause of death in women. It is a significant public health problem, especially in low and middle-income/Gross Domestic Product (GDP) countries. In the past decade, several studies of CC have been published, that identify the main modifiable and non-modifiable CC risk factors for Mexican women. However, there are no studies that attempt to explain the residual spatial variation in CC incidence In Mexico, i.e. spatial variation that cannot be ascribed to known, spatially varying risk factors. This paper uses a spatial statistical methodology that takes into account spatial variation in socio-economic factors and accessibility to health services, whilst allowing for residual, unexplained spatial variation in risk. To describe residual spatial variations in CC risk, we used generalised linear mixed models (GLMM) with both spatially structured and unstructured random effects, using a Bayesian approach to inference. The highest risk is concentrated in the southeast, where the Matlapa and Aquismón municipalities register excessive risk, with posterior probabilities greater than 0.8. The lack of coverage of Cervical Cancer-Screening Programme (CCSP) (RR 1.17, 95 % CI 1.12-1.22), Marginalisation Index (RR 1.05, 95 % CI 1.03-1.08), and lack of accessibility to health services (RR 1.01, 95 % CI 1.00-1.03) were significant covariates. There are substantial differences between municipalities, with high-risk areas mainly in low-resource areas lacking accessibility to health services for CC. Our results clearly indicate the presence of spatial patterns, and the relevance of the spatial analysis for public health intervention. Ignoring the spatial variability means to continue a public policy that does not tackle deficiencies in its national CCSP and to keep disadvantaging and disempowering Mexican women in regard to their health care.

Finding big shots: small-area mapping and spatial modelling of obesity among Swiss male conscripts.

PubMed

Panczak, Radoslaw; Held, Leonhard; Moser, André; Jones, Philip A; Rühli, Frank J; Staub, Kaspar

2016-01-01

In Switzerland, as in other developed countries, the prevalence of overweight and obesity has increased substantially since the early 1990s. Most of the analyses so far have been based on sporadic surveys or self-reported data and did not offer potential for small-area analyses. The goal of this study was to investigate spatial variation and determinants of obesity among young Swiss men using recent conscription data. A complete, anonymized dataset of conscription records for the 2010-2012 period were provided by Swiss Armed Forces. We used a series of Bayesian hierarchical logistic regression models to investigate the spatial pattern of obesity across 3,187 postcodes, varying them by type of random effects (spatially unstructured and structured), level of adjustment by individual (age and professional status) and area-based [urbanicity and index of socio-economic position (SEP)] characteristics. The analysed dataset consisted of 100,919 conscripts, out of which 5,892 (5.8 %) were obese. Crude obesity prevalence increased with age among conscripts of lower individual and area-based SEP and varied greatly over postcodes. Best model's estimates of adjusted odds ratios of obesity on postcode level ranged from 0.61 to 1.93 and showed a strong spatial pattern of obesity risk across the country. Odds ratios above 1 concentrated in central and north Switzerland. Smaller pockets of elevated obesity risk also emerged around cities of Geneva, Fribourg and Lausanne. Lower estimates were observed in North-East and East as well as south of the Alps. Importantly, small regional outliers were observed and patterning did not follow administrative boundaries. Similarly as with crude obesity prevalence, the best fitting model confirmed increasing risk of obesity with age and among conscripts of lower professional status. The risk decreased with higher area-based SEP and, to a lesser degree - in rural areas. In Switzerland, there is a substantial spatial variation in obesity risk among young Swiss men. Small-area estimates of obesity risk derived from conscripts records contribute to its understanding and could be used to design further studies and interventions.

Regional Gradients in Institutional Cesarean Delivery Rates: Evidence from Five Countries in Asia.

PubMed

Sepehri, Ardeshir; Guliani, Harminder

2017-03-01

Although the influence of the type of institutional setting on the risk of cesarean birth is well documented, less is known about the regional variations in institution-specific cesarean rates within countries. Our purpose was to examine regional variations in cesarean rates across public and private facilities in five Asian countries with a sizeable private sector: Bangladesh, India, Indonesia, Pakistan, and the Philippines. Demographic Health Survey data and a hierarchical model were used to assess regional variations in the mode of delivery while controlling for a wide range of socioeconomic, demographic, and maternal risk factors. The risk of cesarean birth was greater in a private facility than in a government hospital by 36-48 percent in India and Indonesia and by 130 percent in Bangladesh. Regional gradients in cesarean birth were found to be steeper for deliveries in private facilities than in government hospitals in India, Indonesia, and the Philippines. The residents of India's high-use states were 55 percent more likely to undergo a cesarean delivery in a government hospital and 83 percent more likely in a private facility than their counterparts in the medium-use states. Similarly, compared to the residents of the Philippines's medium-use provinces, giving birth in a government facility increased the likelihood of a cesarean delivery by 84 percent and by 173 percent in a private facility. Large regional variations in cesarean rates suggest the need for more informed clinical decision making with respect to the selection of cases for cesarean delivery and the establishment of well-developed guidelines and standards at the provincial or state levels. © 2016 Wiley Periodicals, Inc.

Assessment of urban pluvial flood risk and efficiency of adaptation options through simulations - A new generation of urban planning tools

NASA Astrophysics Data System (ADS)

Löwe, Roland; Urich, Christian; Sto. Domingo, Nina; Mark, Ole; Deletic, Ana; Arnbjerg-Nielsen, Karsten

2017-07-01

We present a new framework for flexible testing of flood risk adaptation strategies in a variety of urban development and climate scenarios. This framework couples the 1D-2D hydrodynamic simulation package MIKE FLOOD with the agent-based urban development model DAnCE4Water and provides the possibility to systematically test various flood risk adaptation measures ranging from large infrastructure changes over decentralised water management to urban planning policies. We have tested the framework in a case study in Melbourne, Australia considering 9 scenarios for urban development and climate and 32 potential combinations of flood adaptation measures. We found that the performance of adaptation measures strongly depended on the considered climate and urban development scenario and the other implementation measures implemented, suggesting that adaptive strategies are preferable over one-off investments. Urban planning policies proved to be an efficient means for the reduction of flood risk, while implementing property buyback and pipe increases in a guideline-oriented manner was too costly. Random variations in location and time point of urban development could have significant impact on flood risk and would in some cases outweigh the benefits of less efficient adaptation strategies. The results of our setup can serve as an input for robust decision making frameworks and thus support the identification of flood risk adaptation measures that are economically efficient and robust to variations of climate and urban layout.

Locating spatial variation in the association between wildland fire risk and social vulnerability across six southern states

Treesearch

Neelam Poudyal; Cassandra Johnson Gaither; Scott Goodrick; J.M. Bowker; Jianbang Gan

2012-01-01

Wildland fire in the South commands considerable attention, given the expanding wildland urban interface (WUI) across the region. Much of this growth is propelled by higher income retirees and others desiring natural amenity residential settings. However, population growth in the WUI increases the likelihood of wildfire fire ignition caused by people, as humans account...

Machine learning approaches in medical image analysis: From detection to diagnosis.

PubMed

de Bruijne, Marleen

2016-10-01

Machine learning approaches are increasingly successful in image-based diagnosis, disease prognosis, and risk assessment. This paper highlights new research directions and discusses three main challenges related to machine learning in medical imaging: coping with variation in imaging protocols, learning from weak labels, and interpretation and evaluation of results. Copyright © 2016 Elsevier B.V. All rights reserved.

Increasing age is a major risk factor for susceptibility to heat stress during physical activity.

PubMed

McGinn, Ryan; Poirier, Martin P; Louie, Jeffrey C; Sigal, Ronald J; Boulay, Pierre; Flouris, Andreas D; Kenny, Glen P

2017-11-01

We evaluated the extent to which age, cardiorespiratory fitness, and body fat can independently determine whole-body heat loss (WBHL) in 87 otherwise healthy adults. We show that increasing age is a major predictor for decreasing WBHL in otherwise healthy adults (aged 20-70 years), accounting for 40% of the variation in the largest study to date. While greater body fat also had a minor detrimental impact on WBHL, there was no significant role for cardiorespiratory fitness.

Variation in faecal microbiota in a group of horses managed at pasture over a 12-month period.

PubMed

Salem, Shebl E; Maddox, Thomas W; Berg, Adam; Antczak, Philipp; Ketley, Julian M; Williams, Nicola J; Archer, Debra C

2018-05-31

Colic (abdominal pain) is a common cause of mortality in horses. Change in management of horses is associated with increased colic risk and seasonal patterns of increased risk have been identified. Shifts in gut microbiota composition in response to management change have been proposed as one potential underlying mechanism for colic. However, the intestinal microbiota in normal horses and how this varies over different seasons has not previously been investigated. In this study the faecal microbiota composition was studied over 12 months in a population of horses managed at pasture with minimal changes in management. We hypothesised that gut microbiota would be stable in this population over time. Faecal samples were collected every 14 days from 7 horses for 52 weeks and the faecal microbiota was characterised by next-generation sequencing of 16S rRNA genes. The faecal microbiota was dominated by members of the phylum Firmicutes and Bacteroidetes throughout. Season, supplementary forage and ambient weather conditions were significantly associated with change in the faecal microbiota composition. These results provide important baseline information demonstrating physiologic variation in the faecal microbiota of normal horses over a 12-month period without development of colic.

NDVI-Based analysis on the influence of human activities on vegetation variation on Hainan Island

NASA Astrophysics Data System (ADS)

Luo, Hongxia; Dai, Shengpei; Xie, Zhenghui; Fang, Jihua

2018-02-01

Using the Moderate Resolution Imaging Spectroradiometer-normalized difference vegetation index (NDVI) dataset, we analyzed the predicted NDVI values variation and the influence of human activities on vegetation on Hainan Island during 2001-2015. We investigated the roles of human activities in vegetation variation, particularly from 2002 when implemented the Grain-for-Greenprogram on Hainan Island. The trend analysis, linear regression model and residual analysis were used to analyze the data. The results of the study showed that (1) The predicted vegetation on Hainan Island showed an general upward trend with a linear growth rate of 0.0025/10y (p<0.05) over the past 15 years. The areas where vegetation increasedaccounted for 52.28%, while the areas where vegetation decreased accounted for 47.72%. (2) The residual NDVI values across the region significantly increased, with a growth rate of 0.023/10y.The vegetation increased across 35.95% of Hainan Island, while it decreased in 20.2% of the area as a result of human activities. (3) In general, human activities had played a positive role in the vegetation increase on Hainan Island, and the residual NDVI trend of this region showed positive outcomes for vegetation variation after implementing ecological engineering projects. However, it indicated a growing risk of vegetation degradation in the coastal region of Hainan Island as a result of rapid urbanization, land reclamation.

Variations in BMI and prevalence of health risks in diverse racial and ethnic populations.

PubMed

Stommel, Manfred; Schoenborn, Charlotte A

2010-09-01

When examining health risks associated with the BMI, investigators often rely on the customary BMI thresholds of the 1995 World Health Organization report. However, within-interval variations in morbidity and mortality can be substantial, and the thresholds do not necessarily correspond to identifiable risk increases. Comparing the prevalence of hypertension, diabetes, coronary heart disease (CHD), asthma, and arthritis among non-Hispanic whites, blacks, East Asians and Hispanics, we examine differences in the BMI-health-risk relationships for small BMI increments. The analysis is based on 11 years of data of the National Health Interview Survey (NHIS), with a sample size of 337,375 for the combined 1997-2007 Sample Adult. The analysis uses multivariate logistic regression models, employing a nonparametric approach to modeling the BMI-health-risk relationship, while relying on narrowly defined BMI categories. Rising BMI levels are associated with higher levels of chronic disease burdens in four major racial and ethnic groups, even after adjusting for many socio-demographic characteristics and three important health-related behaviors (smoking, physical activity, alcohol consumption). For all population groups, except East Asians, a modestly higher disease risk was noted for persons with a BMI <20 compared with persons with BMI in the range of 20-21. Using five chronic conditions as risk criteria, a categorization of the BMI into normal weight, overweight, or obesity appears arbitrary. Although the prevalence of disease risks differs among racial and ethnic groups regardless of BMI levels, the evidence presented here does not support the notion that the BMI-health-risk profile of East Asians and others warrants race-specific BMI cutoff points.

Conditional cold avoidance drives between-population variation in germination behaviour in Calluna vulgaris.

PubMed

Spindelböck, Joachim P; Cook, Zoë; Daws, Matthew I; Heegaard, Einar; Måren, Inger E; Vandvik, Vigdis

2013-09-01

Across their range, widely distributed species are exposed to a variety of climatic and other environmental conditions, and accordingly may display variation in life history strategies. For seed germination in cold climates, two contrasting responses to variation in winter temperature have been documented: first, an increased ability to germinate at low temperatures (cold tolerance) as winter temperatures decrease, and secondly a reduced ability to germinate at low temperatures (cold avoidance) that concentrates germination towards the warmer parts of the season. Germination responses were tested for Calluna vulgaris, the dominant species of European heathlands, from ten populations collected along broad-scale bioclimatic gradients (latitude, altitude) in Norway, covering a substantial fraction of the species' climatic range. Incubation treatments varied from 10 to 25 °C, and germination performance across populations was analysed in relation to temperature conditions at the seed collection locations. Seeds from all populations germinated rapidly and to high final percentages under the warmer incubation temperatures. Under low incubation temperatures, cold-climate populations had significantly lower germination rates and percentages than warm-climate populations. While germination rates and percentages also increased with seed mass, seed mass did not vary along the climatic gradients, and therefore did not explain the variation in germination responses. Variation in germination responses among Calluna populations was consistent with increased temperature requirements for germination towards colder climates, indicating a cold-avoidance germination strategy conditional on the temperature at the seeds' origin. Along a gradient of increasing temperatures this suggests a shift in selection pressures on germination from climatic adversity (i.e. low temperatures and potential frost risk in early or late season) to competitive performance and better exploitation of the entire growing season.

Conditional cold avoidance drives between-population variation in germination behaviour in Calluna vulgaris

PubMed Central

Spindelböck, Joachim P.; Cook, Zoë; Daws, Matthew I.; Heegaard, Einar; Måren, Inger E.; Vandvik, Vigdis

2013-01-01

Background and Aims Across their range, widely distributed species are exposed to a variety of climatic and other environmental conditions, and accordingly may display variation in life history strategies. For seed germination in cold climates, two contrasting responses to variation in winter temperature have been documented: first, an increased ability to germinate at low temperatures (cold tolerance) as winter temperatures decrease, and secondly a reduced ability to germinate at low temperatures (cold avoidance) that concentrates germination towards the warmer parts of the season. Methods Germination responses were tested for Calluna vulgaris, the dominant species of European heathlands, from ten populations collected along broad-scale bioclimatic gradients (latitude, altitude) in Norway, covering a substantial fraction of the species' climatic range. Incubation treatments varied from 10 to 25 °C, and germination performance across populations was analysed in relation to temperature conditions at the seed collection locations. Key Results Seeds from all populations germinated rapidly and to high final percentages under the warmer incubation temperatures. Under low incubation temperatures, cold-climate populations had significantly lower germination rates and percentages than warm-climate populations. While germination rates and percentages also increased with seed mass, seed mass did not vary along the climatic gradients, and therefore did not explain the variation in germination responses. Conclusions Variation in germination responses among Calluna populations was consistent with increased temperature requirements for germination towards colder climates, indicating a cold-avoidance germination strategy conditional on the temperature at the seeds' origin. Along a gradient of increasing temperatures this suggests a shift in selection pressures on germination from climatic adversity (i.e. low temperatures and potential frost risk in early or late season) to competitive performance and better exploitation of the entire growing season. PMID:23884396

Fall-related injuries among initially 75- and 80-year old people during a 10-year follow-up.

PubMed

Saari, Päivi; Heikkinen, Eino; Sakari-Rantala, Ritva; Rantanen, Taina

2007-01-01

The aim of this study was to investigate the occurrence, type, scene and seasonal variation of fall related injuries, and the impact of socio-economic factors, mobility limitation, and the most common diseases on the risk of injurious falls over a 10-year follow-up. Elderly residents of Jyväskylä, Finland, aged initially 75 and 80 years, took part in the study in 1989-1990. The health and functional capacity assessments were carried out at the baseline. Injurious falls were monitored over a 10-year period. The rate of injurious falls per thousand person-years was 188 among women and 78 among men. Of all fall-related diagnoses, head injuries comprised 32%, upper limb injuries 27% and hip injuries 19%. Majority of injurious falls took place indoors and no seasonal variation in fall occurrence was observed. Recurring falls were more likely to take place in institutions. Osteoarthritis increased the risk of injurious falls but no effect was observed for coronary heart diseases or mobility limitation. All in all, intrinsic factors, such as chronic diseases and mobility limitation had only minor effect on risk of injurious falls among older people. The current results suggest that preventive interventions for injurious falls among older people should pay attention to the risk factors present indoors.

Quantifying Neonatal Sucking Performance: Promise of New Methods.

PubMed

Capilouto, Gilson J; Cunningham, Tommy J; Mullineaux, David R; Tamilia, Eleonora; Papadelis, Christos; Giannone, Peter J

2017-04-01

Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The impact of environmental temperature on the diagnosis of gestational diabetes mellitus.

PubMed

Vasileiou, Vasiliki; Kyratzoglou, Eleni; Paschou, Stavroula A; Kyprianou, Miltiades; Anastasiou, Eleni

2018-03-01

To investigate a probable impact of seasons on the diagnosis of GDM, as well as the specific effect of the environmental temperature on the diagnosis of this clinical entity. Two observational studies, one retrospective and one prospective, were conducted in a referral center. Study A included retrospectively 7618 pregnant women who underwent a 3-h 100 g OGTT during the 3rd trimester of gestation. Study B prospectively included 768 pregnant women tested in the 3rd trimester of gestation with a 75 g OGTT. Temperature was recorded every day at 09:00 h. Retrospective Study A: GDM prevalence differed significantly by season: winter = 28.1%, summer = 39.2%, spring = 32.4% and autumn = 32.4% ( P  < 0.0001). The odds ratio for being diagnosed with GDM was much higher during summer 1.65 (95% CI: 1.43-1.90), with spring and autumn following with 1.23 (95% CI: 1.08-1.39) compared to winter. Glucose levels during OGTT were measured: significantly increased blood glucose values were observed at 60, 120 and 180 min in summer, which remained significant after adjustment for age, gestational age, BMI, weight gain during pregnancy and blood pressure. Prospective Study B: At temperatures above 25°C, the average glucose 60-min and 120-min levels were increased. The relative risk for abnormal glucose values at 60 min, when the environmental temperature increased over 25°C, was 2.2 (1.5-3.3). GDM prevalence in Greece presents seasonal variation, with higher risk during summer due to post glucose load level variations. These variations could be attributed to differences in environmental temperature. © 2018 European Society of Endocrinology.

Geographical Variations in the Environmental Determinants of Physical Inactivity among U.S. Adults.

PubMed

An, Ruopeng; Li, Xinye; Jiang, Ning

2017-10-31

Physical inactivity is a major modifiable risk factor for morbidity, disability and premature mortality worldwide. This study assessed the geographical variations in the impact of environmental quality on physical inactivity among U.S. adults. Data on county-level prevalence of leisure-time physical inactivity came from the Behavioral Risk Factor Surveillance System. County environment was measured by the Environmental Quality Index (EQI), a comprehensive index of environmental conditions that affect human health. The overall EQI consists of five subdomains-air, water, land, social, and built environment. Geographically weighted regressions (GWRs) were performed to estimate and map county-specific impact of overall EQI and its five subdomains on physical inactivity prevalence. The prevalence of leisure-time physical inactivity among U.S. counties was 25% in 2005. On average, one standard deviation decrease in the overall EQI was associated with an increase in county-level prevalence of leisure-time physical inactivity by nearly 1%. However, substantial geographical variations in the estimated environmental determinants of physical inactivity were present. The estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the overall EQI ranged from an increase of over 3% to a decrease of nearly 2% across U.S. counties. Analogous, the estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the EQI air, water, land, social, and built environment subdomains ranged from an increase of 2.6%, 1.5%, 2.9%, 3.3%, and 1.7% to a decrease of 2.9%, 1.4%, 2.4%, 2.4%, and 0.8% across U.S. counties, respectively. Given the substantial heterogeneities in the environmental determinants of physical inactivity, locally customized physical activity interventions are warranted to address the most concerning area-specific environmental issue.

Fundamental Frequency Variation of Neonatal Spontaneous Crying Predicts Language Acquisition in Preterm and Term Infants.

PubMed

Shinya, Yuta; Kawai, Masahiko; Niwa, Fusako; Imafuku, Masahiro; Myowa, Masako

2017-01-01

Spontaneous cries of infants exhibit rich melodic features (i.e., time variation of fundamental frequency [ F 0 ]) even during the neonatal period, and the development of these characteristics might provide an essential base for later expressive prosody in language. However, little is known about the melodic features of spontaneous cries in preterm infants, who have a higher risk of later language-related problems. Thus, the present study investigated how preterm birth influenced melodic features of spontaneous crying at term-equivalent age as well as how these melodic features related to language outcomes at 18 months of corrected age in preterm and term infants. At term, moderate-to-late preterm (MLP) infants showed spontaneous cries with significantly higher F 0 variation and melody complexity than term infants, while there were no significant differences between very preterm (VP) and term infants. Furthermore, larger F 0 variation within cry series at term was significantly related to better language and cognitive outcomes, particularly expressive language skills, at 18 months. On the other hand, no other melodic features at term predicted any developmental outcomes at 18 months. The present results suggest that the additional postnatal vocal experience of MLP preterm infants increased F 0 variation and the complexity of spontaneous cries at term. Additionally, the increases in F 0 variation may partly reflect the development of voluntary vocal control, which, in turn, contributes to expressive language in infancy.

Development of Organ-Specific Donor Risk Indices

PubMed Central

Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

2012-01-01

Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; use of the Liver Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. PMID:22287036

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.

PubMed

Krinsley, James S; Egi, Moritoki; Kiss, Alex; Devendra, Amin N; Schuetz, Philipp; Maurer, Paula M; Schultz, Marcus J; van Hooijdonk, Roosmarijn T M; Kiyoshi, Morita; Mackenzie, Iain M J; Annane, Djillali; Stow, Peter; Nasraway, Stanley A; Holewinski, Sharon; Holzinger, Ulrike; Preiser, Jean-Charles; Vincent, Jean-Louis; Bellomo, Rinaldo

2013-03-01

Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients. This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes. Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands>or=140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG<70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV>or=20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes. Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.

Childhood adversity, recent life stressors and suicidal behavior in Chinese college students.

PubMed

You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population.

Genetic variations of E6 and long control region of human papillomavirus type 16 from patients with cervical lesion in Liaoning, China.

PubMed

Sun, Zhengrong; Lu, Zhitao; Liu, Jianhua; Wang, Guili; Zhou, Weiqiang; Yang, Lianxia; Liu, Chao; Wang, Bo; Ruan, Qiang

2013-10-07

High-risk human papillomavirus type 16 (HPV16) is a risk factor for cervical cancer. Previous studies suggest that polymorphisms in the E6 gene or the long control region(LCR)of HPV16 may alter the oncogenic potential of the virus. The aims of this study were to investigate the genetic variations of HPV16 E6 gene and LCR in isolates from Chinese population and correlation of the E6 and LCR polymorphisms with disease status of infected patients. HPV16 positive endocervical specimens were collected from 304 women living in Northeast of China. Sequences of E6 gene and LCR were analyzed by PCR-sequencing. Two lineages were found in the populations, including EUR lineage and As lineage. Based on the HPV16 prototype, the most frequent variation in the E6 gene was T178A/G (48.7%), followed by mutations of G94A (12.2%) and T350G (9.9%). The rank orders of incidence of E6 variations in amino acid were as follows: D25E (46.3%), L83V (9.9%) and H78Y (4.3%). Nucleotide variations in LCR were found in all the 304 isolates from HPV16 positive cervical samples. The most commonly observed LCR variations were the transition replacement G7193T, 7434CIns, G7521A and 7863ADel (100%). The As lineage was associated with HPV persistent infections and with disease status of ≥CIN2,3. The EUR lineage variants showed a negative trend of association with the severity of ≥CIN2,3. Among 41 variations found in LCR, 25 (61.0%) were located at the binding sites for transcription factors. Occurrence of ≥CIN2,3 was significantly associated with the mutations of R10G/L83V in E6 and the C7294T co-variation in LCR, after adjusting for ages of infected patients. Associations between As lineage and HPV persistent infections, and with disease status of ≥CIN2,3, and an association between the EUR lineage and negative trend of association with the severity of ≥CIN2,3 were found in this study. An association between a co-variation of R10G/L83V in E6 and C7294T in LCR and an increased risk for developing CIN-2,3 was found in a HPV16 infected population of Chinese women. These findings indicate that HPV16 polymorphism influences development of CIN-2,3.

Implementation of equity in resource allocation for regional earthquake risk mitigation using two-stage stochastic programming.

PubMed

Zolfaghari, Mohammad R; Peyghaleh, Elnaz

2015-03-01

This article presents a new methodology to implement the concept of equity in regional earthquake risk mitigation programs using an optimization framework. It presents a framework that could be used by decisionmakers (government and authorities) to structure budget allocation strategy toward different seismic risk mitigation measures, i.e., structural retrofitting for different building structural types in different locations and planning horizons. A two-stage stochastic model is developed here to seek optimal mitigation measures based on minimizing mitigation expenditures, reconstruction expenditures, and especially large losses in highly seismically active countries. To consider fairness in the distribution of financial resources among different groups of people, the equity concept is incorporated using constraints in model formulation. These constraints limit inequity to the user-defined level to achieve the equity-efficiency tradeoff in the decision-making process. To present practical application of the proposed model, it is applied to a pilot area in Tehran, the capital city of Iran. Building stocks, structural vulnerability functions, and regional seismic hazard characteristics are incorporated to compile a probabilistic seismic risk model for the pilot area. Results illustrate the variation of mitigation expenditures by location and structural type for buildings. These expenditures are sensitive to the amount of available budget and equity consideration for the constant risk aversion. Most significantly, equity is more easily achieved if the budget is unlimited. Conversely, increasing equity where the budget is limited decreases the efficiency. The risk-return tradeoff, equity-reconstruction expenditures tradeoff, and variation of per-capita expected earthquake loss in different income classes are also presented. © 2015 Society for Risk Analysis.

Mexican-origin youth's risk behavior from adolescence to young adulthood: The role of familism values.

PubMed

Wheeler, Lorey A; Zeiders, Katharine H; Updegraff, Kimberly A; Umaña-Taylor, Adriana J; Rodríguez de Jesús, Sue A; Perez-Brena, Norma J

2017-01-01

Engagement in risk behavior has implications for individuals' academic achievement, health, and well-being, yet there is a paucity of developmental research on the role of culturally relevant strengths in individual and family differences in risk behavior involvement among ethnic minority youth. In this study, we used a longitudinal cohort-sequential design to chart intraindividual trajectories of risk behavior and test variation by gender and familism values in 492 youth from 12 to 22 years of age. Participants were older and younger siblings from 246 Mexican-origin families who reported on their risk behaviors in interviews spaced over 8 years. Multilevel cohort-sequential growth models revealed that youth reported an increase in risk behavior from 12 to 18 years of age, and then a decline to age 22. Male youth reported greater overall levels and a steeper increase in risk behavior from ages 12 to 18, compared to female youth. For familism values, on occasions when youth reported higher levels, they also reported lower levels of risk behavior (i.e., within-person effect). For sibling dyads characterized by higher average levels of familism values, youth reported lower average levels of risk behavior (i.e., between-family effect). Findings provide unique insights into risk behavior from adolescence to young adulthood among Mexican-origin youth. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Body-Weight Fluctuations and Outcomes in Coronary Disease.

PubMed

Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; DeMicco, David A; Messerli, Franz H; Waters, David D

2017-04-06

Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).

EXERCISES THAT FACILITATE OPTIMAL HAMSTRING AND QUADRICEPS CO-ACTIVATION TO HELP DECREASE ACL INJURY RISK IN HEALTHY FEMALES: A SYSTEMATIC REVIEW OF THE LITERATURE.

PubMed Central

Dedinsky, Rachel; Baker, Lindsey; Imbus, Samuel; Bowman, Melissa

2017-01-01

Background Anterior cruciate ligament (ACL) injury is common among females due to many anatomic, hormonal, and neuromuscular risk factors. One modifiable risk factor that places females at increased risk of ACL injury is a poor hamstrings: quadriceps (H:Q) co-activation ratio, which should be 0.6 or greater in order to decrease the stress placed on the ACL. Exercises that produce more quadriceps dominant muscle activation can add to the tension placed upon the ACL, potentially increasing the risk of ACL injury. Hypothesis/Purpose The purpose of this systematic review was to compare quadriceps and hamstring muscle activation during common closed kinetic chain therapeutic exercises in healthy female knees to determine what exercises are able to produce adequate H:Q co-activation ratios. Study Design Systematic Review Methods Multiple online databases were systematically searched and screened for inclusion. Eight articles were identified for inclusion. Data on mean electromyography (EMG) activation of both quadriceps and hamstring muscles, % maximal voluntary isometric contraction (MVIC), and H:Q co-activation ratios were extracted from the studies. Quality assessment was performed on all included studies. Results Exercises analyzed in the studies included variations of the double leg squat, variations of the single leg squat, lateral step-up, Fitter, Stairmaster® (Core Health and Fitness, Vancouver, WA), and slide board. All exercises, except the squat machine with posterior support at the level of the scapula and feet placed 50 cm in front of the hips, produced higher quadriceps muscle activation compared to hamstring muscle activation. Conclusion Overall, two leg squats demonstrate poor H:Q co-activation ratios. Single leg exercises, when performed between 30 and 90 degrees of knee flexion, produce adequate H:Q ratios, thereby potentially reducing the risk of tensile stress on the ACL and ACL injury. Level of Evidence 2a- Systematic Review of Cohort Studies PMID:28217412

Cost variation in a laparoscopic cholecystectomy and the association with outcomes across a single health system: implications for standardization and improved resource utilization.

PubMed

Brauer, David G; Hawkins, William G; Strasberg, Steven M; Brunt, L Michael; Jaques, David P; Mercurio, Nicholas R; Hall, Bruce L; Fields, Ryan C

2015-12-01

Payers and regulatory bodies are increasingly placing emphasis on cost containment, quality/outcome measurement and transparent reporting. Significant cost variation occurs in many operative procedures without a clear relationship with outcomes. Clear cost-benefit associations will be necessary to justify expenditures in the era of bundled payment structures. All laparoscopic cholecystectomies (LCCKs) performed within a single health system over a 1-year period were analysed for operating room (OR) supply cost. The cost was correlated with American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) outcomes. From July 2013 to June 2014, 2178 LCCKs were performed by 55 surgeons at seven hospitals. The median case OR supply cost was $513 ± 156. There was variation in cost between individual surgeons and within an individual surgeon's practice. There was no correlation between cost and ACS NSQIP outcomes. The majority of cost variation was explained by selection of trocar and clip applier constructs. Significant case OR cost variation is present in LCCK across a single health system, and there is no clear association between increased cost and NSQIP outcomes. Placed within the larger context of overall cost, the opportunity exists for improved resource utilization with no obvious risk for a reduction in the quality of care. © 2015 International Hepato-Pancreato-Biliary Association.

Cost variation in a laparoscopic cholecystectomy and the association with outcomes across a single health system: implications for standardization and improved resource utilization

PubMed Central

Brauer, David G; Hawkins, William G; Strasberg, Steven M; Brunt, L Michael; Jaques, David P; Mercurio, Nicholas R; Hall, Bruce L; Fields, Ryan C

2015-01-01

Background Payers and regulatory bodies are increasingly placing emphasis on cost containment, quality/outcome measurement and transparent reporting. Significant cost variation occurs in many operative procedures without a clear relationship with outcomes. Clear cost-benefit associations will be necessary to justify expenditures in the era of bundled payment structures. Methods All laparoscopic cholecystectomies (LCCKs) performed within a single health system over a 1-year period were analysed for operating room (OR) supply cost. The cost was correlated with American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) outcomes. Results From July 2013 to June 2014, 2178 LCCKs were performed by 55 surgeons at seven hospitals. The median case OR supply cost was $513 ± 156. There was variation in cost between individual surgeons and within an individual surgeon's practice. There was no correlation between cost and ACS NSQIP outcomes. The majority of cost variation was explained by selection of trocar and clip applier constructs. Conclusions Significant case OR cost variation is present in LCCK across a single health system, and there is no clear association between increased cost and NSQIP outcomes. Placed within the larger context of overall cost, the opportunity exists for improved resource utilization with no obvious risk for a reduction in the quality of care. PMID:26345351

Modifiers: Increasing Richness and Nuance of Design Pattern Languages

NASA Astrophysics Data System (ADS)

Kolfschoten, Gwendolyn L.; Briggs, Robert O.; Lukosch, Stephan

One of the challenges when establishing and maintaining a pattern language is to balance richness with simplicity. On the one hand, designers need a variety of useful design patterns to increase the speed of their design efforts and to reduce design risk. On the other hand, the greater the variety of design patterns in a language, the higher the cognitive load to remember and select among them. One solution to this problem is the concept of a modifier design pattern, a design pattern for pattern languages. A modifier pattern is a named, documented variation that can be applied to some set of other design patterns. They create similar, useful changes and refinements to the solutions derived from any pattern to which they are applied. The modifier concept, described in this paper emerged in a relatively new design pattern language for collaborative work practices in which the design patterns are called thinkLets. When analyzing the thinkLet pattern language, we found that many of the patterns we knew were variations and refinements of other patterns. However, we also found patterns in these variations; we found variations that could be applied to different patterns, with similar effects. We document these variations as modifiers. In this paper, we introduce the concept of modifier design patterns and illustrate the use of modifiers with two case studies.

The role of androgens and polymorphisms in the androgen receptor in the epidemiology of breast cancer

PubMed Central

Lillie, Elizabeth O; Bernstein, Leslie; Ursin, Giske

2003-01-01

Testosterone binds to the androgen receptor in target tissue to mediate its effects. Variations in testosterone levels and androgen receptor activity may play a role in the etiology of breast cancer. Here, we review the epidemiologic evidence linking endogenous testosterone to breast cancer risk. Paradoxically, results from observational studies that have examined polymorphisms in the androgen receptor suggest that the low-activity androgen receptor increases breast cancer risk. We review the quality of this evidence and conclude with a discussion of how the androgen receptor and testosterone results coincide. PMID:12793900

Discrete call types referring to predation risk enhance the efficiency of the meerkat sentinel system

PubMed Central

Rauber, R.; Manser, M. B.

2017-01-01

Sentinel behaviour, a form of coordinated vigilance, occurs in a limited range of species, mostly in cooperative breeders. In some species sentinels confirm their presence vocally by giving a single sentinel call type, whereby the rate and subtle acoustic changes provide graded information on the variation of perceived predation risk. In contrast, meerkat (Suricata suricatta) sentinels produce six different sentinel call types. Here we show that manipulation of perception of danger has different effects on the likelihood of emitting these different call types, and that these call types affect foraging individuals differently. Increasing the perceived predation risk by playing back alarm calls decreased the production rate of the common short note calls and increased the production rate of the rare long calls. Playbacks of short note calls increased foraging behaviour and decreased vigilance in the rest of the group, whereas the opposite was observed when playing long calls. This suggests that the common call types act as all-clear signals, while the rare call types have a warning function. Therefore, meerkats increase the efficiency of their sentinel system by producing several discrete call types that represent changes in predation risk and lead to adjustments of the group’s vigilance behaviour. PMID:28303964

COHORT EFFECTS OF SUICIDE MORTALITY ARE SEX SPECIFIC IN THE RAPIDLY DEVELOPED HONG KONG CHINESE POPULATION, 1976-2010.

PubMed

Chung, Roger Y; Yip, Benjamin H K; Chan, Sandra S M; Wong, Samuel Y S

2016-06-01

To examine temporal variations of age, period, and cohort on suicide mortality rate in Hong Kong (HK) from 1976 to 2010, and speculate the macroenvironmental mechanisms of the observed trends. Poisson age-period-cohort modeling was used to delineate the effects of age, period, and cohort on suicide mortality. Analysis by sex was also conducted to examine if gender difference exists for suicidal behaviours. Age-cohort model provides the best fit to the mortality data, implying that the cohort effect is likely to explain more of the contributions to HK's suicide mortality pattern than the period effect. Risk of suicide mortality increases nonlinearly with age and accelerates after age 65-69 for both sexes. Moreover, the cohort effects differ between the sexes-risk of mortality increases continually for men born after 1961, but no change is observed for women since the 1941 cohort. With increased risk of suicide mortality in younger cohorts and the age effect of suicide mortality, we may see future increase in suicide mortality as these younger cohorts age. Further studies are needed to clarify plausible associations between broader sociohistorical changes in the population impacting psychological risk factors and suicidal behaviour to better inform suicide prevention strategies. © 2015 Wiley Periodicals, Inc.

Variation in symptoms of depression and anxiety in midlife women by menopausal status.

PubMed

Mulhall, Stephanie; Andel, Ross; Anstey, Kaarin J

2018-02-01

To examine the association between menopausal status and the risk of symptoms of depression and anxiety in a community-based sample of Australian midlife women. Female participants (mean age 50.6±1.5) who were premenopausal (n=237), perimenopausal (n=249) or naturally postmenopausal (n=225) were drawn from the Personality and Total Health (PATH) Through Life Project, a longitudinal study. Symptoms of depression and anxiety were measured using the Goldberg Depression Scale and Goldberg Anxiety Scale. Generalised linear regression models with a negative binomial log link were used. Relative to premenopause and after adjusting for all relevant covariates, being perimenopausal was associated with increased risk of greater symptoms of depression (incidence rate ratio [IRR]=1.29, p=0.001), while being postmenopausal was associated with increased risk of greater symptoms of anxiety (IRR=1.15, p=0.041). Being perimenopausal or postmenopausal was associated with an increased risk of greater symptoms of depression (IRR=1.35, p=0.008; IRR=1.31, p=0.029) and anxiety (IRR=1.22, p=0.030; IRR=1.32, p=0.006) in women without a history of probable major depressive disorder or generalised anxiety disorder. Risk of symptoms did not differ with menopausal status in women with this history. Menopausal status is associated with the risk of symptoms of depression and anxiety. There is a greater likelihood of increased symptoms of depression during perimenopause and symptoms of anxiety during postmenopause. In women without a history of depression or anxiety, the perimenopause and postmenopausal stages are associated with increased risk of greater symptoms of anxiety and depression relative to premenopause. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing future changes in the occurrence of rainfall-induced landslides at a regional scale.

PubMed

Gariano, S L; Rianna, G; Petrucci, O; Guzzetti, F

2017-10-15

According to the fifth report of the Intergovernmental Panel on Climate Change, an increase in the frequency and the intensity of extreme rainfall is expected in the Mediterranean area. Among different impacts, this increase might result in a variation in the frequency and the spatial distribution of rainfall-induced landslides, and in an increase in the size of the population exposed to landslide risk. We propose a method for the regional-scale evaluation of future variations in the occurrence of rainfall-induced landslides, in response to changes in rainfall regimes. We exploit information on the occurrence of 603 rainfall-induced landslides in Calabria, southern Italy, in the period 1981-2010, and daily rainfall data recorded in the same period in the region. Furthermore, we use high-resolution climate projections based on RCP4.5 and RCP8.5 scenarios. In particular, we consider the mean variations between a 30-year future period (2036-2065) and the reference period 1981-2010 in three variables assumed as proxy for landslide activity: annual rainfall, seasonal cumulated rainfall, and annual maxima of daily rainfall. Based on reliable correlations between landslide occurrence and weather variables estimated in the reference period, we assess future variations in rainfall-induced landslide occurrence for all the municipalities of Calabria. A +45.7% and +21.2% average regional variation in rainfall-induced landslide occurrence is expected in the region for the period 2036-2065, under the RCP4.5 and RCP8.5 scenario, respectively. We also investigate the future variations in the impact of rainfall-induced landslides on the population of Calabria. We find a +80.2% and +54.5% increase in the impact on the population for the period 2036-2065, under the RCP4.5 and RCP8.5 scenario, respectively. The proposed method is quantitative and reproducible, thus it can be applied in similar regions, where adequate landslide and rainfall information is available. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence and timing of presentation of necrotizing enterocolitis in preterm infants.

PubMed

Yee, Wendy H; Soraisham, Amuchou Singh; Shah, Vibhuti S; Aziz, Khalid; Yoon, Woojin; Lee, Shoo K

2012-02-01

To examine the variation in the incidence and to identify the timing of the presentation of necrotizing enterocolitis (NEC) in a cohort of preterm infants within the Canadian Neonatal Network (CNN). This was a population-based cohort of 16 669 infants with gestational age (GA) <33 weeks, admitted to 25 NICUs participating in the CNN between January 1, 2003, and December 31(,) 2008. Variations in NEC incidence among the participating NICUs for the study period were examined. We categorized early-onset NEC as occurring at <14 days of age and late-onset NEC occurring at ≥14 days. Multivariate logistic regression analysis was performed to identify risk factors for early-onset NEC. The overall incidence of NEC was 5.1%, with significant variation in the risk adjusted incidence among the participating NICUs in the CNN. Early-onset NEC occurred at a mean of 7 days compared with 32 days for late-onset NEC. Early-onset NEC infants had lower incidence of respiratory distress syndrome, patent ductus treated with indomethacin, less use of postnatal steroids, and shorter duration of ventilation days. Multivariate logistic regression analysis identified that greater GA and vaginal delivery were associated with increased risk of early-onset NEC. Among infants <33 weeks' gestation, NEC appears to present at mean age of 7 days in more mature infants, whereas onset of NEC is delayed to 32 days of age in smaller, lower GA infants. Further studies are required to understand the etiology of this disease process.

ATM, radiation, and the risk of second primary breast cancer.

PubMed

Bernstein, Jonine L; Concannon, Patrick

2017-10-01

It was first suggested more than 40 years ago that heterozygous carriers for the human autosomal recessive disorder Ataxia-Telangiectasia (A-T) might also be at increased risk for cancer. Subsequent studies have identified the responsible gene, Ataxia-Telangiectasia Mutated (ATM), characterized genetic variation at this locus in A-T and a variety of different cancers, and described the functions of the ATM protein with regard to cellular DNA damage responses. However, an overall model of how ATM contributes to cancer risk, and in particular, the role of DNA damage in this process, remains lacking. This review considers these questions in the context of contralateral breast cancer (CBC). Heterozygous carriers of loss of function mutations in ATM that are A-T causing, are at increased risk of breast cancer. However, examination of a range of genetic variants, both rare and common, across multiple cancers, suggests that ATM may have additional effects on cancer risk that are allele-dependent. In the case of CBC, selected common alleles at ATM are associated with a reduced incidence of CBC, while other rare and predicted deleterious variants may act jointly with radiation exposure to increase risk. Further studies that characterize germline and somatic ATM mutations in breast cancer and relate the detected genetic changes to functional outcomes, particularly with regard to radiation responses, are needed to gain a complete picture of the complex relationship between ATM, radiation and breast cancer.

Mapping intra-urban malaria risk using high resolution satellite imagery: a case study of Dar es Salaam.

PubMed

Kabaria, Caroline W; Molteni, Fabrizio; Mandike, Renata; Chacky, Frank; Noor, Abdisalan M; Snow, Robert W; Linard, Catherine

2016-07-30

With more than half of Africa's population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection. However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements. The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs. In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014. High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam. Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam. Results indicate that the risk of malaria infection varied across the city. The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs. The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors. Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas. The predictive maps produced can serve as valuable resources for municipal councils aiming to shrink the extents of malaria across cities, target resources for vector control or intensify mosquito and disease surveillance. The semi-automated modelling process developed can be replicated in other urban areas to identify factors that influence heterogeneity in malaria risk patterns and detect vulnerable zones. There is a definite need to expand research into the unique epidemiology of malaria transmission in urban areas for focal elimination and sustained control agendas.

Inherited variation in immune response genes in follicular lymphoma and diffuse large B-cell lymphoma.

PubMed

Nielsen, Kaspar Rene; Steffensen, Rudi; Haunstrup, Thure Mors; Bødker, Julie Støve; Dybkær, Karen; Baech, John; Bøgsted, Martin; Johnsen, Hans Erik

2015-01-01

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated survival and proliferation signals from the tumor microenvironment. Inherited genetic variation influences this complex interaction. A total of 89 studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consistent association exists for variation in the tumor necrosis factor alpha (TNFA) and interleukin-10 loci and DLBCL risk; for DLBCL outcome association with the TNFA locus exists. Variations at chromosome 6p31-32 were associated with FL risk. Importantly, individual risk alleles have been shown to interact with each other. We suggest that the pathogenetic impact of polymorphic genes should include gene-gene interaction analysis and should be validated in preclinical model systems of normal B lymphopoiesis and B-cell malignancies. In the future, large cohort studies of interactions and genome-wide association studies are needed to extend the present findings and explore new risk alleles to be studied in preclinical models.

Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.

PubMed

Ross, Lars A; Del Bene, Victor A; Molholm, Sophie; Jae Woo, Young; Andrade, Gizely N; Abrahams, Brett S; Foxe, John J

2017-11-01

Three lines of evidence motivated this study. 1) CNTNAP2 variation is associated with autism risk and speech-language development. 2) CNTNAP2 variations are associated with differences in white matter (WM) tracts comprising the speech-language circuitry. 3) Children with autism show impairment in multisensory speech perception. Here, we asked whether an autism risk-associated CNTNAP2 single nucleotide polymorphism in neurotypical adults was associated with multisensory speech perception performance, and whether such a genotype-phenotype association was mediated through white matter tract integrity in speech-language circuitry. Risk genotype at rs7794745 was associated with decreased benefit from visual speech and lower fractional anisotropy (FA) in several WM tracts (right precentral gyrus, left anterior corona radiata, right retrolenticular internal capsule). These structural connectivity differences were found to mediate the effect of genotype on audiovisual speech perception, shedding light on possible pathogenic pathways in autism and biological sources of inter-individual variation in audiovisual speech processing in neurotypicals. Copyright © 2017 Elsevier Inc. All rights reserved.

Probabilistic flood damage modelling at the meso-scale

NASA Astrophysics Data System (ADS)

Kreibich, Heidi; Botto, Anna; Schröter, Kai; Merz, Bruno

2014-05-01

Decisions on flood risk management and adaptation are usually based on risk analyses. Such analyses are associated with significant uncertainty, even more if changes in risk due to global change are expected. Although uncertainty analysis and probabilistic approaches have received increased attention during the last years, they are still not standard practice for flood risk assessments. Most damage models have in common that complex damaging processes are described by simple, deterministic approaches like stage-damage functions. Novel probabilistic, multi-variate flood damage models have been developed and validated on the micro-scale using a data-mining approach, namely bagging decision trees (Merz et al. 2013). In this presentation we show how the model BT-FLEMO (Bagging decision Tree based Flood Loss Estimation MOdel) can be applied on the meso-scale, namely on the basis of ATKIS land-use units. The model is applied in 19 municipalities which were affected during the 2002 flood by the River Mulde in Saxony, Germany. The application of BT-FLEMO provides a probability distribution of estimated damage to residential buildings per municipality. Validation is undertaken on the one hand via a comparison with eight other damage models including stage-damage functions as well as multi-variate models. On the other hand the results are compared with official damage data provided by the Saxon Relief Bank (SAB). The results show, that uncertainties of damage estimation remain high. Thus, the significant advantage of this probabilistic flood loss estimation model BT-FLEMO is that it inherently provides quantitative information about the uncertainty of the prediction. Reference: Merz, B.; Kreibich, H.; Lall, U. (2013): Multi-variate flood damage assessment: a tree-based data-mining approach. NHESS, 13(1), 53-64.

Retinopathy of prematurity: Risk factors and variability in Canadian neonatal intensive care units.

PubMed

Thomas, K; Shah, P S; Canning, R; Harrison, A; Lee, S K; Dow, K E

2015-01-01

To identify predictors of severe retinopathy of prematurity (ROP) in a large population-based cohort and to examine risk-adjusted variations across units. Retrospective analysis of Canadian Neonatal Network data on neonates with birth weight <1500 g who were screened for ROP between 2003 and 2010. Characteristics of infants with and without ROP were compared and a risk-adjusted model for severe ROP was developed. Rates of severe ROP were compared between sites. 1163 of 9187 (12.7%) infants developed severe ROP. Lower gestational age, male sex, small for gestational age, patent ductus arteriosus, late onset sepsis, more than two blood transfusions, inotrope use, and outborn status were associated with an increased risk of severe ROP. Severe ROP rates varied significantly between units. Younger, smaller and sicker male infants had higher adjusted risks of severe ROP and rates varied significantly among sites.

Necrotizing Enterocolitis Risk

PubMed Central

Gephart, Sheila M.; McGrath, Jacqueline M.; Effken, Judith A.; Halpern, Melissa D.

2012-01-01

Necrotizing enterocolitis (NEC) is the most common cause of gastrointestinal-related morbidity and mortality in the neonatal intensive care unit (NICU). Its onset is sudden and the smallest, most premature infants are the most vulnerable. Necrotizing enterocolitis is a costly disease, accounting for nearly 20% of NICU costs annually. Necrotizing enterocolitis survivors requiring surgery often stay in the NICU more than 90 days and are among those most likely to stay more than 6 months. Significant variations exist in the incidence across regions and units. Although the only consistent independent predictors for NEC remain prematurity and formula feeding, others exist that could increase risk when combined. Awareness of NEC risk factors and adopting practices to reduce NEC risk, including human milk feeding, the use of feeding guidelines, and probiotics, have been shown to reduce the incidence of NEC. The purpose of this review is to examine the state of the science on NEC risk factors and make recommendations for practice and research. PMID:22469959

Overweight is an independent risk factor for cardiovascular disease in Chinese populations.

PubMed

Zhou, Beifan; Wu, Yangfeng; Yang, Jun; Li, Ying; Zhang, Hongye; Zhao, Liancheng

2002-08-01

In the last decade of the 20th century, cardiovascular disease was the leading cause of death in China, accounting for one-third of the total deaths. In comparison with western populations, the mean body weight or body mass index (BMI) of the Chinese population was lower, but showed an increasing trend. Whether the variation within lower levels of BMI or waist circumference was associated with other risk factors of cardiovascular disease, and whether they contribute independently to the risk of cardiovascular disease in the Chinese population, was investigated in this study. In keeping with a uniform study design, in each of 14 study populations at different geographical locations and with different characteristics, the incidence rates of stroke, coronary heart disease (CHD) and the causes of death were monitored in approximately/= 100000 residents from 1991 to 1995 using the MONICA procedure. Risk factors were surveyed in a random cluster sample of 1000 subjects (35-59 years of age) from each population under surveillance using internationally standardized methods and a centralized system to ensure quality control. Among the risk factors, body weight, height, and waist and hip circumferences were measured. Cross-sectional stratified analyses were used to analyse the relationship of BMI (kg m(-2)) or waist circumference to other metabolic risk factors. Ten cohorts among the 14 study populations with 24734 participants were surveyed from 1982 to 1985 as a baseline for further study and were followed-up for 9 years taking the events of stroke, CHD and different causes of death as end-points. Cox regression models were used to explore the association of BMI with the relative risks of stroke, CHD and total death. The survey in 14 random samples with a total number of 19 741 subjects showed that the mean BMI (20.8-25.1) and waist circumference (67.8-86.7 cm) were much lower than those of western populations. There was, however, variation in the anthropometric measurements among populations within China. Thus, rates of overweight varied from 2.7% to 48.1% and obesity from 0% to 9.5% on the basis of the World Health Organization (WHO) classification, but these values were lower than those found in western populations. Data from the 10 cohort samples compared with baseline data in the early 1980s showed that the mean BMIs increased significantly in eight populations during the early 1990s with the differences ranging from 0.5 to 2.5 kg m(-2). Despite the lower level of BMI and the lower rate of overweight, cross-sectional analyses showed that the prevalence of hypertension, high fasting serum glucose, high serum total cholesterol and low high-density lipoprotein cholesterol (HDL-C) and their clustering were all raised with increases in BMI or waist circumference. The prospective cohort study showed that the BMI was one of the independent risk factors for stroke and CHD in Chinese populations. Hence, in a Chinese population characterized by lower levels of BMI and great variability in rates of overweight, variation of BMI was significantly related to the prevalence of other metabolic risk factors and their clustering. Overweight was one of the independent risk factors for stroke and CHD, both at population and individual levels. Given the increasing trends of BMI in the last 10 years, during the period of economic transition there is a need to encourage the population to adopt healthy dietary habits and to increase their physical activity. Health education and health promotion are important for the prevention and non-pharmacological therapy of cardiovascular disease in China.

Increased anaesthesia duration increases venous thromboembolism risk in plastic surgery: A 6-year analysis of over 19,000 cases using the NSQIP dataset.

PubMed

Mlodinow, Alexei S; Khavanin, Nima; Ver Halen, Jon P; Rambachan, Aksharananda; Gutowski, Karol A; Kim, John Y S

2015-01-01

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality, particularly in the postoperative setting. Various risk stratification schema exist in the plastic surgery literature, but do not take into account variations in procedure length. The putative risk of VTE conferred by increased length of time under anaesthesia has never been rigorously explored. The goal of this study is to assess this relationship and to benchmark VTE rates in plastic surgery. A large, multi-institutional quality-improvement database was queried for plastic and reconstructive surgery procedures performed under general anaesthesia between 2005-2011. In total, 19,276 cases were abstracted from the database. Z-scores were calculated based on procedure-specific mean surgical durations, to assess each case's length in comparison to the mean for that procedure. A total of 70 patients (0.36%) experienced a post-operative VTE. Patients with and without post-operative VTE were compared with respect to a variety of demographics, comorbidities, and intraoperative characteristics. Potential confounders for VTE were included in a regression model, along with the Z-scores. VTE occurred in both cosmetic and reconstructive procedures. Longer surgery time, relative to procedural means, was associated with increased VTE rates. Further, regression analysis showed increase in Z-score to be an independent risk factor for post-operative VTE (Odds Ratio of 1.772 per unit, p-value < 0.001). Subgroup analyses corroborated these findings. This study validates the long-held view that increased surgical duration confers risk of VTE, as well as benchmarks VTE rates in plastic surgery procedures. While this in itself does not suggest an intervention, surgical time under general anaesthesia would be a useful addition to existing risk models in plastic surgery.

Germany wide seasonal flood risk analysis for agricultural crops

NASA Astrophysics Data System (ADS)

Klaus, Stefan; Kreibich, Heidi; Kuhlmann, Bernd; Merz, Bruno; Schröter, Kai

2016-04-01

In recent years, large-scale flood risk analysis and mapping has gained attention. Regional to national risk assessments are needed, for example, for national risk policy developments, for large-scale disaster management planning and in the (re-)insurance industry. Despite increasing requests for comprehensive risk assessments some sectors have not received much scientific attention, one of these is the agricultural sector. In contrast to other sectors, agricultural crop losses depend strongly on the season. Also flood probability shows seasonal variation. Thus, the temporal superposition of high flood susceptibility of crops and high flood probability plays an important role for agricultural flood risk. To investigate this interrelation and provide a large-scale overview of agricultural flood risk in Germany, an agricultural crop loss model is used for crop susceptibility analyses and Germany wide seasonal flood-frequency analyses are undertaken to derive seasonal flood patterns. As a result, a Germany wide map of agricultural flood risk is shown as well as the crop type most at risk in a specific region. The risk maps may provide guidance for federal state-wide coordinated designation of retention areas.

A population health approach to reducing observational intensity bias in health risk adjustment: cross sectional analysis of insurance claims.

PubMed

Wennberg, David E; Sharp, Sandra M; Bevan, Gwyn; Skinner, Jonathan S; Gottlieb, Daniel J; Wennberg, John E

2014-04-10

To compare the performance of two new approaches to risk adjustment that are free of the influence of observational intensity with methods that depend on diagnoses listed in administrative databases. Administrative data from the US Medicare program for services provided in 2007 among 306 US hospital referral regions. Cross sectional analysis. 20% sample of fee for service Medicare beneficiaries residing in one of 306 hospital referral regions in the United States in 2007 (n = 5,153,877). The effect of health risk adjustment on age, sex, and race adjusted mortality and spending rates among hospital referral regions using four indices: the standard Centers for Medicare and Medicaid Services--Hierarchical Condition Categories (HCC) index used by the US Medicare program (calculated from diagnoses listed in Medicare's administrative database); a visit corrected HCC index (to reduce the effects of observational intensity on frequency of diagnoses); a poverty index (based on US census); and a population health index (calculated using data on incidence of hip fractures and strokes, and responses from a population based annual survey of health from the Centers for Disease Control and Prevention). Estimated variation in age, sex, and race adjusted mortality rates across hospital referral regions was reduced using the indices based on population health, poverty, and visit corrected HCC, but increased using the standard HCC index. Most of the residual variation in age, sex, and race adjusted mortality was explained (in terms of weighted R2) by the population health index: R2=0.65. The other indices explained less: R2=0.20 for the visit corrected HCC index; 0.19 for the poverty index, and 0.02 for the standard HCC index. The residual variation in age, sex, race, and price adjusted spending per capita across the 306 hospital referral regions explained by the indices (in terms of weighted R2) were 0.50 for the standard HCC index, 0.21 for the population health index, 0.12 for the poverty index, and 0.07 for the visit corrected HCC index, implying that only a modest amount of the variation in spending can be explained by factors most closely related to mortality. Further, once the HCC index is visit corrected it accounts for almost none of the residual variation in age, sex, and race adjusted spending. Health risk adjustment using either the poverty index or the population health index performed substantially better in terms of explaining actual mortality than the indices that relied on diagnoses from administrative databases; the population health index explained the majority of residual variation in age, sex, and race adjusted mortality. Owing to the influence of observational intensity on diagnoses from administrative databases, the standard HCC index over-adjusts for regional differences in spending. Research to improve health risk adjustment methods should focus on developing measures of risk that do not depend on observation influenced diagnoses recorded in administrative databases.

Sperm competition risk generates phenotypic plasticity in ovum fertilizability.

PubMed

Firman, Renée C; Simmons, Leigh W

2013-12-07

Theory predicts that sperm competition will generate sexual conflict that favours increased ovum defences against polyspermy. A recent study on house mice has shown that ovum resistance to fertilization coevolves in response to increased sperm fertilizing capacity. However, the capacity for the female gamete to adjust its fertilizability as a strategic response to sperm competition risk has never, to our knowledge, been studied. We sourced house mice (Mus domesticus) from natural populations that differ in the level of sperm competition and sperm fertilizing capacity, and manipulated the social experience of females during their sexual development to simulate conditions of either a future 'risk' or 'no risk' of sperm competition. Consistent with coevolutionary predictions, we found lower fertilization rates in ova produced by females from a high sperm competition population compared with ova from a low sperm competition population, indicating that these populations are divergent in the fertilizability of their ova. More importantly, females exposed to a 'risk' of sperm competition produced ova that had greater resistance to fertilization than ova produced by females reared in an environment with 'no risk'. Consequently, we show that variation in sperm competition risk during development generates phenotypic plasticity in ova fertilizability, which allows females to prepare for prevailing conditions during their reproductive life.

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

PubMed Central

Whalley, H C; Papmeyer, M; Sprooten, E; Romaniuk, L; Blackwood, D H; Glahn, D C; Hall, J; Lawrie, S M; Sussmann, Je; McIntosh, A M

2012-01-01

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD. PMID:22760554

Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

PubMed

Jaques, Alice M; Collins, Veronica R; Muggli, Evelyne E; Amor, David J; Francis, Ivan; Sheffield, Leslie J; Halliday, Jane L

2010-06-01

To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

Paludification and forest retreat in northern oceanic environments.

PubMed

Crawford, R M M; Jeffree, C E; Rees, W G

2003-01-01

Examination of temperature variations over the past century for Europe and the Arctic from northern Norway to Siberia suggests that variations in the North Atlantic Oscillation are associated with an increase in oceanicity in certain maritime regions. A southward depression of the tree line in favour of wet heaths, bogs and wetland tundra communities is also observed in northern oceanic environments. The physiological basis for this change in ecological succession from forest to bog is discussed in relation to the long-term effects of flooding on tree survival. The heightened values currently detected in the North Atlantic Oscillation Index, together with rising winter temperatures, and increased rainfall in many areas in northern Europe, presents an increasing risk of paludification with adverse consequences for forest regeneration, particularly in areas with oceanic climates. Climatic warming in oceanic areas may increase the area covered by bogs and, contrary to general expectations, lead to a retreat rather than an advance in the northern limit of the boreal forest. High water-table levels are not automatically detrimental to forest survival as can be seen in swamp, bottom land and mangrove forests. Consequently, the inhibitory effects of flooding on tree survival and regeneration in northern regions should not be uncritically accepted as merely due to high water levels. Evidence is discussed which suggests that physiological and ecological factors may interact to inhibit forest regeneration in habitats where there is a risk of prolonged winter-flooding combined with warmer winters and cool moist summers.

Paludification and Forest Retreat in Northern Oceanic Environments

PubMed Central

CRAWFORD, R. M. M.; JEFFREE, C. E.; REES, W. G.

2003-01-01

Examination of temperature variations over the past century for Europe and the Arctic from northern Norway to Siberia suggests that variations in the North Atlantic Oscillation are associated with an increase in oceanicity in certain maritime regions. A southward depression of the treeline in favour of wet heaths, bogs and wetland tundra communities is also observed in northern oceanic environments. The physiological basis for this change in ecological succession from forest to bog is discussed in relation to the long‐term effects of flooding on tree survival. The heightened values currently detected in the North Atlantic Oscillation Index, together with rising winter temperatures, and increased rainfall in many areas in northern Europe, presents an increasing risk of paludification with adverse consequences for forest regeneration, particularly in areas with oceanic climates. Climatic warming in oceanic areas may increase the area covered by bogs and, contrary to general expectations, lead to a retreat rather than an advance in the northern limit of the boreal forest. High water‐table levels are not automatically detrimental to forest survival as can be seen in swamp, bottomland and mangrove forests. Consequently, the inhibitory effects of flooding on tree survival and regeneration in northern regions should not be uncritically accepted as merely due to high water levels. Evidence is discussed which suggests that physiological and ecological factors may interact to inhibit forest regeneration in habitats where there is a risk of prolonged winter‐flooding combined with warmer winters and cool moist summers. PMID:12509342

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts

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

Schneider, Uwe, E-mail: uwe.schneider@uzh.ch; Walsh, Linda

Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend themore » risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.« less

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

PubMed

Schneider, Uwe; Walsh, Linda

2015-08-01

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.

Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression.

PubMed

Hameed, Iqra; Masoodi, Shariq R; Malik, Perveez A; Mir, Shahnaz A; Ghazanfar, Khalid; Ganai, Bashir A

2018-06-30

Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-β) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). Individual SNP analysis showed highest association of IL-1β rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ± 1.11) in DN. TNF-α, IL-6 and IL-1β transcript levels were significantly modulated by promoter region SNPs. The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1β gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects. Copyright © 2018 Elsevier B.V. All rights reserved.

Forest fire risk zonation mapping using remote sensing technology

NASA Astrophysics Data System (ADS)

Chandra, Sunil; Arora, M. K.

2006-12-01

Forest fires cause major losses to forest cover and disturb the ecological balance in our region. Rise in temperature during summer season causing increased dryness, increased activity of human beings in the forest areas, and the type of forest cover in the Garhwal Himalayas are some of the reasons that lead to forest fires. Therefore, generation of forest fire risk maps becomes necessary so that preventive measures can be taken at appropriate time. These risk maps shall indicate the zonation of the areas which are in very high, high, medium and low risk zones with regard to forest fire in the region. In this paper, an attempt has been made to generate the forest fire risk maps based on remote sensing data and other geographical variables responsible for the occurrence of fire. These include altitude, temperature and soil variations. Key thematic data layers pertaining to these variables have been generated using various techniques. A rule-based approach has been used and implemented in GIS environment to estimate fuel load and fuel index leading to the derivation of fire risk zonation index and subsequently to fire risk zonation maps. The fire risk maps thus generated have been validated on the ground for forest types as well as for forest fire risk areas. These maps would help the state forest departments in prioritizing their strategy for combating forest fires particularly during the fire seasons.

Locating Spatial Variation in the Association Between Wildland Fire Risk and Social Vulnerability Across Six Southern States

NASA Astrophysics Data System (ADS)

Poudyal, Neelam C.; Johnson-Gaither, Cassandra; Goodrick, Scott; Bowker, J. M.; Gan, Jianbang

2012-03-01

Wildland fire in the South commands considerable attention, given the expanding wildland urban interface (WUI) across the region. Much of this growth is propelled by higher income retirees and others desiring natural amenity residential settings. However, population growth in the WUI increases the likelihood of wildfire fire ignition caused by people, as humans account for 93% of all wildfires fires in the South. Coexisting with newly arrived, affluent WUI populations are working class, poor or otherwise socially vulnerable populations. The latter groups typically experience greater losses from environmental disasters such as wildfire because lower income residents are less likely to have established mitigation programs in place to help absorb loss. We use geographically weighted regression to examine spatial variation in the association between social vulnerability (SOVUL) and wildfire risk. In doing so, we identify "hot spots" or geographical clusters where SOVUL varies positively with wildfire risk across six Southern states—Alabama, Arkansas, Florida, Georgia, Mississippi, and South Carolina. These clusters may or may not be located in the WUI. These hot spots are most prevalent in South Carolina and Florida. Identification of these population clusters can aid wildfire managers in deciding which communities to prioritize for mitigation programming.

Acarological Risk of Borrelia burgdorferi Sensu Lato Infections Across Space and Time in The Netherlands.

PubMed

Takken, Willem; van Vliet, Arnold J H; Verhulst, Niels O; Jacobs, Frans H H; Gassner, Fedor; Hartemink, Nienke; Mulder, Sara; Sprong, Hein

2017-02-01

A longitudinal investigation on tick populations and their Borrelia infections in the Netherlands was undertaken between 2006 and 2011 with the aim to assess spatial and temporal patterns of the acarological risk in forested sites across the country and to assess variations in Borrelia genospecies diversity. Ticks were collected monthly in 11 sites and nymphs were examined for Borrelia infections. Tick populations expressed strong seasonal variations, with consistent and significant differences in mean tick densities between sites. Borrelia infections were present in all study sites, with a site-specific mean prevalence per month ranging from 7% to 26%. Prevalence was location-dependent and was not associated with tick densities. Mean Borrelia prevalence was lowest in January (4%), gradually increasing to reach a maximum (24%) in August. Borrelia afzelii represented 70% of all infections, with Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia valaisiana represented with 4%, 8%, and 10%, respectively. The density of infected nymphs and the proportional distribution of the four Borrelia genospecies, were significantly different between sites. The results show a consistent and significant spatial and temporal difference in acarological risk across the Netherlands.

Most genetic risk for autism resides with common variation.

PubMed

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J; Bodea, Corneliu A; Goldberg, Arthur P; Lee, Ann B; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M; Devlin, Bernie; Roeder, Kathryn; Buxbaum, Joseph D

2014-08-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.

Regulatory Focus Affects Physician Risk Tolerance

PubMed Central

Veazie, Peter J.; McIntosh, Scott; Chapman, Benjamin P.; Dolan, James G.

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention – regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (P=0.01). The Cohen’s d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (P=0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor. PMID:25431799

Hodgkin Lymphoma has a seasonal pattern of incidence and mortality that depends on latitude.

PubMed

Borchmann, Sven; Müller, Horst; Engert, Andreas

2017-11-02

Seasonal variations in incidence and mortality after a Hodgkin lymphoma (HL) diagnosis have been previously described with partly conflicting results. The goal of this analysis is to provide a comprehensive analysis of these seasonal variations. In total, 41,405 HL cases diagnosed between 1973 and 2012 in the 18 Surveillance, Epidemiology, and End Results registries were included. Cosinor analysis and Cox proportional-hazards models were employed to analyze seasonality of incidence and mortality, respectively. HL shows a sinusoid seasonal incidence pattern (p < 0.001). Estimated incidence in March is 15.4% [95%-CI: 10.8-20.0] higher than in September. This sinusoid pattern is more pronounced at higher latitudes (p = 0.023). The risk of dying within the first three years after a HL diagnosis in winter is significantly increased compared to a HL diagnosis in summer at higher latitudes (HR = 1.082 [95%-CI: 1.009-1.161], p = 0.027). Furthermore, increasing northern latitude increases the additional mortality risk conferred by a diagnosis in winter (p interaction 0.033). The seasonality patterns presented here provide epidemiological evidence that Vitamin D might play a protective role in HL. Further evidence on the direct association between Vitamin D levels and the clinical course of HL needs to be collected to advance the understanding of the role of Vitamin D in HL.

Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma.

PubMed

Daniel, Carrie R; Cross, Amanda J; Graubard, Barry I; Park, Yikyung; Ward, Mary H; Rothman, Nathaniel; Hollenbeck, Albert R; Chow, Wong-Ho; Sinha, Rashmi

2012-01-01

The evidence for meat intake and renal cell carcinoma (RCC) risk is inconsistent. Mutagens related to meat cooking and processing, and variation by RCC subtype may be important to consider. In a large US cohort, we prospectively investigated intake of meat and meat-related compounds in relation to risk of RCC, as well as clear cell and papillary RCC histologic subtypes. Study participants (492,186) completed a detailed dietary assessment linked to a database of heme iron, heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAHs), nitrate, and nitrite concentrations in cooked and processed meats. Over 9 (mean) y of follow-up, we identified 1814 cases of RCC (498 clear cell and 115 papillary adenocarcinomas). HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Red meat intake [62.7 g (quintile 5) compared with 9.8 g (quintile 1) per 1000 kcal (median)] was associated with a tendency toward an increased risk of RCC [HR: 1.19; 95% CI: 1.01, 1.40; P-trend = 0.06] and a 2-fold increased risk of papillary RCC [P-trend = 0.002]. Intakes of benzo(a)pyrene (BaP), a marker of PAHs, and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), an HCA, were associated with a significant 20-30% elevated risk of RCC and a 2-fold increased risk of papillary RCC. No associations were observed for the clear cell subtype. Red meat intake may increase the risk of RCC through mechanisms related to the cooking compounds BaP and PhIP. Our findings for RCC appeared to be driven by strong associations with the rarer papillary histologic variant. This study is registered at clinicaltrials.gov as NCT00340015.

Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk.

PubMed

Merhi, Mahmoud; Demirdjian, Sally; Hariri, Essa; Sabbah, Nada; Youhanna, Sonia; Ghassibe-Sabbagh, Michella; Naoum, Joseph; Haber, Marc; Othman, Raed; Kibbani, Samer; Chammas, Elie; Kanbar, Roy; Bayeh, Hamid El; Chami, Youssef; Abchee, Antoine; Platt, Daniel E; Zalloua, Pierre; Khazen, Georges

2015-06-01

The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis. The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD. CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension. rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137). This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.

Surgeon Perception of Risk and Benefit in the Decision to Operate.

PubMed

Sacks, Greg D; Dawes, Aaron J; Ettner, Susan L; Brook, Robert H; Fox, Craig R; Maggard-Gibbons, Melinda; Ko, Clifford Y; Russell, Marcia M

2016-12-01

To determine how surgeons' perceptions of treatment risks and benefits influence their decisions to operate. Little is known about what makes one surgeon choose to operate on a patient and another chooses not to operate. Using an online study, we presented a national sample of surgeons (N = 767) with four detailed clinical vignettes (mesenteric ischemia, gastrointestinal bleed, bowel obstruction, appendicitis) where the best treatment option was uncertain and asked them to: (1) judge the risks (probability of serious complications) and benefits (probability of recovery) for operative and nonoperative management and (2) decide whether or not they would recommend an operation. Across all clinical vignettes, surgeons varied markedly in both their assessments of the risks and benefits of operative and nonoperative management (narrowest range 4%-100% for all four predictions across vignettes) and in their decisions to operate (49%-85%). Surgeons were less likely to operate as their perceptions of operative risk increased [absolute difference (AD) = -29.6% from 1.0 standard deviation below to 1.0 standard deviation above mean (95% confidence interval, CI: -31.6, -23.8)] and their perceptions of nonoperative benefit increased [AD = -32.6% (95% CI: -32.8,--28.9)]. Surgeons were more likely to operate as their perceptions of operative benefit increased [AD = 18.7% (95% CI: 12.6, 21.5)] and their perceptions of nonoperative risk increased [AD = 32.7% (95% CI: 28.7, 34.0)]. Differences in risk/benefit perceptions explained 39% of the observed variation in decisions to operate across the four vignettes. Given the same clinical scenarios, surgeons' perceptions of treatment risks and benefits vary and are highly predictive of their decisions to operate.

The Role of School and Individual Differences in the Academic Attainment of Learners with Special Educational Needs and Disabilities: A Multi-Level Analysis

ERIC Educational Resources Information Center

Humphrey, Neil; Wigelsworth, Michael; Barlow, Alexandra; Squires, Garry

2013-01-01

Students with special educational needs and disabilities (SEND) are at a greatly increased risk of poor academic outcomes. Understanding the factors that influence their attainment is a crucial first step towards developing more effective provision. In the current study we present a multi-level, natural variation analysis which highlights…

Direct and inverse modelling for environmental risk assessment and emission control

NASA Astrophysics Data System (ADS)

Penenko, V.; Baklanov, A.; Tsvetova, E.; Mahura, A.

2009-04-01

A concept of environmental modelling and its applications for Siberian regions are presented. The regions are considered both as sources and receptors of pollution as elements of the global climatic system. A methodology has been developed to build the combined methods of forward and inverse modelling for the problems of the air quality, environmental risk assessment and control. It is based on variational principles and methods of adjoint sensitivity theory. This allows obtaining the optimal numerical schemes and universal algorithm of the forward-inverse modelling. Following the concept, the functionals (describing the generalised characteristics of the processes, data, and models) are considered together with the basic model components. To combine all these elements in the frames of forward and inverse relations, we suppose that each of them may contain uncertainty. In this case, it is naturally to formulate a weak-constraint variational principle for the augmented functional which contains the model description in the form of integral identity and the cost functional including the total measure of all uncertainties. The stationary conditions for the augmented functional with respect to the variations its functional arguments define the mutually agreed structure of numerical schemes for forward and adjoint problems, and sensitivity relations. For quantitative risk assessment the following characteristics are useful: (i) values of goal functionals and their variations in a form of sensitivity relations; (ii) risk and sensitivity functions to the variations of the sources. It is convenient to take the risk function multiplied by the source function as a distributed risk measure. The variational technique provides the backward propagation of information, contained in the target functionals, to parameters and sources of the models through the sensitivity and uncertainty functions. This gives a base for realisation of the feedback algorithms and methods of control theory, which are necessary for formulation of multi-criteria optimisation accounting different constraints of ecological, economical, and social essence while solving environmental problems such as air pollution control, placement design for new industrial units, etc. The problems of the long-term environmental forecasting demand revealing the dynamical active zones and the areas of increased sensitivity to the variations of forcings (model parameters). The proposed methodology of accounting the climatic data into environmental studies is suitable for studying such problems. Analysis of the long-term behaviour of the global climatic system and orthogonal decomposition of the multivariate series of meteorological data with respect to the scales of processes allows identifying the activity centers and using this information for construction of scenarios for assessment of risk/vulnerability for sources/receptors. Such analysis for Siberian regions showed that Siberia is situated in areas which separate circulation systems of high energy activity. For winter, they are the Pacific and Atlantic energy-active zones, whereas the Arctic and South-Asian zones withstand in Siberia in summer. These facts allow an interpretation of climatic instability inherent in the region. During the autumn-winter season, the instability expresses as sharp alteration of weather cycles. The formation of Altai-Sayan cyclogenesis (which is of the same intensity as the Mediterranean) is observed for the warm seasons in the southern Siberia. In climatology it is referred as a lee-type cyclogenesis. This is the large scale phenomenon in the climatic system of the central part of Eurasia. Such specific hydrodynamic background defines environment quality in Siberia. From the point of view of system analysis, the methods of sensitivity theory, risk assessment and control along with scenario approach offer a tool which allows bringing the results of the global atmospheric and climatic studies onto the regional level. Namely, this level puts the concrete questions on the environment quality and its changes such as a choice of plausible strategy for sources control and mitigation of the man-induced impact on environment. Some environmental problems for Siberian regions are discussed, and a number of forward, adjoint and inverse problems for different risk sites and goal functionals are presented.

Copy Number Variation of TLR-7 Gene and its Association with the Development of Systemic Lupus Erythematosus in Female Patients from Yucatan Mexico

PubMed Central

Pacheco, Guillermo Valencia; Cruz, Darig Cámara; González Herrera, Lizbeth J; Pérez Mendoza, Gerardo J; Adrián Amaro, Guadalupe I; Nakazawa Ueji, Yumi E; Angulo Ramírez, Angélica V

2014-01-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies against self-antigens, which occurs most often in women between 15 and 40 years of age. The innate immunity is involved in the pathogenesis of SLE through TLR- 7. Genetic factors such as copy number variation (CNV) of target genes may contribute to disease development, but this possible risk has not yet been studied in SLE patients from Yucatan, Mexico. The CNV of TLR-7 gene was determined by quantitative polymerase chain reaction assay using TaqMan probes in 80 SLE women and 150 control subjects. The results showed that 10% of SLE patients exhibited more than two copies of TLR-7 gene, whereas no mRNA overexpression was detected. These data suggested that increased CNV of the TLR-7 gene in Yucatan SLE women can be a risk factor for this disease. PMID:25512712

A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

PubMed Central

Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

2015-01-01

Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

[Investigation into the relationship between mitochondrial 12 S rRNA gene, tRNA gene and cytochrome oxidase Ⅱ gene variations and the risk of noise-induced hearing loss].

PubMed

Jiao, J; Gu, G Z; Chen, G S; Li, Y H; Zhang, H L; Yang, Q Y; Xu, X R; Zhou, W H; Wu, H; He, L H; Zheng, Y X; Yu, S F

2017-01-06

Objective: To explore the relationship between mitochondrial 12 S rRNA gene variation, tRNA gene variation and cytochrome oxidase Ⅱ gene point mutations and the risk of noise-induced hearing loss (NIHL). Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory in Henan province, China, from January 1, 2006 to December 31, 2015. Subjects whose average hearing threshold was more than 40 dB(A) in high frequency were defined as the case group, and subjects whose average hearing threshold was less than 35 dB(A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. Subjects was recruited into the case group ( n =286) and the control group ( n= 286) according to gender, age, job category and time of exposure to noise, and a 1∶1 case-control study was carried out. We genotyped eight single nucleotide polymorphisms in the mitochondrial 12 S rRNA gene, the mitochondrial tRNA gene and the mitochondrial cytochrome oxidase Ⅱ gene using SNPscan high-throughput genotyping technology from the recruited subjects. The relationship between polymorphic sites and NIHL, adjusted for covariates, was analyzed using conditional logistic regression analysis, as were the subgroup data. Results: The average age of the recruited subjects was (40.3±8.1) years and the length of service exposure to noise was (18.6±8.9) years. The range of noise exposed levels and cumulative noise exposure (CNE) was 80.1- 93.4 dB (A) and 86.8- 107.9 dB (A) · year, respectively. For workers exposed to noise at a CNE level<98 dB (A) · year, smokers showed an increased risk of NIHL of 1.88 (1.16-3.05) compared with non-smokers; for workers exposed to noise at a CNE level ≥98 dB(A) · year, smokers showed an increased risk of NIHL of 2.53 (1.49- 4.30) compared with non-smokers. For workers exposed to noise at a CNE level<98 dB (A) · year, the results of univariate analysis and multifactor analysis, adjusted by smoking and CNE, suggested that the risk of NIHL in workers exposed to noise carrying the GG genotype (G827A) was lower than that of NIHL workers exposed to noise carrying the AA genotype (G827A) [ OR (95% CI ) were 0.18 (0.04- 0.82) and 0.19 (0.04- 0.88), respectively]. Conclusion: Smoking increased the risk of NIHL in the present study. For workers subjected to a CNE<98 dB(A)·year, the mitochondrial genetic variant G827A was found to be significantly associated with the risk of NIHL.

[Mortality from Suicide in the Municipalities of Mainland Portugal: Spatio-Temporal Evolution between 1980 and 2015].

PubMed

Loureiro, Adriana; Almendra, Ricardo; Costa, Cláudia; Santana, Paula

2018-01-31

Suicide is considered a public health priority. It is a complex phenomenon resulting from the interaction of several factors, which do not depend solely on individual conditions. This study analyzes the spatio-temporal evolution of suicide mortality between 1980 and 2015, identifying areas of high risk, and their variation, in the 278 municipalities of Continental Portugal. Based on the number of self-inflicted injuries and deaths from suicide and the resident population, the spatio-temporal evolution of the suicide mortality rate was assessed via: i) a Poisson joinpoint regression model, and ii) spatio-temporal clustering methods. The suicide mortality rate evolution showed statistically significant increases over three periods (1980 - 1984; 1999 - 2002 and 2006 - 2015) and two statistically significant periods of decrease (1984 - 1995 and 1995 - 1999). The spatio-temporal analysis identified five clusters of high suicide risk (relative risk >1) and four clusters of low suicide risk (relative risk < 1). The periods when suicide mortality increases seem to overlap with times of economic and financial instability. The geographical pattern of suicide risk has changed: presently, the suicide rates from the municipalities in the Center and North are showing more similarity with those seen in the South, thus increasing the ruralization of the phenomenon of suicide. Between 1980 and 2015 the spacio-temporal pattern of mortality from suicide has been changing and is a phenomenon that is currently experiencing a growing trend (since 2006) and is of higher risk in rural areas.

Potential threats to the effective communication of genetic risk information: the case of cystic fibrosis.

PubMed

Dillard, James Price; Shen, Lijiang; Laxova, Anita; Farrell, Phillip

2008-01-01

The dramatic increase in genetic knowledge engendered by the mapping of the human genome brings with it a need for greater understanding of how to effectively communicate genetic risk information. Using a combination of observational and self-report data, this study examined potential threats to effective risk communication in 17 families whose infant received a positive newborn screening test for cystic fibrosis. Five specific problems are identified: (a) copresence of interactants (or the lack thereof), (b) disruptions in the communication environment, (c) variations in parents' initial knowledge, (d) rigidity in counselors' behavioral scripts, and (e) emotional interference with information acquisition. We advance 3 proposals for research aimed at improving our understanding of these potential threats.

Evaluating mitochondrial DNA variation in autism spectrum disorders

PubMed Central

HADJIXENOFONTOS, ATHENA; SCHMIDT, MICHAEL A.; WHITEHEAD, PATRICE L.; KONIDARI, IOANNA; HEDGES, DALE J.; WRIGHT, HARRY H.; ABRAMSON, RUTH K.; MENON, RAMKUMAR; WILLIAMS, SCOTT M.; CUCCARO, MICHAEL L.; HAINES, JONATHAN L.; GILBERT, JOHN R.; PERICAK-VANCE, MARGARET A.; MARTIN, EDEN R.; MCCAULEY, JACOB L.

2012-01-01

SUMMARY Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD. In phase 2 we genotyped the major European mitochondrial haplogroup-defining variants within an expanded set of autism probands and controls. Finally in phase 3, we resequenced the entire mtDNA in a subset of our Caucasian samples (~400 proband-father pairs). In each phase we tested whether mitochondrial variation showed evidence of association to ASD. Despite a thorough interrogation of mtDNA variation, we found no evidence to suggest a major role for mtDNA variation in ASD susceptibility. Accordingly, while there may be attractive biological hints suggesting the role of mitochondria in ASD our data indicate that mtDNA variation is not a major contributing factor to the development of ASD. PMID:23130936

Six-fold difference in the stomach cancer mortality rate between northern and southern Iran.

PubMed

Zendehdel, Kazem; Marzban, Maryam; Nahvijou, Azin; Jafari, Nahid

2012-12-01

Stomach cancer is the most common cancer in Iran. A multi-ethnic population and wide variation in the environmental risk factors may lead to variations in cancer risk within this country. We have designed an ecological study and evaluated geographical variation regarding mortality from stomach cancer and its established risk factors in Iran.  We used the Iranian National Causes of Death Registry and estimated the age-standardized mortality rates (ASMR) of stomach cancer in 29 Iranian provinces, stratified by sex and area of residence (rural/urban).  The average ASMR of stomach cancer among Iranian males was 15 per 100,000 and for females it was 8.1 per 100,000. The highest and lowest mortality rates were observed in Kurdistan with an ASMR of 29.1 per 100,000 in northwestern Iran and Hormozgan that had an ASMR of 5.0 per 100,000 in southern Iran. Males had approximately a two-fold higher ASMR compared to females, as did rural residents when compared with urban residents. The prevalence of H. pylori infection was about 90% in the province of Ardabil (a high-risk area) and 27% in the province of Sistan-Baluchistan (a low-risk area).  The wide geographical variation and high mortality rate of stomach cancer in Iran is likely due to differences in the exposure to the environmental risk factors among people living in the high- and low-risk areas, particularly H. pylori infection, a well-established risk factor of stomach cancer.

Long-term temporal changes in the occurrence of a high forest fire danger in Finland

NASA Astrophysics Data System (ADS)

Mäkelä, H. M.; Laapas, M.; Venäläinen, A.

2012-08-01

Climate variation and change influence several ecosystem components including forest fires. To examine long-term temporal variations of forest fire danger, a fire danger day (FDD) model was developed. Using mean temperature and total precipitation of the Finnish wildfire season (June-August), the model describes the climatological preconditions of fire occurrence and gives the number of fire danger days during the same time period. The performance of the model varied between different regions in Finland being best in south and west. In the study period 1908-2011, the year-to-year variation of FDD was large and no significant increasing or decreasing tendencies could be found. Negative slopes of linear regression lines for FDD could be explained by the simultaneous, mostly not significant increases in precipitation. Years with the largest wildfires did not stand out from the FDD time series. This indicates that intra-seasonal variations of FDD enable occurrence of large-scale fires, despite the whole season's fire danger is on an average level. Based on available monthly climate data, it is possible to estimate the general fire conditions of a summer. However, more detailed input data about weather conditions, land use, prevailing forestry conventions and socio-economical factors would be needed to gain more specific information about a season's fire risk.

Demand elasticities and service selection incentives among competing private health plans.

PubMed

Ellis, Randall P; Martins, Bruno; Zhu, Wenjia

2017-12-01

We examine selection incentives by health plans while refining the selection index of McGuire et al. (2014) to reflect not only service predictability and predictiveness but also variation in cost sharing, risk-adjusted profits, profit margins, and newly-refined demand elasticities across 26 disaggregated types of service. We contrast selection incentives, measured by service selection elasticities, across six plan types using privately-insured claims data from 73 large employers from 2008 to 2014. Compared to flat capitation, concurrent risk adjustment reduces the elasticity by 47%, prospective risk adjustment by 43%, simple reinsurance system by 32%, and combined concurrent risk adjustment with reinsurance by 60%. Reinsurance significantly reduces the variability of individual-level profits, but increases the correlation of expected spending with profits, which strengthens selection incentives. Copyright © 2017 Elsevier B.V. All rights reserved.

Phase-dependent climate-predator interactions explain three decades of variation in neonatal caribou survival.

PubMed

Bastille-Rousseau, Guillaume; Schaefer, James A; Lewis, Keith P; Mumma, Matthew A; Ellington, E Hance; Rayl, Nathaniel D; Mahoney, Shane P; Pouliot, Darren; Murray, Dennis L

2016-03-01

Climate can have direct and indirect effects on population dynamics via changes in resource competition or predation risk, but this influence may be modulated by density- or phase-dependent processes. We hypothesized that for ungulates, climatic conditions close to parturition have a greater influence on the predation risk of neonates during population declines, when females are already under nutritional stress triggered by food limitation. We examined the presence of phase-dependent climate-predator (PDCP) interactions on neonatal ungulate survival by comparing spatial and temporal fluctuations in climatic conditions, cause-specific mortality and per capita resource limitation. We determined cause-specific fates of 1384 caribou (Rangifer tarandus) from 10 herds in Newfoundland, spanning more than 30 years during periods of numerical increase and decline, while exposed to predation from black bears (Ursus americanus) and coyotes (Canis latrans). We conducted Cox proportional hazards analysis for competing risks, fit as a function of weather metrics, to assess pre- and post-partum climatic influences on survival on herds in population increase and decline phases. We used cumulative incidence functions to compare temporal changes in risk from predators. Our results support our main hypothesis; when caribou populations increased, weather conditions preceding calving were the main determinants of cause-specific mortality, but when populations declined, weather conditions during calving also influenced predator-driven mortality. Cause-specific analysis showed that weather conditions can differentially affect predation risk between black bears and coyotes with specific variables increasing the risk from one species and decreasing the risk from the other. For caribou, nutritional stress appears to increase predation risk on neonates, an interaction which is exacerbated by susceptibility to climatic events. These findings support the PDCP interactions framework, where maternal body condition influences susceptibility to climate-related events and, subsequently, risk from predation. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Strength training in the elderly: effects on risk factors for age-related diseases.

PubMed

Hurley, B F; Roth, S M

2000-10-01

Strength training (ST) is considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure that is associated with advanced age. This reversal is thought to result in improvements in functional abilities and health status in the elderly by increasing muscle mass, strength and power and by increasing bone mineral density (BMD). In the past couple of decades, many studies have examined the effects of ST on risk factors for age-related diseases or disabilities. Collectively, these studies indicate that ST in the elderly: (i) is an effective intervention against sarcopenia because it produces substantial increases in the strength, mass, power and quality of skeletal muscle; (ii) can increase endurance performance; (iii) normalises blood pressure in those with high normal values; (iv) reduces insulin resistance; (v) decreases both total and intra-abdominal fat; (vi) increases resting metabolic rate in older men; (vii) prevents the loss of BMD with age; (viii) reduces risk factors for falls; and (ix) may reduce pain and improve function in those with osteoarthritis in the knee region. However, contrary to popular belief, ST does not increase maximal oxygen uptake beyond normal variations, improve lipoprotein or lipid profiles, or improve flexibility in the elderly.

London-born black Caribbean children are at increased risk of atopic dermatitis.

PubMed

Williams, H C; Pembroke, A C; Forsdyke, H; Boodoo, G; Hay, R J; Burney, P G

1995-02-01

Previous reports suggest that atopic dermatitis is more common in black Caribbean children born in the United Kingdom than in white children. It is unclear whether these differences are caused by selection bias or variations in the use of the word "eczema" in the groups studied. Our objective was to explore ethnic group differences in the prevalence of atopic dermatitis in London schoolchildren. A cross-sectional prevalence survey of 693 junior school children in three schools was performed. Atopic dermatitis was defined in three ways: (1) by a dermatologist, (2) by visible flexural dermatitis as recorded by an independent observer, and (3) by a history of flexural dermatitis according to the child's parents. The prevalence of atopic dermatitis according to examination by a dermatologist was 16.3% in black Caribbean children and 8.7% in white children. This increased risk was present for different methods of defining of a atopic dermatitis and persisted after adjustment for potential confounders. London-born black Caribbean children appear to be at an increased risk of having atopic dermatitis.

Probabilistic, meso-scale flood loss modelling

NASA Astrophysics Data System (ADS)

Kreibich, Heidi; Botto, Anna; Schröter, Kai; Merz, Bruno

2016-04-01

Flood risk analyses are an important basis for decisions on flood risk management and adaptation. However, such analyses are associated with significant uncertainty, even more if changes in risk due to global change are expected. Although uncertainty analysis and probabilistic approaches have received increased attention during the last years, they are still not standard practice for flood risk assessments and even more for flood loss modelling. State of the art in flood loss modelling is still the use of simple, deterministic approaches like stage-damage functions. Novel probabilistic, multi-variate flood loss models have been developed and validated on the micro-scale using a data-mining approach, namely bagging decision trees (Merz et al. 2013). In this presentation we demonstrate and evaluate the upscaling of the approach to the meso-scale, namely on the basis of land-use units. The model is applied in 19 municipalities which were affected during the 2002 flood by the River Mulde in Saxony, Germany (Botto et al. submitted). The application of bagging decision tree based loss models provide a probability distribution of estimated loss per municipality. Validation is undertaken on the one hand via a comparison with eight deterministic loss models including stage-damage functions as well as multi-variate models. On the other hand the results are compared with official loss data provided by the Saxon Relief Bank (SAB). The results show, that uncertainties of loss estimation remain high. Thus, the significant advantage of this probabilistic flood loss estimation approach is that it inherently provides quantitative information about the uncertainty of the prediction. References: Merz, B.; Kreibich, H.; Lall, U. (2013): Multi-variate flood damage assessment: a tree-based data-mining approach. NHESS, 13(1), 53-64. Botto A, Kreibich H, Merz B, Schröter K (submitted) Probabilistic, multi-variable flood loss modelling on the meso-scale with BT-FLEMO. Risk Analysis.

Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.

PubMed

Li, Tsai-Chung; Yang, Chun-Pai; Tseng, Shih-Ting; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chiang, Jen-Huai; Lin, Cheng-Chieh

2017-09-01

The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA 1c ) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA 1c and other traditional risk factors in such patients. Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD ( n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA 1c , drug-related variables, and comorbidities, both FPG CV and HbA 1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA 1c CV. FPG CV and HbA 1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA 1c CV can be valuable therapeutic targets for patients with T2DM at risk. © 2017 by the American Diabetes Association.

The impact of an electronic health record on nurse sensitive patient outcomes: an interrupted time series analysis.

PubMed

Dowding, Dawn W; Turley, Marianne; Garrido, Terhilda

2012-01-01

To evaluate the impact of electronic health record (EHR) implementation on nursing care processes and outcomes. Interrupted time series analysis, 2003-2009. A large US not-for-profit integrated health care organization. 29 hospitals in Northern and Southern California. An integrated EHR including computerized physician order entry, nursing documentation, risk assessment tools, and documentation tools. Percentage of patients with completed risk assessments for hospital acquired pressure ulcers (HAPUs) and falls (process measures) and rates of HAPU and falls (outcome measures). EHR implementation was significantly associated with an increase in documentation rates for HAPU risk (coefficient 2.21, 95% CI 0.67 to 3.75); the increase for fall risk was not statistically significant (0.36; -3.58 to 4.30). EHR implementation was associated with a 13% decrease in HAPU rates (coefficient -0.76, 95% CI -1.37 to -0.16) but no decrease in fall rates (-0.091; -0.29 to 0.11). Irrespective of EHR implementation, HAPU rates decreased significantly over time (-0.16; -0.20 to -0.13), while fall rates did not (0.0052; -0.01 to 0.02). Hospital region was a significant predictor of variation for both HAPU (0.72; 0.30 to 1.14) and fall rates (0.57; 0.41 to 0.72). The introduction of an integrated EHR was associated with a reduction in the number of HAPUs but not in patient fall rates. Other factors, such as changes over time and hospital region, were also associated with variation in outcomes. The findings suggest that EHR impact on nursing care processes and outcomes is dependent on a number of factors that should be further explored.

Does equality legislation reduce intergroup differences? Religious affiliation, socio-economic status and mortality in Scotland and Northern Ireland: A cohort study of 400,000 people.

PubMed

Wright, David M; Rosato, Michael; Raab, Gillian; Dibben, Chris; Boyle, Paul; O'Reilly, Dermot

2017-05-01

Religion frequently indicates membership of socio-ethnic groups with distinct health behaviours and mortality risk. Determining the extent to which interactions between groups contribute to variation in mortality is often challenging. We compared socio-economic status (SES) and mortality rates of Protestants and Catholics in Scotland and Northern Ireland, regions in which interactions between groups are profoundly different. Crucially, strong equality legislation has been in place for much longer and Catholics form a larger minority in Northern Ireland. Drawing linked Census returns and mortality records of 404,703 people from the Scottish and Northern Ireland Longitudinal Studies, we used Poisson regression to compare religious groups, estimating mortality rates and incidence rate ratios. We fitted age-adjusted and fully adjusted (for education, housing tenure, car access and social class) models. Catholics had lower SES than Protestants in both countries; the differential was larger in Scotland for education, housing tenure and car access but not social class. In Scotland, Catholics had increased age-adjusted mortality risk relative to Protestants but variation among groups was attenuated following adjustment for SES. Those reporting no religious affiliation were at similar mortality risk to Protestants. In Northern Ireland, there was no mortality differential between Catholics and Protestants either before or after adjustment. Men reporting no religious affiliation were at increased mortality risk but this differential was not evident among women. In Scotland, Catholics remained at greater socio-economic disadvantage relative to Protestants than in Northern Ireland and were also at a mortality disadvantage. This may be due to a lack of explicit equality legislation that has decreased inequality by religion in Northern Ireland during recent decades. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

PubMed

Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

2017-09-12

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol

PubMed Central

Alvarez, Monica I.; Glover, Luke C.; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H.; Walton, Eric M.; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I.; McClean, Colleen M.; Chinh, Nguyen Tran; Medina, Marisa W.; Dunstan, Sarah J.

2017-01-01

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S. Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S. Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches. PMID:28827342

Impact of meteorological factors on the spatiotemporal patterns of dengue fever incidence.

PubMed

Chien, Lung-Chang; Yu, Hwa-Lung

2014-12-01

Dengue fever is one of the most widespread vector-borne diseases and has caused more than 50 million infections annually over the world. For the purposes of disease prevention and climate change health impact assessment, it is crucial to understand the weather-disease associations for dengue fever. This study investigated the nonlinear delayed impact of meteorological conditions on the spatiotemporal variations of dengue fever in southern Taiwan during 1998-2011. We present a novel integration of a distributed lag nonlinear model and Markov random fields to assess the nonlinear lagged effects of weather variables on temporal dynamics of dengue fever and to account for the geographical heterogeneity. This study identified the most significant meteorological measures to dengue fever variations, i.e., weekly minimum temperature, and the weekly maximum 24-hour rainfall, by obtaining the relative risk (RR) with respect to disease counts and a continuous 20-week lagged time. Results show that RR increased as minimum temperature increased, especially for the lagged period 5-18 weeks, and also suggest that the time to high disease risks can be decreased. Once the occurrence of maximum 24-hour rainfall is >50 mm, an associated increased RR lasted for up to 15 weeks. A temporary one-month decrease in the RR of dengue fever is noted following the extreme rain. In addition, the elevated incidence risk is identified in highly populated areas. Our results highlight the high nonlinearity of temporal lagged effects and magnitudes of temperature and rainfall on dengue fever epidemics. The results can be a practical reference for the early warning of dengue fever. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates.

PubMed

Vissing, Nadja H; Chawes, Bo L K; Bisgaard, Hans

2013-11-15

The frequency of pneumonia and bronchiolitis exhibits considerable variation in otherwise healthy children, and suspected risk factors explain only a minor proportion of the variation. We hypothesized that alterations in the airway microbiome in early life may be associated with susceptibility to pneumonia and bronchiolitis in young children. To investigate the relation between neonatal airway colonization and pneumonia and bronchiolitis during the first 3 years of life. Participants comprised children of the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a prospective birth cohort study of 411 children born to mothers with asthma. Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Clinical information on pneumonia and bronchiolitis within the first 3 years of life was prospectively collected by the research physicians at the center. Analyses were adjusted for covariates associated with pneumonia and bronchiolitis and bacterial airway colonization. Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were available for 265 children. Of these, 56 (21%) neonates were colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization with at least one of these microorganisms (but not S. aureus) was significantly associated with increased incidence of pneumonia and bronchiolitis (adjusted incidence rate ratio, 1.79 [1.29-2.48]; P < 0.005) independently of concurrent or later asthma. Neonatal airway colonization with S. pneumoniae, H. influenzae, or M. catarrhalis is associated with increased risk of pneumonia and bronchiolitis in early life independently of asthma. This suggests a role of pathogenic bacterial colonization of the airways in neonates for subsequent susceptibly to pneumonia and bronchiolitis.

Single Versus Customized Treatment Planning for Image-guided High-Dose-Rate Brachytherapy for Cervical Cancer: Dosimetric Comparison and Predicting Factor for Organs at Risk Overdose With Single Plan Approach

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

Chi, Alexander; Gao Mingcheng; Sinacore, James

2009-09-01

Purpose: To compare the dose distribution between customized planning (CP) and adopting a single plan (SP) in multifractionated high-dose-rate brachytherapy and to establish predictors for the necessity of CP in a given patient. Methods and Materials: A total of 50 computed tomography-based plans for 10 patients were evaluated. Each patient had received 6 Gy for five fractions. The clinical target volume and organs at risk (i.e., rectum, bladder, sigmoid, and small bowel) were delineated on each computed tomography scan. For the SP approach, the same dwell position and time was used for all fractions. For the CP approach, the dwellmore » position and time were reoptimized for each fraction. Applicator position variation was determined by measuring the distance between the posterior bladder wall and the tandem at the level of the vaginal fornices. Results: The organs at risk D{sub 2cc} (dose to 2 cc volume) was increased with the SP approach. The dose variation was statistically similar between the tandem and ring and tandem and ovoid groups. The bladder D{sub 2cc} dose was 81.95-105.42 Gy{sub 2} for CP and 82.11-122.49 Gy{sub 2} for SP. In 5 of the 10 patients, the bladder would have been significantly overdosed with the SP approach. The variation of the posterior bladder wall distance from that in the first fraction was correlated with the increase in the bladder D{sub 2cc} (SP/CP), with a correlation coefficient of -0.59. Conclusion: Our results support the use of CP instead of the SP approach to help avoid a significant overdose to the bladder. This is especially true for a decrease in the posterior wall distance of {>=}0.5 cm compared with that in the first fraction.« less

WDR36 and P53 Gene Variants and Susceptibility to Primary Open-Angle Glaucoma: Analysis of Gene-Gene Interactions

PubMed Central

Blanco-Marchite, Cristina; Sánchez-Sánchez, Francisco; López-Garrido, María-Pilar; Iñigez-de-Onzoño, Mercedes; López-Martínez, Francisco; López-Sánchez, Enrique; Alvarez, Lydia; Rodríguez-Calvo, Pedro-Pablo; Méndez-Hernández, Carmen; Fernández-Vega, Luis; García-Sánchez, Julián; Coca-Prados, Miguel; García-Feijoo, Julián

2011-01-01

Purpose. To investigate the role of WDR36 and P53 sequence variations in POAG susceptibility. Methods. The authors performed a case-control genetic association study in 268 unrelated Spanish patients (POAG1) and 380 control subjects matched for sex, age, and ethnicity. WDR36 sequence variations were screened by either direct DNA sequencing or denaturing high-performance liquid chromatography. P53 polymorphisms p.R72P and c.97–147ins16bp were analyzed by single-nucleotide polymorphism (SNP) genotyping and PCR, respectively. Positive SNP and haplotype associations were reanalyzed in a second sample of 211 patients and in combined cases (n = 479). Results. The authors identified almost 50 WDR36 sequence variations, of which approximately two-thirds were rare and one-third were polymorphisms. Approximately half the variants were novel. Eight patients (2.9%) carried rare mutations that were not identified in the control group (P = 0.001). Six Tag SNPs were expected to be structured in three common haplotypes. Haplotype H2 was consistently associated with the disease (P = 0.0024 in combined cases). According to a dominant model, genotypes containing allele P of the P53 p.R72P SNP slightly increased glaucoma risk. Glaucoma susceptibility associated with different WDR36 genotypes also increased significantly in combination with the P53 RP risk genotype, indicating the existence of a genetic interaction. For instance, the OR of the H2 diplotype estimated for POAG1 and combined cases rose approximately 1.6 times in the two-locus genotype H2/RP. Conclusions. Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in POAG susceptibility, although this finding must be confirmed in other populations. PMID:21931130

High-risk regions and outbreak modelling of tularemia in humans.

PubMed

Desvars-Larrive, A; Liu, X; Hjertqvist, M; Sjöstedt, A; Johansson, A; Rydén, P

2017-02-01

Sweden reports large and variable numbers of human tularemia cases, but the high-risk regions are anecdotally defined and factors explaining annual variations are poorly understood. Here, high-risk regions were identified by spatial cluster analysis on disease surveillance data for 1984-2012. Negative binomial regression with five previously validated predictors (including predicted mosquito abundance and predictors based on local weather data) was used to model the annual number of tularemia cases within the high-risk regions. Seven high-risk regions were identified with annual incidences of 3·8-44 cases/100 000 inhabitants, accounting for 56·4% of the tularemia cases but only 9·3% of Sweden's population. For all high-risk regions, most cases occurred between July and September. The regression models explained the annual variation of tularemia cases within most high-risk regions and discriminated between years with and without outbreaks. In conclusion, tularemia in Sweden is concentrated in a few high-risk regions and shows high annual and seasonal variations. We present reproducible methods for identifying tularemia high-risk regions and modelling tularemia cases within these regions. The results may help health authorities to target populations at risk and lay the foundation for developing an early warning system for outbreaks.

Huntingtin gene repeat size variations affect risk of lifetime depression.

PubMed

Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

2017-12-11

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

Prevalence and risk factors of childhood allergic diseases in eight metropolitan cities in China: a multicenter study.

PubMed

Li, Fei; Zhou, Yingchun; Li, Shenghui; Jiang, Fan; Jin, Xingming; Yan, Chonghuai; Tian, Ying; Zhang, Yiwen; Tong, Shilu; Shen, Xiaoming

2011-06-06

Several studies conducted during the past two decades suggested increasing trend of childhood allergic diseases in China. However, few studies have provided detailed description of geographic variation and explored risk factors of these diseases. This study investigated the pattern and risk factors of asthma, allergic rhinitis and eczema in eight metropolitan cities in China. We conducted a cross-sectional survey during November-December 2005 in eight metropolitan cities in China. A total of 23791 children aged 6-13 years participated in this survey. Questions from the standard questionnaire of the International Study of Asthma and Allergies in Children (ISAAC) were used to examine the pattern of current asthma, allergic rhinitis and eczema. Logistic regression analyses were performed to assess the risk factors for childhood allergies. The average prevalence of childhood asthma, allergic rhinitis and eczema across the eight cities was 3.3% (95% Confidence interval (CI): 3.1%, 3.6%), 9.8% (95% CI: 9.4%, 10.2%) and 5.5% (95% CI: 5.2%, 5.8%), respectively. Factors related to lifestyle, mental health and socio-economic status were found to be associated with the prevalence of childhood allergies. These risk factors were unevenly distributed across cities and disproportionately affected the local prevalence. There was apparent geographic variation of childhood allergies in China. Socio-environmental factors had strong impacts on the prevalence of childhood allergies; but these impacts differed across regions. Thus public health policies should specifically target at the local risk factors for each individual area.

Birth order and risk of non-hodgkin lymphoma--true association or bias?

PubMed

Grulich, Andrew E; Vajdic, Claire M; Falster, Michael O; Kane, Eleanor; Smedby, Karin Ekstrom; Bracci, Paige M; de Sanjose, Silvia; Becker, Nikolaus; Turner, Jenny; Martinez-Maza, Otoniel; Melbye, Mads; Engels, Eric A; Vineis, Paolo; Costantini, Adele Seniori; Holly, Elizabeth A; Spinelli, John J; La Vecchia, Carlo; Zheng, Tongzhang; Chiu, Brian C H; Franceschi, Silvia; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard K; Cerhan, James R; Breen, Elizabeth C; Birmann, Brenda; Cozen, Wendy

2010-09-15

There is inconsistent evidence that increasing birth order may be associated with risk of non-Hodgkin lymphoma (NHL). The authors examined the association between birth order and related variables and NHL risk in a pooled analysis (1983-2005) of 13,535 cases and 16,427 controls from 18 case-control studies within the International Lymphoma Epidemiology Consortium (InterLymph). Overall, the authors found no significant association between increasing birth order and risk of NHL (P-trend = 0.082) and significant heterogeneity. However, a significant association was present for a number of B- and T-cell NHL subtypes. There was considerable variation in the study-specific risks which was partly explained by study design and participant characteristics. In particular, a significant positive association was present in population-based studies, which had lower response rates in cases and controls, but not in hospital-based studies. A significant positive association was present in higher-socioeconomic-status (SES) participants only. Results were very similar for the related variable of sibship size. The known correlation of high birth order with low SES suggests that selection bias related to SES may be responsible for the association between birth order and NHL.

Regional variation in thyroid cancer incidence in Belgium is associated with variation in thyroid imaging and thyroid disease management.

PubMed

Van den Bruel, Annick; Francart, Julie; Dubois, Cecile; Adam, Marielle; Vlayen, Joan; De Schutter, Harlinde; Stordeur, Sabine; Decallonne, Brigitte

2013-10-01

Increased thyroid cancer incidence is at least partially attributed to increased detection and shows considerable regional variation. We investigated whether regional variation in cancer incidence was associated with variations in thyroid disease management. We conducted a retrospective population-based cohort study that involved linking data from the Belgian Health Insurance database and the Belgian Cancer Registry to compare thyroid-related procedures between regions with high and low cancer incidence. Primary outcome measures were rates of TSH testing, imaging, fine-needle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes were proportions of subjects with thyrotoxicosis and nodular disease treated with surgery, of subjects treated with surgery preceded by FNAC or with synchronous lymph node dissection, and of thyroid cancer diagnosis after surgery. The rate of TSH testing was similar, but the rate of imaging was lower in the low incidence region. The rate of FNAC was similar, whereas the rate of surgery was lower in the low incidence region (34 [95% CI 33; 35 ] vs 80 [95% CI 79; 81 ] per 100,000 person years in the high incidence region; P < .05). In the low incidence region compared to the high incidence region, surgery represented a less chosen therapy for euthyroid nodular disease patients (47% [95% CI 46; 48] vs 69% [95% CI 68; 70]; P < .05), proportionally more surgery was preceded by FNAC, more cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had more preoperative FNAC and synchronous lymph node dissection. Regional variation in thyroid cancer incidence, most marked for low-risk disease, is associated with different usage of thyroid imaging and surgery, supporting variable detection as a key determinant in geographic variation.

Effect of change in coding rules on recording diabetes in hospital administrative datasets.

PubMed

Assareh, Hassan; Achat, Helen M; Guevarra, Veth M; Stubbs, Joanne M

2016-10-01

During 2008-2011 Australian Coding Standards mandated a causal relationship between diabetes and inpatient care as a criterion for recording diabetes as a comorbidity in hospital administrative datasets. We aim to measure the effect of the causality mandate on recorded diabetes and associated inter-hospital variations. For patients with diabetes, all admissions between 2004 and 2013 to all New South Wales acute public hospitals were investigated. Poisson mixed models were employed to derive adjusted rates and variations. The non-recorded diabetes incidence rate was 20.7%. The causality mandate increased the incidence rate four fold during the change period, 2008-2011, compared to the pre- or post-change periods (32.5% vs 8.4% and 6.9%). The inter-hospital variation was also higher, with twice the difference in the non-recorded rate between hospitals with the highest and lowest rates (50% vs 24% and 27% risk gap). The variation decreased during the change period (29%), while the rate continued to rise (53%). Admission characteristics accounted for over 44% of the variation compared with at most two per cent attributable to patient or hospital characteristics. Contributing characteristics explained less of the variation within the change period compared to pre- or post-change (46% vs 58% and 53%). Hospital relative performance was not constant over time. The causality mandate substantially increased the non-recorded diabetes rate and associated inter-hospital variation. Longitudinal accumulation of clinical information at the patient level, and the development of appropriate adoption protocols to achieve comprehensive and timely implementation of coding changes are essential to supporting the integrity of hospital administrative datasets. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predicting impacts of climate change on Fasciola hepatica risk.

PubMed

Fox, Naomi J; White, Piran C L; McClean, Colin J; Marion, Glenn; Evans, Andy; Hutchings, Michael R

2011-01-10

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits.

Polycyclic aromatic hydrocarbons (PAHs) in water from three estuaries of China: Distribution, seasonal variations and ecological risk assessment.

PubMed

Yan, Jinxia; Liu, Jingling; Shi, Xuan; You, Xiaoguang; Cao, Zhiguo

2016-08-15

The distribution, seasonal variations and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in water from three estuaries in Hai River Basin of China, which has been suffering from different anthropogenic pressures, were investigated. In three estuaries, the average concentration of ΣPAHs was the lowest in Luan River estuary, followed by Hai River estuary, and the highest in Zhangweixin River estuary. There were significant seasonal variations in ΣPAHs, the concentrations of ΣPAHs were higher in November than in May and August. The composition profiles of PAHs in different sites were significantly different, and illustrated seasonal variations. Generally, 2-ring (Nap) and 3-ring PAHs (Acp, Fl and Phe) were the most abundant components at most sampling sites in three estuaries. The PAHs in three estuaries were mainly originated from pyrogenic sources. A method based on toxic equivalency factors (TEFs) and risk quotient (RQ) was proposed to assess the ecological risk of ΣPAHs, with the ecological risk of individual PAHs being considered separately. The results showed that the ecological risks caused by ΣPAHs were high in Hai River estuary and Zhangweixin River estuary, and moderate in Luan River estuary. The mean values of ecological risk in August were lower than those in November. The contributions of individual PAHs to ecological risk were different in May, August and November. 3-ring and 4-ring PAHs accounted for much more ecological risk than 2-ring, 5-ring and 6-ring, although the contributions of 5-ring and 6-ring to ecological risk were higher than these to PAHs concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Socioeconomic variations in nicotine dependence in rural southwest China.

PubMed

Cai, Le; Cui, Wenlong; You, Dingyun; He, Jianhui; Zhao, Keying

2015-11-23

This study examines how nicotine dependence is distributed across socioeconomic gradients in rural Yunnan province, which has the most ethnic minorities in one province in southwest China. A cross-sectional survey was conducted in four rural areas of Yunnan province among 17,158 consenting individuals aged ≥18 years in 2011. Information on demographic characteristics and smoking habits was obtained using a standard questionnaire. The Fagerstrom Test for Nicotine Dependence (FTND) was applied to assess nicotine dependence. Multilevel logistic regression was used to model the variation in prevalence of nicotine dependence. In the study population, the overall prevalence of current smokers and nicotine dependence was 32.4 % and 31.6 %, respectively. Females were much less likely to have nicotine addiction than males: odds ratio (OR) of 0.01 (95 % CI: 0.008 - 0.012). Higher annual household income was associated with a greater risk of nicotine dependence (OR 1.09, 95 % CI: 1.01 - 1.17). Adults who grew tobacco were more likely to have nicotine addiction (OR 1.22, 95 % CI 1.07 - 1.41). Individual educational level was inversely associated with the probability of nicotine dependence (OR 0.63, 95 % CI 0.55 - 0.72), lower community educational level was also associated with an increased risk of nicotine dependence (OR 0.94, 95 % CI 0.92 - 0.98). Nicotine dependence showed significant variations across different indicators of both contextual and individual socioeconomic status in rural southwest China. Future interventions on tobacco cessation should give increased attention to men, tobacco farmers, less educated or poorer persons, and lower educational level communities.

Spatial variation of pneumonia hospitalization risk in Twin Cities metro area, Minnesota.

PubMed

Iroh Tam, P Y; Krzyzanowski, B; Oakes, J M; Kne, L; Manson, S

2017-11-01

Fine resolution spatial variability in pneumonia hospitalization may identify correlates with socioeconomic, demographic and environmental factors. We performed a retrospective study within the Fairview Health System network of Minnesota. Patients 2 months of age and older hospitalized with pneumonia between 2011 and 2015 were geocoded to their census block group, and pneumonia hospitalization risk was analyzed in relation to socioeconomic, demographic and environmental factors. Spatial analyses were performed using Esri's ArcGIS software, and multivariate Poisson regression was used. Hospital encounters of 17 840 patients were included in the analysis. Multivariate Poisson regression identified several significant associations, including a 40% increased risk of pneumonia hospitalization among census block groups with large, compared with small, populations of ⩾65 years, a 56% increased risk among census block groups in the bottom (first) quartile of median household income compared to the top (fourth) quartile, a 44% higher risk in the fourth quartile of average nitrogen dioxide emissions compared with the first quartile, and a 47% higher risk in the fourth quartile of average annual solar insolation compared to the first quartile. After adjusting for income, moving from the first to the second quartile of the race/ethnic diversity index resulted in a 21% significantly increased risk of pneumonia hospitalization. In conclusion, the risk of pneumonia hospitalization at the census-block level is associated with age, income, race/ethnic diversity index, air quality, and solar insolation, and varies by region-specific factors. Identifying correlates using fine spatial analysis provides opportunities for targeted prevention and control.

Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery.

PubMed

Poeran, Jashvant; Mazumdar, Madhu; Rasul, Rehana; Meyer, Joanne; Sacks, Henry S; Koll, Brian S; Wallach, Frances R; Moskowitz, Alan; Gelijns, Annetine C

2016-02-01

Antibiotic use, particularly type and duration, is a crucial modifiable risk factor for Clostridium difficile. Cardiac surgery is of particular interest because prophylactic antibiotics are recommended for 48 hours or less (vs ≤24 hours for noncardiac surgery), with increasing vancomycin use. We aimed to study associations between antibiotic prophylaxis (duration/vancomycin use) and C difficile among patients undergoing coronary artery bypass grafting. We extracted data on coronary artery bypass grafting procedures from the national Premier Perspective claims database (2006-2013, n = 154,200, 233 hospitals). Multilevel multivariable logistic regressions measured associations between (1) duration (<2 days, "standard" vs ≥2 days, "extended") and (2) type of antibiotic used ("cephalosporin," "cephalosporin + vancomycin," "vancomycin") and C difficile as outcome. Overall C difficile prevalence was 0.21% (n = 329). Most patients (59.7%) received a cephalosporin only; in 33.1% vancomycin was added, whereas 7.2% received vancomycin only. Extended prophylaxis was used in 20.9%. In adjusted analyses, extended prophylaxis (vs standard) was associated with significantly increased C difficile risk (odds ratio, 1.43; confidence interval, 1.07-1.92), whereas no significant associations existed for vancomycin use as adjuvant or primary prophylactic compared with the use of cephalosporins (odds ratio, 1.21; confidence interval, 0.92-1.60, and odds ratio, 1.39; confidence interval, 0.94-2.05, respectively). Substantial inter-hospital variation exists in the percentage of extended antibiotic prophylaxis (interquartile range, 2.5-35.7), use of adjuvant vancomycin (interquartile range, 4.2-61.1), and vancomycin alone (interquartile range, 2.3-10.4). Although extended use of antibiotic prophylaxis was associated with increased C difficile risk after coronary artery bypass grafting, vancomycin use was not. The observed hospital variation in antibiotic prophylaxis practices suggests great potential for efforts aimed at standardizing practices that subsequently could reduce C difficile risk. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The Variation of Work Productivity and Muscle Activities at Different Levels of Production Target

NASA Astrophysics Data System (ADS)

Nur, Nurhayati Mohd; Dawal, Siti Zawiah Md; Dahari, Mahidzal; Zuhairah Mahmud Zuhudi, Nurul

2017-10-01

This paper aims to investigate the variation of work productivity and muscle activities among workers performing industrial repetitive tasks at four different levels of production target. The work productivity and muscle activities data were recorded from twenty workers at four levels of production target corresponding to “participative (PS1)”, “normal (PS2)”, “high (PS3)” and “very high (PS4)”. The results showed that worker productivity was found to increase at higher production target and there was a significant change (p < 0.005) in work productivity across the four different production targets. The muscle activities were found to increase at higher production target and correspond to more discomfort and a higher rate of muscle fatigue. The results indicated that working with a higher production target results in higher worker productivity, but could lead to higher risk of WMSDs.

Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population.

PubMed

Rots, Dmitrijs; Kreile, Madara; Nikulshin, Sergejs; Kovalova, Zhanna; Gailite, Linda

2018-02-01

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study. The study included 81 patients with childhood ALL. DNA samples of both or one biological parent were available for 62 of ALL patients and 130 age and gender adjusted healthy samples were used as a control group. Analyzed IL15 gene variations: rs10519612, rs10519613 and rs17007695 were genotyped using PCR-RFLP assay. Our results shows that IL15 gene variations haplotypes are associated with the risk of developing childhood ALL (p < 0.05), although there is no such association for the variations separately. The variations rs10519612 and rs1059613 in a recessive pattern of inheritance were associated with hyperdiploidy (p = 0.048). Analyzed genetic variations had no impact on other clinical features and treatment response (assessed by the minimal residual disease) in our study.

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

PubMed

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

2018-05-01

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

Habitat selection responses of parents to offspring predation risk: An experimental test

USGS Publications Warehouse

Fontaine, J.J.; Martin, T.E.

2006-01-01

The ability of nest predation to influence habitat settlement decisions in birds is widely debated, despite its importance in limiting fitness. Here, we experimentally manipulated nest predation risk across a landscape and asked the question, do migratory birds assess and respond to variation in nest predation risk when choosing breeding habitats? We examined habitat preference by quantifying the density and settlement date of eight species of migratory passerines breeding in areas with and without intact nest predator communities. We found consistently more individuals nesting in areas with reduced nest predation than in areas with intact predator assemblages, although predation risk had no influence on settlement or breeding phenology. Additionally, those individuals occupying safer nesting habitats exhibited increased singing activity. These findings support a causal relationship between habitat choice and nest predation risk and suggest the importance of nest predation risk in shaping avian community structure and breeding activity. ?? 2006 by The University of Chicago. All rights reserved.

The many faces of fear: a synthesis of the methodological variation in characterizing predation risk.

PubMed

Moll, Remington J; Redilla, Kyle M; Mudumba, Tutilo; Muneza, Arthur B; Gray, Steven M; Abade, Leandro; Hayward, Matt W; Millspaugh, Joshua J; Montgomery, Robert A

2017-07-01

Predators affect prey by killing them directly (lethal effects) and by inducing costly antipredator behaviours in living prey (risk effects). Risk effects can strongly influence prey populations and cascade through trophic systems. A prerequisite for assessing risk effects is characterizing the spatiotemporal variation in predation risk. Risk effects research has experienced rapid growth in the last several decades. However, preliminary assessments of the resultant literature suggest that researchers characterize predation risk using a variety of techniques. The implications of this methodological variation for inference and comparability among studies have not been well recognized or formally synthesized. We couple a literature survey with a hierarchical framework, developed from established theory, to quantify the methodological variation in characterizing risk using carnivore-ungulate systems as a case study. Via this process, we documented 244 metrics of risk from 141 studies falling into at least 13 distinct subcategories within three broader categories. Both empirical and theoretical work suggest risk and its effects on prey constitute a complex, multi-dimensional process with expressions varying by spatiotemporal scale. Our survey suggests this multi-scale complexity is reflected in the literature as a whole but often underappreciated in any given study, which complicates comparability among studies and leads to an overemphasis on documenting the presence of risk effects rather than their mechanisms or scale of influence. We suggest risk metrics be placed in a more concrete conceptual framework to clarify inference surrounding risk effects and their cascading effects throughout ecosystems. We recommend studies (i) take a multi-scale approach to characterizing risk; (ii) explicitly consider 'true' predation risk (probability of predation per unit time); and (iii) use risk metrics that facilitate comparison among studies and the evaluation of multiple competing hypotheses. Addressing the pressing questions in risk effects research, including how, to what extent and on what scale they occur, requires leveraging the advantages of the many methods available to characterize risk while minimizing the confusion caused by variability in their application. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Most genetic risk for autism resides with common variation

PubMed Central

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J.; Bodea, Corneliu A.; Goldberg, Arthur P.; Lee, Ann B.; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M.; Devlin, Bernie

2014-01-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation. PMID:25038753

Constitutional sequence variation in the Fanconi anaemia group C (FANCC) gene in childhood acute myeloid leukaemia.

PubMed

Barber, Lisa M; McGrath, Helen E N; Meyer, Stefan; Will, Andrew M; Birch, Jillian M; Eden, Osborn B; Taylor, G Malcolm

2003-04-01

The extent to which genetic susceptibility contributes to the causation of childhood acute myeloid leukaemia (AML) is not known. The inherited bone marrow failure disorder Fanconi anaemia (FA) carries a substantially increased risk of AML, raising the possibility that constitutional variation in the FA (FANC) genes is involved in the aetiology of childhood AML. We have screened genomic DNA extracted from remission blood samples of 97 children with sporadic AML and 91 children with sporadic acute lymphoblastic leukaemia (ALL), together with 104 cord blood DNA samples from newborn children, for variations in the Fanconi anaemia group C (FANCC) gene. We found no evidence of known FANCC pathogenic mutations in children with AML, ALL or in the cord blood samples. However, we detected 12 different FANCC sequence variants, of which five were novel to this study. Among six FANCC variants leading to amino-acid substitutions, one (S26F) was present at a fourfold greater frequency in children with AML than in the cord blood samples (odds ratio: 4.09, P = 0.047; 95% confidence interval 1.08-15.54). Our results thus do not exclude the possibility that this polymorphic variant contributes to the risk of a small proportion of childhood AML.

Polygenic risk score of shorter telomere length and risk of depression and anxiety in women.

PubMed

Chang, Shun-Chiao; Prescott, Jennifer; De Vivo, Immaculata; Kraft, Peter; Okereke, Olivia I

2018-05-26

Prior studies have reported significant cross-sectional associations between depression or anxiety and shorter telomere lengths, but the temporality of associations is uncertain. Little is known regarding whether shorter telomere length is related to increased risk of developing depression or anxiety. In this study, using the genetic tool of polygenic risk score (PRS), we evaluated the association between genetic predisposition to shorter telomere length and the risks of lifetime clinically significant depression (defined by self-reported clinician/physician diagnosis, antidepressant use, and/or presence of severe depressive symptoms) and of clinically meaningful anxiety symptoms among 17,693 female participants of European ancestry. The weighted PRS of telomere lengths (TLs) combined the dosage of nine alleles that were significantly associated with inter-individual variation in TLs in published genome-wide association studies. Higher score of PRS, corresponding to shorter TL in the literature, was significantly associated with shorter relative TLs (p = 0.008). However, higher PRS was not associated with the lifetime risk of either depression or anxiety. Furthermore, higher PRS was not associated with long-term patterns of depressive symptom trajectories or specifically with later-life onset of depression or anxiety. In summary, this study did not observe a significant association between genetic predisposition to shorter telomere length and risk of depression and anxiety in a large sample of mid-life and older white women. However, these genetic variants jointly account for a limited proportion of interpersonal variation in leukocyte telomere length. Future studies will need to incorporate more genetic variants to improve the accuracy of predicted power, as such data become available. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of ionic current variability on human ventricular cellular electrophysiology.

PubMed

Romero, Lucía; Pueyo, Esther; Fink, Martin; Rodríguez, Blanca

2009-10-01

Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict arrhythmic risk preclinically challenging. Our goal is to investigate the role of ionic current properties and their variability in modulating cellular biomarkers of arrhythmic risk to improve risk stratification and identification in humans. A systematic investigation into the sensitivity of the main preclinical biomarkers of arrhythmic risk to changes in ionic current conductances and kinetics was performed using computer simulations. Four stimulation protocols were applied to the ten Tusscher and Panfilov human ventricular model to quantify the impact of +/-15 and +/-30% variations in key model parameters on action potential (AP) properties, Ca(2+) and Na(+) dynamics, and their rate dependence. Simulations show that, in humans, AP duration is moderately sensitive to changes in all repolarization current conductances and in L-type Ca(2+) current (I(CaL)) and slow component of the delayed rectifier current (I(Ks)) inactivation kinetics. AP triangulation, however, is strongly dependent only on inward rectifier K(+) current (I(K1)) and delayed rectifier current (I(Kr)) conductances. Furthermore, AP rate dependence (i.e., AP duration rate adaptation and restitution properties) and intracellular Ca(2+) and Na(+) levels are highly sensitive to both I(CaL) and Na(+)/K(+) pump current (I(NaK)) properties. This study provides quantitative insights into the sensitivity of preclinical biomarkers of arrhythmic risk to variations in ionic current properties in humans. The results show the importance of sensitivity analysis as a powerful method for the in-depth validation of mathematical models in cardiac electrophysiology.

TCDD and cancer: A critical review of epidemiologic studies

PubMed Central

Boffetta, Paolo; Mundt, Kenneth A; Adami, Hans-Olov; Cole, Philip; Mandel, Jack S

2011-01-01

The authors reviewed the epidemiologic studies on exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer risk, published since the last full-scale review made by the International Agency for Research on Cancer Monographs program in 1997. The update of a cohort of US herbicide producers generated negative results overall; the internal analysis provided evidence of an increased “all-cancer” risk in the highest exposure category, with a statistically significant exposure-response association in some of the many analyses performed.The update of a similar Dutch cohort did not confirm the previously observed association with TCDD exposure. The updated surveillance of the Seveso population provided evidence of increased all-cancer mortality 15-20 years after exposure among those living in the most contaminated area but might also reflect random variation, as overall excesses in the most recent follow-up were not observed. Corresponding data on cancer incidence offer little support to the mortality results. Updated results from cohort studies of Vietnam veterans potentially exposed to TCDD did not consistently suggest an increased risk of cancer. Results of additional, smaller studies of other occupational groups potentially exposed to TCDD, and of community-based case-control studies, did not provide consistent evidence of an increased cancer risk. In conclusion, recent epidemiological evidence falls far short of conclusively demonstrating a causal link between TCDD exposure and cancer risk in humans. The emphasis on results for overall cancer risk—rather than risk for specific neoplasms—is notjustified on epidemiologic grounds and is nota reason for ignoring the weaknesses of the available evidence. PMID:21718216

Upper midwest climate variations: farmer responses to excess water risks.

PubMed

Morton, Lois Wright; Hobbs, Jonathan; Arbuckle, J Gordon; Loy, Adam

2015-05-01

Persistent above average precipitation and runoff and associated increased sediment transfers from cultivated ecosystems to rivers and oceans are due to changes in climate and human action. The US Upper Midwest has experienced a 37% increase in precipitation (1958-2012), leading to increased crop damage from excess water and off-farm loss of soil and nutrients. Farmer adaptive management responses to changing weather patterns have potential to reduce crop losses and address degrading soil and water resources. This research used farmer survey ( = 4778) and climate data (1971-2011) to model influences of geophysical context, past weather, on-farm flood and saturated soils experiences, and risk and vulnerability perceptions on management practices. Seasonal precipitation varied across six Upper Midwest subregions and was significantly associated with variations in management. Increased warm-season precipitation (2007-2011) relative to the past 40 yr was positively associated with no-till, drainage, and increased planting on highly erodible land (HEL). Experience with saturated soils was significantly associated with increased use of drainage and less use of no-till, cover crops, and planting on HEL. Farmers in counties with a higher percentage of soils considered marginal for row crops were more likely to use no-till, cover crops, and plant on HEL. Respondents who sell corn through multiple markets were more likely to have planted cover crops and planted on HEL in 2011.This suggests that regional climate conditions may not well represent individual farmers' actual and perceived experiences with changing climate conditions. Accurate climate information downscaled to localized conditions has potential to influence specific adaptation strategies. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Association of IRF5 polymorphisms with activation of the interferon α pathway

PubMed Central

Rullo, Ornella J; Woo, Jennifer M P; Wu, Hui; Hoftman, Alice D C; Maranian, Paul; Brahn, Brittany A; McCurdy, Deborah; Cantor, Rita M; Tsao, Betty P

2011-01-01

Objective The genetic association of interferon regulatory factor 5 (IRF5) with systemic lupus erythematosus (SLE) susceptibility has been convincingly established. To gain understanding of the effect of IRF5 variation in individuals without SLE, a study was undertaken to examine whether such genetic variation predisposes to activation of the interferon α (IFNα) pathway. Methods Using a computer simulated approach, 14 single nucleotide polymorphisms (SNPs) and haplotypes of IRF5 were tested for association with mRNA expression levels of IRF5, IFNα and IFN-inducible genes and chemokines in lymphoblastoid cell lines (LCLs) from individuals of European (CEU), Han Chinese (CHB), Japanese (JPT) and Yoruba Nigerian (YRI) backgrounds. IFN-inducible gene expression was assessed in LCLs from children with SLE in the presence and absence of IFNα stimulation. Results The major alleles of IRF5 rs13242262 and rs2280714 were associated with increased IRF5 mRNA expression levels in the CEU, CHB+JPT and YRI samples. The minor allele of IRF5 rs10488631 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU (pc=0.0005, 0.01 and 0.04, respectively). A haplotype containing these risk alleles of rs13242262, rs10488631 and rs2280714 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU LCLs. In vitro studies showed specific activation of IFN-inducible genes in LCLs by IFNα. Conclusions SNPs of IRF5 in healthy individuals of a number of ethnic groups were associated with increased mRNA expression of IRF5. In European-derived individuals, an IRF5 haplotype was associated with increased IRF5, IFNα and IFN-inducible chemokine expression. Identifying individuals genetically predisposed to increased IFN-inducible gene and chemokine expression may allow early detection of risk for SLE. PMID:19854706

N-terminal pro-B-type natriuretic peptide variability in stable dialysis patients.

PubMed

Fahim, Magid A; Hayen, Andrew; Horvath, Andrea R; Dimeski, Goce; Coburn, Amanda; Johnson, David W; Hawley, Carmel M; Campbell, Scott B; Craig, Jonathan C

2015-04-07

Monitoring N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful for assessing cardiovascular risk in dialysis patients. However, its biologic variation is unknown, hindering the accurate interpretation of serial concentrations. The aims of this prospective cohort study were to estimate the within- and between-person coefficients of variation of NT-proBNP in stable dialysis patients, and derive the critical difference between measurements needed to exclude biologic and analytic variation. Fifty-five prevalent hemodialysis and peritoneal dialysis patients attending two hospitals were assessed weekly for 5 weeks and then monthly for 4 months between October 2010 and April 2012. Assessments were conducted at the same time in the dialysis cycle and entailed NT-proBNP testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they became unstable. This study analyzed 136 weekly and 113 monthly NT-proBNP measurements from 40 and 41 stable patients, respectively. Results showed that 22% had ischemic heart disease; 9% and 87% had left ventricular systolic and diastolic dysfunction, respectively. Respective between- and within-person coefficients of variation were 153% and 27% for weekly measurements, and 148% and 35% for monthly measurements. Within-person variation was unaffected by dialysis modality, hydration status, inflammation, or cardiac comorbidity. NT-proBNP concentrations measured at weekly intervals needed to increase by at least 46% or decrease by 84% to exclude change due to biologic and analytic variation alone with 90% certainty, whereas monthly measurements needed to increase by at least 119% or decrease by 54%. The between-person variation of NT-proBNP was large and markedly greater than within-person variation, indicating that NT-proBNP testing might better be applied in the dialysis population using a relative-change strategy. Serial NT-proBNP concentrations need to double or halve to confidently exclude change due to analytic and biologic variation alone. Copyright © 2015 by the American Society of Nephrology.

Burden of cancer mortality and differences attributable to demographic aging and risk factors in Argentina, 1986-2011.

PubMed

Pou, Sonia Alejandra; Tumas, Natalia; Coquet, Julia Becaria; Niclis, Camila; Román, María Dolores; Díaz, María Del Pilar

2017-03-09

The world faces an aging population that implies a large number of people affected with chronic diseases. Argentina has reached an advanced stage of demographic transition and presents a comparatively high rate of cancer mortality within Latin America. The objectives of this study were to examine cancer mortality trends in the province of Córdoba, Argentina, between 1986 and 2011, and to analyze the differences attributable to risk variations and demographic changes. Longitudinal series of age-standardized mortality rates for overall, breast and prostate cancers were modeled by Joinpoint regression to estimate the annual percent change. The Bashir & Estève method was used to split crude mortality rate variation into three components: mortality risk, population age structure and population size. A decreasing cancer age-standardized mortality rates trend was observed (1986-2011 annual percent change: -1.4, 95%CI: -1.6, -1.2 in men; -0.8, 95%CI: -1.0, -0.6 in women), with a significant shift in 1996. There were positive crude mortality rate net changes for overall female cancer, breast and prostate cancers, which were primarily attributable to demographic changes. Inversely, overall male cancer crude mortality rate showed a 9.15% decrease, mostly due to mortality risk. Despite favorable age-standardized mortality rates trends, the influence of population aging reinforces the challenge to control cancer in populations with an increasingly aged demographic structure.

Downscaling MODIS Land Surface Temperature for Urban Public Health Applications

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad; Crosson, William; Estes, Maurice, Jr.; Estes, Sue; Quattrochi, Dale; Johnson, Daniel

2013-01-01

This study is part of a project funded by the NASA Applied Sciences Public Health Program, which focuses on Earth science applications of remote sensing data for enhancing public health decision-making. Heat related death is currently the number one weather-related killer in the United States. Mortality from these events is expected to increase as a function of climate change. This activity sought to augment current Heat Watch/Warning Systems (HWWS) with NASA remotely sensed data, and models used in conjunction with socioeconomic and heatrelated mortality data. The current HWWS do not take into account intra-urban spatial variation in risk assessment. The purpose of this effort is to evaluate a potential method to improve spatial delineation of risk from extreme heat events in urban environments by integrating sociodemographic risk factors with estimates of land surface temperature (LST) derived from thermal remote sensing data. In order to further improve the consideration of intra-urban variations in risk from extreme heat, we also developed and evaluated a number of spatial statistical techniques for downscaling the 1-km daily MODerate-resolution Imaging Spectroradiometer (MODIS) LST data to 60 m using Landsat-derived LST data, which have finer spatial but coarser temporal resolution than MODIS. In this paper, we will present these techniques, which have been demonstrated and validated for Phoenix, AZ using data from the summers of 2000-2006.

Seasonal hazards and health risks in lower-income countries: field testing a multi-disciplinary approach.

PubMed

Few, Roger; Lake, Iain; Hunter, Paul R; Tran, Pham Gia; Thien, Vu Trong

2009-12-21

Understanding how risks to human health change as a result of seasonal variations in environmental conditions is likely to become of increasing importance in the context of climatic change, especially in lower-income countries. A multi-disciplinary approach can be a useful tool for improving understanding, particularly in situations where existing data resources are limited but the environmental health implications of seasonal hazards may be high. This short article describes a multi-disciplinary approach combining analysis of changes in levels of environmental contamination, seasonal variations in disease incidence and a social scientific analysis of health behaviour. The methodology was field-tested in a peri-urban environment in the Mekong Delta, Vietnam, where poor households face alternate seasonal extremes in the local environment as the water level in the Delta changes from flood to dry season. Low-income households in the research sites rely on river water for domestic uses, including provision of drinking water, and it is commonly perceived that the seasonal changes alter risk from diarrhoeal diseases and other diseases associated with contamination of water. The discussion focuses on the implementation of the methodology in the field, and draws lessons from the research process that can help in refining and developing the approach for application in other locations where seasonal dynamics of disease risk may have important consequences for public health.

Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers.

PubMed

Gold, Gabriel; Blouin, Jean-Louis; Herrmann, François R; Michon, Agnès; Mulligan, Reinhild; Duriaux Saïl, Geneviève; Bouras, Constantin; Giannakopoulos, Panteleimon; Antonarakis, Stylianos E

2003-05-15

Alzheimer disease (AD) is characterized neuropathologically by neurofibrillary tangles and senile plaques. A key component of plaques is A beta, a polypeptide derived from A beta-precursor protein (APP) through proteolytic cleavage catalyzed by beta and gamma-secretase. We hypothesized that sequence variation in genes BACE1 (on chromosome 11q23.3) and BACE2 (on chromosome 21q22.3), which encode two closely related proteases that seem to act as the APP beta-secretase, may represent a genetic risk factor for AD. We analyzed the frequencies of single nucleotide polymorphisms (SNPs) in BACE1 and BACE2 genes in a community-based sample of 96 individuals with late-onset AD and 170 controls selected randomly among residents of the same community. The genotype data in both study groups did not demonstrate any association between AD and BACE1 or BACE2. After stratification for APOE status, however, an association between a BACE1 polymorphism located within codon V262 and AD in APOE epsilon 4 carriers was observed (P = 0.03). We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone. Copyright 2003 Wiley-Liss, Inc.

Development of organ-specific donor risk indices.

PubMed

Akkina, Sanjeev K; Asrani, Sumeet K; Peng, Yi; Stock, Peter; Kim, W Ray; Israni, Ajay K

2012-04-01

Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; the use of the LDRI has limited this practice. Significant regional variations in donor quality, as measured by the LDRI, remain in the United States. We also review other potential indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. Copyright © 2012 American Association for the Study of Liver Diseases.

Incorporating Comorbidity Within Risk Adjustment for UK Pediatric Cardiac Surgery.

PubMed

Brown, Katherine L; Rogers, Libby; Barron, David J; Tsang, Victor; Anderson, David; Tibby, Shane; Witter, Thomas; Stickley, John; Crowe, Sonya; English, Kate; Franklin, Rodney C; Pagel, Christina

2017-07-01

When considering early survival rates after pediatric cardiac surgery it is essential to adjust for risk linked to case complexity. An important but previously less well understood component of case mix complexity is comorbidity. The National Congenital Heart Disease Audit data representing all pediatric cardiac surgery procedures undertaken in the United Kingdom and Ireland between 2009 and 2014 was used to develop and test groupings for comorbidity and additional non-procedure-based risk factors within a risk adjustment model for 30-day mortality. A mixture of expert consensus based opinion and empiric statistical analyses were used to define and test the new comorbidity groups. The study dataset consisted of 21,838 pediatric cardiac surgical procedure episodes in 18,834 patients with 539 deaths (raw 30-day mortality rate, 2.5%). In addition to surgical procedure type, primary cardiac diagnosis, univentricular status, age, weight, procedure type (bypass, nonbypass, or hybrid), and era, the new risk factor groups of non-Down congenital anomalies, acquired comorbidities, increased severity of illness indicators (eg, preoperative mechanical ventilation or circulatory support) and additional cardiac risk factors (eg, heart muscle conditions and raised pulmonary arterial pressure) all independently increased the risk of operative mortality. In an era of low mortality rates across a wide range of operations, non-procedure-based risk factors form a vital element of risk adjustment and their presence leads to wide variations in the predicted risk of a given operation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Childhood Adversity, Recent Life Stressors and Suicidal Behavior in Chinese College Students

PubMed Central

You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Background Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. Method 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Results Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Conclusions Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population. PMID:24681891

Spatial sensitivity of grassland yields to weather variations in Austria and its implications for the future☆

PubMed Central

Neuwirth, Christian; Hofer, Barbara

2013-01-01

Agricultural production fulfills economic, ecological and structural functions. Despite technological advances, agricultural production remains sensitive to climate variations. In central Europe, climate change is predicted to bring more rainfall in winter, less rainfall in summer, and increased drought risk among other effects. Grassland agriculture, which is the dominant land use in Alpine regions, may be significantly affected by these climatic changes in the future. Motivated by this issue, the susceptibility of grassland yields to weather variations in Austria is empirical evaluated as a case study. The major objective of this study is to derive spatially distributed indications for climate change exposure by assessing the impacts of weather variations on past yield. It is assumed that reduced water supply during summer constitutes a threat to grassland productivity in regions that are warmer and drier already today. On the contrary, increased spring temperatures may improve grassland productivity in cooler regions like Alpine valleys, since the earlier snow melt leads to an extension of the growth period. Regression analyses are used for evaluating the relation between yearly yields and spring temperatures or water supply in summer, respectively. Water supply is thereby expressed by aggregated precipitation sums and the Climatic Water Balance (CWB). Input data are a meteorological time series as well as yearly yields available for 25 years between 1970 and 2010 and 99 districts in Austria. Yearly yields show a significant (P < 0.05) and positive dependency on water supply in summer for the eastern Austrian lowlands. The combination of temperature in spring and CWB in summer is only significant for six districts in the east of Austria. The positive impact of higher spring temperatures could not be verified. Generally, the regression coefficients are not very high, which indicates that temperature and water supply do not fully describe grassland productivity. Projected climate change may increasingly constitute a risk to yield reliability in the east of the country. That in turn, requires consideration in agricultural development plans and a quantification of these impacts from a social-economic perspective. PMID:25843990

Epidemiology of Knee Sprains in Youth, High School, and Collegiate American Football Players.

PubMed

Clifton, Daniel R; Onate, James A; Schussler, Eric; Djoko, Aristarque; Dompier, Thomas P; Kerr, Zachary Y

2017-05-01

  Variations in knee-sprain incidence among competition levels are unclear but may help inform prevention strategies in American football players.   To describe the epidemiology of knee sprains in youth, high school, and collegiate football players.   Descriptive epidemiology study.   Injury and athlete-exposure (AE) data were collected from 3 injury-surveillance programs at the youth, high school, and collegiate competition levels.   Data from 310 youth, 184 high school, and 71 collegiate football team-seasons were collected during the 2012 through 2014 seasons.   Knee-sprain rates and risks were calculated for each competition level. Injury rate ratios (IRRs) and risk ratios (RRs) compared knee-sprain rates by competition level. Injury proportion ratios (IPRs) compared differences in surgery needs, recurrence, injury mechanism, and injury activity by competition level.   Knee-sprain rates in youth, high school, and collegiate football were 0.16/1000 AEs, 0.25/1000 AEs, and 0.69/1000 AEs, respectively. Knee-sprain rates increased as the competition level increased (high school versus youth: IRR = 1.60; 95% confidence interval [CI] = 1.12, 2.30; collegiate versus high school: IRR = 2.73; 95% CI = 2.38, 3.96). Knee-sprain risk was highest in collegiate (4.3%), followed by high school (2.0%) and youth (0.5%) athletes. Knee-sprain risk increased as the competition level increased (high school versus youth: RR = 3.73; 95% CI = 2.60, 5.34; collegiate versus high school: RR = 2.14; 95% CI = 1.83, 2.51). Collegiate football had the lowest proportion of knee sprains that were noncontact injuries (collegiate versus youth: IPR = 0.54; 95% CI = 0.31, 0.95; collegiate versus high school: IPR = 0.59; 95% CI = 0.44, 0.79) and the lowest proportion that occurred while being tackled (collegiate versus youth: IPR = 0.44; 95% CI = 0.26, 0.76; collegiate versus high school: IPR = 0.71; 95% CI = 0.51, 0.98).   Knee-sprain incidence was highest in collegiate football. However, level-specific variations in the distributions of knee sprains by injury activity may highlight the need to develop level-specific policies and prevention strategies that ensure safe sports play.

The alignment between phenotypic plasticity, the major axis of genetic variation and the response to selection.

PubMed

Lind, Martin I; Yarlett, Kylie; Reger, Julia; Carter, Mauricio J; Beckerman, Andrew P

2015-10-07

Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments. © 2015 The Authors.

The exponential rise of induced seismicity with increasing stress levels in the Groningen gas field and its implications for controlling seismic risk

NASA Astrophysics Data System (ADS)

Bourne, S. J.; Oates, S. J.; van Elk, J.

2018-06-01

Induced seismicity typically arises from the progressive activation of recently inactive geological faults by anthropogenic activity. Faults are mechanically and geometrically heterogeneous, so their extremes of stress and strength govern the initial evolution of induced seismicity. We derive a statistical model of Coulomb stress failures and associated aftershocks within the tail of the distribution of fault stress and strength variations to show initial induced seismicity rates will increase as an exponential function of induced stress. Our model provides operational forecasts consistent with the observed space-time-magnitude distribution of earthquakes induced by gas production from the Groningen field in the Netherlands. These probabilistic forecasts also match the observed changes in seismicity following a significant and sustained decrease in gas production rates designed to reduce seismic hazard and risk. This forecast capability allows reliable assessment of alternative control options to better inform future induced seismic risk management decisions.

Childhood cancer incidence in relation to distance from the former nuclear testing site in Semipalatinsk, Kazakhstan.

PubMed

Zaridze, D G; Li, N; Men, T; Duffy, S W

1994-11-15

Rates of childhood cancer between 1981 and 1990 in the 4 administrative zones of Kazakhstan were studied to assess the relationship, if any, with distance from nuclear testing sites. Risk of various cancers among children aged 14 years or younger were estimated in relation to distance from (1) a site where testing in air was performed before 1963, (2) a site where underground testing took place thereafter, and (3) a reservoir, known as "Atom Lake," created by 4 nuclear explosions in 1965. Risk of acute leukaemia rose significantly with increasing proximity of residence to the testing areas, although the absolute value of the risk gradient was relatively small. The relative risk for those living less than 200 km from the air-testing site was 1.76 compared with those living 400 km or more away from the site. Similar relative risks were observed for the underground site and "Atom Lake." There was also some evidence of increased risk of brain tumours in association with proximity to the test sites. In 2 of the 4 zones studied, there was substantial regional variation in acute leukaemia rates which was not attributable to distance from the test site. The findings may be affected by potential confounders, notably urban/rural status and ethnic factors.

Do self- or parent-reported dietary, physical activity, and sedentary behaviors predict worsening obesity in children?

PubMed

Dorsey, Karen B; Mauldon, Maria; Magraw, Ruth; Yu, Sunkyung; Krumholz, Harlan M

2010-10-01

To determine whether information gathered during routine healthcare visits regarding obesity related risk factors and risk behaviors predicts increases in BMI z-score over time among overweight and obese children. Medical records from 168 overweight and 441 obese patients seen for repeated visits between September 2003 and April 2006 were examined for reported dietary, physical activity, and sedentary behaviors, family history of obesity and diabetes mellitus, documented Acanthosis nigricans, and BMI values. Random-effects regression analysis was done to determine whether demographic, familial, or behavioral data predicted changes in BMI z-score over time. The presence of A nigricans and a family history of obesity were associated with an increase in BMI z-score (beta=0.56, SE=0.09, P<.001 and beta=0.31, SE=0.13, P=.021). These risk factors explained 8% and 7% of the variation in BMI z-score respectively. Self- or parent-reported dietary and physical activity behaviors did not predict change in BMI z-score. Our findings suggest that the risk factors and self- or parent-reported risk behaviors routinely assessed by pediatric clinicians have limited ability to predict future growth trends, demonstrating the difficulty in determining which patients have the greatest risk of progression of obesity. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study

PubMed Central

2013-01-01

Introduction Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients. Methods This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes. Results Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands >140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV >20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes. Conclusions Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes. See related commentary by Krinsley, http://ccforum.com/content/17/2/131 See related commentary by Finfer and Billot, http://ccforum.com/content/17/2/134 PMID:23452622

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features

PubMed Central

Marques, Diego; Ferreira-Costa, Layse Raynara; Ferreira-Costa, Lorenna Larissa; Correa, Romualdo da Silva; Borges, Aline Maciel Pinheiro; Ito, Fernanda Ribeiro; Ramos, Carlos Cesar de Oliveira; Bortolin, Raul Hernandes; Luchessi, André Ducati; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Silbiger, Vivian Nogueira

2017-01-01

AIM To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. METHODS One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring. RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings. PMID:29085228

Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population.

PubMed

Gawron, Andrew J; Fought, Angela J; Lissowska, Jolanta; Ye, Weimin; Zhang, Xiao; Chow, Wong-Ho; Beane Freeman, Laura E; Hou, Lifang

2011-03-01

To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival. The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models. Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80 C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5 IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0). Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies.

Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

PubMed Central

Jing, Lijun; Su, Li; Ring, Brian Z.

2014-01-01

The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed. PMID:24901479

Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters.

PubMed

Kulanuwat, Sirikul; Phonrat, Benjaluck; Tungtrongchitr, Anchalee; Limwongse, Chanin; Chongviriyaphan, Nalinee; Tungtrongchitr, Rungsunn; Santiprabhob, Jeerunda

2014-01-01

Single nucleotide polymorphisms (SNPs) in PCSK1, namely, rs6234, rs6235, and rs271939 have been linked to obesity in European population; and rs3811951 has also been connected to type 2 diabetes and obesity parameters in Chinese population. In this family-based case-control study, we analyzed links between PCSK1 genetic variants and obesity in Thai children and their families. Eleven obese children with a percent weight for height > or = 140 who had family history of obesity and 69 family members were recruited. SNPs rs6234, rs6235, rs3811951, and rs271939 of PCSK1 were analyzed using PCR and gene sequencing methods. DNA of 200 normal weight subjects was used as control. Participants with variant genotypes in the rs6234-6235 pair are at significantly more risk of being obese [OR = 2.44 (1.35-4.43), p = 0.003], and also at increased risk of being severely obese (obese class III) [OR = 3.03 (1.20-7.66), p = 0.015]. Variant rs3811951 showed no association with being obese, but is significantly linked to an increased risk of being severely obese [OR = 3.59 (1.42-9.08) p = 0.005]. Moreover, high density lipoprotein (HDL)-C levels between normal and variant rs3811951 group differed considerably, with patients with variant genotype having a lower HDL-C level (p = 0.037). Thus, Thais carrying SNPs rs6234-5 are at increased risk of being obese, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Furthermore, patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.

Differences in Colonoscopy Quality Among Facilities: Development of a Post-Colonoscopy Risk-Standardized Rate of Unplanned Hospital Visits.

PubMed

Ranasinghe, Isuru; Parzynski, Craig S; Searfoss, Rana; Montague, Julia; Lin, Zhenqiu; Allen, John; Vender, Ronald; Bhat, Kanchana; Ross, Joseph S; Bernheim, Susannah; Krumholz, Harlan M; Drye, Elizabeth E

2016-01-01

Colonoscopy is a common procedure, yet little is known about variations in colonoscopy quality among outpatient facilities. We developed an outcome measure to profile outpatient facilities by estimating risk-standardized rates of unplanned hospital visits within 7 days of colonoscopy. We used a 20% sample of 2010 Medicare outpatient colonoscopy claims (331,880 colonoscopies performed at 8140 facilities) from patients ≥65 years or older, and developed a patient-level logistic regression model to estimate the risk of unplanned hospital visits (ie, emergency department visits, observation stays, and inpatient admissions) within 7 days of colonoscopy. We then used the patient-level risk model variables and hierarchical logistic regression to estimate facility rates of risk-standardized unplanned hospital visits using data from the Healthcare Cost and Utilization Project (325,811 colonoscopies at 992 facilities), from 4 states containing 100% of colonoscopies per facility. Outpatient colonoscopies were followed by 5412 unplanned hospital visits within 7 days (16.3/1000 colonoscopies). Hemorrhage, abdominal pain, and perforation were the most common causes of unplanned hospital visits. Fifteen variables were independently associated with unplanned hospital visits (c = 0.67). A history of fluid and electrolyte imbalance (odds ratio [OR] = 1.43; 95% confidence interval [CI]: 1.29-1.58), psychiatric disorders (OR = 1.34; 95% CI: 1.22-1.46), and, in the absence of prior arrhythmia, increasing age past 65 years (aged >85 years vs 65-69 years: OR = 1.87; 95% CI: 1.54-2.28) were most strongly associated. The facility risk-standardized unplanned hospital visits calculated using Healthcare Cost and Utilization Project data showed significant variation (median 12.3/1000; 5th-95th percentile, 10.5-14.6/1000). Median risk-standardized unplanned hospital visits were comparable between ambulatory surgery centers and hospital outpatient departments (each was 10.2/1000), and ranged from 16.1/1000 in the Northeast to 17.2/1000 in the Midwest. We calculated a risk-adjusted measure of outpatient colonoscopy quality, which shows important variation in quality among outpatient facilities. This measure can make transparent the extent to which patients require follow-up hospital care, help inform patient choices, and assist in quality-improvement efforts. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Does the Reliability of Reporting in Injury Surveillance Studies Depend on Injury Definition?

PubMed

Cross, Matthew; Williams, Sean; Kemp, Simon P T; Fuller, Colin; Taylor, Aileen; Brooks, John; Trewartha, Grant; Stokes, Keith

2018-03-01

Choosing an appropriate definition for injury in injury surveillance studies is essential to ensure a balance among reporting reliability, providing an accurate representation of injury risk, and describing the nature of the clinical demand. To provide guidance on the choice of injury definition for injury surveillance studies by comparing within- and between-team variability in injury incidence with >24-hour and >7-day time-loss injury definitions in a large multiteam injury surveillance study. Cohort study (diagnosis); Level of evidence, 2. Injury data were reported for 2248 professional rugby union players from 15 Premiership Rugby clubs over 12 seasons. Within-team percentage coefficient of variation and mean between-team standard deviation (expressed as a percentage coefficient of variation) in injury incidence rates (injuries per 1000 player match hours) were calculated. For both variables, a comparison was made between >24-hour and >7-day injury incidence rates in terms of the magnitude of the observed effects. The overall mean incidence across the population with a >24-hour time-loss injury definition was approximately double the reported incidence with the >7-day definition. There was a 10% higher between-team variation in match injury incidence rates with the >24-hour time-loss definition versus the >7-day definition. There was a likely higher degree of between-team variation in match injury incidence rates with a >24-hour time-loss definition than with a >7-day definition of injury. However, in professional sports settings, it is likely that the benefits of using a more inclusive definition of injury (improved understanding of clinical demand and the appropriate and accurate reporting of injury risk) outweigh the small increase in variation in reporting consistency.

Does the Reliability of Reporting in Injury Surveillance Studies Depend on Injury Definition?

PubMed Central

Cross, Matthew; Williams, Sean; Kemp, Simon P.T.; Fuller, Colin; Taylor, Aileen; Brooks, John; Trewartha, Grant; Stokes, Keith

2018-01-01

Background: Choosing an appropriate definition for injury in injury surveillance studies is essential to ensure a balance among reporting reliability, providing an accurate representation of injury risk, and describing the nature of the clinical demand. Purpose: To provide guidance on the choice of injury definition for injury surveillance studies by comparing within- and between-team variability in injury incidence with >24-hour and >7-day time-loss injury definitions in a large multiteam injury surveillance study. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Injury data were reported for 2248 professional rugby union players from 15 Premiership Rugby clubs over 12 seasons. Within-team percentage coefficient of variation and mean between-team standard deviation (expressed as a percentage coefficient of variation) in injury incidence rates (injuries per 1000 player match hours) were calculated. For both variables, a comparison was made between >24-hour and >7-day injury incidence rates in terms of the magnitude of the observed effects. Results: The overall mean incidence across the population with a >24-hour time-loss injury definition was approximately double the reported incidence with the >7-day definition. There was a 10% higher between-team variation in match injury incidence rates with the >24-hour time-loss definition versus the >7-day definition. Conclusion: There was a likely higher degree of between-team variation in match injury incidence rates with a >24-hour time-loss definition than with a >7-day definition of injury. However, in professional sports settings, it is likely that the benefits of using a more inclusive definition of injury (improved understanding of clinical demand and the appropriate and accurate reporting of injury risk) outweigh the small increase in variation in reporting consistency. PMID:29581994

Can better infrastructure and quality reduce hospital infant mortality rates in Mexico?

PubMed

Aguilera, Nelly; Marrufo, Grecia M

2007-02-01

Preliminary evidence from hospital discharges hints enormous disparities in infant hospital mortality rates. At the same time, public health agencies acknowledge severe deficiencies and variations in the quality of medical services across public hospitals. Despite these concerns, there is limited evidence of the contribution of hospital infrastructure and quality in explaining variations in outcomes among those who have access to medical services provided at public hospitals. This paper provides evidence to address this question. We use probabilistic econometric methods to estimate the impact of material and human resources and hospital quality on the probability that an infant dies controlling for socioeconomic, maternal and reproductive risk factors. As a measure of quality, we calculate for the first time for Mexico patient safety indicators developed by the AHRQ. We find that the probability to die is affected by hospital infrastructure and by quality. In this last regard, having been treated in a hospital with the worse quality incidence doubles the probability to die. This paper also presents evidence on the contribution of other risk factors on perinatal mortality rates. The conclusions of this paper suggest that lower infant mortality rates can be reached by implementing a set of coherent public policy actions including an increase and reorganization of hospital infrastructure, quality improvement, and increasing demand for health by poor families.

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.

Genetic variation in the vascular endothelial growth factor gene is associated with biliary atresia.

PubMed

Lee, Hung-Chang; Chang, Tzu-Yang; Yeung, Chun-Yan; Chan, Wai-Tao; Jiang, Chuen-Bin; Chen, Wei-Fang; Chan, Hui-Wen; Liu, Hsin-Fu; Lin, Marie; Lee, Yann-Jinn

2010-02-01

Biliary atresia (BA) is a chronic inflammatory disease of the bile ducts resulting in biliary cirrhosis. Vascular endothelial growth factor (VEGF) has been implicated in cell-mediated inflammatory reactions. We aimed to study the relationship between genetic variations of the VEGF gene and susceptibility to BA using both case-control and family-based methodologies. A total of 45 Taiwanese children with BA, 160 ethnically matched healthy controls, and 40 families (consisting of parents, affected children, and unaffected siblings) were studied. Three functional VEGF polymorphisms (-2578 A/C, -634 G/C, and +936 C/T) were assessed by using TaqMan assay. The +936 CC genotype [odds ratio (OR) 3.51, 95% confidence interval 1.54-8.01, P(c)=0.006] and C allele (OR 3.19, 95% confidence interval 1.48-6.90, P(c)=0.004) were significantly associated with increased risk of BA. The association of the +936 C allele with BA was also confirmed in a family-based association study (OR 5.7, chi2=9.8, P(c)=0.005). None of the haplotypes studied significantly influenced the risk to BA in either the case-control or family data sets. The VEGF +936 C/T polymorphism and particularly the C allele are associated with BA, possibly conferring increased susceptibility to the disease.

A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia.

PubMed

Houenou, Josselin; Boisgontier, Jennifer; Henrion, Annabelle; d'Albis, Marc-Antoine; Dumaine, Anne; Linke, Julia; Wessa, Michèle; Daban, Claire; Hamdani, Nora; Delavest, Marine; Llorca, Pierre-Michel; Lançon, Christophe; Schürhoff, Franck; Szöke, Andrei; Le Corvoisier, Philippe; Barau, Caroline; Poupon, Cyril; Etain, Bruno; Leboyer, Marion; Jamain, Stéphane

2017-10-25

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25 , rs6039769 , that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b / SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders. Copyright © 2017 the authors 0270-6474/17/3710390-09$15.00/0.

Frailty Models for Familial Risk with Application to Breast Cancer.

PubMed

Gorfine, Malka; Hsu, Li; Parmigiani, Giovanni

2013-12-01

In evaluating familial risk for disease we have two main statistical tasks: assessing the probability of carrying an inherited genetic mutation conferring higher risk; and predicting the absolute risk of developing diseases over time, for those individuals whose mutation status is known. Despite substantial progress, much remains unknown about the role of genetic and environmental risk factors, about the sources of variation in risk among families that carry high-risk mutations, and about the sources of familial aggregation beyond major Mendelian effects. These sources of heterogeneity contribute substantial variation in risk across families. In this paper we present simple and efficient methods for accounting for this variation in familial risk assessment. Our methods are based on frailty models. We implemented them in the context of generalizing Mendelian models of cancer risk, and compared our approaches to others that do not consider heterogeneity across families. Our extensive simulation study demonstrates that when predicting the risk of developing a disease over time conditional on carrier status, accounting for heterogeneity results in a substantial improvement in the area under the curve of the receiver operating characteristic. On the other hand, the improvement for carriership probability estimation is more limited. We illustrate the utility of the proposed approach through the analysis of BRCA1 and BRCA2 mutation carriers in the Washington Ashkenazi Kin-Cohort Study of Breast Cancer.

Geographic Variations of Colorectal and Breast Cancer Late-Stage Diagnosis and the Effects of Neighborhood-Level Factors.

PubMed

Lin, Yan; Wimberly, Michael C

2017-04-01

The purpose of this study was to examine the geographic variations of late-stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood-level factors-socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care-on the late-stage risks. This study used population-based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two-level logistic regression models were used to analyze the risk of late-stage CRC and breast cancer. For CRC, there was a small geographic variation across census tracts in late-stage diagnosis, and residing in isolated small rural areas was significantly associated with late-stage risk. However, this association became nonsignificant after adjusting for census-tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late-stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late-stage risk. For breast cancer, no geographic variation in the late-stage diagnosis was observed across census tracts, and none of the 3 neighborhood-level factors was significantly associated with late-stage risk. Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late-stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas. © 2016 National Rural Health Association.

Risk Assessment and Control through Countermeasure System Iplementation for Long-term Crew Exposure to Microgravity

NASA Technical Reports Server (NTRS)

Gernand, Jeremy M.

2004-01-01

Experience with the International Space Station (ISS) program demonstrates the degree to which engineering design and operational solutions must protect crewmembers from health risks due to long-term exposure to the microgravity environment. Risks to safety and health due to degradation in the microgravity environment include crew inability to complete emergency or nominal activities, increased risk of injury, and inability to complete safe return to the ground due to reduced strength or embrittled bones. These risks without controls slowly increase in probability for the length of the mission and become more significant for increasing mission durations. Countermeasures to microgravity include hardware systems that place a crewmember s body under elevated stress to produce an effect similar to daily exposure to gravity. The ISS countermeasure system is predominately composed of customized exercise machines. Historical treatment of microgravity countermeasure systems as medical research experiments unintentionally reduced the foreseen importance and therefore the capability of the systems to function in a long-term operational role. Long-term hazardous effects and steadily increasing operational risks due to non-functional countermeasure equipment require a more rigorous design approach and incorporation of redundancy into seemingly non- mission-critical hardware systems. Variations in the rate of health degradation and responsiveness to countermeasures among the crew population drastically increase the challenge for design requirements development and verification of the appropriate risk control strategy. The long-term nature of the hazards and severe limits on logistical re-supply mass, volume and frequency complicates assessment of hardware availability and verification of an adequate maintenance and sparing plan. Design achievement of medically defined performance requirements by microgravity countermeasure systems and incorporation of adequate failure tolerance significantly reduces these risks. Future implementation of on-site monitoring hardware for critical health parameters such as bone mineral density would allow greater responsiveness, efficiency, and optimized design of the countermeasures system.

Inadequate vitamin D status: does it contribute to the disorders comprising syndrome 'X'?

PubMed

Boucher, B J

1998-04-01

Environmental factors are important in the aetiology of glucose intolerance, type II diabetes and IHD. The lack of vitamin D, which is necessary for adequate insulin secretion, relates demographically to increased risk of myocardial infarction. These disorders are connected, degenerative vascular disease increasing with glucose intolerance and diabetes and, with its risk factors, comprising syndrome 'X'. Evidence is presented suggesting that vitamin D deficiency may be an avoidable risk factor for syndrome 'X', adding another preventative measure to current recommendations which are aimed at reducing the worldwide epidemic of these disorders. Experimentally, vitamin D deficiency progressively reduces insulin secretion; glucose intolerance follows and becomes irreversible. Relationships between vitamin D status, glucose tolerance and 30 min insulin secretion during oral glucose tolerance tests are reported in British Asians; insulin secretion, but not glycaemia, improving with short-term supplementation. Studies showing reduction in blood pressure and in risk of heart attack and diabetes with exercise (usually outdoor), rarely consider the role of vitamin D status. Glycaemia and insulin secretion in elderly European men, however, relate to vitamin D status, independent of season or physical activity. Prolonged supplementation can improve glycaemia. Hypertension improves with vitamin D treatment with or without initial deficiency. Vitamin D status and climate are reviewed as risk factors for myocardial infarction; the risk reducing with altitude despite increasing cold. Glycaemia and fibrinogenaemia improve with insulin secretion increases in summer. Variation in vitamin D requirements could arise from genetic differences in vitamin D processing since bone density can vary with vitamin D-receptor genotype. Vitamin D receptors are present in islet beta cells and we report insulin secretion in healthy Asians differing profoundly with the Apa I genotype, being independent of vitamin D status. Those at risk of vitamin D deficiency include the elderly, those living indoors or having a covered-up style of dress, especially dark-skinned immigrants, and pregnant women, and these are groups recognized as being at increased risk of diabetes.

[Development of lipids and carbohydrates metabolism disorders caused by drinkable water with high content of chlorine organic compounds].

PubMed

Luzhetsky, K P; Ustinova, O Yu; Shur, P Z; Kiryanov, D A; Dolgikh, O V; Chigvintsev, v M; Perevalov, A Ya

2015-01-01

Evaluation of effects caused by environmental peroral exposure to chlorine organic compounds revealed that individuals with AG variation of HTR2A gene are a community with increased sensitivity to chloroform and a risk group for lipid and carbohydrates metabolism disorders. Individual risk of endocrine disorders (ICD: E67.8 excessive nutrition and E66.0 obesity) in these individuals is higher than in general population exposed to chloroform at residence (HQ1.72). Serum serotonin level, that is functionally connected with HTR2A gene, is 1.3 times lower vs. the reference group value.

Past and future weather-induced risk in crop production

NASA Astrophysics Data System (ADS)

Elliott, J. W.; Glotter, M.; Russo, T. A.; Sahoo, S.; Foster, I.; Benton, T.; Mueller, C.

2016-12-01

Drought-induced agricultural loss is one of the most costly impacts of extreme weather and may harm more people than any other consequence of climate change. Improvements in farming practices have dramatically increased crop productivity, but yields today are still tightly linked to climate variation. We report here on a number of recent studies evaluating extreme event risk and impacts under historical and near future conditions, including studies conducted as part of the Agricultural Modeling Intercomparison and Improvement Project (AgMIP), the Inter-Sectoral Impacts Model Intercomparison Project (ISI-MIP) and the UK-US Taskforce on Extreme Weather and Global Food System Resilience.

Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

PubMed Central

Kiryluk, Krzysztof; Li, Yifu; Sanna-Cherchi, Simone; Rohanizadegan, Mersedeh; Suzuki, Hitoshi; Eitner, Frank; Snyder, Holly J.; Choi, Murim; Hou, Ping; Scolari, Francesco; Izzi, Claudia; Gigante, Maddalena; Gesualdo, Loreto; Savoldi, Silvana; Amoroso, Antonio; Cusi, Daniele; Zamboli, Pasquale; Julian, Bruce A.; Novak, Jan; Wyatt, Robert J.; Mucha, Krzysztof; Perola, Markus; Kristiansson, Kati; Viktorin, Alexander; Magnusson, Patrik K.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Boland, Anne; Metzger, Marie; Thibaudin, Lise; Wanner, Christoph; Jager, Kitty J.; Goto, Shin; Maixnerova, Dita; Karnib, Hussein H.; Nagy, Judit; Panzer, Ulf; Xie, Jingyuan; Chen, Nan; Tesar, Vladimir; Narita, Ichiei; Berthoux, Francois; Floege, Jürgen; Stengel, Benedicte; Zhang, Hong; Lifton, Richard P.; Gharavi, Ali G.

2012-01-01

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10−32–3×10−10), with heterogeneity detected only at the PSMB9/TAP1 locus (I2 = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10−4). A seven–SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10−128). This model paralleled the known East–West gradient in disease risk. Moreover, the prediction of a South–North axis was confirmed by registry data showing that the prevalence of IgAN–attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN. PMID:22737082

Lifestyle changes lower FABP4 plasma concentration in patients with cardiovascular risk.

PubMed

Lázaro, Iolanda; Ferré, Raimon; Plana, Núria; Aragonès, Gemma; Girona, Josefa; Merino, Jordi; Heras, Mercedes; Cabré, Anna; Masana, Lluís

2012-02-01

To analyze the impact of lifestyle changes on adipocyte fatty acid-binding protein (FABP4) plasma levels in patients with cardiovascular risk. A 1-year prospective study enrolled 140 patients with cardiovascular risk but without previous cardiovascular disease to evaluate the impact of therapeutic lifestyle changes on cardiovascular risk, focusing on tobacco, nutrition education, and physical activity. The FABP4 variation was inversely associated to physical activity changes (MET·h/wk). FABP4 significantly decreased in patients with increased physical activity, whereas it increased with physical activity reduction. These FABP4 changes were also associated with modifications in body mass index and insulin resistance parameters; however, the correlations between physical activity and FABP4 remained after adjusting for these confounding variables. Changes in physical activity were the main predictors of FABP4 modifications. FABP4 reductions were directly associated with low-density lipoprotein-cholesterol and apolipoprotein B reductions. Neither tobacco cessation nor diet composition modified FABP4 concentrations. Increasing aerobic physical activity can decrease FABP4 plasma levels, independently of weight reduction. If a causal role of FABP4 in metabolic and vascular alterations could be established, our results would add new positive effects on metabolic and cardiovascular risk of both physical activity and avoiding obesity. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Assessing the probability of infection by Salmonella due to sewage sludge use in agriculture under several exposure scenarios for crops and soil ingestion.

PubMed

Krzyzanowski, Flávio; de Souza Lauretto, Marcelo; Nardocci, Adelaide Cássia; Sato, Maria Inês Zanoli; Razzolini, Maria Tereza Pepe

2016-10-15

A deeper understanding about the risks involved in sewage sludge practice in agriculture is required. The aims of the present study were to determine the annual risk of infection of consuming lettuce, carrots and tomatoes cultivated in soil amended with sewage sludge. The risk to agricultural workers of accidental ingestion of sludge or amended soil was also investigated. A Quantitative Microbial Risk Assessment was conducted based on Salmonella concentrations from five WWTPs were used to estimate the probability of annual infection associated with crops and soil ingestion. The risk of infection was estimated for nine exposure scenarios considering concentration of the pathogen, sewage sludge dilution in soil, variation of Salmonella concentration in soil, soil attachment to crops, seasonal average temperatures, hours of post-harvesting exposure, Salmonella regrowth in lettuce and tomatoes, Salmonella inhibition factor in carrots, crop ingestion and frequency of exposure, sludge/soil ingestion by agricultural workers and frequency of exposure. Annual risks values varied across the scenarios evaluated. Highest values of annual risk were found for scenarios in which the variation in the concentration of Salmonella spp. in both soil and crops (scenario 1) and without variation in the concentration of Salmonella spp. in soil and variation in crops (scenario 3) ranging from 10(-3) to 10(-2) for all groups considered. For agricultural workers, the highest annual risks of infection were found when workers applied sewage sludge to agricultural soils (2.26×10(-2)). Sensitivity analysis suggests that the main drivers for the estimated risks are Salmonella concentration and ingestion rate. These risk values resulted from conservative scenarios since some assumptions were derived from local or general studies. Although these scenarios can be considered conservative, the sensitivity analysis yielded the drivers of the risks, which can be useful for managing risks from the fresh products chain with stakeholders' involvement. Copyright © 2016. Published by Elsevier B.V.

Variations in mortality rates among Canadian neonatal intensive care units

PubMed Central

Sankaran, Koravangattu; Chien, Li-Yin; Walker, Robin; Seshia, Mary; Ohlsson, Arne; Lee, Shoo K.

2002-01-01

Background Most previous reports of variations in mortality rates for infants admitted to neonatal intensive care units (NICUs) have involved small groups of subpopulations, such as infants with very low birth weight. Our aim was to examine the incidence and causes of death and the risk-adjusted variation in mortality rates for a large group of infants of all birth weights admitted to Canadian NICUs. Methods We examined the deaths that occurred among all 19 265 infants admitted to 17 tertiary-level Canadian NICUs from January 1996 to October 1997. We used multivariate analysis to examine the risk factors associated with death and the variations in mortality rates, adjusting for risks in the baseline population, severity of illness on admission and whether the infant was outborn (born at a different hospital from the one where the NICU was located). Results The overall mortality rate was 4% (795 infants died). Forty percent of the deaths (n = 318) occurred within 2 days of NICU admission, 50% (n = 397) within 3 days and 75% (n = 596) within 12 days. The major conditions associated with death were gestational age less than 24 weeks (59 deaths [7%]), gestational age 24–28 weeks (325 deaths [41%]), outborn status (340 deaths [42%]), congenital anomalies (270 deaths [34%]), surgery (141 deaths [18%]), infection (108 deaths [14%]), hypoxic–ischemic encephalopathy (128 deaths [16%]) and small for gestational age (i.e., less than the third percentile) (77 deaths [10%]). There was significant variation in the risk-adjusted mortality rates (range 1.6% to 5.5%) among the 17 NICUs. Interpretation Most NICU deaths occurred within the first few days after admission. Preterm birth, outborn status and congenital anomalies were the conditions most frequently associated with death in the NICU. The significant variation in risk-adjusted mortality rates emphasizes the importance of risk adjustment for valid comparison of NICU outcomes. PMID:11826939

Molecular epidemiology, cancer-related symptoms, and cytokines pathway

PubMed Central

Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay

2012-01-01

The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalised and more effective therapies for persistent symptoms. PMID:18672213

Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.

PubMed

Simopoulos, Artemis P

2010-07-01

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

Accountability for end-stage organ care: implications of geographic variation in access to kidney transplantation.

PubMed

Axelrod, David A; Lentine, Krista L; Xiao, Huiling; Bubolz, Thomas; Goodman, David; Freeman, Richard; Tuttle-Newhall, Janet E; Schnitzler, Mark A

2014-05-01

The provision of effective surgical care for end-stage renal disease (ESRD) requires efficient evaluation and transplantation. Prior assessments of transplant access have focused primarily on waitlisted patients rather than the overall populations served by "accountable" providers of transplant services. Novel transplant referral regions (TRRs) were defined using United Network for Organ Sharing registry data for 301,092 kidney transplant listings to assign zip codes to "accountable" transplant programs. Subsequently, risk-adjusted observed to expected (O:E) rates of listing and transplant procedures were calculated for each TRR. Finally, the impact of variation in TRR listing and transplant rates on mortality was assessed for ESRD patients <60 years old diagnosed between 2000 and 2008. In total, 113 TRRs were defined, 51% of which included >1 transplant center. The likelihood of being evaluated and listed for transplant varied significantly between TRRs (risk-adjusted O:E, 0.58-1.95). Variation was greater for the overall transplant rate (0.62-2.19), living donor transplantation (0.36-3.08), and donation after cardiac death transplant (0-15.4) than for standard criteria donors (0.64-2.86). Mortality was decreased for ESRD patients living in TRRs in the highest tertile of listings (hazard ratio, 0.89; P < .0001) and transplantation (0.90; P < .0001). Residence in a TRR with care delivery systems that increase access to transplant services is associated with significant, risk-adjusted decreases in ESRD-related mortality. Transplant centers should continue to focus on improving access to care within the communities they serve. Copyright © 2014 Mosby, Inc. All rights reserved.

Resolving uncertainties in the urban air quality, climate, and vegetation nexus through citizen science, satellite imagery, and atmospheric modeling

NASA Astrophysics Data System (ADS)

Jenerette, D.; Wang, J.; Chandler, M.; Ripplinger, J.; Koutzoukis, S.; Ge, C.; Castro Garcia, L.; Kucera, D.; Liu, X.

2017-12-01

Large uncertainties remain in identifying the distribution of urban air quality and temperature risks across neighborhood to regional scales. Nevertheless, many cities are actively expanding vegetation with an expectation to moderate both climate and air quality risks. We address these uncertainties through an integrated analysis of satellite data, atmospheric modeling, and in-situ environmental sensor networks maintained by citizen scientists. During the summer of 2017 we deployed neighborhood-scale networks of air temperature and ozone sensors through three campaigns across urbanized southern California. During each five-week campaign we deployed six sensor nodes that included an EPA federal equivalent method ozone sensor and a suite of meteorological sensors. Each node was further embedded in a network of 100 air temperature sensors that combined a randomized design developed by the research team and a design co-created by citizen scientists. Between 20 and 60 citizen scientists were recruited for each campaign, with local partners supporting outreach and training to ensure consistent deployment and data gathering. We observed substantial variation in both temperature and ozone concentrations at scales less than 4km, whole city, and the broader southern California region. At the whole city scale the average spatial variation with our ozone sensor network just for city of Long Beach was 26% of the mean, while corresponding variation in air temperature was only 7% of the mean. These findings contrast with atmospheric model estimates of variation at the regional scale of 11% and 1%. Our results show the magnitude of fine-scale variation underestimated by current models and may also suggest scaling functions that can connect neighborhood and regional variation in both ozone and temperature risks in southern California. By engaging citizen science with high quality sensors, satellite data, and real-time forecasting, our results help identify magnitudes of climate and air quality risk variation across scales and can guide individual decisions and urban policies surrounding vegetation to moderate these risks.

Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients.

PubMed

Yue, Yong; Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

2017-02-01

To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Median age was 69 y (range, 46-86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response-driven adaptive RT.

Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in She ethnic minority of China.

PubMed

Lin, Yinghua; Lai, Xiaolan; Chen, Bin; Xu, Yuan; Huang, Baoying; Chen, Zichun; Zhu, Shaoheng; Yao, Jin; Jiang, Qiqin; Huang, Huibin; Wen, Junping; Chen, Gang

2011-12-01

Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China. The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model. As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (β = -1.17, P = 0.002 and β = -0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (β = -0.56, P=0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4. We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Widespread covariation of early environmental exposures and trait-associated polygenic variation.

PubMed

Krapohl, E; Hannigan, L J; Pingault, J-B; Patel, H; Kadeva, N; Curtis, C; Breen, G; Newhouse, S J; Eley, T C; O'Reilly, P F; Plomin, R

2017-10-31

Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample ( n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age ( R 2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding ( R 2 = 0.021; P = 7e-30), maternal smoking during pregnancy ( R 2 = 0.008; P = 5e-13), parental smacking ( R 2 = 0.01; P = 4e-15), household income ( R 2 = 0.032; P = 1e-22), watching television ( R 2 = 0.034; P = 5e-47), and maternal education ( R 2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

The Effects of Urban Form on Ambient Air Pollution and Public Health Risk: A Case Study in Raleigh, North Carolina

PubMed Central

Rodriguez, Daniel A.; Huegy, Joseph; Gibson, Jacqueline MacDonald

2014-01-01

Since motor vehicles are a major air pollution source, urban designs that decrease private automobile use could improve air quality and decrease air pollution health risks. Yet, the relationships among urban form, air quality, and health are complex and not fully understood. To explore these relationships, we model the effects of three alternative development scenarios on annual average fine particulate matter (PM2.5) concentrations in ambient air and associated health risks from PM2.5 exposure in North Carolina’s Raleigh-Durham-Chapel Hill area. We integrate transportation demand, land-use regression, and health risk assessment models to predict air quality and health impacts for three development scenarios: current conditions, compact development, and sprawling development. Compact development slightly decreases (−0.2%) point estimates of regional annual average PM2.5 concentrations, while sprawling development slightly increases (+1%) concentrations. However, point estimates of health impacts are in opposite directions: compact development increases (+39%) and sprawling development decreases (−33%) PM2.5-attributable mortality. Further, compactness increases local variation in PM2.5 concentrations and increases the severity of local air pollution hotspots. Hence, this research suggests that while compact development may improve air quality from a regional perspective, it may also increase the concentration of PM2.5 in local hotspots and increase population exposure to PM2.5. Health effects may be magnified if compact neighborhoods and PM2.5 hotspots are spatially co-located. We conclude that compactness alone is an insufficient means of reducing the public health impacts of transportation emissions in automobile-dependent regions. Rather, additional measures are needed to decrease automobile dependence and the health risks of transportation emissions. PMID:25490890