Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease

NASA Astrophysics Data System (ADS)

2014-01-01

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

PubMed

Cruchaga, Carlos; Karch, Celeste M; Jin, Sheng Chih; Benitez, Bruno A; Cai, Yefei; Guerreiro, Rita; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, Raphael J; Hernandez, Dena G; Lupton, Michelle K; Powell, John; Forabosco, Paola; Ridge, Perry G; Corcoran, Christopher D; Tschanz, JoAnn T; Norton, Maria C; Munger, Ronald G; Schmutz, Cameron; Leary, Maegan; Demirci, F Yesim; Bamne, Mikhil N; Wang, Xingbin; Lopez, Oscar L; Ganguli, Mary; Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Brkanac, Zoran; Scott, Erick; Topol, Eric; Morgan, Kevin; Rogaeva, Ekaterina; Singleton, Andy; Hardy, John; Kamboh, M Ilyas; George-Hyslop, Peter St; Cairns, Nigel; Morris, John C; Kauwe, John S K; Goate, Alison M

2014-01-23

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Two-tier Haddon matrix approach to fault analysis of accidents and cybernetic search for relationship to effect operational control: a case study at a large construction site.

PubMed

Mazumdar, Atmadeep; Sen, Krishna Nirmalya; Lahiri, Balendra Nath

2007-01-01

The Haddon matrix is a potential tool for recognizing hazards in any operating engineering system. This paper presents a case study of operational hazards at a large construction site. The fish bone structure helps to visualize and relate the chain of events, which led to the failure of the system. The two-tier Haddon matrix approach helps to analyze the problem and subsequently prescribes preventive steps. The cybernetic approach has been undertaken to establish the relationship among event variables and to identify the ones with most potential. Those event variables in this case study, based on the cybernetic concepts like control responsiveness and controllability salience, are (a) uncontrolled swing of sheet contributing to energy, (b) slippage of sheet from anchor, (c) restricted longitudinal and transverse swing or rotation about the suspension, (d) guilt or uncertainty of the crane driver, (e) safe working practices and environment.

Optimization under variability and uncertainty: a case study for NOx emissions control for a gasification system.

PubMed

Chen, Jianjun; Frey, H Christopher

2004-12-15

Methods for optimization of process technologies considering the distinction between variability and uncertainty are developed and applied to case studies of NOx control for Integrated Gasification Combined Cycle systems. Existing methods of stochastic optimization (SO) and stochastic programming (SP) are demonstrated. A comparison of SO and SP results provides the value of collecting additional information to reduce uncertainty. For example, an expected annual benefit of 240,000 dollars is estimated if uncertainty can be reduced before a final design is chosen. SO and SP are typically applied to uncertainty. However, when applied to variability, the benefit of dynamic process control is obtained. For example, an annual savings of 1 million dollars could be achieved if the system is adjusted to changes in process conditions. When variability and uncertainty are treated distinctively, a coupled stochastic optimization and programming method and a two-dimensional stochastic programming method are demonstrated via a case study. For the case study, the mean annual benefit of dynamic process control is estimated to be 700,000 dollars, with a 95% confidence range of 500,000 dollars to 940,000 dollars. These methods are expected to be of greatest utility for problems involving a large commitment of resources, for which small differences in designs can produce large cost savings.

Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread to the larger community.

PubMed

Iser, B P M; Lima, H C A V; de Moraes, C; de Almeida, R P A; Watanabe, L T; Alves, S L A; Lemos, A P S; Gorla, M C O; Gonçalves, M G; Dos Santos, D A; Sobel, J

2012-05-01

SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P<0·01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1·11-43·9, P<0·02). Mass vaccination (>10 000 plant employees) stopped propagation in the plant, but not in the larger community.

Maximum likelihood estimation for Cox's regression model under nested case-control sampling.

PubMed

Scheike, Thomas H; Juul, Anders

2004-04-01

Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazards model. The MLE is computed by the EM-algorithm, which is easy to implement in the proportional hazards setting. Standard errors are estimated by a numerical profile likelihood approach based on EM aided differentiation. The work was motivated by a nested case-control study that hypothesized that insulin-like growth factor I was associated with ischemic heart disease. The study was based on a population of 3784 Danes and 231 cases of ischemic heart disease where controls were matched on age and gender. We illustrate the use of the MLE for these data and show how the maximum likelihood framework can be used to obtain information additional to the relative risk estimates of covariates.

Calcium and vitamin D and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland and Labrador and Ontario.

PubMed

Sun, Zhuoyu; Wang, Peizhong Peter; Roebothan, Barbara; Cotterchio, Michelle; Green, Roger; Buehler, Sharon; Zhao, Jinhui; Squires, Josh; Zhao, Jing; Zhu, Yun; Dicks, Elizabeth; Campbell, Peter T; Mclaughlin, John R; Parfrey, Patrick S

2011-01-01

Previous epidemiological studies have been suggestive but inconclusive in demonstrating inverse associations of calcium, vitamin D, dairy product intakes with risk of colorectal cancer (CRC). We conducted a large population-based comparison of such associations in Newfoundland and Labrador (NL) and Ontario (ON). A case control study design was used. Colorectal cancer cases were new CRC patients aged 20-74 years. Controls were a sex and age-group matched random sample of the population in each province. 1760 cases and 2481 controls from NL and ON were analyzed. Information on dietary intake and lifestyle was collected using self-administered food frequency and personal history questionnaires. Controls reported higher mean daily intakes of total calcium and total vitamin D than cases in both provinces. In ON, significant reduced CRC risk was associated with intakes of total calcium (OR of highest vs. lowest quintiles was 0.57, 95% CI 0.42-0.77, p(trend) = 0.03), total vitamin D (OR = 0.73, 95% CI 0.54-1.00), dietary calcium (OR = 0.76, 95% CI 0.60-0.97), dietary vitamin D (OR = 0.77, 95% CI 0.61-0.99), total dairy products and milk (OR = 0.78, 95% CI 0.60-1.00), calcium-containing supplements use (OR = 0.76). In NL, the inverse associations of calcium, vitamin D with CRC risk were most pronounced among calcium- or vitamin D-containing supplement users (OR = 0.67, 0.68, respectively). Results of this study add to the evidence that total calcium, dietary calcium, total vitamin D, dietary vitamin D, calcium- or vitamin D-containing supplement use may reduce the risk of CRC. The inverse associations of CRC risk with intakes of total dairy products and milk may be largely due to calcium and vitamin D.

A general regression framework for a secondary outcome in case-control studies.

PubMed

Tchetgen Tchetgen, Eric J

2014-01-01

Modern case-control studies typically involve the collection of data on a large number of outcomes, often at considerable logistical and monetary expense. These data are of potentially great value to subsequent researchers, who, although not necessarily concerned with the disease that defined the case series in the original study, may want to use the available information for a regression analysis involving a secondary outcome. Because cases and controls are selected with unequal probability, regression analysis involving a secondary outcome generally must acknowledge the sampling design. In this paper, the author presents a new framework for the analysis of secondary outcomes in case-control studies. The approach is based on a careful re-parameterization of the conditional model for the secondary outcome given the case-control outcome and regression covariates, in terms of (a) the population regression of interest of the secondary outcome given covariates and (b) the population regression of the case-control outcome on covariates. The error distribution for the secondary outcome given covariates and case-control status is otherwise unrestricted. For a continuous outcome, the approach sometimes reduces to extending model (a) by including a residual of (b) as a covariate. However, the framework is general in the sense that models (a) and (b) can take any functional form, and the methodology allows for an identity, log or logit link function for model (a).

Personality as a risk factor in large bowel cancer: data from the Melbourne Colorectal Cancer Study.

PubMed

Kune, G A; Kune, S; Watson, L F; Bahnson, C B

1991-02-01

In a case control study which formed one arm of a large, population-based investigation of colorectal cancer incidence, aetiology and survival. 'The Melbourne Colorectal Cancer Study', among others, 22 psychosocially orientated questions were asked by personal interview of 637 histologically confirmed new cases of colorectal cancer and 714 age/sex frequency matched community controls, from Melbourne (population 2.81 million). Self-reported childhood or adult life 'unhappiness' was statistically significantly more common among the cancer cases, while 'unhappiness with retirement' was similarly distributed among cases and controls. Questions which were formulated to test a particular personality profile as a cancer risk, and which included the elements of denial and repression of anger and of other negative emotions, a commitment to prevailing social norms resulting in the external appearance of a 'nice' or 'good' person, a suppression of reactions which may offend others and the avoidance of conflict, showed a statistically significant discrimination between cases and controls. The risk of colorectal cancer with respect to this model was independent of the previously found risk factors of diet, beer intake, and family history of colorectal cancer, and was also independent of other potential confounding factors of socioeconomic level, marital status, religion and country of birth. Although the results must be interpreted with caution, the data are consistent with the hypothesis that this personality type may play a role in the clinical expression of colorectal cancer and merits further study.

The National Birth Defects Prevention Study: a review of the methods

PubMed Central

Reefhuis, Jennita; Gilboa, Suzanne M.; Anderka, Marlene; Browne, Marilyn L.; Feldkamp, Marcia L.; Hobbs, Charlotte A.; Jenkins, Mary M.; Langlois, Peter H.; Newsome, Kimberly B.; Olshan, Andrew F.; Romitti, Paul A.; Shapira, Stuart K.; Shaw, Gary M.; Tinker, Sarah C.; Honein, Margaret A.

2015-01-01

Background The National Birth Defects Prevention Study (NBDPS) is a large population-based multi-center case-control study of major birth defects in the United States. Methods Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases via either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father and infant (if living). Results There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%) respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. Conclusion The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. PMID:26033852

The National Birth Defects Prevention Study: A review of the methods.

PubMed

Reefhuis, Jennita; Gilboa, Suzanne M; Anderka, Marlene; Browne, Marilyn L; Feldkamp, Marcia L; Hobbs, Charlotte A; Jenkins, Mary M; Langlois, Peter H; Newsome, Kimberly B; Olshan, Andrew F; Romitti, Paul A; Shapira, Stuart K; Shaw, Gary M; Tinker, Sarah C; Honein, Margaret A

2015-08-01

The National Birth Defects Prevention Study (NBDPS) is a large population-based multicenter case-control study of major birth defects in the United States. Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn, or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases by means of either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father, and infant (if living). There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%), respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. © 2015 Wiley Periodicals, Inc.

Morphological Features in Children with Autism Spectrum Disorders: A Matched Case-Control Study

ERIC Educational Resources Information Center

Ozgen, Heval; Hellemann, Gerhard S.; Stellato, Rebecca K.; Lahuis, Bertine; van Daalen, Emma; Staal, Wouter G.; Rozendal, Marije; Hennekam, Raoul C.; Beemer, Frits A.; van Engeland, Herman

2011-01-01

This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs.…

Comparative study of control selection in a national population-based case-control study: Estimating risk of smoking on cancer deaths in Chinese men.

PubMed

Jiang, Jingmei; Liu, Boqi; Nasca, Philip C; Han, Wei; Zou, Xiaonong; Zeng, Xianjia; Tian, Xiaobing; Wu, Yanping; Zhao, Ping; Li, Junyao

2009-10-28

To assess the validation of a novel control selection design by comparing the consistency between the new design and a routine design in a large case-control study that was incorporated into a nationwide mortality survey in China. A nationwide mortality study was conducted during 1989-1991. Surviving spouses or other relatives of all adults who died during 1986-1988 provided detailed information about their own as well as the deceased person's smoking history. In this study, 130,079 males who died of various smoking-related cancers at age 35 or over were taken as cases, while 103,248 male surviving spouses (same age range with cases) of women who died during the same period and 49,331 males who died from causes other than those related to smoking were used as control group 1 and control group 2, respectively. Consistency in the results when comparing cases with each of the control groups was assessed. Consistency in the results was observed in the analyses using different control groups although cancer deaths varied with region and age. Equivalence could be ascertained using a 15% criterion in most cancer deaths which had high death rates in urban areas, but they were uncertain for most cancers in rural areas irrespective of whether the hypothesis testing showed significant differences or not. Sex-matched living spouse control design as an alternative control selection for a case-control study is valid and feasible, and the basic principles of the equivalence study are also supported by epidemiological survey data.

Genetic Basis of Autoantibody Positive and Negative Rheumatoid Arthritis Risk in a Multi-ethnic Cohort Derived from Electronic Health Records

PubMed Central

Kurreeman, Fina; Liao, Katherine; Chibnik, Lori; Hickey, Brendan; Stahl, Eli; Gainer, Vivian; Li, Gang; Bry, Lynn; Mahan, Scott; Ardlie, Kristin; Thomson, Brian; Szolovits, Peter; Churchill, Susanne; Murphy, Shawn N.; Cai, Tianxi; Raychaudhuri, Soumya; Kohane, Isaac; Karlson, Elizabeth; Plenge, Robert M.

2011-01-01

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies. PMID:21211616

IT Governance in SMEs: Trust or Control?

NASA Astrophysics Data System (ADS)

Devos, Jan; van Landeghem, Hendrik; Deschoolmeester, Dirk

It is believed by many scholars that a small and medium-sized enterprise (SME) cannot be seen through the lens of a large firm. Theories which explain IT governance in large organizations and methodologies used by practitioners can therefore not be extrapolated to SMEs, which have a completely different economic, cultural and managerial environment. SMEs suffer from resource poverty, have less IS experience and need more external support. SMEs largely contribute to the failure of many IS projects. We define an outsourced information system failure (OISF) as a failure of IT governance in an SME environment and propose a structure for stating propositions derived from both agency theory and theory of trust. The theoretical question addressed in this paper is: how and why do OISFs occur in SMEs? We have chosen a qualitative and positivistic IS case study research strategy based on multiple cases. Eight cases of IS projects were selected. We found that trust is more important than control issues like output-based contracts and structured controls for eliminating opportunistic behaviour in SMEs. We conclude that the world of SMEs is significantly different from that of large companies. This necessitates extra care to be taken on the part of researchers and practitioners when designing artefacts for SMEs.

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk.

PubMed

Vrijheid, Martine; Deltour, Isabelle; Krewski, Daniel; Sanchez, Marie; Cardis, Elisabeth

2006-07-01

This paper examines the effects of systematic and random errors in recall and of selection bias in case-control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte-Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case-control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure-response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case-control studies of mobile phone use and cancer risk, including the INTERPHONE study.

Control Variate Estimators of Survivor Growth from Point Samples

Treesearch

Francis A. Roesch; Paul C. van Deusen

1993-01-01

Two estimators of the control variate type for survivor growth from remeasured point samples are proposed and compared with more familiar estimators. The large reductionsin variance, observed in many cases forestimators constructed with control variates, arealso realized in thisapplication. A simulation study yielded consistent reductions in variance which were often...

A case-control study of Nocardia mastitis in Nova Scotia dairy herds

PubMed Central

Ferns, Lyn; Dohoo, Ian; Donald, Alan

1991-01-01

A case-control study was conducted to identify herd production, housing, and hygienic and therapeutic factors associated with a diagnosis of Nocardia mastitis in dairy herds in Nova Scotia. The data were collected by on-farm interviews with owners of 54 case and 54 control herds. Logistic regression was used to study risk factors. The use of dry cow products containing neomycin, including two specific dry cow products, was strongly associated with a diagnosis of Nocardia mastitis in a herd. Other factors which increased the risk of Nocardia mastitis were higher levels of production, larger herd size, and a large percentage of cows treated with dry cow products. These results are compared to results from a similar study carried out in Ontario. PMID:17423896

Rare coding variants in Phospholipase D3 (PLD3) confer risk for Alzheimer's disease

PubMed Central

Cruchaga, Carlos; Benitez, Bruno A.; Cai, Yefei; Guerreiro, Rita; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T.; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, Raphael J.; Hernandez, Dena G.; Lupton, Michelle K.; Powell, John; Forabosco, Paola; Ridge, Perry G.; Corcoran, Christopher D.; Tschanz, JoAnn T.; Norton, Maria C.; Munger, Ronald G.; Schmutz, Cameron; Leary, Maegan; Demirci, F. Yesim; Bamne, Mikhil N.; Wang, Xingbin; Lopez, Oscar L.; Ganguli, Mary; Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Brkanac, Zoran; Scott, Erick; Topol, Eric; Morgan, Kevin; Rogaeva, Ekaterina; Singleton, Andy; Hardy, John; Kamboh, M. Ilyas; George-Hyslop, Peter St; Cairns, Nigel; Morris, John C.; Kauwe, John S.K.; Goate, Alison M.

2014-01-01

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1,2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low frequency coding variants with large effects on LOAD risk, we performed whole exome-sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large case-control datasets. A rare variant in PLD3 (phospholipase-D family, member 3, rs145999145; V232M) segregated with disease status in two independent families and doubled risk for AD in seven independent case-control series (V232M meta-analysis; OR= 2.10, CI=1.47-2.99; p= 2.93×10-5, 11,354 cases and controls of European-descent). Gene-based burden analyses in 4,387 cases and controls of European-descent and 302 African American cases and controls, with complete sequence data for PLD3, indicate that several variants in this gene increase risk for AD in both populations (EA: OR= 2.75, CI=2.05-3.68; p=1.44×10-11, AA: OR= 5.48, CI=1.77-16.92; p=1.40×10-3). PLD3 is highly expressed in brain regions vulnerable to AD pathology, including hippocampus and cortex, and is expressed at lower levels in neurons from AD brains compared to control brains (p=8.10×10-10). Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may be used to identify rare variants with large effects on risk for disease or other complex traits. PMID:24336208

Comments on: blood product transfusion in emergency department patients: a case control study of practice patterns and impact on outcome.

PubMed

Karami, Manoochehr; Khazaei, Salman

2017-12-06

Clinical decision makings according studies result require the valid and correct data collection, andanalysis. However, there are some common methodological and statistical issues which may ignore by authors. In individual matched case- control design bias arising from the unconditional analysis instead of conditional analysis. Using an unconditional logistic for matched data causes the imposition of a large number of nuisance parameters which may result in seriously biased estimates.

Nitrosamine and related food intake and gastric and oesophageal cancer risk: A systematic review of the epidemiological evidence

PubMed Central

Jakszyn, Paula; González, Carlos Alberto

2006-01-01

AIM: To study the association between nitrite and nitrosamine intake and gastric cancer (GC), between meat and processed meat intake, GC and oesophageal cancer (OC), and between preserved fish, vegetable and smoked food intake and GC. METHODS: In this article we reviewed all the published cohort and case-control studies from 1985-2005, and analyzed the relationship between nitrosamine and nitrite intake and the most important related food intake (meat and processed meat, preserved vegetables and fish, smoked foods and beer drinking) and GC or OC risk. Sixty-one studies, 11 cohorts and 50 case-control studies were included. RESULTS: Evidence from case-control studies supported an association between nitrite and nitrosamine intake with GC but evidence was insufficient in relation to OC. A high proportion of case-control studies found a positive association with meat intake for both tumours (11 of 16 studies on GC and 11 of 18 studies on OC). A relatively large number of case-control studies showed quite consistent results supporting a positive association between processed meat intake and GC and OC risk (10 of 14 studies on GC and 8 of 9 studies on OC). Almost all the case-control studies found a positive and significant association between preserved fish, vegetable and smoked food intake and GC. The evidence regarding OC was more limited. Overall the evidence from cohort studies was insufficient or more inconsistent than that from case-control studies. CONCLUSION: The available evidence supports a positive association between nitrite and nitrosamine intake and GC, between meat and processed meat intake and GC and OC, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive. PMID:16865769

Recall bias in the assessment of exposure to mobile phones.

PubMed

Vrijheid, Martine; Armstrong, Bruce K; Bédard, Daniel; Brown, Julianne; Deltour, Isabelle; Iavarone, Ivano; Krewski, Daniel; Lagorio, Susanna; Moore, Stephen; Richardson, Lesley; Giles, Graham G; McBride, Mary; Parent, Marie-Elise; Siemiatycki, Jack; Cardis, Elisabeth

2009-05-01

Most studies of mobile phone use are case-control studies that rely on participants' reports of past phone use for their exposure assessment. Differential errors in recalled phone use are a major concern in such studies. INTERPHONE, a multinational case-control study of brain tumour risk and mobile phone use, included validation studies to quantify such errors and evaluate the potential for recall bias. Mobile phone records of 212 cases and 296 controls were collected from network operators in three INTERPHONE countries over an average of 2 years, and compared with mobile phone use reported at interview. The ratio of reported to recorded phone use was analysed as measure of agreement. Mean ratios were virtually the same for cases and controls: both underestimated number of calls by a factor of 0.81 and overestimated call duration by a factor of 1.4. For cases, but not controls, ratios increased with increasing time before the interview; however, these trends were based on few subjects with long-term data. Ratios increased by level of use. Random recall errors were large. In conclusion, there was little evidence for differential recall errors overall or in recent time periods. However, apparent overestimation by cases in more distant time periods could cause positive bias in estimates of disease risk associated with mobile phone use.

Conceiving semi-active control devices for large-size monolithic monuments

NASA Astrophysics Data System (ADS)

Casciati, Fabio; El Attar, Adel; Casciati, Sara

2001-07-01

CHIME is a research project, funded by the European Union, which investigates the adoption of innovative structural control techniques in view of the seismic rehabilitation of the wide monumental cultural heritage in Mediterranean countries as Egypt, Tunisia and Cyprus. The structural control devices are mainly of the semi-active type. In this particular paper one reports the first results achieved within a case study. It considers an Egyptian large size monolithic monument. Alternative solutions for its seismic rehabilitation are eventually conceived and discussed.

Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

PubMed

Salkeld, Daniel J

2017-09-01

The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

Outcome of strict implementation of infection prevention control measures during an outbreak of Middle East respiratory syndrome.

PubMed

El Bushra, Hassan E; Al Arbash, Hussain A; Mohammed, Mutaz; Abdalla, Osman; Abdallah, Mohamed N; Al-Mayahi, Zayid K; Assiri, Abdallah M; BinSaeed, Abdulaziz A

2017-05-01

The objective of this retrospective cohort study was to assess the impact of implementation of different levels of infection prevention and control (IPC) measures during an outbreak of Middle East respiratory syndrome (MERS) in a large tertiary hospital in Saudi Arabia. The setting was an emergency room (ER) in a large tertiary hospital and included primary and secondary MERS patients. Rapid response teams conducted repeated assessments of IPC and monitored implementation of corrective measures using a detailed structured checklist. We ascertained the epidemiologic link between patients and calculated the secondary attack rate per 10,000 patients visiting the ER (SAR/10,000) in 3 phases of the outbreak. In phase I, 6 primary cases gave rise to 48 secondary cases over 4 generations, including a case that resulted in 9 cases in the first generation of secondary cases and 21 cases over a chain of 4 generations. During the second and third phases, the number of secondary cases sharply dropped to 18 cases and 1 case, respectively, from a comparable number of primary cases. The SAR/10,000 dropped from 75 (95% confidence interval [CI], 55-99) in phase I to 29 (95% CI, 17-46) and 3 (95% CI, 0-17) in phases II and III, respectively. The study demonstrated salient evidence that proper institution of IPC measures during management of an outbreak of MERS could remarkably change the course of the outbreak. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Fetal Growth and Childhood Cancer: A Population-Based Study

PubMed Central

Sørensen, Henrik Toft; Grotmol, Tom; Engeland, Anders; Stephansson, Olof; Gissler, Mika; Tretli, Steinar; Troisi, Rebecca

2013-01-01

OBJECTIVE: The etiology of childhood cancers is largely unknown. Studies have suggested that birth characteristics may be associated with risk. Our goal was to evaluate the risk of childhood cancers in relation to fetal growth. METHODS: We conducted a case-control study nested within Nordic birth registries. The study included cancer cases diagnosed in Denmark, Finland, Norway, and Sweden among children born from 1967 to 2010 and up to 10 matched controls per case, totaling 17 698 cases and 172 422 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived from conditional logistic regression. RESULTS: Risks of all childhood cancers increased with increasing birth weight (Ptrend ≤ .001). Risks of acute lymphoid leukemia and Wilms tumor were elevated when birth weight was >4000 g and of central nervous system tumors when birth weight was >4500 g. Newborns large for gestational age were at increased risk of Wilms tumor (OR: 2.1 [95% CI: 1.2–3.6]) and connective/soft tissue tumors (OR: 2.1 [95% CI: 1.1–4.4]). In contrast, the risk of acute myeloid leukemia was increased among children born small for gestational age (OR: 1.8 [95% CI: 1.1–3.1]). Children diagnosed with central nervous system tumors at <1 year of age had elevated risk with increasing head circumference (Ptrend < .001). Those with head circumference >39 cm had the highest risk (OR: 4.7 [95% CI: 2.5–8.7]). CONCLUSIONS: In this large, Nordic population-based study, increased risks for several childhood tumors were associated with measures of fetal growth, supporting the hypothesis that tumorigenesis manifesting in childhood is initiated in utero. PMID:24167169

A case-control study of the association between ulcerative colitis and hyperthyroidism in an Asian population.

PubMed

Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

2017-06-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P<.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24-1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27-2.05). Furthermore, we analysed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18-39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04-3.79). This study demonstrated an association between UC and hyperthyroidism. © 2017 John Wiley & Sons Ltd.

What are the risk factors for dislocation in primary total hip arthroplasty? A multicenter case-control study of 128 unstable and 438 stable hips.

PubMed

Fessy, M H; Putman, S; Viste, A; Isida, R; Ramdane, N; Ferreira, A; Leglise, A; Rubens-Duval, B; Bonin, N; Bonnomet, F; Combes, A; Boisgard, S; Mainard, D; Leclercq, S; Migaud, H

2017-09-01

Dislocation after total hip arthroplasty (THA) is a leading reason for surgical revision. The risk factors for dislocation are controversial, particularly those related to the patient and to the surgical procedure itself. The differences in opinion on the impact of these factors stem from the fact they are often evaluated using retrospective studies or in limited patient populations. This led us to carry out a prospective case-control study on a large population to determine: 1) the risk factors for dislocation after THA, 2) the features of these dislocations, and 3) the contribution of patient-related factors and surgery-related factors. Risk factors for dislocation related to the patient and procedure can be identified using a large case-control study. A multicenter, prospective case-control study was performed between January 1 and December 31, 2013. Four patients with stable THAs were matched to each patient with a dislocated THA. This led to 566 primary THA cases being included: 128 unstable, 438 stable. The primary matching factors were sex, age, initial diagnosis, surgical approach, implantation date and type of implants (bearing size, standard or dual-mobility cup). The patients with unstable THAs were 67±12 [37-73]years old on average; there were 61 women (48%) and 67 men (52%). Hip osteoarthritis (OA) was the main reason for the THA procedure in 71% (91/128) of the unstable group. The dislocation was posterior in 84 cases and anterior in 44 cases. The dislocation occurred within 3 months of the primary surgery in 48 cases (38%), 3 to 12 months after in 23 cases (18%), 1 to 5years after in 20 cases (16%), 5 to 10years after in 17 cases (13%) and more than 10years later in 20 cases. The dislocation recurred within 6 months of the initial dislocation in 23 of the 128 cases (18%). The risk factors for instability were a high ASA score with an odds ratio (OR) of 1.93 (95% CI: 1.4-2.6), neurological disability (cognitive, motor or psychiatric disorders) with an OR of 3.9 (95% CI: 2.15-7.1), history of spinal disease (lumbar stenosis, spinal fusion, discectomy, scoliosis and injury sequelae) with an OR of 1.89 (95% CI: 1.0-3.6), unrepaired joint capsule (all approaches) with an OR of 4.1 (95% CI: 2.3-7.37), unrepaired joint capsule (posterior approach) with an OR of 6.0 (95% CI: 2.2-15.9), and cup inclination outside Lewinnek's safe zone (30°-50°) with OR of 2.4 (95% CI: 1.4-4.0). This large comparative study isolated important patient-related factors for dislocation that surgeons must be aware of. We also found evidence that implanting the cup in 30° to 50° inclination has a major impact on preventing dislocation. Level III; case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015.

PubMed

Bulage, Lilian; Masiira, Ben; Ario, Alex R; Matovu, Joseph K B; Nsubuga, Peter; Kaharuza, Frank; Nankabirwa, Victoria; Routh, Janell; Zhu, Bao-Ping

2017-09-25

Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (OR adj  = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (OR adj  = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (OR adj  = 9.0, 95%CI = 1.1-78). Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment.

Hyperthyroidism and erectile dysfunction: a population-based case-control study.

PubMed

Keller, J; Chen, Y-K; Lin, H-C

2012-01-01

Dysthyroidism has been highlighted as a common endocrine disorder associated with erectile dysfunction (ED); however, to date, no large-scale population-based study has investigated the association between hyperthyroidism and ED. This case-control study aimed to explore the association between ED and hyperthyroidism using a population-based data set. In total, 6310 adult patients who received new diagnoses of ED were recruited as cases together with 18 930 matched enrollees with no history of ED who served as controls. Conditional logistic regressions were conducted to explore the association between ED and having been previously diagnosed with hyperthyroidism. In total, 569 (2.3%) of the 25 240 sampled subjects had been diagnosed with hyperthyroidism before the index date; hyperthyroidism was found in 207 (3.3%) cases and 362 (1.90%) controls. After adjusting for potential confounding factors, the odds ratio (OR) of prior hyperthyroidism among cases was 1.64 (95% confidence interval=1.37-1.96, P<0.001) than that of controls. No association was detected between prior hyperthyroidism and ED for the 18-30, 30-39 and >70 age groups. Subjects aged between 60 and 69 years had the highest ORs for prior hyperthyroidism among cases when compared to controls (OR=1.84; 95% confidence interval=1.20-2.84; P<0.001). Our study further confirms the existence of an association between ED and prior hyperthyroidism.

Valid statistical inference methods for a case-control study with missing data.

PubMed

Tian, Guo-Liang; Zhang, Chi; Jiang, Xuejun

2018-04-01

The main objective of this paper is to derive the valid sampling distribution of the observed counts in a case-control study with missing data under the assumption of missing at random by employing the conditional sampling method and the mechanism augmentation method. The proposed sampling distribution, called the case-control sampling distribution, can be used to calculate the standard errors of the maximum likelihood estimates of parameters via the Fisher information matrix and to generate independent samples for constructing small-sample bootstrap confidence intervals. Theoretical comparisons of the new case-control sampling distribution with two existing sampling distributions exhibit a large difference. Simulations are conducted to investigate the influence of the three different sampling distributions on statistical inferences. One finding is that the conclusion by the Wald test for testing independency under the two existing sampling distributions could be completely different (even contradictory) from the Wald test for testing the equality of the success probabilities in control/case groups under the proposed distribution. A real cervical cancer data set is used to illustrate the proposed statistical methods.

Detailed Investigation of the Role of Common and Low-Frequency WFS1 Variants in Type 2 Diabetes Risk

PubMed Central

Fawcett, Katherine A.; Wheeler, Eleanor; Morris, Andrew P.; Ricketts, Sally L.; Hallmans, Göran; Rolandsson, Olov; Daly, Allan; Wasson, Jon; Permutt, Alan; Hattersley, Andrew T.; Glaser, Benjamin; Franks, Paul W.; McCarthy, Mark I.; Wareham, Nicholas J.; Sandhu, Manjinder S.; Barroso, Inês

2010-01-01

OBJECTIVE Wolfram syndrome 1 (WFS1) single nucleotide polymorphisms (SNPs) are associated with risk of type 2 diabetes. In this study we aimed to refine this association and investigate the role of low-frequency WFS1 variants in type 2 diabetes risk. RESEARCH DESIGN AND METHODS For fine-mapping, we sequenced WFS1 exons, splice junctions, and conserved noncoding sequences in samples from 24 type 2 diabetic case and 68 control subjects, selected tagging SNPs, and genotyped these in 959 U.K. type 2 diabetic case and 1,386 control subjects. The same genomic regions were sequenced in samples from 1,235 type 2 diabetic case and 1,668 control subjects to compare the frequency of rarer variants between case and control subjects. RESULTS Of 31 tagging SNPs, the strongest associated was the previously untested 3′ untranslated region rs1046320 (P = 0.008); odds ratio 0.84 and P = 6.59 × 10−7 on further replication in 3,753 case and 4,198 control subjects. High correlation between rs1046320 and the original strongest SNP (rs10010131) (r2 = 0.92) meant that we could not differentiate between their effects in our samples. There was no difference in the cumulative frequency of 82 rare (minor allele frequency [MAF] <0.01) nonsynonymous variants between type 2 diabetic case and control subjects (P = 0.79). Two intermediate frequency (MAF 0.01–0.05) nonsynonymous changes also showed no statistical association with type 2 diabetes. CONCLUSIONS We identified six highly correlated SNPs that show strong and comparable associations with risk of type 2 diabetes, but further refinement of these associations will require large sample sizes (>100,000) or studies in ethnically diverse populations. Low frequency variants in WFS1 are unlikely to have a large impact on type 2 diabetes risk in white U.K. populations, highlighting the complexities of undertaking association studies with low-frequency variants identified by resequencing. PMID:20028947

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

PubMed

Csermely, Gyula; Czeizel, Andrew E; Veszprémi, Béla

2015-02-01

Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA. © 2014 Wiley Periodicals, Inc.

Investigation of occupational and environmental causes of respiratory cancers (ICARE): a multicenter, population-based case-control study in France.

PubMed

Luce, Danièle; Stücker, Isabelle

2011-12-14

Occupational causes of respiratory cancers need to be further investigated: the role of occupational exposures in the aetiology of head and neck cancers remains largely unknown, and there are still substantial uncertainties for a number of suspected lung carcinogens. The main objective of the study is to examine occupational risk factors for lung and head and neck cancers. ICARE is a multi-center, population-based case-control study, which included a group of 2926 lung cancer cases, a group of 2415 head and neck cancer cases, and a common control group of 3555 subjects. Incident cases were identified in collaboration with cancer registries, in 10 geographical areas. The control group was a random sample of the population of these areas, with a distribution by sex and age comparable to that of the cases, and a distribution by socioeconomic status comparable to that of the population. Subjects were interviewed face to face, using a standardized questionnaire collecting particularly information on tobacco and alcohol consumption, residential history and a detailed description of occupational history. Biological samples were also collected from study subjects. The main occupational exposures of interest are asbestos, man-made mineral fibers, formaldehyde, polycyclic aromatic hydrocarbons, chromium and nickel compounds, arsenic, wood dust, textile dust, solvents, strong acids, cutting fluids, silica, diesel fumes, welding fumes. The complete list of exposures of interest includes more than 60 substances. Occupational exposure assessment will use several complementary methods: case-by-case evaluation of exposure by experts; development and use of algorithms to assess exposure from the questionnaires; application of job-exposure matrices. The large number of subjects should allow to uncover exposures associated with moderate increase in risks, and to evaluate risks associated with infrequent or widely dispersed exposures. It will be possible to study joint effects of exposure to different occupational risk factors, to examine the interactions between occupational exposures, tobacco smoking, alcohol drinking, and genetic risk factors, and to estimate the proportion of respiratory cancers attributable to occupational exposures in France. In addition, information on many non-occupational risk factors is available, and the study will provide an excellent framework for numerous studies in various fields.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

PubMed

Milbrandt, Melissa; Winter, Anke C; Nevin, Remington L; Pakpahan, Ratna; Bradwin, Gary; De Marzo, Angelo M; Elliott, Debra J; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Rifai, Nader; Sokoll, Lori J; Zenilman, Jonathan M; Platz, Elizabeth A; Sutcliffe, Siobhan

2017-05-01

To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk. © 2017 Wiley Periodicals, Inc.

Genome-wide association analysis of secondary imaging phenotypes from the Alzheimer's disease neuroimaging initiative study.

PubMed

Zhu, Wensheng; Yuan, Ying; Zhang, Jingwen; Zhou, Fan; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-02-01

The aim of this paper is to systematically evaluate a biased sampling issue associated with genome-wide association analysis (GWAS) of imaging phenotypes for most imaging genetic studies, including the Alzheimer's Disease Neuroimaging Initiative (ADNI). Specifically, the original sampling scheme of these imaging genetic studies is primarily the retrospective case-control design, whereas most existing statistical analyses of these studies ignore such sampling scheme by directly correlating imaging phenotypes (called the secondary traits) with genotype. Although it has been well documented in genetic epidemiology that ignoring the case-control sampling scheme can produce highly biased estimates, and subsequently lead to misleading results and suspicious associations, such findings are not well documented in imaging genetics. We use extensive simulations and a large-scale imaging genetic data analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to evaluate the effects of the case-control sampling scheme on GWAS results based on some standard statistical methods, such as linear regression methods, while comparing it with several advanced statistical methods that appropriately adjust for the case-control sampling scheme. Copyright © 2016 Elsevier Inc. All rights reserved.

The Value of Large-Scale Randomised Control Trials in System-Wide Improvement: The Case of the Reading Catch-Up Programme

ERIC Educational Resources Information Center

Fleisch, Brahm; Taylor, Stephen; Schöer, Volker; Mabogoane, Thabo

2017-01-01

This article illustrates the value of large-scale impact evaluations with counterfactual components. It begins by exploring the limitations of small-scale impact studies, which do not allow reliable inference to a wider population or which do not use valid comparison groups. The paper then describes the design features of a recent large-scale…

Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

PubMed

Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

2018-01-01

An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

Pain Sensitivity Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case Control Study

PubMed Central

Greenspan, Joel D.; Slade, Gary D.; Bair, Eric; Dubner, Ronald; Fillingim, Roger B.; Ohrbach, Richard; Knott, Charlie; Mulkey, Flora; Rothwell, Rebecca; Maixner, William

2011-01-01

Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified five components labeled: (1) heat pain ratings, (2) heat pain aftersensations and tolerance, (3) mechanical cutaneous pain sensitivity, (4) pressure pain thresholds, and (5) heat pain temporal summation. These results demonstrate that, compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extra-cranial body sites, and provides for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures. PMID:22074753

Spatial processes decouple management from objectives in a heterogeneous landscape: predator control as a case study.

PubMed

Mahoney, Peter J; Young, Julie K; Hersey, Kent R; Larsen, Randy T; McMillan, Brock R; Stoner, David C

2018-04-01

Predator control is often implemented with the intent of disrupting top-down regulation in sensitive prey populations. However, ambiguity surrounding the efficacy of predator management, as well as the strength of top-down effects of predators in general, is often exacerbated by the spatially implicit analytical approaches used in assessing data with explicit spatial structure. Here, we highlight the importance of considering spatial context in the case of a predator control study in south-central Utah. We assessed the spatial match between aerial removal risk in coyotes (Canis latrans) and mule deer (Odocoileus hemionus) resource selection during parturition using a spatially explicit, multi-level Bayesian model. With our model, we were able to evaluate spatial congruence between management action (i.e., coyote removal) and objective (i.e., parturient deer site selection) at two distinct scales: the level of the management unit and the individual coyote removal. In the case of the former, our results indicated substantial spatial heterogeneity in expected congruence between removal risk and parturient deer site selection across large areas, and is a reflection of logistical constraints acting on the management strategy and differences in space use between the two species. At the level of the individual removal, we demonstrated that the potential management benefits of a removed coyote were highly variable across all individuals removed and in many cases, spatially distinct from parturient deer resource selection. Our methods and results provide a means of evaluating where we might anticipate an impact of predator control, while emphasizing the need to weight individual removals based on spatial proximity to management objectives in any assessment of large-scale predator control. Although we highlight the importance of spatial context in assessments of predator control strategy, we believe our methods are readily generalizable in any management or large-scale experimental framework where spatial context is likely an important driver of outcomes. © 2018 by the Ecological Society of America.

Pernicious anemia and colorectal cancer risk - A nested case-control study.

PubMed

Boursi, Ben; Mamtani, Ronac; Haynes, Kevin; Yang, Yu-Xiao

2016-11-01

Hypergastrinemia was shown to stimulate colonic epithelial cell proliferation. To evaluate the association between pernicious anemia (PA), a disease with hypergastrinemia, and colorectal cancer (CRC) risk. We conducted a nested case-control study within a large database from the UK. Cases were defined as all individuals in the cohort with at least one medical code for CRC. Controls were selected based on incidence-density sampling. For each case, up to four eligible controls were matched on age at diagnosis, sex, practice-site, and both duration and calendar time of follow-up. Exposure of interest was diagnosis of PA prior to CRC diagnosis date. The primary analysis was a multivariable conditional logistic regression. Our study included 22,098 CRC cases and 85,969 matched controls. We identified 154 (0.70%) cases and 563 (0.65%) controls with past history of PA. The adjusted OR for the association between PA and CRC risk was 1.02 (95% CI 0.85-1.22). There was no difference in the results after stratification according to sex. In a sensitivity analysis only among individuals without chronic use of proton pump inhibitors (PPIs) the adjusted OR was 1.14 (95% CI 0.90-1.45). There was no association between duration of PA and CRC risk. PA is not associated with higher CRC risk. Copyright © 2016. Published by Elsevier Ltd.

Epidemiologic study of residential proximity to transmission lines and childhood cancer in California: description of design, epidemiologic methods and study population

PubMed Central

Kheifets, Leeka; Crespi, Catherine M; Hooper, Chris; Oksuzyan, Sona; Cockburn, Myles; Ly, Thomas; Mezei, Gabor

2015-01-01

We conducted a large epidemiologic case-control study in California to examine the association between childhood cancer risk and distance from the home address at birth to the nearest high-voltage overhead transmission line as a replication of the study of Draper et al. in the United Kingdom. We present a detailed description of the study design, methods of case ascertainment, control selection, exposure assessment and data analysis plan. A total of 5788 childhood leukemia cases and 3308 childhood central nervous system cancer cases (included for comparison) and matched controls were available for analysis. Birth and diagnosis addresses of cases and birth addresses of controls were geocoded. Distance from the home to nearby overhead transmission lines was ascertained on the basis of the electric power companies’ geographic information system (GIS) databases, additional Google Earth aerial evaluation and site visits to selected residences. We evaluated distances to power lines up to 2000 m and included consideration of lower voltages (60–69 kV). Distance measures based on GIS and Google Earth evaluation showed close agreement (Pearson correlation >0.99). Our three-tiered approach to exposure assessment allowed us to achieve high specificity, which is crucial for studies of rare diseases with low exposure prevalence. PMID:24045429

Investigation of Maternal Genotype Effects in Autism by Genome-Wide Association

PubMed Central

Yuan, Han; Dougherty, Joseph D.

2014-01-01

Lay Abstract Autism spectrum disorders (ASDs) are pervasive developmental disorders which have both a genetic and environmental component. One source of the environmental component is the in utero (prenatal) environment. The maternal genome can potentially contribute to the risk of autism in children by altering this prenatal environment. In this study, the possibility of maternal genotype effects was explored by looking for common variants (single nucleotide polymorphisms, or SNPs) in the maternal genome associated with increased risk of autism in children. We performed a case/control genome-wide association study (GWAS) using mothers of probands as cases and either fathers of probands or normal females as controls, using two collections of families with autism. We did not identify any SNP that reached significance and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles each carrying a small effect. This suggested that if there is a contribution to autism risk through common-variant maternal genetic effects, it may be the result of multiple loci of small effects. We did not investigate rare variants in this study. Scientific Abstract Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings. In this study, the possibility of maternal genotype effects was examined by looking for common variants (single nucleotide polymorphisms, or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome-wide association study (GWAS) was performed using mothers of probands as cases and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange (AGRE) and Illumina Genotype Control Database (iCon) were used as our discovery cohort (n=1616). The same analysis was then replicated on Simon Simplex Collection (SSC) and Study of Addiction: Genetics and Environment (SAGE) datasets (n=2732). We did not identify any SNP that reached genome-wide significance (p<10−8) and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect. PMID:24574247

Development and validation of a melanoma risk score based on pooled data from 16 case-control studies

PubMed Central

Davies, John R; Chang, Yu-mei; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adele; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Lee, Tim K; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus, Linda; Zens, Michael S; Ziegler, Andreas; Gallagher, Richard P.; Barrett, Jennifer H; Newton-Bishop, Julia

2015-01-01

Background We report the development of a cutaneous melanoma risk algorithm based upon 7 factors; hair colour, skin type, family history, freckling, nevus count, number of large nevi and history of sunburn, intended to form the basis of a self-assessment webtool for the general public. Methods Predicted odds of melanoma were estimated by analysing a pooled dataset from 16 case-control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th and 90th centiles were used to distribute individuals into four risk groups for their age, sex and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case-control study dataset. Results Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset (area under the curve 0.75, 95% CI 0.73-0.78). 29% of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases. Conclusion We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset. Impact This score may be a useful tool to inform members of the public about their melanoma risk. PMID:25713022

Effect of using an audience response system on learning environment, motivation and long-term retention, during case-discussions in a large group of undergraduate veterinary clinical pharmacology students.

PubMed

Doucet, Michèle; Vrins, André; Harvey, Denis

2009-12-01

Teaching methods that provide an opportunity for individual engagement and focussed feedback are required to create an active learning environment for case-based teaching in large groups. A prospective observational controlled study was conducted to evaluate whether the use of an audience response system (ARS) would promote an active learning environment during case-based discussions in large groups, have an impact on student motivation and improve long-term retention. Group A (N = 83) participated in large group case discussions where student participation was voluntary, while for group B (N = 86) an ARS was used. Data collection methods included student and teacher surveys, student focus group interviews, independent observations and 1-year post-course testing. Results indicated that the use of an ARS provided an active learning environment during case-based discussions in large groups by favouring engagement, observation and critical reflection and by increasing student and teacher motivation. Although final exam results were significantly improved in group B, long-term retention was not significantly different between groups. It was concluded that ARS use significantly improved the learning experience associated with case-based discussions in a large group of undergraduate students.

Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.

PubMed

Gonzalez Murcia, Josue D; Schmutz, Cameron; Munger, Caitlin; Perkes, Ammon; Gustin, Aaron; Peterson, Michael; Ebbert, Mark T W; Norton, Maria C; Tschanz, Joann T; Munger, Ronald G; Corcoran, Christopher D; Kauwe, John S K

2013-12-01

Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases and 2540 control subjects) from the Cache County study using a custom TaqMan assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with an odds ratio of 3.5 (95% confidence interval, 1.3-8.8; p = 0.0076). The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant. Copyright © 2013 Elsevier Inc. All rights reserved.

Working with a fixed operating room team on consecutive similar cases and the effect on case duration and turnover time.

PubMed

Stepaniak, Pieter S; Vrijland, Wietske W; de Quelerij, Marcel; de Vries, Guus; Heij, Christiaan

2010-12-01

If variation in procedure times could be controlled or better predicted, the cost of surgeries could be reduced through improved scheduling of surgical resources. This study on the impact of similar consecutive cases on the turnover, surgical, and procedure times tests the perception that repeating the same manual tasks reduces the duration of these tasks. We hypothesize that when a fixed team works on similar consecutive cases the result will be shorter turnover and procedure duration as well as less variation as compared with the situation without a fixed team. Case-control study. St Franciscus Hospital, a large general teaching hospital in Rotterdam, the Netherlands. Two procedures, inguinal hernia repair and laparoscopic cholecystectomy, were selected and divided across a control group and a study group. Patients were randomly assigned to the study or control group. Preparation time, surgical time, procedure time, and turnover time. For inguinal hernia repair, we found a significantly lower preparation time and 10 minutes less procedure time in the study group, as compared with the control group. Variation in the study group was lower, as compared with the control group. For laparoscopic cholecystectomy, preparation time was significantly lower in the study group, as compared with the control group. For both procedures, there was a significant decrease in turnover time. Scheduling similar consecutive cases and performing with a fixed team results in lower turnover times and preparation times. The procedure time of the inguinal hernia repair decreased significantly and has practical scheduling implications. For more complex surgery, like laparoscopic cholecystectomy, there is no effect on procedure time.

Impact of aggregating exposure information from cases and controls when building a population-based job-exposure matrix from past expert evaluations.

PubMed

Kirkham, Tracy L; Siemiatycki, Jack; Labrèche, France; Lavoué, Jérôme

2016-07-01

To assess whether the inclusion of data from cases would bias a job-exposure matrix (JEM), we evaluated whether exposures were systematically different between cases and controls from a large historical case-control study. Data included 10 381 jobs assessed for occupational exposure to 294 agents within a lung cancer case-control study. For each sex, 1 JEM was developed from case jobs, and 1 from control jobs: with occupation (four-digit occupational codes), time period (1945-1959, 1960-1984, 1985-1995) and agent axes. We estimated concordance in exposure status (defined as probability of exposure threshold ≥5%) and exposure metrics of probability and intensity of exposure, between the 2 JEMs. Of all hypothetical occupation-period-agent combinations, most had no or few observations. Among males there were 8136 common cells (24-occupational codes, 3-periods, 226-agents), containing sufficient observations for comparison with 92% concordance in exposure status; discordance was equally likely to be towards cases or controls. Females had 1710 common cells (9-occupational codes, 3-periods, 114-agents) with 93% concordance in exposure status; discordant cells were more likely to reflect greater exposure among cases. Among concordantly exposed cells, probability and intensity of exposures were highly correlated between the case JEM and control JEM (Kendall τ>0.50), and absolute differences were small (median difference in probability <1.5%, median ratio in intensity=1.00) for both sexes. Agreement between the case JEM and control JEM was high, suggesting that aggregating the case and control information in our study into a single JEM is justifiable given the benefits of increased sample size. 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/

What factors play a role in preventing self-immolation? Results from a case-control study in Iran

PubMed Central

Karim, Hosein; Schwebel, David C.; Bazargan-Hejazi, Shahrzad; Mohammadi, Reza; Choubsaz, Mansour; Heidari Zadie, Zahra; Ahmadi, Alireza

2015-01-01

Abstract: Background: To investigate factors related to prevention of self-immolation in west of Iran. Methods: In a case-control study, 30 consecutive cases of deliberate self-inflicted burns admitted to the regional burn center (Imam Khomeini hospital in Kermanshah province, Iran) were compared with controls selected from the community and matched by sex, age, district-county of residence, and rural vs urban living environment. The following characteristics relevant to preventing self-immolation were collected from all cases and controls: main domestic fuel used in the household, awareness about complications of burn injuries, and use of counseling services. Results: Descriptive analyses revealed that kerosene was the main domestic fuel in the household for 83% of cases. Not surprisingly, the main means of self-immolation in 93% of the patients was kerosene, with other fuels such as petrol and domestic gas used in remaining cases. The majority of cases and controls were aware of the potential complications of burn injuries. Use of counseling services was more common in controls. Conclusions: All three aspects of preventing self-immolation – having kerosene and other fuels in the home, being aware of the complications of burn injuries, and using counseling services were present in both the cases and controls. This suggests a large portion of residents in rural Iran are potential self-immolation victims. Increasing preventive strategies may reduce risk of suicide by self-immolation. PMID:26081518

Size does matter - span of control in hospitals.

PubMed

Holm-Petersen, Christina; Østergaard, Sussanne; Andersen, Per Bo Noergaard

2017-04-10

Purpose Centralization, mergers and cost reductions have generally led to increasing levels of span of control (SOC), and thus potentially to lower leadership capacity. The purpose of this paper is to explore how a large SOC impacts hospital staff and their leaders. Design/methodology/approach The study is based on a qualitative explorative case study of three large inpatient wards. Findings The study finds that the nursing staff and their frontline leaders experience challenges in regard to visibility and role of the leader, e.g., in creating overview, coordination, setting-up clear goals, following up and being in touch. However, large wards also provide flexibility and development possibilities. Practical implications The authors discuss the implications of these findings for decision makers in deciding future SOC and for future SOC research. Originality/value Only few studies have qualitatively explored the consequences of large SOC in hospitals.

Investigation of established genetic risk variants for glioma in prediagnostic samples from a population-based nested case-control study.

PubMed

Wibom, Carl; Späth, Florentin; Dahlin, Anna M; Langseth, Hilde; Hovig, Eivind; Rajaraman, Preetha; Johannesen, Tom Børge; Andersson, Ulrika; Melin, Beatrice

2015-05-01

Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case-control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. ©2015 American Association for Cancer Research.

Tularemia Outbreak Investigation in Kosovo: Case Control and Environmental Studies

PubMed Central

Dedushaj, Isuf; Gjini, Ardiana; Jorgensen, Tine Rikke; Cotter, Benvon; Lieftucht, Alfons; D’Ancona, Fortunato; Dennis, David T.; Kosoy, Michael A.; Mulliqi-Osmani, Gjyle; Grunow, Roland; Kalaveshi, Ariana; Gashi, Luljeta; Humolli, Isme

2002-01-01

A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation. PMID:11749751

Dyslexia and Dyscalculia: Two Learning Disorders with Different Cognitive Profiles

ERIC Educational Resources Information Center

Landerl, Karin; Fussenegger, Barbara; Moll, Kristina; Willburger, Edith

2009-01-01

This study tests the hypothesis that dyslexia and dyscalculia are associated with two largely independent cognitive deficits, namely a phonological deficit in the case of dyslexia and a deficit in the number module in the case of dyscalculia. In four groups of 8- to 10-year-olds (42 control, 21 dyslexic, 20 dyscalculic, and 26…

The Mortality Penalty of Incarceration: Evidence from a Population-based Case-control Study of Working-age Males.

PubMed

Pridemore, William Alex

2014-06-01

There is a growing body of research on the effects of incarceration on health, though there are few studies in the sociological literature of the association between incarceration and premature mortality. This study examined the risk of male premature mortality associated with incarceration. Data came from the Izhevsk (Russia) Family Study, a large-scale population-based case-control design. Cases (n = 1,750) were male deaths aged 25 to 54 in Izhevsk between October 2003 and October 2005. Controls (n = 1,750) were selected at random from a city population register. The key independent variable was lifetime prevalence of incarceration. I used logistic regression to estimate mortality odds ratios, controlling for age, hazardous drinking, smoking status, marital status, and education. Seventeen percent of cases and 5 percent of controls had been incarcerated. Men who had been incarcerated were more than twice as likely as those who had not to experience premature mortality (odds ratio = 2.2, 95 percent confidence interval: 1.6-3.0). Relative to cases with no prior incarceration, cases who had been incarcerated were more likely to die from infectious diseases, respiratory diseases, non-alcohol-related accidental poisonings, and homicide. Taken together with other recent research, these results from a rigorous case-control design reveal not only that incarceration has durable effects on illness, but that its consequences extend to a greater risk of early death. I draw on the sociology of health literature on exposure, stress, and social integration to speculate about the reasons for this mortality penalty of incarceration. © American Sociological Association 2014.

Early rigorous control interventions can largely reduce dengue outbreak magnitude: experience from Chaozhou, China.

PubMed

Liu, Tao; Zhu, Guanghu; He, Jianfeng; Song, Tie; Zhang, Meng; Lin, Hualiang; Xiao, Jianpeng; Zeng, Weilin; Li, Xing; Li, Zhihao; Xie, Runsheng; Zhong, Haojie; Wu, Xiaocheng; Hu, Wenbiao; Zhang, Yonghui; Ma, Wenjun

2017-08-02

Dengue fever is a severe public heath challenge in south China. A dengue outbreak was reported in Chaozhou city, China in 2015. Intensified interventions were implemented by the government to control the epidemic. However, it is still unknown the degree to which intensified control measures reduced the size of the epidemics, and when should such measures be initiated to reduce the risk of large dengue outbreaks developing? We selected Xiangqiao district as study setting because the majority of the indigenous cases (90.6%) in Chaozhou city were from this district. The numbers of daily indigenous dengue cases in 2015 were collected through the national infectious diseases and vectors surveillance system, and daily Breteau Index (BI) data were reported by local public health department. We used a compartmental dynamic SEIR (Susceptible, Exposed, Infected and Removed) model to assess the effectiveness of control interventions, and evaluate the control effect of intervention timing on dengue epidemic. A total of 1250 indigenous dengue cases was reported from Xiangqiao district. The results of SEIR modeling using BI as an indicator of actual control interventions showed a total of 1255 dengue cases, which is close to the reported number (n = 1250). The size and duration of the outbreak were highly sensitive to the intensity and timing of interventions. The more rigorous and earlier the control interventions implemented, the more effective it yielded. Even if the interventions were initiated several weeks after the onset of the dengue outbreak, the interventions were shown to greatly impact the prevalence and duration of dengue outbreak. This study suggests that early implementation of rigorous dengue interventions can effectively reduce the epidemic size and shorten the epidemic duration.

Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PubMed

Le Calvez-Kelm, Florence; Lesueur, Fabienne; Damiola, Francesca; Vallée, Maxime; Voegele, Catherine; Babikyan, Davit; Durand, Geoffroy; Forey, Nathalie; McKay-Chopin, Sandrine; Robinot, Nivonirina; Nguyen-Dumont, Tù; Thomas, Alun; Byrnes, Graham B; Hopper, John L; Southey, Melissa C; Andrulis, Irene L; John, Esther M; Tavtigian, Sean V

2011-01-18

Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions. Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substitution data observed in case-control mutation-screening studies. The method involves stratifying rare missense substitutions observed in cases and/or controls into a series of grades ordered a priori from least to most likely to be evolutionarily deleterious, followed by a logistic regression test for trends to compare the frequency distributions of the graded missense substitutions in cases versus controls. Here we used this approach to analyze CHEK2 mutation-screening data from a population-based series of 1,303 female breast cancer patients and 1,109 unaffected female controls. We found evidence of risk associated with rare, evolutionarily unlikely CHEK2 missense substitutions. Additional findings were that (1) the risk estimate for the most severe grade of CHEK2 missense substitutions (denoted C65) is approximately equivalent to that of CHEK2 protein-truncating variants; (2) the population attributable fraction and the familial relative risk explained by the pool of rare missense substitutions were similar to those explained by the pool of protein-truncating variants; and (3) post hoc power calculations implied that scaling up case-control mutation screening to examine entire biochemical pathways would require roughly 2,000 cases and controls to achieve acceptable statistical power. This study shows that CHEK2 harbors many rare sequence variants that confer increased risk of breast cancer and that a substantial proportion of these are missense substitutions. The study validates our analytic approach to rare missense substitutions and provides a method to combine data from protein-truncating variants and rare missense substitutions into a one degree of freedom per gene test.

A comparison of 'cough and cold' and pneumonia: risk factors for pneumonia in children under 5 years revisited.

PubMed

Fatmi, Zafar; White, Franklin

2002-12-01

The aim of this study was to identify and measure the risk factors differentiating upper respiratory infection from pneumonia. The World Health Organization's acute respiratory infection case management criteria were used. We studied 259 cases of pneumonia (cases) and 187 cases of 'cough and cold' (controls) among children under 5 years of age at a large tertiary-care hospital in Gilgit, Pakistan. While previous studies used healthy controls, in this study we used controls who had mild infection ('cough and cold'). In the multivariate logistic regression analysis, lack of immunization (adjusted odds ratio (AOR)=1.54, 95% CI 1.0, 2.3), previous history of pneumonia (AOR=1.77, 95% CI 1.16, 2.7), younger age (AOR for each preceding month in children aged up to 59 months=1.01, 95% CI 0.99, 1.03) and malnutrition (wasting) (AOR=2.2, 95% CI 1.0, 5.23) were revealed as important risk factors for pneumonia. Some of the factors reported in previous studies that used healthy controls were not found to be significant when 'cough and cold' children were used as controls. Nonetheless, malnutrition, younger age, low coverage of immunization and also early childhood mismanagement and respiratory damage were found to be significant factors for development of pneumonia.

Shape determination and control for large space structures

NASA Technical Reports Server (NTRS)

Weeks, C. J.

1981-01-01

An integral operator approach is used to derive solutions to static shape determination and control problems associated with large space structures. Problem assumptions include a linear self-adjoint system model, observations and control forces at discrete points, and performance criteria for the comparison of estimates or control forms. Results are illustrated by simulations in the one dimensional case with a flexible beam model, and in the multidimensional case with a finite model of a large space antenna. Modal expansions for terms in the solution algorithms are presented, using modes from the static or associated dynamic mode. These expansions provide approximated solutions in the event that a used form analytical solution to the system boundary value problem is not available.

Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

PubMed

Schumacher, Fredrick R; Schmit, Stephanie L; Jiao, Shuo; Edlund, Christopher K; Wang, Hansong; Zhang, Ben; Hsu, Li; Huang, Shu-Chen; Fischer, Christopher P; Harju, John F; Idos, Gregory E; Lejbkowicz, Flavio; Manion, Frank J; McDonnell, Kevin; McNeil, Caroline E; Melas, Marilena; Rennert, Hedy S; Shi, Wei; Thomas, Duncan C; Van Den Berg, David J; Hutter, Carolyn M; Aragaki, Aaron K; Butterbach, Katja; Caan, Bette J; Carlson, Christopher S; Chanock, Stephen J; Curtis, Keith R; Fuchs, Charles S; Gala, Manish; Giovannucc, Edward L; Giocannucci, Edward L; Gogarten, Stephanie M; Hayes, Richard B; Henderson, Brian; Hunter, David J; Jackson, Rebecca D; Kolonel, Laurence N; Kooperberg, Charles; Küry, Sébastien; Kury, Sebastian; LaCroix, Andrea; Laurie, Cathy C; Laurie, Cecelia A; Lemire, Mathieu; Lemire, Mathiew; Levine, David; Ma, Jing; Makar, Karen W; Qu, Conghui; Taverna, Darin; Ulrich, Cornelia M; Wu, Kana; Kono, Suminori; West, Dee W; Berndt, Sonja I; Bezieau, Stéphane; Brenner, Hermann; Campbell, Peter T; Chan, Andrew T; Chang-Claude, Jenny; Coetzee, Gerhard A; Conti, David V; Duggan, David; Figueiredo, Jane C; Fortini, Barbara K; Gallinger, Steven J; Gauderman, W James; Giles, Graham; Green, Roger; Haile, Robert; Harrison, Tabitha A; Hoffmeister, Michael; Hopper, John L; Hudson, Thomas J; Jacobs, Eric; Iwasaki, Motoki; Jee, Sun Ha; Jenkins, Mark; Jia, Wei-Hua; Joshi, Amit; Li, Li; Lindor, Noralene M; Matsuo, Keitaro; Moreno, Victor; Mukherjee, Bhramar; Newcomb, Polly A; Potter, John D; Raskin, Leon; Rennert, Gad; Rosse, Stephanie; Severi, Gianluca; Schoen, Robert E; Seminara, Daniela; Shu, Xiao-Ou; Slattery, Martha L; Tsugane, Shoichiro; White, Emily; Xiang, Yong-Bing; Zanke, Brent W; Zheng, Wei; Le Marchand, Loic; Casey, Graham; Gruber, Stephen B; Peters, Ulrike

2015-07-07

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

Birth outcomes of cases with conotruncal defects of heart - a population-based case-control study.

PubMed

Vereczkey, Attila; Kósa, Zsolt; Csáky-Szunyogh, Melinda; Gerencsér, Balázs; Czeizel, Andrew E

2015-03-01

The aim of this study was to evaluate the birth outcomes of cases with four types of conotruncal defects (CTDs), i.e. common truncus, transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle. Birth outcomes of 597 live-born cases with CTD and 38,151 population controls without any defects were compared in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities completed by socio-demographic variables of their mothers. There was a male excess in cases with CTD (56.8%) with the same mean gestational age (39.4 versus 39.4 weeks) and preterm birth rate (8.2 versus 9.2%), but their mean birth weight was smaller (3077 versus 3276 g) with a high rate of low birthweight (14.6 versus 5.7%) compared to the birth outcomes of population controls. These data indicate intrauterine growth restriction of fetuses affected with transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle particularly in females, while there were a shorter mean gestational age and smaller mean birth weigh in cases with common truncus. In general CTD, except common truncus, had no effect for gestational age but associated with a high risk for intrauterine fetal growth restriction particularly in female cases.

ICU telemedicine and critical care mortality: a national effectiveness study

PubMed Central

Kahn, Jeremy M; Le, Tri Q.; Barnato, Amber E.; Hravnak, Marilyn; Kuza, Courtney C.; Pike, Francis; Angus, Derek C.

2015-01-01

Background Intensive care unit (ICU) telemedicine is an increasingly common strategy for improving the outcome of critical care, but its overall impact is uncertain. Objectives To determine the effectiveness of ICU telemedicine in a national sample of hospitals and quantify variation in effectiveness across hospitals. Research design We performed a multi-center retrospective case-control study using 2001–2010 Medicare claims data linked to a national survey identifying United States hospitals adopting ICU telemedicine. We matched each adopting hospital (cases) to up to 3 non-adopting hospitals (controls) based on size, case-mix and geographic proximity during the year of adoption. Using ICU admissions from 2 years before and after the adoption date, we compared outcomes between case and control hospitals using a difference-in-differences approach. Results 132 adopting case hospitals were matched to 389 similar non-adopting control hospitals. The pre- and post-adoption unadjusted 90-day mortality was similar in both case hospitals (24.0% vs. 24.3%, p=0.07) and control hospitals (23.5% vs. 23.7%, p<0.01). In the difference-in-differences analysis, ICU telemedicine adoption was associated with a small relative reduction in 90-day mortality (ratio of odds ratios: 0.96, 95% CI = 0.95–0.98, p<0.001). However, there was wide variation in the ICU telemedicine effect across individual hospitals (median ratio of odds ratios: 1.01; interquartile range 0.85–1.12; range 0.45–2.54). Only 16 case hospitals (12.2%) experienced statistically significant mortality reductions post-adoption. Hospitals with a significant mortality reduction were more likely to have large annual admission volumes (p<0.001) and be located in urban areas (p=0.04) compared to other hospitals. Conclusions Although ICU telemedicine adoption resulted in a small relative overall mortality reduction, there was heterogeneity in effect across adopting hospitals, with large-volume urban hospitals experiencing the greatest mortality reductions. PMID:26765148

Identifying Etiological Agents Causing Diarrhea in Low Income Ecuadorian Communities

PubMed Central

Vasco, Gabriela; Trueba, Gabriel; Atherton, Richard; Calvopiña, Manuel; Cevallos, William; Andrade, Thamara; Eguiguren, Martha; Eisenberg, Joseph N. S.

2014-01-01

Continued success in decreasing diarrheal disease burden requires targeted interventions. To develop such interventions, it is crucial to understand which pathogens cause diarrhea. Using a case-control design we tested stool samples, collected in both rural and urban Ecuador, for 15 pathogenic microorganisms. Pathogens were present in 51% of case and 27% of control samples from the urban community, and 62% of case and 18% of control samples collected from the rural community. Rotavirus and Shigellae were associated with diarrhea in the urban community; co-infections were more pathogenic than single infection; Campylobacter and Entamoeba histolytica were found in large numbers in cases and controls; and non-typhi Salmonella and enteropathogenic Escherichia coli were not found in any samples. Consistent with the Global Enteric Multicenter Study, focused in south Asia and sub-Saharan Africa, we found that in Ecuador a small group of pathogens accounted for a significant amount of the diarrheal disease burden. PMID:25048373

Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China.

PubMed

Zhao, Jin-Kou; Wu, Ming; Kim, Claire H; Jin, Zi-Yi; Zhou, Jin-Yi; Han, Ren-Qiang; Yang, Jie; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Gu, Xiaoping; Su, Ming; Hu, Xu; Sun, Zheng; Li, Gang; Li, Liming; Mu, Lina; Zhang, Zuo-Feng

2017-07-01

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

Neuromuscular assessment in elderly workers with and without work related shoulder/neck trouble: the NEW-study design and physiological findings.

PubMed

Sjøgaard, G; Søgaard, K; Hermens, H J; Sandsjö, L; Läubli, T; Thorn, S; Vollenbroek-Hutten, M M R; Sell, L; Christensen, H; Klipstein, A; Kadefors, R; Merletti, R

2006-01-01

Musculoskeletal disorders in the neck and shoulder area are a major occupational concern in the European countries especially among elderly females. The aim was to assess these disorders based on quantitative EMG indicators and functional tests. 252 female computer users (45-68 years) were recruited from four European countries in two contrast groups: (1) 88 neck/shoulder (NS) cases reporting trouble in the neck and/or shoulder region for more than 30 days during the last year, and (2) 164 NS-controls reporting such trouble for no more than 7 days. Questionnaires, functional/clinical tests, and physiological recordings were performed in workplace related field studies. The results showed no differences in anthropometrics but NS-cases reported more strained head positions and more eye problems than controls. The psychosocial working factors were similar, although, NS-controls had slightly better scores on working conditions, general health, and vitality compared to cases. The NS-cases had lower maximal voluntary contraction (MVC) during shoulder elevation (mean (SD) 310 (122) N) compared to the controls (364 (122) N). During 30% MVC electromyography (EMGrms) in the trapezius muscle was lower in NS-cases (194 (105) muV) than in controls (256 (169) muV), while no differences were found regarding endurance time. Estimated conduction velocity was not different between NS-cases and -controls. Four functional computer tests were performed equally well by NS-cases and -controls, and the corresponding EMG variables also did not differ. A major finding in this large-scale epidemiological study is the significantly lower MVC in NS-cases compared with NS-controls together with lower EMGrms value at 30% MVC, while computer tasks were performed at similar relative muscle activation. The study was unable to reveal quantitative EMG indicators and functional tests that could objectively assess disorders in NS-cases.

[Design requirements for clinical trials on re-evaluation of safety and efficacy of post-marketed Chinese herbs].

PubMed

Xie, Yanming; Wei, Xu

2011-10-01

Re-evaluation of post-marketed based on pharmacoepidemiology is to study and collect clinical medicine safety in large population under practical applications for a long time. It is necessary to conduct re-evaluation of clinical effectiveness because of particularity of traditional Chinese medicine (TCM). Right before carrying out clinical trials on re-evaluation of post-marketed TCM, we should determine the objective of the study and progress it in the assessment mode of combination of disease and syndrome. Specical population, involving children and seniors who were excluded in pre-marketed clinical trial, were brought into drug monitoring. Sample size needs to comply with statistical requirement. We commonly use cohort study, case-control study, nested case-control, pragmatic randomized controlled trials.

Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.

PubMed

Dicks, Ed; Song, Honglin; Ramus, Susan J; Oudenhove, Elke Van; Tyrer, Jonathan P; Intermaggio, Maria P; Kar, Siddhartha; Harrington, Patricia; Bowtell, David D; Group, Aocs Study; Cicek, Mine S; Cunningham, Julie M; Fridley, Brooke L; Alsop, Jennifer; Jimenez-Linan, Mercedes; Piskorz, Anna; Goranova, Teodora; Kent, Emma; Siddiqui, Nadeem; Paul, James; Crawford, Robin; Poblete, Samantha; Lele, Shashi; Sucheston-Campbell, Lara; Moysich, Kirsten B; Sieh, Weiva; McGuire, Valerie; Lester, Jenny; Odunsi, Kunle; Whittemore, Alice S; Bogdanova, Natalia; Dürst, Matthias; Hillemanns, Peter; Karlan, Beth Y; Gentry-Maharaj, Aleksandra; Menon, Usha; Tischkowitz, Marc; Levine, Douglas; Brenton, James D; Dörk, Thilo; Goode, Ellen L; Gayther, Simon A; Pharoah, D P Paul

2017-08-01

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10 -3 ). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2 , where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P=0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P=0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P=0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality.

Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men.

PubMed

Villeneuve, Paul J; Parent, Marie-Élise; Sahni, Vanita; Johnson, Kenneth C

2011-07-01

The International Agency for Research on Cancer classifies diesel exhaust as a probable human carcinogen; this decision is based largely from lung cancer evidence. Gasoline exhaust is classified as a possible carcinogen. Epidemiological studies are needed that improve upon some of the limitations of previous research with respect to the characterization of exposure, and the control for the potential confounding influence of smoking and other occupational exposures. Our objective was to investigate associations between occupational exposure to diesel and gasoline engine emissions and lung cancer. We used a case-control study design that involved men 40 years of age and older at the time of interview. Analyses are based on 1681 incident cases of lung cancer and 2,053 population controls. A self-reported questionnaire elicited a lifetime occupational history, including general tasks, and information on other potential risk factors. Occupational exposures to diesel and gasoline emissions, crystalline silica, and asbestos were assigned to each job held by study subjects by industrial hygienists who were blind to case-control status. Exposure metrics for diesel and gasoline emissions that were modeled included: ever exposure, cumulative exposure, and concentration of exposure. We found a dose-response relationship between cumulative occupational exposure to diesel engine emissions and lung cancer. This association was more pronounced for the squamous and large cell subtypes with adjusted odds ratios across the three increasing tertiles of cumulative lifetime exposure relative to those with no exposure of 0.99, 1.25, and 1.32 (p=0.04) for squamous cell carcinoma, and 1.06, 1.19, 1.68 (p=0.02) for large cell carcinoma. While the association with cumulative exposure to gasoline was weakly positive, it was not statistically significant. Our findings suggest that exposure to diesel engine emissions increases the risk of lung cancer particularly for squamous and large cell carcinoma subtypes. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Maternal characteristics and birth outcomes of pregnant women who had offspring with congenital ear abnormalities - a population-based case-control study.

PubMed

Paput, László; Bánhidy, Ferenc; Czeizel, Andrew E

2011-09-01

To describe the maternal characteristics and birth outcomes of newborn infants affected with isolated ear congenital abnormalities (IECA), mainly isolated anotia/microtia and unclassified multiple congenital abnormalities (CAs) including anotia/microtia (UMAM). Cases with IECA and UMAM were compared with their matched controls and all controls without any defect and malformed controls affected with other defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The mothers of 354 cases with IECA did not show significant difference in age, but their mean birth order was higher while their socio-economic status based on the maternal employment status was lower compared to the figures of their matched controls. There was a male excess among cases with microtia and mainly with UMAM. The evaluation of birth outcomes of newborns affected with IECA indicated intrauterine fetal growth retardation. Newborn infants with isolated microtia had intrauterine growth retardation and the association of this developmental defect localized for a small region of head with the general fetal development raises interesting theoretical question.

A large Great Britain-wide outbreak of STEC O157 phage type 8 linked to handling of raw leeks and potatoes.

PubMed

Launders, N; Locking, M E; Hanson, M; Willshaw, G; Charlett, A; Salmon, R; Cowden, J; Harker, K S; Adak, G K

2016-01-01

Between December 2010 and July 2011, 252 cases of STEC O157 PT8 stx1 + 2 infection were reported in England, Scotland and Wales. This was the largest outbreak of STEC reported in England and the second largest in the UK to date. Eighty cases were hospitalized, with two cases of haemolytic uraemic syndrome and one death reported. Routine investigative data were used to generate a hypothesis but the subsequent case-control study was inconclusive. A second, more detailed, hypothesis generation exercise identified consumption or handling of vegetables as a potential mode of transmission. A second case-control study demonstrated that cases were more likely than controls to live in households whose members handled or prepared leeks bought unwrapped [odds ratio (OR) 40, 95% confidence interval (CI) 2·08-769·4], and potatoes bought in sacks (OR 13·13, 95% CI 1·19-145·3). This appears to be the first outbreak of STEC O157 infection linked to the handling of leeks.

Psychosocial factors in childhood pedestrian injury: a matched case-control study. Kid's'n'Cars Team.

PubMed

Christoffel, K K; Donovan, M; Schofer, J; Wills, K; Lavigne, J V

1996-01-01

Psychosocial factors--such as hyperactivity and low family cohesion--contribute to the risk for child pedestrian injury (PI), even after controlling for known demographic risk factors. Urban PI victims aged 5 to 12 years were recruited from one large, urban pediatric trauma center in a large city. One hundred twenty-eight cases were matched to uninjured children on age, sex, race, location of residence, and parental education. Among matched cases: 70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control comparisons on 19 psychosocial variables drawn from interviews and standardized tests, using one-tailed matched-pairs t tests and conditional logistic regression analyses. Cases had higher reported physical quotient [PQ] (P = .01), self-help quotient (P = .04), and family stress (P = .02), and lower family supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI) 1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26-3.61]), and that cases had lower family supportiveness (25-point decrease: OR 1.43 [1.25-1.63]). It also identified household crowding as a factor for non-black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]). Even when controlling for demographic risk, several family factors and one child factor place children at risk for PI. Clinicians may choose to use these as indicators for injury prevention counseling. Research on family effects may help clarify means to protect children who are demographically at risk for PI.

Public opinion on media presence in the courthouse.

PubMed

Fusco, Nina Marie; Sabourin, Michel

2012-01-01

Very little attention has been devoted to the public's opinion of media coverage of court cases despite extensive research on pretrial publicity (PTP). Following a provincial judgment to restrict media access in Quebec courthouses, a preliminary unpublished study found that the public was largely in support of these restrictions. The present study sought to expand on this finding in a more widely generalizable sample. Subjects were recruited from continuing education classes and completed a questionnaire that assessed their support for restricting journalists in courthouses. Nearly 80% of the 243 participants supported media restrictions. Although participants in the four experimental conditions and one of the control groups were largely in favor of the restrictions, one control group was opposed to the restrictions. The results suggest that the public prefers that journalists have restricted access to courtroom participants, resonating research on PTP and the Supreme Court's decision on the case. Copyright © 2011 Elsevier Ltd. All rights reserved.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease

PubMed Central

Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Choi, Seung-Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez-Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O’Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li-san; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

2013-01-01

Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease. PMID:24162737

A Mixed-Method Analysis of Reports on 100 Cases of Improper Prescribing of Controlled Substances

PubMed Central

DuBois, James M.; Chibnall, John T.; Anderson, Emily E.; Eggers, Michelle; Baldwin, Kari; Vasher, Meghan

2017-01-01

Improper prescribing of controlled substances contributes to opioid addictions and deaths by overdose. Studies conducted to-date have largely lacked a theoretical framework and ignored the interaction of individual with environmental factors. We conducted a mixed-method analysis of published reports on 100 cases that occurred in the United States. An average of 17 reports (e.g., from medical boards) per case were coded for 38 dichotomous variables describing the physician, setting, patients, and investigation. A theory on how the case occurred was developed for each case. Explanatory typologies were developed and then validated through hierarchical cluster analysis. Most cases involved physicians who were male (88%), >40 years old (90%), non-board certified (63%), and in small private practices (97%); 54% of cases reported facts about the physician indicative of self-centered personality traits. Three explanatory typologies were validated. Increasing oversight provided by peers and trainees may help prevent improper prescribing of controlled substances. PMID:28663601

Association between aircraft, road and railway traffic noise and depression in a large case-control study based on secondary data.

PubMed

Seidler, Andreas; Hegewald, Janice; Seidler, Anna Lene; Schubert, Melanie; Wagner, Mandy; Dröge, Patrik; Haufe, Eva; Schmitt, Jochen; Swart, Enno; Zeeb, Hajo

2017-01-01

Few studies have examined the relationship between traffic noise and depression providing inconclusive results. This large case-control study is the first to assess and directly compare depression risks by aircraft, road traffic and railway noise. The study population included individuals aged ≥40 years that were insured by three large statutory health insurance funds and were living in the region of Frankfurt international airport. Address-specific exposure to aircraft, road and railway traffic noise in 2005 was estimated. Based on insurance claims and prescription data, 77,295 cases with a new clinical depression diagnosis between 2006 and 2010 were compared with 578,246 control subjects. For road traffic noise, a linear exposure-risk relationship was found with an odds ratio (OR) of 1.17 (95% CI=1.10-1.25) for 24-h continuous sound levels ≥70dB. For aircraft noise, the risk estimates reached a maximum OR of 1.23 (95% CI=1.19-1.28) at 50-55dB and decreased at higher exposure categories. For railway noise, risk estimates peaked at 60-65dB (OR=1.15, 95% CI=1.08-1.22). The highest OR of 1.42 (95% CI=1.33-1.52) was found for a combined exposure to noise above 50dB from all three sources. This study indicates that traffic noise exposure might lead to depression. As a potential explanation for the decreasing risks at high traffic noise levels, vulnerable people might actively cope with noise (e.g. insulate or move away). Copyright © 2016 Elsevier Inc. All rights reserved.

Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database.

PubMed

Behr, Sigrid; Andersohn, Frank; Garbe, Edeltraut

2010-07-01

Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulation. This study investigated the risk of ICH for phenprocoumon which is the most widely used oral anticoagulant in Germany. We conducted a nested case-control study in a cohort of 13.4 million insurants of 4 German statutory health insurances (SHIs) who were continuously enrolled for 6 months prior to cohort entry. Cases were patients hospitalized for ICH. Ten controls were matched to each case by SHI, birth year, and sex using incidence density sampling. Rate ratios (RR) of ICH for current phenprocoumon use as compared to non-use were estimated from odds ratios calculated by conditional logistic regression analyses considering multiple risk factors. Analysis of the full cohort revealed a strong increase in incidence of ICH with increasing age. In the nested case-control study including 8138 cases of ICH and 81,373 matched controls, we observed an increased risk of ICH for current phenprocoumon exposure that varied with age. The phenprocoumon-associated risk of ICH was lower in older age groups with RRs from 4.20 (95% confidence interval (CI) 2.44-7.21) for phenprocoumon users less than 55 years of age to 2.43 (95%CI, 1.81-3.27) for those older than 85 years. Our study confirmed known risk factors of ICH. Phenprocoumon exposure was associated with an increased risk of ICH. The interaction of risk for phenprocoumon with age was unexpected and needs further study. (c) 2010 John Wiley & Sons, Ltd.

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

Experimental Studies of Low-Pressure Turbine Flows and Flow Control

NASA Technical Reports Server (NTRS)

Volino, Ralph J.

2012-01-01

This report summarizes research performed in support of the NASA Glenn Research Center (GRC) Low-Pressure Turbine (LPT) Flow Physics Program. The work was performed experimentally at the U.S. Naval Academy faculties. The geometry corresponded to "Pak B" LPT airfoil. The test section simulated LPT flow in a passage. Three experimental studies were performed: (a) Boundary layer measurements for ten baseline cases under high and low freestream turbulence conditions at five Reynolds numbers of 25,000, 50,000, 100,000, 200,000, and 300,000, based on passage exit velocity and suction surface wetted length; (b) Passive flow control studies with three thicknesses of two-dimensional bars, and two heights of three-dimensional circular cylinders with different spanwise separations, at same flow conditions as the 10 baseline cases; (c) Active flow control with oscillating synthetic (zero net mass flow) vortex generator jets, for one case with low freestream turbulence and a low Reynolds number of 25,000. The Passive flow control was successful at controlling the separation problem at low Reynolds numbers, with varying degrees of success from case to case and varying levels of impact at higher Reynolds numbers. The active flow control successfully eliminated the large separation problem for the low Reynolds number case. Very detailed data was acquired using hot-wire anemometry, including single and two velocity components, integral boundary layer quantities, turbulence statistics and spectra, turbulent shear stresses and their spectra, and intermittency, documenting transition, separation and reattachment. Models were constructed to correlate the results. The report includes a summary of the work performed and reprints of the publications describing the various studies.

Calcified Neurocysticercosis Associates with Hippocampal Atrophy: A Population-Based Study

PubMed Central

Del Brutto, Oscar H.; Salgado, Perla; Lama, Julio; Del Brutto, Victor J.; Campos, Xavier; Zambrano, Mauricio; García, Héctor H.

2015-01-01

Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings. PMID:25349375

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

PubMed Central

Epplein, Meira; Shvetsov, Yurii B; Wilkens, Lynne R; Franke, Adrian A; Cooney, Robert V; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2009-01-01

Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk. PMID:19619335

Bayes and empirical Bayes methods for reduced rank regression models in matched case-control studies.

PubMed

Satagopan, Jaya M; Sen, Ananda; Zhou, Qin; Lan, Qing; Rothman, Nathaniel; Langseth, Hilde; Engel, Lawrence S

2016-06-01

Matched case-control studies are popular designs used in epidemiology for assessing the effects of exposures on binary traits. Modern studies increasingly enjoy the ability to examine a large number of exposures in a comprehensive manner. However, several risk factors often tend to be related in a nontrivial way, undermining efforts to identify the risk factors using standard analytic methods due to inflated type-I errors and possible masking of effects. Epidemiologists often use data reduction techniques by grouping the prognostic factors using a thematic approach, with themes deriving from biological considerations. We propose shrinkage-type estimators based on Bayesian penalization methods to estimate the effects of the risk factors using these themes. The properties of the estimators are examined using extensive simulations. The methodology is illustrated using data from a matched case-control study of polychlorinated biphenyls in relation to the etiology of non-Hodgkin's lymphoma. © 2015, The International Biometric Society.

Direct heuristic dynamic programming for damping oscillations in a large power system.

PubMed

Lu, Chao; Si, Jennie; Xie, Xiaorong

2008-08-01

This paper applies a neural-network-based approximate dynamic programming method, namely, the direct heuristic dynamic programming (direct HDP), to a large power system stability control problem. The direct HDP is a learning- and approximation-based approach to addressing nonlinear coordinated control under uncertainty. One of the major design parameters, the controller learning objective function, is formulated to directly account for network-wide low-frequency oscillation with the presence of nonlinearity, uncertainty, and coupling effect among system components. Results include a novel learning control structure based on the direct HDP with applications to two power system problems. The first case involves static var compensator supplementary damping control, which is used to provide a comprehensive evaluation of the learning control performance. The second case aims at addressing a difficult complex system challenge by providing a new solution to a large interconnected power network oscillation damping control problem that frequently occurs in the China Southern Power Grid.

Childhood Adversities Increase the Risk of Psychosis: A Meta-analysis of Patient-Control, Prospective- and Cross-sectional Cohort Studies

PubMed Central

Varese, Filippo; Smeets, Feikje; Drukker, Marjan; Lieverse, Ritsaert; Lataster, Tineke; Viechtbauer, Wolfgang; Read, John; van Os, Jim; Bentall, Richard P.

2012-01-01

Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis. PMID:22461484

Cross-sectional study of the association of abomasal displacement or volvulus with serum electrolyte and mineral concentrations in dairy cows.

PubMed Central

Delgado-Lecaroz, R; Warnick, L D; Guard, C L; Smith, M C; Barry, D A

2000-01-01

The objective of this study was to evaluate serum mineral and electrolyte concentrations at the time of on-farm diagnosis of left displaced abomasum, right displaced abomasum, or abomasal volvulus in dairy cows. Data were collected from 104 affected cows and 96 control cows matched with cases, based on herd, parity, and stage of lactation. Cows with abomasal displacement or volvulus had significantly lower calcium, phosphorous, magnesium, potassium, and chloride concentrations and increased anion gap at the time of diagnosis compared with control cows from the same herds. The percentages of cases and controls with total serum calcium concentrations below the lower limit of the laboratory reference range (2.08 mmol/L [8.3 mg/dL]) were 70% and 23%, respectively. Based on the large percentage of cases with hypocalcemia, administering calcium salts at the time of treatment of field cases of abomasal displacement or volvulus may be beneficial. PMID:10769767

Experimental Studies of Low-Pressure Turbine Flows and Flow Control. Streamwise Pressure Profiles and Velocity Profiles

NASA Technical Reports Server (NTRS)

Volino, Ralph

2012-01-01

This report summarizes research performed in support of the NASA Glenn Research Center (GRC) Low-Pressure Turbine (LPT) Flow Physics Program. The work was performed experimentally at the U.S. Naval Academy faculties. The geometry corresponded to "Pak B" LPT airfoil. The test section simulated LPT flow in a passage. Three experimental studies were performed: (a) Boundary layer measurements for ten baseline cases under high and low freestream turbulence conditions at five Reynolds numbers of 25,000, 50,000, 100,000, 200,000, and 300,000, based on passage exit velocity and suction surface wetted length; (b) Passive flow control studies with three thicknesses of two-dimensional bars, and two heights of three-dimensional circular cylinders with different spanwise separations, at same flow conditions as the 10 baseline cases; (c) Active flow control with oscillating synthetic (zero net mass flow) vortex generator jets, for one case with low freestream turbulence and a low Reynolds number of 25,000. The Passive flow control was successful at controlling the separation problem at low Reynolds numbers, with varying degrees of success from case to case and varying levels of impact at higher Reynolds numbers. The active flow control successfully eliminated the large separation problem for the low Reynolds number case. Very detailed data was acquired using hot-wire anemometry, including single and two velocity components, integral boundary layer quantities, turbulence statistics and spectra, turbulent shear stresses and their spectra, and intermittency, documenting transition, separation and reattachment. Models were constructed to correlate the results. The report includes a summary of the work performed and reprints of the publications describing the various studies.This report summarizes research performed in support of the NASA Glenn Research Center (GRC) Low-Pressure Turbine (LPT) Flow Physics Program. The work was performed experimentally at the U.S. Naval Academy faculties. The geometry corresponded to "Pak B" LPT airfoil. The test section simulated LPT flow in a passage. Three experimental studies were performed: (a) Boundary layer measurements for ten baseline cases under high and low freestream turbulence conditions at five Reynolds numbers of 25,000, 50,000, 100,000, 200,000, and 300,000, based on passage exit velocity and suction surface wetted length; (b) Passive flow control studies with three thicknesses of two-dimensional bars, and two heights of three-dimensional circular cylinders with different spanwise separations, at same flow conditions as the 10 baseline cases; (c) Active flow control with oscillating synthetic (zero net mass flow) vortex generator jets, for one case with low freestream turbulence and a low Reynolds number of 25,000. The Passive flow control was successful at controlling the separation problem at low Reynolds numbers, with varying degrees of success from case to case and varying levels of impact at higher Reynolds numbers. The active flow control successfully eliminated the large separation problem for the low Reynolds number case. Very detailed data was acquired using hot-wire anemometry, including single and two velocity components, integral boundary layer quantities, turbulence statistics and spectra, turbulent shear stresses and their spectra, and intermittency, documenting transition, separation and reattachment. Models were constructed to correlate the results. The report includes a summary of the work performed and reprints of the publications describing the various studies. The folders in this supplement contain processed data in ASCII format. Streamwise pressure profiles and velocity profiles are included. The velocity profiles were acquired using single sensor and cross sensor hot-wire probes which were traversed from the wall to the freestream at various streamwise locations. In some of the flow control cases (3D Trips and Jets) profiles were acquired at multiple spanwise locations.

Maternal butalbital use and selected defects in the national birth defects prevention study.

PubMed

Browne, Marilyn L; Van Zutphen, Alissa R; Botto, Lorenzo D; Louik, Carol; Richardson, Sandra; Druschel, Charlotte M

2014-01-01

Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity. To evaluate associations between butalbital and a wide range of specific birth defects. The National Birth Defects Prevention Study is an ongoing, case-control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self-reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases. Seventy-three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07-8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25-14.62), and secundum-type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07-8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle. We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension-type headaches. © Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study.

PubMed

Rossow, H; Ollgren, J; Klemets, P; Pietarinen, I; Saikku, J; Pekkanen, E; Nikkari, S; Syrjälä, H; Kuusi, M; Nuorti, J P

2014-10-01

Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population information system. Data were collected using a self-administered questionnaire. A conditional logistic regression model addressing missing data with Bayesian full-likelihood modelling included 227 case patients and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9·2, 95% confidence interval (CI) 4·4-22, population-attributable risk (PAR) 82%] and farming activities (aOR 4·3, 95% CI 2·5-7·2, PAR 32%) were independently associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR 6·6, 95% CI 1·9-25·4, PAR 48%) was associated with pneumonic tularaemia. Although the bulk of tularaemia type B disease burden is attributable to mosquito bites, risk factors for ulceroglandular and pneumonic forms of tularaemia are different, enabling targeting of prevention efforts accordingly.

Association between bullous pemphigoid and neurologic diseases: a case-control study.

PubMed

Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

2014-11-01

In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

Three ADIPOR1 Polymorphisms and Cancer Risk: A Meta-Analysis of Case-Control Studies.

PubMed

Ye, Jiaxiang; Jiang, Li; Wu, Changliang; Liu, Aiqun; Mao, Sufei; Ge, Lianying

2015-01-01

Studies have come to conflicting conclusions about whether polymorphisms in the adiponectin receptor 1 gene (ADIPOR1) are associated with cancer risk. To help resolve this question, we meta-analyzed case-control studies in the literature. PubMed, EMBASE, Cochrane Library, the Chinese Biological Medical Database and the Chinese National Knowledge Infrastructure Database were systematically searched to identify all case-control studies published through February 2015 examining any ADIPOR1 polymorphisms and risk of any type of cancer. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 13 case-control studies involving 5,750 cases and 6,762 controls were analyzed. Analysis of the entire study population revealed a significant association between rs1342387(G/A) and overall cancer risk using a homozygous model (OR 0.82, 95%CI 0.72 to 0.94), heterozygous model (OR 0.84, 95%CI 0.76 to 0.93), dominant model (OR 0.85, 95%CI 0.75 to 0.97) and allele contrast model (OR 0.88, 95%CI 0.80 to 0.97). However, subgroup analysis showed that this association was significant only for Asians in the case of colorectal cancer. No significant associations were found between rs12733285(C/T) or rs7539542(C/G) and cancer risk, either in analyses of the entire study population or in analyses of subgroups. Our meta-analysis suggests that the ADIPOR1 rs1342387(G/A) polymorphism, but not rs12733285(C/T) or rs7539542(C/G), may be associated with cancer risk, especially risk of colorectal cancer in Asians. Large, well-designed studies are needed to verify our findings.

Sex Differences in Intimate Partner Violence and the Use of Coercive Control as a Motivational Factor for Intimate Partner Violence

ERIC Educational Resources Information Center

Tanha, Marieh; Beck, Connie J. A.; Figueredo, Aurelio Jose; Raghavan, Chitra

2010-01-01

Research argues that coercive control (CC) is a special case of intimate partner violence (IPV). The present study hypothesized that instead CC is the "motivator" for other types of IPV, with control of the victim as the goal. When CC fails, physical types of IPV are used. This hypothesized relationship was tested using a large matched sample of…

Differences in child versus parent reports of the child's health-related quality of life in children with epilepsy and healthy siblings.

PubMed

Baca, Christine Bower; Vickrey, Barbara G; Hays, Ron D; Vassar, Stefanie D; Berg, Anne T

2010-01-01

Self versus proxy perspectives may produce different results that are important for clinical decision-making and for assessing outcomes in research studies. We examined differences in child versus parent report of the child's health-related quality of life (HRQOL) in a large prospective, community-based study of newly diagnosed childhood epilepsy that included children with epilepsy (case) and sibling controls. HRQOL was assessed 8 to 9 years after initial diagnosis of epilepsy in a subset of 143 case-control matched pairs using the Child Health Questionnaire (CHQ), a generic HRQOL measure with child (CHQ-CF87), and parent (CHQ-PF50) versions. There were no significant differences between self-reported case and sibling control HRQOL scores on 9 of 11 scales or 2 global items. Nevertheless, parent ratings were significantly better (higher HRQOL) for sibling controls compared with epilepsy cases on 10 of 12 scales, global behavior and general health items, and the physical and psychosocial summary scores (P≤0.05). Parent-child agreement was low for cases and controls (kappa 0.27-0.33) for three single-item questions with the same wording on parent and child versions. Parent ratings of the case's HRQOL were often significantly associated with 5-year remission status and current antiepileptic drug use, but the case's self-reported HRQOL scores were not. In contrast, current pharmacoresistance was often associated with the child and parent ratings of the child's HRQOL. Children with epilepsy report HRQOL that is comparable to that of sibling controls, while parents rate children with epilepsy as having lower HRQOL than sibling controls. Measuring outcomes in studies of this population should incorporate both perspectives. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Home pesticide exposures and risk of childhood leukemia: Findings from the Childhood Leukemia International Consortium

PubMed Central

Bailey, Helen D; Infante-Rivard, Claire; Metayer, Catherine; Clavel, Jacqueline; Lightfoot, Tracy; Kaatsch, Peter; Roman, Eve; Magnani, Corrado; Spector, Logan G; Petridou, Eleni; Milne, Elizabeth; Dockerty, John D; Miligi, Lucia; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Simpson, Jill; Zhang, Luoping; Rondelli, Roberto; Baka, Margarita; Orsi, Laurent; Moschovi, Maria; Kang, Alice Y; Schüz, Joachim

2015-01-01

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium (CLIC). Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukaemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval (CI) 1.25, 1.55) (using (2,785 cases, 3635 controls), 1.43 (95% CI 1.32, 1.54) (5,055 cases, 7,370 controls) and 1.36 (95% CI 1.23, 1.51) (4,162 cases 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukaemia (AML) were 1.49 (95% CI 1.02, 2.16) (173 cases, 1,789 controls), 1.55 (95% CI 1.21, 1.99) (344 cases, 4,666 controls) and 1.08 (95% CI 0.76, 1.53) (198 cases, 2,655 controls) respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukaemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants’ exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate associations between home pesticide use and childhood leukaemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood. PMID:26061779

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.

PubMed

Sadetzki, Siegal; Langer, Chelsea Eastman; Bruchim, Revital; Kundi, Michael; Merletti, Franco; Vermeulen, Roel; Kromhout, Hans; Lee, Ae-Kyoung; Maslanyj, Myron; Sim, Malcolm R; Taki, Masao; Wiart, Joe; Armstrong, Bruce; Milne, Elizabeth; Benke, Geza; Schattner, Rosa; Hutter, Hans-Peter; Woehrer, Adelheid; Krewski, Daniel; Mohipp, Charmaine; Momoli, Franco; Ritvo, Paul; Spinelli, John; Lacour, Brigitte; Delmas, Dominique; Remen, Thomas; Radon, Katja; Weinmann, Tobias; Klostermann, Swaantje; Heinrich, Sabine; Petridou, Eleni; Bouka, Evdoxia; Panagopoulou, Paraskevi; Dikshit, Rajesh; Nagrani, Rajini; Even-Nir, Hadas; Chetrit, Angela; Maule, Milena; Migliore, Enrica; Filippini, Graziella; Miligi, Lucia; Mattioli, Stefano; Yamaguchi, Naohito; Kojimahara, Noriko; Ha, Mina; Choi, Kyung-Hwa; Mannetje, Andrea 't; Eng, Amanda; Woodward, Alistair; Carretero, Gema; Alguacil, Juan; Aragones, Nuria; Suare-Varela, Maria Morales; Goedhart, Geertje; Schouten-van Meeteren, A Antoinette Y N; Reedijk, A Ardine M J; Cardis, Elisabeth

2014-01-01

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.

Landscape and Residential Variables Associated with Plague-Endemic Villages in the West Nile Region of Uganda

PubMed Central

MacMillan, Katherine; Enscore, Russell E.; Ogen-Odoi, Asaph; Borchert, Jeff N.; Babi, Nackson; Amatre, Gerald; Atiku, Linda A.; Mead, Paul S.; Gage, Kenneth L.; Eisen, Rebecca J.

2011-01-01

Plague, caused by the bacteria Yersinia pestis, is a severe, often fatal disease. This study focuses on the plague-endemic West Nile region of Uganda, where limited information is available regarding environmental and behavioral risk factors associated with plague infection. We conducted observational surveys of 10 randomly selected huts within historically classified case and control villages (four each) two times during the dry season of 2006 (N = 78 case huts and N = 80 control huts), which immediately preceded a large plague outbreak. By coupling a previously published landscape-level statistical model of plague risk with this observational survey, we were able to identify potential residence-based risk factors for plague associated with huts within historic case or control villages (e.g., distance to neighboring homestead and presence of pigs near the home) and huts within areas previously predicted as elevated risk or low risk (e.g., corn and other annual crops grown near the home, water storage in the home, and processed commercial foods stored in the home). The identified variables are consistent with current ecologic theories on plague transmission dynamics. This preliminary study serves as a foundation for future case control studies in the area. PMID:21363983

Does case misclassification threaten the validity of studies investigating the relationship between neck manipulation and vertebral artery dissection stroke? No.

PubMed

Murphy, Donald R; Schneider, Michael J; Perle, Stephen M; Bise, Christopher G; Timko, Michael; Haas, Mitchell

2016-01-01

The purported relationship between cervical manipulative therapy (CMT) and stroke related to vertebral artery dissection (VAD) has been debated for several decades. A large number of publications, from case reports to case-control studies, have investigated this relationship. A recent article suggested that case misclassification in the case-control studies on this topic resulted in biased odds ratios in those studies. Given its rarity, the best epidemiologic research design for investigating the relationship between CMT and VAD is the case-control study. The addition of a case-crossover aspect further strengthens the scientific rigor of such studies by reducing bias. The most recent studies investigating the relationship between CMT and VAD indicate that the relationship is not causal. In fact, a comparable relationship between vertebral artery-related stroke and visits to a primary care physician has been observed. The statistical association between visits to chiropractors and VAD can best be explained as resulting from a patient with early manifestation of VAD (neck pain with or without headache) seeking the services of a chiropractor for relief of this pain. Sometime after the visit the patient experiences VAD-related stroke that would have occurred regardless of the care received. This explanation has been challenged by a recent article putting forth the argument that case misclassification is likely to have biased the odds ratios of the case-control studies that have investigated the association between CMT and vertebral artery related stroke. The challenge particularly focused on one of the case-control studies, which had concluded that the association between CMT and vertebral artery related stroke was not causal. It was suggested by the authors of the recent article that misclassification led to an underestimation of risk. We argue that the information presented in that article does not support the authors' claim for a variety of reasons, including the fact that the assumptions upon which their analysis is based lack substantiation and the fact that any possible misclassification would not have changed the conclusion of the study in question. Current evidence does not support the notion that misclassification threatens the validity of recent case-control studies investigating the relationship between CMT and VAD. Hence, the recent re-analysis cannot refute the conclusion from previous studies that CMT is not a cause of VAD.

Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

PubMed

Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

2016-01-01

Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

Segment-Wise Genome-Wide Association Analysis Identifies a Candidate Region Associated with Schizophrenia in Three Independent Samples

PubMed Central

Rietschel, Marcella; Mattheisen, Manuel; Breuer, René; Schulze, Thomas G.; Nöthen, Markus M.; Levinson, Douglas; Shi, Jianxin; Gejman, Pablo V.; Cichon, Sven; Ophoff, Roel A.

2012-01-01

Recent studies suggest that variation in complex disorders (e.g., schizophrenia) is explained by a large number of genetic variants with small effect size (Odds Ratio∼1.05–1.1). The statistical power to detect these genetic variants in Genome Wide Association (GWA) studies with large numbers of cases and controls (∼15,000) is still low. As it will be difficult to further increase sample size, we decided to explore an alternative method for analyzing GWA data in a study of schizophrenia, dramatically reducing the number of statistical tests. The underlying hypothesis was that at least some of the genetic variants related to a common outcome are collocated in segments of chromosomes at a wider scale than single genes. Our approach was therefore to study the association between relatively large segments of DNA and disease status. An association test was performed for each SNP and the number of nominally significant tests in a segment was counted. We then performed a permutation-based binomial test to determine whether this region contained significantly more nominally significant SNPs than expected under the null hypothesis of no association, taking linkage into account. Genome Wide Association data of three independent schizophrenia case/control cohorts with European ancestry (Dutch, German, and US) using segments of DNA with variable length (2 to 32 Mbp) was analyzed. Using this approach we identified a region at chromosome 5q23.3-q31.3 (128–160 Mbp) that was significantly enriched with nominally associated SNPs in three independent case-control samples. We conclude that considering relatively wide segments of chromosomes may reveal reliable relationships between the genome and schizophrenia, suggesting novel methodological possibilities as well as raising theoretical questions. PMID:22723893

Using genetic prediction from known complex disease Loci to guide the design of next-generation sequencing experiments.

PubMed

Jostins, Luke; Levine, Adam P; Barrett, Jeffrey C

2013-01-01

A central focus of complex disease genetics after genome-wide association studies (GWAS) is to identify low frequency and rare risk variants, which may account for an important fraction of disease heritability unexplained by GWAS. A profusion of studies using next-generation sequencing are seeking such risk alleles. We describe how already-known complex trait loci (largely from GWAS) can be used to guide the design of these new studies by selecting cases, controls, or families who are most likely to harbor undiscovered risk alleles. We show that genetic risk prediction can select unrelated cases from large cohorts who are enriched for unknown risk factors, or multiply-affected families that are more likely to harbor high-penetrance risk alleles. We derive the frequency of an undiscovered risk allele in selected cases and controls, and show how this relates to the variance explained by the risk score, the disease prevalence and the population frequency of the risk allele. We also describe a new method for informing the design of sequencing studies using genetic risk prediction in large partially-genotyped families using an extension of the Inside-Outside algorithm for inference on trees. We explore several study design scenarios using both simulated and real data, and show that in many cases genetic risk prediction can provide significant increases in power to detect low-frequency and rare risk alleles. The same approach can also be used to aid discovery of non-genetic risk factors, suggesting possible future utility of genetic risk prediction in conventional epidemiology. Software implementing the methods in this paper is available in the R package Mangrove.

Non-linear coherent mode interactions and the control of shear layers

NASA Technical Reports Server (NTRS)

Nikitopoulos, D. E.; Liu, J. T. C.

1990-01-01

A nonlinear integral formulation, based on local linear stability considerations, is used to study the collective interactions between discrete wave-modes associated with large-scale structures and the mean flow in a developing shear layer. Aspects of shear layer control are examined in light of the sensitivity of these interactions to the initial frequency parameter, modal energy contents and modal phases. Manipulation of the large-scale structure is argued to be an effective means of controlling the flow, including the small-scale turbulence dominated region far downstream. Cases of fundamental, 1st and 2nd subharmonic forcing are discussed in conjunction with relevant experiments.

Laterality defects in the national birth defects prevention study 1998-2007 birth prevalence and descriptive epidemiology

USDA-ARS?s Scientific Manuscript database

Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007...

Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies

USDA-ARS?s Scientific Manuscript database

Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three la...

Moving into a new era of periodontal genetic studies: relevance of large case-control samples using severe phenotypes for genome-wide association studies.

PubMed

Vaithilingam, R D; Safii, S H; Baharuddin, N A; Ng, C C; Cheong, S C; Bartold, P M; Schaefer, A S; Loos, B G

2014-12-01

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial 'hypothesis-dependent' candidate-gene polymorphism studies did not report valid genetic risk loci. Following a large-scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of 'hypothesis-free' genome-wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published - one reported genome-wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well-designed genetic study with large and sufficiently powered case-control samples of severe phenotypes, are also discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish nationwide case-control study.

PubMed

Mourtzinis, Georgios; Adamsson Eryd, Samuel; Rosengren, Annika; Björck, Lena; Adiels, Martin; Johannsson, Gudmundur; Manhem, Karin

2018-05-01

Background Atrial fibrillation is associated with hyperthyroidism. Patients with primary aldosteronism have an increased prevalence of atrial fibrillation. However, the prevalence of primary aldosteronism in the atrial fibrillation population is unknown. Aim This nationwide case-control study aimed to compare the prevalence of primary aldosteronism and thyroid disorders in patients with atrial fibrillation with that of age- and sex-matched controls. Methods We identified all atrial fibrillation cases in Sweden between 1987 and 2013 ( n = 713,569) by using the Swedish National Patient Register. A control cohort without atrial fibrillation was randomly selected from the Swedish Total Population Register with a case to control ratio of 1:2. This control cohort was matched for age, sex and place of birth ( n = 1,393,953). Results The prevalence of primary aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and 0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9% in the atrial fibrillation cohort and 3.7% in controls. The prevalence of hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls. Conclusion This study shows, for the first time, a doubled prevalence of primary aldosteronism in a large cohort of patients with atrial fibrillation compared with the general population. There is also an increased prevalence of hypo- and hyper-thyroidism in patients with atrial fibrillation compared with the general population.

Premalignant gastric lesions in patients with gastric mucosa-associated lymphoid tissue lymphoma and metachronous gastric adenocarcinoma: a case-control study.

PubMed

Capelle, Lisette G; den Hoed, Caroline M; de Vries, Annemarie C; Biermann, Katharina; Casparie, Mariel K; Meijer, Gerrit A; Kuipers, Ernst J

2012-01-01

Patients with gastric mucosa-associated lymphoid tissue lymphoma or diffuse large B-cell lymphoma have an increased risk of developing gastric carcinoma (GC). Identifying patients at high GC risk may lead to improved survival and prognosis. The aim of this case-control study was to evaluate whether premalignant gastric lesions are more prevalent and severe in gastric lymphoma (GL) patients with a subsequent diagnosis of GC than in those without GC. Patients with a first GL diagnosis from 1991-2008 were identified in the Dutch histopathology registry (PALGA). Cases were patients with a diagnosis of GL and a subsequent diagnosis of GC. Controls were patients with a diagnosis of GL without GC development. In total, eight cases (mean follow-up 5.5 years) and 31 controls (mean follow-up 5.3 years) were included (mean age 60 years). At lymphoma diagnosis, six (75%) cases were diagnosed with premalignant lesions, whereas in the control group, 21 (68%) had histological evidence for premalignant lesions (P=0.69). At GC diagnosis, five (63%) cases showed intestinal metaplasia in the surrounding gastric mucosa. In 22 (71%) controls premalignant lesions were present at the end of follow-up (P=0.47). No differences were demonstrated in the prevalence of premalignant lesions of cases and controls at GL diagnosis or the end of follow-up. As the prevalence of premalignant lesions is substantial in both the groups of patients, careful endoscopic surveillance of GL patients is warranted not only for recurrence of lymphoma, but also for progression to adenocarcinoma.

[The IARC carcinogenicity evaluation of radio-frequency electromagnetic field: with special reference to epidemiology of mobile phone use and brain tumor risk].

PubMed

Yamaguchi, Naohito

2013-01-01

The International Agency for Research on Cancer of World Health Organization announced in May 2011 the results of evaluation of carcinogenicity of radio-frequency electromagnetic field. In the overall evaluation, the radio-frequency electromagnetic field was classified as "possibly carcinogenic to humans", on the basis of the fact that the evidence provided by epidemiological studies and animal bioassays was limited. Regarding epidemiology, the results of the Interphone Study, an international collaborative case-control study, were of special importance, together with the results of a prospective cohort study in Denmark, case-control studies in several countries, and a case-case study in Japan. The evidence obtained was considered limited, because the increased risk observed in some studies was possibly spurious, caused by selection bias or recall bias as well as residual effects of confounding factors. Further research studies, such as large-scale multinational epidemiological studies, are crucially needed to establish a sound evidence base from which a more conclusive judgment can be made for the carcinogenicity of the radio-frequency electromagnetic field.

Application of Standard Project Management Tools to Research--A Case Study from a Multi-National Clinical Trial

ERIC Educational Resources Information Center

Gist, Peter; Langley, David

2007-01-01

PRINCE2, which stands for Projects in Controlled Environments, is a project management method covering the organisation, management, and control of projects and is widely used in both government and commercial IT and building projects in the UK. This paper describes the application of PRINCE2 to the management of large clinical trials…

Data Management and Data Quality in PERCH, a Large International Case-Control Study of Severe Childhood Pneumonia.

PubMed

Watson, Nora L; Prosperi, Christine; Driscoll, Amanda J; Higdon, Melissa M; Park, Daniel E; Sanza, Megan; DeLuca, Andrea N; Awori, Juliet O; Goswami, Doli; Hammond, Emily; Hossain, Lokman; Johnson, Catherine; Kamau, Alice; Kuwanda, Locadiah; Moore, David P; Neyzari, Omid; Onwuchekwa, Uma; Parker, David; Sapchookul, Patranuch; Seidenberg, Phil; Shamsul, Arifin; Siazeele, Kazungu; Srisaengchai, Prasong; Sylla, Mamadou; Levine, Orin S; Murdoch, David R; O'Brien, Katherine L; Wolff, Mark; Deloria Knoll, Maria

2017-06-15

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Modeling the effect of control on the wake of a utility-scale turbine via large-eddy simulation

NASA Astrophysics Data System (ADS)

Yang, Xiaolei; Annoni, Jennifer; Seiler, Pete; Sotiropoulos, Fotis

2014-06-01

A model of the University of Minnesota EOLOS research turbine (Clipper Liberty C96) is developed, integrating the C96 torque control law with a high fidelity actuator line large- eddy simulation (LES) model. Good agreement with the blade element momentum theory is obtained for the power coefficient curve under uniform inflow. Three different cases, fixed rotor rotational speed ω, fixed tip-speed ratio (TSR) and generator torque control, have been simulated for turbulent inflow. With approximately the same time-averaged ω, the time- averaged power is in good agreement with measurements for all three cases. Although the time-averaged aerodynamic torque is nearly the same for the three cases, the root-mean-square (rms) of the aerodynamic torque fluctuations is significantly larger for the case with fixed ω. No significant differences have been observed for the time-averaged flow fields behind the turbine for these three cases.

A large outbreak of mumps in the postvaccine era.

PubMed

Wharton, M; Cochi, S L; Hutcheson, R H; Bistowish, J M; Schaffner, W

1988-12-01

During a county-wide mumps outbreak in Nashville, Tennessee, 332 cases of mumps were identified at a public high school (attack rate, 18.8%). A pep rally 17 d before the peak of the outbreak at a single public high school may have provided an opportunity for point-source exposure. A case-control study demonstrated that vaccine efficacy was 75% (we used provider-verified records and excluded students with a history of mumps disease). Although school records were nonuniform, mumps immunization status was correct, compared with provider-verified records, in at least 85% of both cases and controls. Parental reports were much less reliable. The cost of the outbreak was estimated at $154/case. Receiving mumps vaccine at a vaccine clinic held after the outbreak had peaked was associated with a decrease in risk of mumps disease. Thus, these clinics may have a role in the control of such outbreaks.

Frictional processes of bimaterial interfaces at seismic slip rates.

NASA Astrophysics Data System (ADS)

Passelegue, F. X.; Fabbri, O.; Leclère, H.; Spagnuolo, E.; Di Toro, G.

2017-12-01

Large subduction earthquakes ruptures propagate from crustal rock toward the sea floor along frictional interfaces of different lythologies. Up to now, frictional processes of rocks were mainly investigated along single material experimental faults. Here, we present the results of high velocity friction experiments coupled with high frequency acoustic monitoring system on biomaterial interfaces including gabbro, pyroxenite and serpentinized peridotite (>95%), following a recent field investigation highlighting bimaterial contacts in the Corsica ophiolitic nappe. We first studied the frictional processes of single materials which result in a mechanical behaviour comparable to previous studies. Both gabbro and pyroxenite exhibit two weakening stages. The first one corresponds to flash heating and the second stage occurs concomitantly with complete melting of the interface. In the case of serpentinite, only one weakening stage is observed, after a weakening slip distance of only few centimeters. We then conducted bimaterial experiments. The two couples tested were gabbro/pyroxenite and gabbro/serpentinite, as observed along natural fault zones (Corsica, France). In the case of gabbro/serpentinite, we observe that frictional processes are controlled by serpentinite. Mechanical curves replicate the behaviour of single serpentinite friction experiments. We observe that few melting occurs, and that the product of experiments consists in fine grained cataclasite, as observed in the field. The case of gabbro/pyroxenite is more complicated. The first weakening is controlled by the lithology of the sample installed on the static part of the rotary apparatus. However, the second weakening is controlled by the gabbro and mechanical curves are identical than those obtained in the case of single gabbro experiments. Supported by microstructural analysis and acoustic activity, our results suggest that frictional processes of bimaterial interfaces are controlled by the material presenting the lower weakening temperature. Finally, we show that bimaterial interfaces are expected to affect locally the rate of the stress transfer during large earthquakes, and induce accelerations or decelerations of the rupture front, explaining local emissions of high frequencies recorded during large ruptures.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

PubMed

Litvan, Irene; Lees, Peter S J; Cunningham, Christopher R; Rai, Shesh N; Cambon, Alexander C; Standaert, David G; Marras, Connie; Juncos, Jorge; Riley, David; Reich, Stephen; Hall, Deborah; Kluger, Benzi; Bordelon, Yvette; Shprecher, David R

2016-05-01

The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control Studies Conducted Between 1985 and 2010

PubMed Central

Olsson, Ann C.; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W.; ‘t Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

2013-01-01

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

α1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

PubMed Central

Sørheim, Inga-Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G.; Johannessen, Ane; Gaarder, Per I.; Campbell, Edward J.; Agustí, Alvar; Calverley, Peter M. A.; Donner, Claudio F.; Make, Barry J.; Rennard, Stephen I.; Vestbo, Jørgen; Wouters, Emiel F. M.; Paré, Peter D.; Levy, Robert D.; Coxson, Harvey O.; Lomas, David A.; Hersh, Craig P.

2010-01-01

Background: Severe α1-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1-antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals. PMID:20595457

Data Integrity-A Study of Current Regulatory Thinking and Action.

PubMed

Shafiei, Nader; De Montardy, Regis; Rivera-Martinez, Edwin

2015-01-01

In reaction to breaches of data integrity in the pharmaceutical industry, regulatory authorities have introduced inspection approaches or initiatives with the aim of reducing occurrences of data integrity problems. This review article-based on study of 65 cases of regulatory action from 2002 to 2014-provides an overview of current regulatory thinking and action on breaches of data integrity affecting GxP (health-related regulations) processes supporting non-clinical studies, clinical studies, laboratory controls, and production controls. These case studies largely represent position of the U.S. Food and Drug Administration and the regulatory agencies affiliated with the European Medicines Agency. Also discussed is the role of human factors as a potential source of data integrity problems. The article concludes by recommending some remedial controls that could be established to avoid or reduce occurrences of data integrity problems.Lay Abstract: In fulfilling their mission to protect public health, regulatory agencies (e.g., U.S. Food and Drug Administration, European Medicines Agency) must establish confidence that medical products they approve are fit for their intended use. In so doing they rely on scientific and operational data generated during research, development, manufacturing, sales, marketing, distribution, and post-marketing surveillance activities. The level of confidence they build is directly proportional to the scientific validity and integrity of data presented to them by the sponsors of medical products. In this article we present analysis of 65 case studies that document regulatory action taken by various regulatory agencies on breach of data integrity between 2002 and 2014. The ensuing discussion on current trends largely represents position of the U.S. Food and Drug Administration and European Medicines Agency. The article concludes by proposing some remedial controls that could be established by pharmaceutical companies to avoid or reduce occurrences of data integrity problems. © PDA, Inc. 2015.

Analyzing self-controlled case series data when case confirmation rates are estimated from an internal validation sample.

PubMed

Xu, Stanley; Clarke, Christina L; Newcomer, Sophia R; Daley, Matthew F; Glanz, Jason M

2018-05-16

Vaccine safety studies are often electronic health record (EHR)-based observational studies. These studies often face significant methodological challenges, including confounding and misclassification of adverse event. Vaccine safety researchers use self-controlled case series (SCCS) study design to handle confounding effect and employ medical chart review to ascertain cases that are identified using EHR data. However, for common adverse events, limited resources often make it impossible to adjudicate all adverse events observed in electronic data. In this paper, we considered four approaches for analyzing SCCS data with confirmation rates estimated from an internal validation sample: (1) observed cases, (2) confirmed cases only, (3) known confirmation rate, and (4) multiple imputation (MI). We conducted a simulation study to evaluate these four approaches using type I error rates, percent bias, and empirical power. Our simulation results suggest that when misclassification of adverse events is present, approaches such as observed cases, confirmed case only, and known confirmation rate may inflate the type I error, yield biased point estimates, and affect statistical power. The multiple imputation approach considers the uncertainty of estimated confirmation rates from an internal validation sample, yields a proper type I error rate, largely unbiased point estimate, proper variance estimate, and statistical power. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environment And Genetics in Lung cancer Etiology (EAGLE) study: an integrative population-based case-control study of lung cancer.

PubMed

Landi, Maria Teresa; Consonni, Dario; Rotunno, Melissa; Bergen, Andrew W; Goldstein, Alisa M; Lubin, Jay H; Goldin, Lynn; Alavanja, Michael; Morgan, Glen; Subar, Amy F; Linnoila, Ilona; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Tucker, Margaret; Wacholder, Sholom; Pesatori, Angela C; Caporaso, Neil E; Bertazzi, Pier Alberto

2008-06-06

Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor cases in Spain.

PubMed

Louis, Elan D; Benito-León, Julian; Moreno-García, Sara; Vega, Saturio; Romero, Juan Pablo; Bermejo-Pareja, Felix; Gerbin, Marina; Viner, Amanda S; Factor-Litvak, Pam; Jiang, Wendy; Zheng, Wei

2013-01-01

Environmental correlates for essential tremor (ET) are largely unexplored. The search for such environmental factors has involved the study of a number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin. In two prior case-control studies in New York, we demonstrated that blood harmane concentration was elevated in ET patients vs. controls, and especially in familial ET cases. These findings, however, have been derived from a study of cases ascertained through a single tertiary referral center in New York. Our objective was to determine whether blood harmane concentrations are elevated in familial and sporadic ET cases, ascertained from central Spain, compared to controls without ET. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method. The median harmane concentrations were: 2.09 g(-10)/ml (138 controls), 2.41 g(-10)/ml (68 sporadic ET), and 2.90 g(-10)/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood harmane concentration was not significantly associated with diagnosis (familial ET vs. control): odds ratio=1.56, p=0.26. In a logistic regression analysis that adjusted for evaluation start time, which was an important confounding variable, the odds ratio increased to 2.35, p=0.049. Blood harmane levels were slightly elevated in a group of familial ET cases compared to a group of controls in Spain. These data seem to further extend our observations from New York to a second cohort of ET cases in Spain. This neurotoxin continues to be a source of interest for future confirmatory research. Copyright © 2012 Elsevier Inc. All rights reserved.

BLOOD HARMANE (1-METHYL-9H-PYRIDO[3,4-B]INDOLE) CONCENTRATION IN ESSENTIAL TREMOR CASES IN SPAIN

PubMed Central

Louis, Elan D.; Benito-León, Julian; Moreno-García, Sara; Vega, Saturio; Romero, Juan Pablo; Bermejo-Pareja, Felix; Gerbin, Marina; Viner, Amanda S.; Factor-Litvak, Pam; Jiang, Wendy; Zheng, Wei

2012-01-01

Background Environmental correlates for essential tremor (ET) are largely unexplored. The search for such environmental factors has involved the study of a number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin. In two prior case-control studies in New York, we demonstrated that blood harmane concentration was elevated in ET patients vs. controls, and especially in familial ET cases. These findings, however, have been derived from a study of cases ascertained through a single tertiary referral center in New York. Objective Our objective was to determine whether blood harmane concentrations are elevated in familial and sporadic ET cases, ascertained from central Spain, compared to controls without ET. Methods Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method. Results The median harmane concentrations were: 2.09 g−10/ml (138 controls), 2.41 g−10/ml (68 sporadic ET), and 2.90 g−10/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood harmane concentration was not significantly associated with diagnosis (familial ET vs. control): odds ratio = 1.56, p = 0.26. In a logistic regression analysis that adjusted for evaluation start time, which was an important confounding variable, the odds ratio increased to 2.35, p = 0.049. Conclusions Blood harmane levels were slightly elevated in a group of familial ET cases compared to a group of controls in Spain. These data seem to further extend our observations from New York to a second cohort of ET cases in Spain. This neurotoxin continues to be a source of interest for future confirmatory research. PMID:22981972

Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New Guinea in the era of conjugate vaccines: study methods and challenges.

PubMed

Blyth, Christopher C; Ford, Rebecca; Sapura, Joycelyn; Kumani, Tonny; Masiria, Geraldine; Kave, John; Yuasi, Lapule; Greenhill, Andrew; Hwaihwanje, Ilomo; Lang, Amanda; Lehmann, Deborah; Pomat, William

2017-01-01

Pneumonia and meningitis are common causes of severe childhood illness in Papua New Guinea (PNG). The etiology of both clinical conditions in PNG has not been recently assessed. Changes in lifestyle, provision and access to healthcare, antimicrobial utilization and resistance, and the national childhood vaccination schedule necessitate reassessment. A prospective case-control study was undertaken, enrolling children <5 years of age to determine the contemporary etiology of clinically defined moderate or severe pneumonia or suspected meningitis. Cases were identified following presentation for inpatient or outpatient care in Goroka town, the major population centre in the Eastern Highlands Province. Following enrolment, routine diagnostic specimens including blood, nasopharyngeal swabs, urine and (if required) cerebrospinal fluid, were obtained. Cases residing within one hour's drive of Goroka were followed up, and recruitment of healthy contemporaneous controls was undertaken in the cases' communities. 998 cases and 978 controls were enrolled over 3 years. This included 784 cases (78.6%) with moderate pneumonia, 187 (18.7%) with severe pneumonia and 75 (7.5%) with suspected meningitis, of whom 48 (4.8%) had concurrent pneumonia. The median age of cases was 7.8 months (Interquartile range [IQR] 3.9-14.3), significantly lower than community controls, which was 20.8 months (IQR 8.2-36.4). Half the cases were admitted to hospital (500/998; 50.1%). Recruitment of cases and controls and successful collection of diagnostic specimens improved throughout the study, with blood volume increasing and rates of blood culture contamination decreasing. The overall case fatality rate was 18/998 (1.8%). Of cases eligible for follow-up, outcome data was available from 76.7%. Low but increasing coverage of Haemophilus influenzae type B conjugate vaccines on the national schedule was observed during the study period: three dose DTPw-HepB-Hib coverage in children >3 months increased from 14.9 to 43.0% and 29.0 to 47.7% in cases and controls (both p  < 0.001). Despite inclusion in the national immunization program in 2014, 2015 PCV13 three-dose coverage in cases and controls >3 months was only 4.0 and 6.5%. Recruitment of large numbers of pediatric pneumonia and meningitis cases and community controls in a third-world setting presents unique challenges. Successful enrolment of 998 cases and 978 controls with comprehensive clinical data, biological specimens and follow up was achieved. Increased vaccine coverage remains an ongoing health priority.

Laryngopyocele: report of a rare case and systematic review.

PubMed

Al-Yahya, Syarifah N; Baki, Marina Mat; Saad, Sakina Mohd; Azman, Mawaddah; Mohamad, Abdullah Sani

2016-01-01

A systematic review on laryngopyoceles across Ovid, PubMed, and Google Scholar database was conducted. A total of 61 papers published between 1952 and 2015 were found. Of these, 23 cases written in English, which described the number of cases, surgical approaches, resort to tracheostomy, complications, and outcomes, were shortlisted. Four cases of laryngopyoceles were managed endoscopically using a cold instrument, microdebrider, or laser. Eighteen cases were operated via an external approach, and 1 case applied both approaches. One of 4 endoscopic and 10 of 18 external approaches involved tracheostomy. The present study aimed to report a case of large mixed laryngopyocele that was successfully drained and marsupialized endoscopically using suction diathermy without requiring tracheostomy. Management using suction diathermy for excision and marsupialization of a laryngopyocele has never been reported and can be recommended as a feasible method due to its widespread availability. In the presence of a large laryngopyocele impeding the airway, tracheostomy may be averted in a controlled setting. None specified.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

2015-03-01

To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

Baldness and testicular cancer: the EPSAM case-control study.

PubMed

Moirano, G; Zugna, D; Grasso, C; Lista, P; Ciuffreda, L; Segnan, N; Merletti, F; Richiardi, L

2016-03-01

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk. © 2016 American Society of Andrology and European Academy of Andrology.

Experimental comparison of conventional and nonlinear model-based control of a mixing tank

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

Haeggblom, K.E.

1993-11-01

In this case study concerning control of a laboratory-scale mixing tank, conventional multiloop single-input single-output (SISO) control is compared with model-based'' control where the nonlinearity and multivariable characteristics of the process are explicitly taken into account. It is shown, especially if the operating range of the process is large, that the two outputs (level and temperature) cannot be adequately controlled by multiloop SISO control even if gain scheduling is used. By nonlinear multiple-input multiple-output (MIMO) control, on the other hand, very good control performance is obtained. The basic approach to nonlinear control used in this study is first to transformmore » the process into a globally linear and decoupled system, and then to design controllers for this system. Because of the properties of the resulting MIMO system, the controller design is very easy. Two nonlinear control system designs based on a steady-state and a dynamic model, respectively, are considered. In the dynamic case, both setpoint tracking and disturbance rejection can be addressed separately.« less

Risk Factors for SARS among Persons without Known Contact with SARS Patients, Beijing, China

PubMed Central

Wu, Jiang; Xu, Fujie; Zhou, Weigong; Feikin, Daniel R.; Lin, Chang-Ying; He, Xiong; Zhu, Zonghan; Liang, Wannian; Chin, Daniel P.

2004-01-01

Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing’s strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community’s use of this strategy. PMID:15030685

Systemic arterial embolization in patients with hemoptysis: initial experience with ethylene vinyl alcohol copolymer in 15 cases.

PubMed

Khalil, Antoine; Fartoukh, Muriel; Bazot, Marc; Parrot, Antoine; Marsault, Claude; Carette, Marie-France

2010-01-01

The purpose of this study was a preliminary evaluation of the use of ethylene vinyl alcohol copolymer to treat patients with hemoptysis of systemic arterial origin. We reviewed the cases of 15 consecutively registered patients (10 men, five women; mean age, 53.7 years) who underwent endovascular administration of ethylene vinyl alcohol copolymer in the management of hemoptysis. The indications, immediate control of hemoptysis, and clinical tolerability were analyzed. The indications for embolization were mainly early recurrence of hemoptysis with reperfusion of systemic arteries in seven cases; unstable microcatheter in two cases; large ectopic bronchial artery in two cases; and, in one case each, bronchial arterial bleeding through a small anastomotic network, aneurysm of the left internal thoracic artery in a patient with invasive aspergillosis, a potentially risky connection between the bronchial and right coronary arteries, and occlusion of a systemic artery due to Pryce type 1 intralobar lung sequestration. Hemoptysis was controlled in all but one case and did not recur in the other 14 cases. The injection procedure was well tolerated. Ethylene vinyl alcohol copolymer embolization for hemoptysis of systemic arterial origin is feasible. The agent seems beneficial in the care of patients with recurrent hemoptysis after previous bronchial arterial embolization, patients who would be at high risk during embolization with microparticles, and patients who need embolization of large systemic arteries through small-caliber anastomoses.

Transport of fluorobenzoate tracers in a vegetated hydrologic control volume: 1. Experimental results

NASA Astrophysics Data System (ADS)

Queloz, Pierre; Bertuzzo, Enrico; Carraro, Luca; Botter, Gianluca; Miglietta, Franco; Rao, P. S. C.; Rinaldo, Andrea

2015-04-01

This paper reports about the experimental evidence collected on the transport of five fluorobenzoate tracers injected under controlled conditions in a vegetated hydrologic volume, a large lysimeter (fitted with load cells, sampling ports, and an underground chamber) where two willows prompting large evapotranspiration fluxes had been grown. The relevance of the study lies in the direct and indirect measures of the ways in which hydrologic fluxes, in this case, evapotranspiration from the upper surface and discharge from the bottom drainage, sample water and solutes in storage at different times under variable hydrologic forcings. Methods involve the accurate control of hydrologic inputs and outputs and a large number of suitable chemical analyses of water samples in discharge waters. Mass extraction from biomass has also been performed ex post. The results of the 2 year long experiment established that our initial premises on the tracers' behavior, known to be sorption-free under saturated conditions which we verified in column leaching tests, were unsuitable as large differences in mass recovery appeared. Issues on reactivity thus arose and were addressed in the paper, in this case attributed to microbial degradation and solute plant uptake. Our results suggest previously unknown features of fluorobenzoate compounds as hydrologic tracers, potentially interesting for catchment studies owing to their suitability for distinguishable multiple injections, and an outlook on direct experimental closures of mass balance in hydrologic transport volumes involving fluxes that are likely to sample differently stored water and solutes.

Epidemiological evidence of carcinogenicity of chlorinated organics in drinking water.

PubMed

Cantor, K P

1982-12-01

Concern has recently been voiced over possible chronic toxicity associated with chlorination of public drinking water supplies in the United States. This paper reviews the available evidence and the studies underway to further evaluate hypothesized associations between cancer risk and byproducts of chlorination. Preliminary data from measures of halogenated volatiles and personal exposure histories from respondents in a large epidemiologic study of bladder cancer are presented. These data support the use in epidemiologic studies of categorical measures of exposure and suggest that results from completed case-control studies, based on death certificates, may have underestimated the true risk of exposure to chlorination by-products. The current generation of studies which use a case-control interview design offer many advantages over earlier efforts to evaluate this issue.

Epidemiological evidence of carcinogenicity of chlorinated organics in drinking water.

PubMed Central

Cantor, K P

1982-01-01

Concern has recently been voiced over possible chronic toxicity associated with chlorination of public drinking water supplies in the United States. This paper reviews the available evidence and the studies underway to further evaluate hypothesized associations between cancer risk and byproducts of chlorination. Preliminary data from measures of halogenated volatiles and personal exposure histories from respondents in a large epidemiologic study of bladder cancer are presented. These data support the use in epidemiologic studies of categorical measures of exposure and suggest that results from completed case-control studies, based on death certificates, may have underestimated the true risk of exposure to chlorination by-products. The current generation of studies which use a case-control interview design offer many advantages over earlier efforts to evaluate this issue. PMID:6759108

Nonlinear neural control with power systems applications

NASA Astrophysics Data System (ADS)

Chen, Dingguo

1998-12-01

Extensive studies have been undertaken on the transient stability of large interconnected power systems with flexible ac transmission systems (FACTS) devices installed. Varieties of control methodologies have been proposed to stabilize the postfault system which would otherwise eventually lose stability without a proper control. Generally speaking, regular transient stability is well understood, but the mechanism of load-driven voltage instability or voltage collapse has not been well understood. The interaction of generator dynamics and load dynamics makes synthesis of stabilizing controllers even more challenging. There is currently increasing interest in the research of neural networks as identifiers and controllers for dealing with dynamic time-varying nonlinear systems. This study focuses on the development of novel artificial neural network architectures for identification and control with application to dynamic electric power systems so that the stability of the interconnected power systems, following large disturbances, and/or with the inclusion of uncertain loads, can be largely enhanced, and stable operations are guaranteed. The latitudinal neural network architecture is proposed for the purpose of system identification. It may be used for identification of nonlinear static/dynamic loads, which can be further used for static/dynamic voltage stability analysis. The properties associated with this architecture are investigated. A neural network methodology is proposed for dealing with load modeling and voltage stability analysis. Based on the neural network models of loads, voltage stability analysis evolves, and modal analysis is performed. Simulation results are also provided. The transient stability problem is studied with consideration of load effects. The hierarchical neural control scheme is developed. Trajectory-following policy is used so that the hierarchical neural controller performs as almost well for non-nominal cases as they do for the nominal cases. The adaptive hierarchical neural control scheme is also proposed to deal with the time-varying nature of loads. Further, adaptive neural control, which is based on the on-line updating of the weights and biases of the neural networks, is studied. Simulations provided on the faulted power systems with unknown loads suggest that the proposed adaptive hierarchical neural control schemes should be useful for practical power applications.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw.

PubMed

Borromeo, Gelsomina L; Brand, Caroline; Clement, John G; McCullough, Michael; Crighton, Lisa; Hepworth, Graham; Wark, John D

2014-06-01

This study sought to investigate, using a case-control study design, the association between bisphosphonate therapy and delayed dental healing and osteonecrosis of the jaw. Identification of potential cases of delayed dental healing was by consecutive screening of Specialist Oral and Maxillofacial and Special Needs Dentist clinic records for patients aged older than 50 years, during a 6-month window, in Victoria, Australia. Cases were confirmed by a case adjudication panel blinded to bisphosphonate status. Cases associated with malignancy or local radiotherapy were excluded. Controls were matched for age, sex, and source of dental referral (1:4, n = 160 controls). Variables of interest were dental precipitants, dental clinic type, smoking history, and medical comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio (OR) for developing delayed dental healing when taking an oral bisphosphonate was 13.1 (95% confidence interval [CI] 4.4 to 39.3; p < 0.001). There were no cases associated with intravenous bisphosphonate use. There was some evidence of an interaction with age, sex, and clinic type. When adjusted for smoking, the estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an association between having another illness and delayed dental healing (OR = 2.3; 95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed dental healing cases. An important association between bisphosphonate use and delayed dental healing in the setting of benign bone disease, predominately in individuals with a dental precipitant, has been demonstrated. © 2014 American Society for Bone and Mineral Research.

Medical and Non-Medical Factors Influencing Utilization of Delayed Pushing in the Second Stage

PubMed Central

FREY, Heather A.; TUULI, Methodius G.; CORTEZ, Sarah; ODIBO, Anthony O.; ROEHL, Kimberly A.; SHANKS, Anthony L.; MACONES, George A.; CAHILL, Alison G.

2014-01-01

Objective To evaluate factors impacting selection to delayed pushing in the second stage of labor. Study design This case-control study was a secondary analysis of a large retrospective cohort study. Cases included women who delayed pushing for 60 minutes or more in the second stage of labor. Controls began pushing prior to 60 minutes from the time of diagnosis of complete dilation. Demographic, labor, and nonmedical factors were compared among cases and controls. Logistic regression modelling was used to identify factors independently associated with delayed pushing. Results We identified 471 women who delayed pushing and 4,819 controls. Nulliparity, maternal body mass index > 25, high fetal station at complete dilation, regional anesthesia use, and start of second stage during staffing shift change were independent factors associated with increased use of delayed pushing. On the other hand, black race and second stage management during night shift were associated with lower odds of employing delayed pushing. Delayed pushing was more commonly employed in nulliparous women, but 38.9% of multiparous women also delayed pushing. Conclusion We identified multiple factors associated with use of delayed pushing. This study helps to define current patterns of second stage labor management. PMID:23208765

STREET SURFACE STORAGE FOR CONTROL OF COMBINED SEWER SURCHARGE

EPA Science Inventory

One type of Best Management Practices (BMPs) available is the use of street storage systems to prevent combined sewer surcharging and to mitigate basement flooding. A case study approach, based primarily on two largely implemented street storage systems, will be used to explain ...

Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

PubMed

2011-09-01

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

Novel application of the matched case-control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016.

PubMed

Inns, Thomas; Cleary, Paul; Bundle, Nick; Foulkes, Sarah; Sharp, Ashley; Utsi, Lara; McBrien, Chris; Teagle, Rehman; Waldram, Alison; Williams, Chris; McCann, Cathy; Smith, Rob; Saleh, Sepeedeh; McCarthy, Noel; Vivancos, Roberto; Hawker, Jeremy; Decraene, Valerie

2018-05-01

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of Escherichia coli O157 PT34 infection in the United Kingdom in 2016 indicated that catering venues associated with multiple cases had used salad leaves sourced from one supplier. Our aim was to investigate whether catering venues linked to cases were more likely to have used salad leaves from this supplier. We conducted a matched case-control study, with catering venues as the units of analysis. We compared venues linked to cases to those without known linked cases. We included 43 study pairs and obtained information on salad leaf products received by each venue. The odds of a case venue being supplied with salad leaves by Supplier A were 7.67 times (95% confidence interval: 2.30-25.53) those of control venues. This association provided statistical evidence to support the findings of the other epidemiological investigations undertaken for this outbreak. This is a novel approach which is labour-intensive but which addresses the challenge of investigating exposures to food across a complex distribution network.

Optimal decentralized feedback control for a truss structure

NASA Technical Reports Server (NTRS)

Cagle, A.; Ozguner, U.

1989-01-01

One approach to the decentralized control of large flexible space structures involves the design of controllers for the substructures of large systems and their subsequent application to the entire coupled system. This approach is presently developed for the case of active vibration damping on an experimental large struss structure. The isolated boundary loading method is used to define component models by FEM; component controllers are designed using an interlocking control concept which minimizes the motion of the boundary nodes, thereby reducing the exchange of mechanical disturbances among components.

Patterns of anti-inflammatory drug use and risk of dementia: a matched case-control study.

PubMed

Dregan, A; Chowienczyk, P; Armstrong, D

2015-11-01

There is limited primary-care-based evidence about a potential association between anti-inflammatory therapy and dementia subtypes. The present study addressed this limitation by using electronic health records from a large primary care database. A case-control study was implemented using electronic medical records. Cases had a diagnosis of dementia between 1992 and 2014. Up to four controls matched on age, gender, family practice and index date were selected for each case. Use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoid drugs represented the exposure variables. Primary outcome measures included all-cause dementia and main dementia subtypes, including Alzheimer disease (AD), vascular dementia (VaD) and Lewy body dementia (LBD). Data were analysed using conditional logistic regression. The study identified 31,083 patients with AD, 23,465 with VaD and 1694 with LBD. Ever-used NSAIDs were associated with a modest increase in the risk of all-cause dementia (odds ratio 1.04, 95% confidence interval 1.02-1.05, P < 0.006), whilst no association was apparent for ever-used glucocorticoids (0.98, 0.96-1.01, P = 0.152). There was no evidence for an association between NSAIDs and AD (1.03, 0.99-1.06, P = 0.07) or LBD (1.13, 0.99-1.29, P = 0.08). However, a significant increase in the risk for VaD (1.33, 1.29-1.38, P < 0.001) was observed. Similar patterns emerged for glucocorticoid therapy. In a large primary care population, there was no robust evidence for a potential association between anti-inflammatory drugs and risk of AD or LBD. NSAIDs and glucocorticoid drugs were associated with higher risk of VaD. © 2015 EAN.

Theoretical and experimental study on active sound transmission control based on single structural mode actuation using point force actuators.

PubMed

Sanada, Akira; Tanaka, Nobuo

2012-08-01

This study deals with the feedforward active control of sound transmission through a simply supported rectangular panel using vibration actuators. The control effect largely depends on the excitation method, including the number and locations of actuators. In order to obtain a large control effect at low frequencies over a wide frequency, an active transmission control method based on single structural mode actuation is proposed. Then, with the goal of examining the feasibility of the proposed method, the (1, 3) mode is selected as the target mode and a modal actuation method in combination with six point force actuators is considered. Assuming that a single input single output feedforward control is used, sound transmission in the case minimizing the transmitted sound power is calculated for some actuation methods. Simulation results showed that the (1, 3) modal actuation is globally effective at reducing the sound transmission by more than 10 dB in the low-frequency range for both normal and oblique incidences. Finally, experimental results also showed that a large reduction could be achieved in the low-frequency range, which proves the validity and feasibility of the proposed method.

Iodinated Contrast Media-Induced Thyroid Dysfunction in Euthyroid Nodular Goiter Patients.

PubMed

Kornelius, Edy; Chiou, Jeng-Yuan; Yang, Yi-Sun; Lo, Shih-Chang; Peng, Chiung-Huei; Lai, Yung-Rung; Huang, Chien-Ning

2016-08-01

The risks of thyroid dysfunction after iodinated contrast media exposure in patients with euthyroid nodular goiter are largely unknown. This observational, retrospective cohort study included a random selection of one million people in Taiwan. All patients with iodinated contrast media exposure during this study period were selected. Patients with euthyroid nodular goiter were identified as cases, while patients without thyroid nodule were selected as controls. We followed these patients until the first event of thyroid dysfunction including hyperthyroidism or hypothyroidism after iodinated contrast media exposure. A total of 334 cases and 2672 matched controls were selected in this study. The mean age of cases and controls were 58.6 and 58.4 years old, and mean follow-up durations were 2.1 and 2 years respectively. After adjustment, patients with euthyroid nodular goiter had a higher risk of thyroid dysfunction (hazard ratio 5.43, [confidence interval (CI) 3.01-9.80]) compared with controls after iodinated contrast media exposure. In the subgroup analysis, the risks of hyperthyroidism and hypothyroidism in cases compared with controls were 5.77 [CI 2.64-12.62] and 4.95 [CI 2.15-11.40] respectively. Half of the euthyroid nodular goiter cases developed thyroid dysfunction within one year after iodinated contrast media exposure. Interestingly, all thyroid-related comorbidities and drug prescriptions did not increase the risk of thyroid dysfunction. Presence of euthyroid nodular goiter was associated with higher risk of thyroid dysfunction including hyperthyroidism and hypothyroidism after iodinated contrast media exposure.

Added value of a household-level study during an outbreak investigation of Salmonella serotype Saintpaul infections, New Mexico 2008

PubMed Central

Boore, A. L.; Jungk, J.; Russo, E.T.; Redd, J.T.; Angulo, F. J.; Williams, I. T.; Cheek, J. E.; Gould, L. H.

2015-01-01

SUMMARY In 2008, nationwide investigations of a Salmonella serotype Saintpaul outbreak led first to consumer warnings for Roma and red round tomatoes, then later for jalapeño and serrano peppers. In New Mexico, where there were a large number of cases but no restaurant-based clusters, the NM Department of Health and the Indian Health Service participated with CDC in individual-level and household-level case-control studies of infections in New Mexico and the Navajo Nation. No food item was associated in the individual-level study. In the household-level study, households with an ill member were more likely to have had jalapeño peppers present during the exposure period and to have reported ever having serrano peppers in the household. This report illustrates the complexity of this investigation, the limitations of traditional individual-level case-control studies when vehicles of infection are ingredients or commonly eaten with other foods, and the added value of a household-level study. PMID:23228507

Added value of a household-level study during an outbreak investigation of Salmonella serotype Saintpaul infections, New Mexico 2008.

PubMed

Boore, A L; Jungk, J; Russo, E T; Redd, J T; Angulo, F J; Williams, I T; Cheek, J E; Gould, L H

2013-10-01

In 2008, nationwide investigations of a Salmonella serotype Saintpaul outbreak led first to consumer warnings for Roma and red round tomatoes, then later for jalapeño and serrano peppers. In New Mexico, where there were a large number of cases but no restaurant-based clusters, the NM Department of Health and the Indian Health Service participated with CDC in individual-level and household-level case-control studies of infections in New Mexico and the Navajo Nation. No food item was associated in the individual-level study. In the household-level study, households with an ill member were more likely to have had jalapeño peppers present during the exposure period and to have reported ever having serrano peppers in the household. This report illustrates the complexity of this investigation, the limitations of traditional individual-level case-control studies when vehicles of infection are ingredients or commonly eaten with other foods, and the added value of a household-level study.

Economic impact of Clostridium difficile infection in a multihospital cohort of academic health centers.

PubMed

Pakyz, Amy; Carroll, Norman V; Harpe, Spencer E; Oinonen, Michael; Polk, Ronald E

2011-06-01

To assess the economic impact of Clostridium difficile infection (CDI) in a large multihospital cohort. Retrospective case-control study. Administrative claims data from 45 academic medical centers. A total of 10,857 patients who developed health care-associated CDI and were discharged between April 1, 2002, and March 31, 2007 (cases); each case patient was matched by hospital, age, quarter and year of hospital discharge, and diagnosis related group to at least one control patient who did not develop health care-associated CDI (19,214 controls). Patients with health care-associated CDI were identified by using a previously validated method combining the International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI with specific CDI drug therapy (oral or intravenous metronidazole, or oral vancomycin). Costs were determined from charges by using standardized cost:charges ratios and were adjusted for age, All Patient Refined-Diagnosis Related Group (APR-DRG) severity of illness level, race, and sex with use of multivariable linear regression. The adjusted mean cost for cases was significantly higher than that for controls ($55,769 vs $28,609), and adjusted mean length of stay was twice as long (21.1 vs 10.0 days). The interaction between CDI and APR-DRG severity of illness level was significant; the effect of CDI on costs and length of stay decreased as severity of illness increased. This large CDI economic evaluation confirms that health care-associated cases of CDI are associated with significantly higher mean cost and longer length of stay than those of matched controls, with the greatest effect on costs at the lowest level of severity of illness.

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

PubMed

Gathani, Toral; Barnes, Isobel; Ali, Raghib; Arumugham, Rajkumar; Chacko, Raju; Digumarti, Raghunadharao; Jivarajani, Parimal; Kannan, Ravi; Loknatha, Dasappa; Malhotra, Hemant; Mathew, Beela S

2017-01-18

The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

Use of case-based reasoning to enhance intensive management of patients on insulin pump therapy.

PubMed

Schwartz, Frank L; Shubrook, Jay H; Marling, Cynthia R

2008-07-01

This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments. Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions. Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician. This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.

Risk factors for acute pesticide poisoning in Sri Lanka.

PubMed

van der Hoek, Wim; Konradsen, Flemming

2005-06-01

This report describes the characteristics of patients with acute pesticide poisoning in a rural area of Sri Lanka and, for intentional self-poisoning cases, explores the relative importance of the different determinants. Data were collected for 239 acute pesticide-poisoning cases, which were admitted to two rural hospitals in Sri Lanka. Sociodemographic characteristics, negative life events and agricultural practices of the intentional self-poisoning cases were compared with a control group. Most cases occurred among young adults and the large majority (84%) was because of intentional self-poisoning. Case fatality was 18% with extremely high case fatality for poisoning with the insecticide endosulfan and the herbicide paraquat. Cases were generally younger than controls, of lower educational status and were more often unemployed. No agricultural risk factors were found but a family history of pesticide poisoning and having ended an emotional relationship in the past year was clearly associated with intentional self-poisoning. The presence of mental disorders could only be assessed for a subsample of the cases and controls and this showed that alcohol dependence was a risk factor. This study shows that acute pesticide poisoning in Sri Lanka is determined by a combination of sociodemographic and psychological factors. Suggestions are given for interventions that could control the morbidity and mortality due to acute pesticide poisoning in developing countries.

Vacuum extraction failure is associated with a large head circumference.

PubMed

Kabiri, Doron; Lipschuetz, Michal; Cohen, Sarah M; Yagel, Oren; Levitt, Lorinne; Herzberg, Shmuel; Ezra, Yossef; Yagel, Simcha; Amsalem, Hagai

2018-04-24

To determine whether large head circumference increases the risk of vacuum extraction failure. This EMR-based study included all attempted vacuum extractions performed in a tertiary center between January 2010 and June 2015. All term singleton live births were eligible. Cases were divided into four groups: head circumference ≥90th percentile both with birth weight ≥90th percentile and <90th percentile and fetal head circumference <90th percentile with birth weight ≥90th and <90th percentile. Risk of failed vacuum extraction was compared among these groups. Other neonatal and maternal parameters were also evaluated as potential risk factors. Multinomial multivariable regression provided adjusted odds ratio for vacuum extraction failure while controlling for potential confounders. During the study period, 48,007 deliveries met inclusion criteria, of which 3835 had an attempt at vacuum extraction. We identified 215 (5.6%) cases of vacuum extraction failure. The adjusted odds ratios (aOR) for vacuum extraction failure in cases of large fetal head circumference was 2.31 (95%CI, 1.7-3.15, p < .001). Primiparity, prolonged second stage and occipito-posterior presentation were also found to be significant risk factors for failed vacuum extraction. In this study, we found that large head circumference was associated with vacuum extraction failure rather than high birth weight.

Is work organisation associated with work status 3 months after injury? Results from a case-control study of New Zealand workers.

PubMed

Lilley, Rebbecca; Derrett, Sarah; Davie, Gabrielle

2015-01-01

Little empirical examination of the relationship between work organisational factors and return to work following injury has been undertaken despite the growing recognition of examining broader multi-dimensional contexts for recovery following injury. To explore relationships between pre-injury work organisational factors and work status (working/work absent) 3-month after injury among people employed prior to injury. Cases (work absent) and controls (working), selected from a larger study of injury outcomes according to reported work status 3-month after injury, completed a postal questionnaire. Work organisational factors were compared between cases and controls using univariate and multivariable analyses. One hundred and twelve participants completed the questionnaire (44 cases; 68 controls). Of 11 work organisation factors examined, organisational size was the only explanatory variable significantly associated with work status in the multivariable model. Higher odds of work absence were found in small (< 50 employees) (OR 5.6) and large (> 500 employees) (OR 7.2) workplaces, compared with medium-sized (50-500 employees) organisations. Variations in post-injury work patterns among those working pre-injury may be partly explained by organisation size. Future research examining work status following injury should examine the influence of work organisational factors in larger studies.

3D marker-controlled watershed for kidney segmentation in clinical CT exams.

PubMed

Wieclawek, Wojciech

2018-02-27

Image segmentation is an essential and non trivial task in computer vision and medical image analysis. Computed tomography (CT) is one of the most accessible medical examination techniques to visualize the interior of a patient's body. Among different computer-aided diagnostic systems, the applications dedicated to kidney segmentation represent a relatively small group. In addition, literature solutions are verified on relatively small databases. The goal of this research is to develop a novel algorithm for fully automated kidney segmentation. This approach is designed for large database analysis including both physiological and pathological cases. This study presents a 3D marker-controlled watershed transform developed and employed for fully automated CT kidney segmentation. The original and the most complex step in the current proposition is an automatic generation of 3D marker images. The final kidney segmentation step is an analysis of the labelled image obtained from marker-controlled watershed transform. It consists of morphological operations and shape analysis. The implementation is conducted in a MATLAB environment, Version 2017a, using i.a. Image Processing Toolbox. 170 clinical CT abdominal studies have been subjected to the analysis. The dataset includes normal as well as various pathological cases (agenesis, renal cysts, tumors, renal cell carcinoma, kidney cirrhosis, partial or radical nephrectomy, hematoma and nephrolithiasis). Manual and semi-automated delineations have been used as a gold standard. Wieclawek Among 67 delineated medical cases, 62 cases are 'Very good', whereas only 5 are 'Good' according to Cohen's Kappa interpretation. The segmentation results show that mean values of Sensitivity, Specificity, Dice, Jaccard, Cohen's Kappa and Accuracy are 90.29, 99.96, 91.68, 85.04, 91.62 and 99.89% respectively. All 170 medical cases (with and without outlines) have been classified by three independent medical experts as 'Very good' in 143-148 cases, as 'Good' in 15-21 cases and as 'Moderate' in 6-8 cases. An automatic kidney segmentation approach for CT studies to compete with commonly known solutions was developed. The algorithm gives promising results, that were confirmed during validation procedure done on a relatively large database, including 170 CTs with both physiological and pathological cases.

A genome-wide association study of anorexia nervosa.

PubMed

Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

2014-10-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

A genome-wide association study of anorexia nervosa

PubMed Central

Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

2015-01-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

PubMed

Nag, Abhishek; Bochukova, Elena G; Kremeyer, Barbara; Campbell, Desmond D; Muller, Heike; Valencia-Duarte, Ana V; Cardona, Julio; Rivas, Isabel C; Mesa, Sandra C; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D; Romero, Roxana; Fournier, Eduardo; Reus, Victor I; Lowe, Thomas L; Farooqi, I Sadaf; Mathews, Carol A; McGrath, Lauren M; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M; Pauls, David L; Freimer, Nelson B; Plagnol, Vincent; Ruiz-Linares, Andrés

2013-01-01

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1

PubMed Central

Nag, Abhishek; Bochukova, Elena G.; Kremeyer, Barbara; Campbell, Desmond D.; Muller, Heike; Valencia-Duarte, Ana V.; Cardona, Julio; Rivas, Isabel C.; Mesa, Sandra C.; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D.; Romero, Roxana; Fournier, Eduardo; Reus, Victor I.; Lowe, Thomas L.; Farooqi, I. Sadaf; Mathews, Carol A.; McGrath, Lauren M.; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M.; Pauls, David L.; Freimer, Nelson B.; Plagnol, Vincent; Ruiz-Linares, Andrés

2013-01-01

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions. PMID:23533600

Syphilis in the economic center of South China: results from a real-time, web-based surveillance program.

PubMed

Zhang, Wangjian; Du, Zhicheng; Tang, Shaokai; Guo, Pi; Ye, Xingdong; Hao, Yuantao

2015-08-08

Guangzhou is the economic center of South China, which is currently suffering an insidious re-emergence of syphilis. Syphilis epidemic in this area is a matter of serious concern, because of the special economic position of Guangzhou and its large migrant population. Therefore, a comprehensive analysis of surveillance data is needed to provide further information for developing targeted control programs. Case-based surveillance data obtained from a real-time, web-based system were analyzed. A hierarchical clustering method was applied to classify the 12 districts of Guangzhou into several epidemiological regions. The district-level annual incidence and clustering results were displayed on the same map to show the spatial patterns of syphilis in Guangzhou. A total of 60,178 syphilis cases were reported during the period from 2005 to 2013, among which primary/secondary syphilis accounted for 15,864 cases (26.36 %), latent syphilis for 41,078 cases (68.26 %) and congenital syphilis for 2,090 cases (3.47 %). Moreover, primary/secondary syphilis burden slightly decreased from 17.5-18.0 cases per 100,000 people in the first years to 10.6 cases per 100,000 in 2013, with latent syphilis largely increasing from 18.5 cases per 100,000 to 43.4 cases per 100,000. Districts of Guangzhou could be classified into 3 epidemiological regions according to the syphilis burden over the last 3 years of the study period. The burden of primary/secondary syphilis appears to be decreasing in recent years, whereas that of latent syphilis is increasing. Given the epidemiological features and the annual changes found in this study, it is suggested that future control programs should be more population-specific and spatially targeted.

Diarrheagenic Escherichia coli and Acute Gastroenteritis in Children in Davidson County, Tennessee, United States: A Case-control Study.

PubMed

Imdad, Aamer; Foster, Monique A; Iqbal, Junaid; Fonnesbeck, Christopher; Payne, Daniel C; Zhang, Chengxian; Chappell, James D; Halasa, Natasha; Gómez-Duarte, Oscar G

2018-06-01

Diarrheagenic Escherichia coli (DEC) is an important cause of acute gastroenteritis in children; however, there is limited information available on the epidemiology, phylogenetics, serotyping and antibiotic susceptibility of DEC in children in the United States. The aim of this study was to determine the molecular epidemiology of DEC among children with and without acute gastroenteritis in Davidson County, Tennessee. This prospective, frequency matched, case-control study recruited subjects 15 days to 17 years of age and detected DEC with polymerase chain reaction from stool samples. Additional testing was done to define phylogenetics and antibiotics resistance. Among 1267 participants, 857 cases and 410 controls, 5.5% were positive for at least one subtype of DEC. Enteroaggregative E. coli [n = 32 (45%)] was the most common subtype followed by enteropathogenic E. coli (EPEC) [n = 30 (43%)], Shiga toxin-producing E. coli [n = 4 (6%)] and diffusely adherent E. coli [n = 4 (6%)]. No significant difference in prevalence of DEC was found between cases (5%) and controls (7%) [odds ratio: 0.66 (95% confidence interval: 0.4-1.07)], and results were similar when data were stratified by subtypes and adjusted for age, sex, race and ethnicity. Substantial diversity was found among DEC isolates in terms of phylotypes and serotypes, and a large proportion was resistant to, at least, one antibiotic. Enteroaggregative E. coli and enteropathogenic E. coli were frequently found in both cases and controls in this study population. DNA-based methods for detection of these subtypes need further investigation to help differentiate between pathogenic and colonizing strains.

Cardiac glycosides use and the risk of lung cancer: a nested case-control study.

PubMed

Couraud, Sébastien; Azoulay, Laurent; Dell'Aniello, Sophie; Suissa, Samy

2014-08-08

Two studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients. We used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case-control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders. A total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose-response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories. The results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.

Multicentre hospital-based case-control study of diffuse large B-cell lymphoma in Shanghai, China.

PubMed

Fan, Rong; Zhang, Lu-Yao; Wang, Hong; Yang, Bo; Han, Tao; Zhao, Xiao-Li; Wang, Wei; Wang, Xiao-Qin; Lin, Guo-Wei

2012-01-01

Several potential risk factors have been identified for diffuse large B-cell lymphoma (DLBCL); however, epidemiological studies investigating the association between these risk factors and DLBCL have yielded inconsistent results. To investigate potential medical, lifestyle, and environmental risk factors of DLBCL in Shanghai, China through a hospital-based case-control study. One-hundred- and-forty-seven newly diagnosed DLBCL patients and 294 sex- and age-matched controls were recruited from 11 hospitals in Shanghai between 2003 and 2007. A standardized structured questionnaire was used to obtain patient data on demographics, medical history, family history, lifestyle, and environmental exposures. Conditional logistic regression models were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for risk associated with each data category. History of tuberculosis (TB) infection and "living on a farm" were positively associated with DLBCL (TB: OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast, taking traditional Chinese medicine was negatively associated with DLBCL (OR=0.36, 95% CI: 0.14- 0.89). No significant correlation with DLBCL risk was found for any of the other potential risk factors (p>0.05), including but not limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation within one year. Consistent with results from previous studies in other DLBCL case populations, traditional Chinese medicine appeared to have a direct or indirect protective effect against DLBCL. However, this study also identified a possible predisposition for DLBCL in TB sufferers and farmers.

Biomechanical and psychosocial risk factors for low back pain at work.

PubMed Central

Kerr, M S; Frank, J W; Shannon, H S; Norman, R W; Wells, R P; Neumann, W P; Bombardier, C

2001-01-01

OBJECTIVES: This study determined whether the physical and psychosocial demands of work are associated with low back pain. METHODS: A case-control approach was used. Case subjects (n = 137) reported a new episode of low back pain to their employer, a large automobile manufacturing complex. Control subjects were randomly selected from the study base as cases accrued (n = 179) or were matched to cases by exact job (n = 65). Individual, clinical, and psychosocial variables were assessed by interview. Physical demands were assessed with direct workplace measurements of subjects at their usual jobs. The analysis used multiple logistic regression adjusted for individual characteristics. RESULTS: Self-reported risk factors included a physically demanding job, a poor workplace social environment, inconsistency between job and education level, better job satisfaction, and better coworker support. Low job control showed a borderline association. Physical-measure risk factors included peak lumbar shear force, peak load handled, and cumulative lumbar disc compression. Low body mass index and prior low back pain compensation claims were the only significant individual characteristics. CONCLUSIONS: This study identified specific physical and psychosocial demands of work as independent risk factors for low back pain. PMID:11441733

Risk factors and therapy for goat mastitis in a hospital-based case-control study in Bangladesh.

PubMed

Koop, Gerrit; Islam, Md Nurul; Rahman, Md Mizanur; Khatun, Momena; Ferdous, Jinnat; Sayeed, Md Abu; Islam, Shariful; Ahaduzzaman, Md; Akter, Sazeda; Mannan, Abdul; Hassan, Mohammad Mahmudul; Dissanayake, Ravi; Hoque, Md Ahasanul

2016-02-01

Bangladesh has a large population of goats, which contribute to the income, nutrition and welfare of the households of many families. Mastitis in goats has a low incidence, but is often very severe, making veterinary care necessary. The aim of this study was to identify seasonality and risk factors for goat mastitis in a hospital-based matched case-control study in a teaching veterinary hospital in Chittagong, Bangladesh and to describe the range of antimicrobial treatments applied in this situation. Cases of mastitis and controls were drawn from the hospital patient recording system, along with their risk factor status. Multiple imputation was applied to deal with the missing values in the data analysis. Mastitis occurred somewhat more in the rainy season, and comprised about 3% of all goats admitted to the hospital during January 2011-June 2014. Free-ranging farming system, poor body condition score and non-native goat breeds were significantly associated with case status. Treatment of clinical mastitis was variable and unsystematic, but the use of gentamicin was commonly recorded. The need for more prudent and evidence-based antimicrobial therapies is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimal control of energy extraction in LES of large wind farms

NASA Astrophysics Data System (ADS)

Meyers, Johan; Goit, Jay; Munters, Wim

2014-11-01

We investigate the use of optimal control combined with Large-Eddy Simulations (LES) of wind-farm boundary layer interaction for the increase of total energy extraction in very large ``infinite'' wind farms and in finite farms. We consider the individual wind turbines as flow actuators, whose energy extraction can be dynamically regulated in time so as to optimally influence the turbulent flow field, maximizing the wind farm power. For the simulation of wind-farm boundary layers we use large-eddy simulations in combination with an actuator-disk representation of wind turbines. Simulations are performed in our in-house pseudo-spectral code SP-Wind. For the optimal control study, we consider the dynamic control of turbine-thrust coefficients in the actuator-disk model. They represent the effect of turbine blades that can actively pitch in time, changing the lift- and drag coefficients of the turbine blades. In a first infinite wind-farm case, we find that farm power is increases by approximately 16% over one hour of operation. This comes at the cost of a deceleration of the outer layer of the boundary layer. A detailed analysis of energy balances is presented, and a comparison is made between infinite and finite farm cases, for which boundary layer entrainment plays an import role. The authors acknowledge support from the European Research Council (FP7-Ideas, Grant No. 306471). Simulations were performed on the computing infrastructure of the VSC Flemish Supercomputer Center, funded by the Hercules Foundation and the Flemish Govern.

Trivalent inactivated influenza vaccine is not associated with sickle cell crises in children.

PubMed

Hambidge, Simon J; Ross, Colleen; Glanz, Jason; McClure, David; Daley, Matthew F; Xu, Stan; Shoup, Jo Ann; Narwaney, Komal; Baggs, James; Weintraub, Eric

2012-01-01

Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1-March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8-2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75-1.95). This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

Power monitoring and control for large scale projects: SKA, a case study

NASA Astrophysics Data System (ADS)

Barbosa, Domingos; Barraca, João. Paulo; Maia, Dalmiro; Carvalho, Bruno; Vieira, Jorge; Swart, Paul; Le Roux, Gerhard; Natarajan, Swaminathan; van Ardenne, Arnold; Seca, Luis

2016-07-01

Large sensor-based science infrastructures for radio astronomy like the SKA will be among the most intensive datadriven projects in the world, facing very high demanding computation, storage, management, and above all power demands. The geographically wide distribution of the SKA and its associated processing requirements in the form of tailored High Performance Computing (HPC) facilities, require a Greener approach towards the Information and Communications Technologies (ICT) adopted for the data processing to enable operational compliance to potentially strict power budgets. Addressing the reduction of electricity costs, improve system power monitoring and the generation and management of electricity at system level is paramount to avoid future inefficiencies and higher costs and enable fulfillments of Key Science Cases. Here we outline major characteristics and innovation approaches to address power efficiency and long-term power sustainability for radio astronomy projects, focusing on Green ICT for science and Smart power monitoring and control.

Investigation of an outbreak of Salmonella enterica serovar Newport infection.

PubMed

Irvine, W N; Gillespie, I A; Smyth, F B; Rooney, P J; McClenaghan, A; Devine, M J; Tohani, V K

2009-10-01

A large outbreak of Salmonella enterica serotype Newport infection occurred in Northern Ireland during September and October 2004. Typing of isolates from patients confirmed that this strain was indistinguishable from that in concurrent outbreaks in regions of England, in Scotland and in the Isle of Man. A total of 130 cases were distributed unequally across local government district areas in Northern Ireland. The epidemic curve suggested a continued exposure over about 4 weeks. A matched case-control study of 23 cases and 39 controls found a statistically significant association with a history of having eaten lettuce in a meal outside the home and being a case (odds ratio 23.7, 95% confidence interval 1.4-404.3). This exposure was reported by 57% of cases. Although over 300 food samples were tested, none yielded any Salmonella spp. Complexity and limited traceability in salad vegetable distribution hindered further investigation of the ultimate source of the outbreak.

The Distillation of "VISCI": Towards a Better Identification of Suicidal Inmates

ERIC Educational Resources Information Center

Frottier, Patrick; Koenig, Franz; Seyringer, Michaela; Matschnig, Teresa; Fruehwald, Stefan

2009-01-01

The "Viennese Instrument for Suicidality in Correctional Institutions" (VISCI) presented here is based on the results of a large case-control study and on research on literature examining suicide prevention in general and in the prison population in particular. The aim of this study was to validate the properties of the VISCI to differentiate…

Relationships between Phytophthora ramorum canker (sudden oak death) and failure potential in coast live oak

Treesearch

Tedmund J. Swiecki; Elizabeth Bernhardt; Christiana Drake; Laurence R. Costello

2006-01-01

In autumn 2002, we conducted a retrospective study on coast live oak (Quercus agrifolia) failures in Marin County, California, woodlands affected by Phytophthora ramorum canker (sudden oak death). The objectives of this case-control study were to quantify levels of bole, large branch, and root failure in these woodlands and...

Lung cancer risk among bricklayers in a pooled analysis of case–control studies

PubMed Central

Consonni, Dario; Matteis, Sara De; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel CH; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H B(as); Schüz, Joachim; Straif, Kurt

2015-01-01

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. What's new? In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between bricklaying and lung cancer. In this study, the authors used data from the largest collection of case-control studies on lung cancer with complete occupational and smoking history existing today, the SYNERGY project. They found clear evidence that lung cancer risk increases in proportion to the length of time spent working as a bricklayer, paving the way for better protection and compensation for those in this occupation. PMID:24861979

Case-spouse control design in practice: an experience in estimating smoking and chronic obstructive pulmonary disease deaths in Chinese adults.

PubMed

Jiang, Jingmei; Liu, Boqi; Sitas, Freddy; Zeng, Xianjia; Chen, Junshi; Han, Wei; Zou, Xiaonong; Wu, Yanping; Zhao, Ping; Li, Junyao

2010-05-01

We assessed the effect of smoking on death from chronic obstructive pulmonary disease (COPD) in China by employing a large population-based, case-spouse control study design using data from a nationwide survey of mortality. During 1989-1991, a nationwide retrospective survey of mortality was conducted in China. For approximately 1,000,000 adults dying from all causes during 1986-1988, their surviving spouses or other informants provided detailed information about their own as well as the deceased person's smoking history. For this study, 183,393 individuals who died of COPD at age > or = 40 years were taken as cases, while 272,984 sex-matched surviving spouses of subjects who died from any cause were taken as controls. COPD death rates for smokers were more than twice as high as those of non-smokers, with a dose-response risk pattern, despite the fact that COPD death rates varied widely by region and age. Tobacco accounted for 41.4% of COPD deaths in men, but only 13.5% of those in women, who had a lower rate of smoking. A case-spouse control study, as an alternative design, is valid and feasible in utilizing information from population-based, retrospective mortality survey data for an analytical epidemiological study of disease etiology. Copyright 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Vaccination history and risk of childhood leukaemia.

PubMed

Ma, Xiaomei; Does, Monique B; Metayer, Catherine; Russo, Carolyn; Wong, Alan; Buffler, Patricia A

2005-10-01

Previous studies on vaccination and childhood leukaemia generated inconsistent results. In the Northern California Childhood Leukaemia Study, a case-control study with incident cases and matched birth certificate controls, detailed written vaccination records were collected. A total of 323 cases aged 0-14 years at diagnosis and 409 controls were included in this analysis. All vaccinations were censored on the reference date (date of diagnosis for cases and the corresponding date for matched controls). Conditional logistic regression analysis was conducted, adjusting for potential confounding factors. A primary variable of interest is the number of administrations (doses) of various types of vaccines. Vaccinations against diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, and rubella were not associated with the risk of leukaemia. The odds ratio for each dose of Haemophilus influenzae type b (Hib) vaccine was 0.81 (95% CI 0.68-0.96). Compared with children who received two or fewer doses of Hib vaccine, those who received three or more doses had a significantly reduced risk of childhood leukaemia (odds ratio = 0.55, 95% confidence interval 0.32-0.94). The number of doses of hepatitis B vaccine received was not associated with leukaemia risk. Hib vaccination is associated with a reduced risk of childhood leukaemia. Future studies with detailed exposure assessment and large sample sizes are needed to further address the role of vaccinations in the etiology of childhood leukaemia.

Senna treatment in pregnant women and congenital abnormalities in their offspring--a population-based case-control study.

PubMed

Acs, Nándor; Bánhidy, Ferenc; Puhó, Erzsébet H; Czeizel, Andrew E

2009-07-01

Previously, the possible teratogenic effect of frequently used laxative drug, senna has not been checked in case-control epidemiological study. Objective of the study was the comparison of cases with congenital abnormalities (CAs) and their matched controls without CAs in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with CA, 506 (2.2%) had mothers with senna treatment, while of 38,151 control newborn infants without CA, 937 (2.5%) were born to mothers with senna treatment (adjusted OR with 95% CI: 1.0, 0.9-1.1), and of 834 malformed controls with Down syndrome, 26 (3.1%) had mothers with the use of senna (OR with 95% CI: 0.7, 0.5-1.1). The range of senna doses was between 10mg and 30 mg, but most pregnant women used 20mg daily. The mothers with senna treatment showed the characteristics of pregnant women with constipation (elder with larger proportion of primiparae). There was no higher risk for 23 different CA groups after the senna treatment during the second and/or third gestational month of 260 mothers, i.e. in the critical period of most major CAs, compared with their 500 matched controls. Gestational age at delivery was somewhat longer (0.2 week) and the rate of preterm birth was lower (6.6% vs. 9.2%) in newborn infants without CA born to mothers with senna treatment compared with babies born to mothers without senna treatment. In conclusion, senna treatment did not associate with a higher risk of CAs in the offspring of pregnant women with constipation.

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma.

PubMed

Kar, Tushar; Kar, Asaranti; Dhal, Ipsita; Panda, Sasmita; Biswal, Priyadarshini; Nayak, Bhagyalaxmi; Rout, Niranjan; Samantray, Sagarika

2017-12-01

Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

PubMed

Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

2015-01-01

We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Chronic Rhinosinusitis Associated with Erectile Dysfunction: A Population-Based Study.

PubMed

Tai, Shu-Yu; Wang, Ling-Feng; Tai, Chih-Feng; Huang, Yu-Ting; Chien, Chen-Yu

2016-08-31

Few studies have investigated the relationship between chronic rhinosinusitis (CRS) and erectile dysfunction (ED). This case-control study aimed to investigate the association between CRS and the risk of ED in a large national sample. Tapping Taiwan's National Health Insurance Research Database, we identified people 30 years or older with a new primary diagnosis of CRS between 1996 and 2007. The cases were compared with sex- and age-matched controls. We identified 14 039 cases and recruited 140 387 matched controls. Both groups were followed up in the same database until the end of 2007 for instances of ED. Of those with CRS, 294 (2.1%) developed ED during a mean (SD) follow-up of 3.20 (2.33) years, while 1 661 (1.2%) of the matched controls developed ED, mean follow up 2.97 (2.39) years. Cox regression analyses were performed adjusting for sex, age, insurance premium, residence, hypertension, hyperlipidemia, diabetes, obesity, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, asthma, allergic rhinitis, arrhythmia, ischemic stroke, intracerebral hemorrhage, and medications. CRS was revealed to be an independent predictor of ED in the fully adjusted model (HR = 1.51; 95% CI = 1.33-1.73; P < 0.0001).

Medical and nonmedical factors influencing utilization of delayed pushing in the second stage.

PubMed

Frey, Heather A; Tuuli, Methodius G; Cortez, Sarah; Odibo, Anthony O; Roehl, Kimberly A; Shanks, Anthony L; Macones, George A; Cahill, Alison G

2013-08-01

To evaluate factors impacting selection to delayed pushing in the second stage of labor. This case-control study was a secondary analysis of a large retrospective cohort study. Cases included women who delayed pushing for 60 minutes or more in the second stage of labor. Controls began pushing prior to 60 minutes from the time of diagnosis of complete dilation. Demographic, labor, and nonmedical factors were compared among cases and controls. Logistic regression modeling was used to identify factors independently associated with delayed pushing. We identified 471 women who delayed pushing and 4819 controls. Nulliparity, maternal body mass index > 25, high fetal station at complete dilation, regional anesthesia use, and start of second stage during staffing shift change were independent factors associated with increased use of delayed pushing. On the other hand, black race and second-stage management during night shift were associated with lower odds of employing delayed pushing. Delayed pushing was more commonly employed in nulliparous women, but 38.9% of multiparous women also delayed pushing. We identified multiple factors associated with use of delayed pushing. This study helps to define current patterns of second-stage labor management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Lack of association between the Trp719Arg polymorphism in kinesin-like protein 6 and coronary artery disease in 19 case-control studies

PubMed Central

Assimes, Themistocles L; Hólm, Hilma; Kathiresan, Sekar; Reilly, Muredach P; Thorleifsson, Gudmar; Voight, Benjamin F; Erdmann, Jeanette; Willenborg, Christina; Vaidya, Dhananjay; Xie, Changchun; Patterson, Chris C; Morgan, Thomas M; Burnett, Mary Susan; Li, Mingyao; Hlatky, Mark A; Knowles, Joshua W; Thompson, John R; Absher, Devin; Iribarren, Carlos; Go, Alan; Fortmann, Stephen P; Sidney, Stephen; Risch, Neil; Tang, Hua; Myers, Richard M; Berger, Klaus; Stoll, Monika; Shah, Svati H.; Thorgeirsson, Gudmundur; Andersen, Karl; Havulinna, Aki S; Herrera, J. Enrique; Faraday, Nauder; Kim, Yoonhee; Kral, Brian G.; Mathias, Rasika; Ruczinski, Ingo; Suktitipat, Bhoom; Wilson, Alexander F; Yanek, Lisa R.; Becker, Lewis C; Linsel-Nitschke, Patrick; Lieb, Wolfgang; König, Inke R; Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Reinhard, Wibke; Winogradow, Janina; Grassl, Martina; Grosshennig, Anika; Preuss, Michael; Eifert, Sandra; Schreiber, Stefan; Wichmann, H-Erich; Meisinger, Christa; Yee, Jean; Friedlander, Yechiel; Do, Ron; Meigs, James B; Williams, Gordon; Nathan, David M; MacRae, Calum A; Qu, Liming; Wilensky, Robert L; Matthai, William H.; Qasim, Atif N; Hakonarson, Hakon; Pichard, Augusto D; Kent, Kenneth M; Satler, Lowell; Lindsay, Joseph M; Waksman, Ron; Knouff, Christopher W; Waterworth, Dawn M; Walker, Max C; Mooser, Vincent; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Martinelli, Nicola; Olivieri, Oliviero; Trabetti, Elisabetta; Malerba, Giovanni; Pignatti, Pier Franco; Guiducci, Candace; Mirel, Daniel; Parkin, Melissa; Hirschhorn, Joel N; Asselta, Rosanna; Duga, Stefano; Musunuru, Kiran; Daly, Mark J; Purcell, Shaun; Braund, Peter S; Wright, Benjamin J; Balmforth, Anthony J; Ball, Stephen G; Ouwehand, Willem H; Deloukas, Panos; Scholz, Michael; Cambien, Francois; Huge, Andreas; Scheffold, Thomas; Salomaa, Veikko; Girelli, Domenico; Granger, Christopher B.; Peltonen, Leena; McKeown, Pascal P; Altshuler, David; Melander, Olle; Devaney, Joseph M; Epstein, Stephen E; Rader, Daniel J; Elosua, Roberto; Engert, James C; Anand, Sonia S; Hall, Alistair S; Ziegler, Andreas; O’Donnell, Christopher J; Spertus, John A; Siscovick, David; Schwartz, Stephen M; Becker, Diane; Thorsteinsdottir, Unnur; Stefansson, Kari; Schunkert, Heribert; Samani, Nilesh J; Quertermous, Thomas

2011-01-01

Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455) and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with non-carriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in nineteen case-control studies of non-fatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results Over 17 000 cases and 39 000 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the nineteen studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with non-carriers. Regression analyses and fixed effect meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early onset disease (<50 years of age for males and <60 years for females) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. PMID:20933357

Tritium trick

NASA Technical Reports Server (NTRS)

Green, W. V.; Zukas, E. G.; Eash, D. T.

1971-01-01

Large controlled amounts of helium in uniform concentration in thick samples can be obtained through the radioactive decay of dissolved tritium gas to He3. The term, tritium trick, applies to the case when helium, added by this method, is used to simulate (n,alpha) production of helium in simulated hard flux radiation damage studies.

Optimizing Web-Based Instruction: A Case Study Using Poultry Processing Unit Operations

ERIC Educational Resources Information Center

O' Bryan, Corliss A.; Crandall, Philip G.; Shores-Ellis, Katrina; Johnson, Donald M.; Ricke, Steven C.; Marcy, John

2009-01-01

Food companies and supporting industries need inexpensive, revisable training methods for large numbers of hourly employees due to continuing improvements in Hazard Analysis Critical Control Point (HACCP) programs, new processing equipment, and high employee turnover. HACCP-based food safety programs have demonstrated their value by reducing the…

CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk.

PubMed

O'Mara, Tracy A; Ferguson, Kaltin; Fahey, Paul; Marquart, Louise; Yang, Hannah P; Lissowska, Jolanta; Chanock, Stephen; Garcia-Closas, Montserrat; Thompson, Deborah J; Healey, Catherine S; Dunning, Alison M; Easton, Douglas F; Webb, Penelope M; Spurdle, Amanda B

2011-08-01

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

Exploration of large, rare copy number variants associated with psychiatric and neurodevelopmental disorders in individuals with anorexia nervosa.

PubMed

Yilmaz, Zeynep; Szatkiewicz, Jin P; Crowley, James J; Ancalade, NaEshia; Brandys, Marek K; van Elburg, Annemarie; de Kovel, Carolien G F; Adan, Roger A H; Hinney, Anke; Hebebrand, Johannes; Gratacos, Monica; Fernandez-Aranda, Fernando; Escaramis, Georgia; Gonzalez, Juan R; Estivill, Xavier; Zeggini, Eleftheria; Sullivan, Patrick F; Bulik, Cynthia M

2017-08-01

Anorexia nervosa (AN) is a serious and heritable psychiatric disorder. To date, studies of copy number variants (CNVs) have been limited and inconclusive because of small sample sizes. We conducted a case-only genome-wide CNV survey in 1983 female AN cases included in the Genetic Consortium for Anorexia Nervosa. Following stringent quality control procedures, we investigated whether pathogenic CNVs in regions previously implicated in psychiatric and neurodevelopmental disorders were present in AN cases. We observed two instances of the well-established pathogenic CNVs in AN cases. In addition, one case had a deletion in the 13q12 region, overlapping with a deletion reported previously in two AN cases. As a secondary aim, we also examined our sample for CNVs over 1 Mbp in size. Out of the 40 instances of such large CNVs that were not implicated previously for AN or neuropsychiatric phenotypes, two of them contained genes with previous neuropsychiatric associations, and only five of them had no associated reports in public CNV databases. Although ours is the largest study of its kind in AN, larger datasets are needed to comprehensively assess the role of CNVs in the etiology of AN.

Schema therapy for chronic depression: Results of a multiple single case series.

PubMed

Renner, Fritz; Arntz, Arnoud; Peeters, Frenk P M L; Lobbestael, Jill; Huibers, Marcus J H

2016-06-01

The aim of this study was to test the effects of individual schema therapy (ST) for patients with chronic depression. Using a multiple-baseline single case series design, patients with chronic major depressive disorder (N = 25) first entered a 6-24 weeks baseline phase; this phase functioned as a no-treatment control condition. Then, patients started a 12 week exploration phase during which symptoms and underlying schemas were explored; this phase functioned as an attention control condition. Next, patients received up to 65 sessions of individual ST. The Beck Depression Inventory II (BDI-II) and the Quick Inventory of Depressive Symptomatology (QIDS) were the primary outcome measures. The BDI-II was assessed once a week during all phases of the study resulting in 100 repeated assessments per participant on average. Mixed regression analysis was used to contrast change in symptoms during the intervention with change in symptoms during the baseline and exploration control phases. When compared to the no-treatment control period, the intervention had a significant, large effect on depressive symptoms (Cohen's d BDI-II = 1.30; Cohen's d QIDS = 1.22). Effects on secondary continuous outcomes were moderate to large. The small sample size and lack of a control group. These findings provide evidence that ST might be an effective treatment for patients with chronic depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Successful Endovascular Control of Renal Artery in a Transplant Kidney During Nephron Sparing Surgery (NSS) for Large Centrally Located Tumor.

PubMed

Shprits, Sagi; Moskovits, Boaz; Sachner, Robert; Nativ, Ofer

2016-05-01

Renal cell carcinoma in a transplant kidney is a rare condition. Nephron Sparing Surgery (NSS) is the treatment of choice. One of the main technical challenges is obtaining adequate vascular control. We present a rare case of large centrally located hillar tumor in a kidney 18 years after transplantation treated with NSS. Vascular control was achieved by using a novel approach. Post-operative course was uneventful with minimal decrease in renal function. We believe that this unique choice of treatment can be used in cases of NSS where the access to the renal pedicle is limited.

Experience with multiple control groups in a large population-based case-control study on genetic and environmental risk factors.

PubMed

Pomp, E R; Van Stralen, K J; Le Cessie, S; Vandenbroucke, J P; Rosendaal, F R; Doggen, C J M

2010-07-01

We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.

Rarity of the Alzheimer Disease–Protective APP A673T Variant in the United States

PubMed Central

Wang, Li-San; Naj, Adam C.; Graham, Robert R.; Crane, Paul K.; Kunkle, Brian W.; Cruchaga, Carlos; Gonzalez Murcia, Josue D.; Cannon-Albright, Lisa; Baldwin, Clinton T.; Zetterberg, Henrik; Blennow, Kaj; Kukull, Walter A.; Faber, Kelley M.; Schupf, Nicole; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher D.; Rogaeva, Ekaterina; Lin, Chiao-Feng; Dombroski, Beth A.; Cantwell, Laura B.; Partch, Amanda; Valladares, Otto; Hakonarson, Hakon; St George-Hyslop, Peter; Green, Robert C.; Goate, Alison M.; Foroud, Tatiana M.; Carney, Regina M.; Larson, Eric B.; Behrens, Timothy W.; Kauwe, John S. K.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Mayeux, Richard; Schellenberg, Gerard D.

2015-01-01

IMPORTANCE Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. OBJECTIVE To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. DESIGN, SETTING, AND PARTICIPANTS Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. MAIN OUTCOMES AND MEASURES Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). RESULTS The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. CONCLUSIONS AND RELEVANCE The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations. PMID:25531812

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

Impact of long-term filter cigarette usage on lung and larnyx cancer risk: a case-control study

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

Wynder, E.L.; Stellman, S.D.

A case-control study was conducted among 1034 white male and female hospital patients with histologically proved lung cancer (Kreyberg type I) or larynx cancer. After adjustment for duration of the smoking habit, inhalation, and butt length relative risks of developing lung or larynx cancer were consistently lower among long-term of filter cigarettes than among smokers of nonfilter cigarettes, irrespective of quantity smoked. Relative risks in all groups declined with increased years of smoking cessation. The observed risk reduction among current smokers of filter cigarettes was consistent with that expected, considering that these persons had smoked the older high-tar nonfilter cigarettesmore » for a large proportion of their lives.« less

Higher risk of orofacial clefts in children born to mothers with angina pectoris: a population-based case-control study.

PubMed

Czeizel, Andrew E; Vereczkey, Attila; Bánhidy, Ferenc

2015-02-01

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP-diagnoses in the previous study and the recent history of mothers with MAP in a follow-up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty-two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8-7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9-35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3-47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009-2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation. © 2014 Japanese Teratology Society.

Mixed-Method Quasi-Experimental Study of Outcomes of a Large-Scale Multilevel Economic and Food Security Intervention on HIV Vulnerability in Rural Malawi.

PubMed

Weinhardt, Lance S; Galvao, Loren W; Yan, Alice F; Stevens, Patricia; Mwenyekonde, Thokozani Ng'ombe; Ngui, Emmanuel; Emer, Lindsay; Grande, Katarina M; Mkandawire-Valhmu, Lucy; Watkins, Susan C

2017-03-01

The objective of the Savings, Agriculture, Governance, and Empowerment for Health (SAGE4Health) study was to evaluate the impact of a large-scale multi-level economic and food security intervention on health outcomes and HIV vulnerability in rural Malawi. The study employed a quasi-experimental non-equivalent control group design to compare intervention participants (n = 598) with people participating in unrelated programs in distinct but similar geographical areas (control, n = 301). We conducted participant interviews at baseline, 18-, and 36-months on HIV vulnerability and related health outcomes, food security, and economic vulnerability. Randomly selected households (n = 1002) were interviewed in the intervention and control areas at baseline and 36 months. Compared to the control group, the intervention led to increased HIV testing (OR 1.90; 95 % CI 1.29-2.78) and HIV case finding (OR = 2.13; 95 % CI 1.07-4.22); decreased food insecurity (OR = 0.74; 95 % CI 0.63-0.87), increased nutritional diversity, and improved economic resilience to shocks. Most effects were sustained over a 3-year period. Further, no significant differences in change were found over the 3-year study period on surveys of randomly selected households in the intervention and control areas. Although there were general trends toward improvement in the study area, only intervention participants' outcomes were significantly better. Results indicate the intervention can improve economic and food security and HIV vulnerability through increased testing and case finding. Leveraging the resources of economic development NGOs to deliver locally-developed programs with scientific funding to conduct controlled evaluations has the potential to accelerate the scientific evidence base for the effects of economic development programs on health.

Childhood leukaemia and distance from power lines in California: a population-based case-control study.

PubMed

Crespi, Catherine M; Vergara, Ximena P; Hooper, Chris; Oksuzyan, Sona; Wu, Sheng; Cockburn, Myles; Kheifets, Leeka

2016-06-28

Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated.

KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control

PubMed Central

Le Calvez-Kelm, Florence; Foll, Matthieu; Wozniak, Magdalena B.; Delhomme, Tiffany M.; Durand, Geoffroy; Chopard, Priscilia; Pertesi, Maroulio; Fabianova, Eleonora; Adamcakova, Zora; Holcatova, Ivana; Foretova, Lenka; Janout, Vladimir; Vallee, Maxime P.; Rinaldi, Sabina; Brennan, Paul; McKay, James D.; Byrnes, Graham B.; Scelo, Ghislaine

2016-01-01

The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series. PMID:27705932

Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh.

PubMed

Kancherla, Vijaya; Ibne Hasan, Md Omar Sharif; Hamid, Rezina; Paul, Ligi; Selhub, Jacob; Oakley, Godfrey; Quamruzzaman, Quazi; Mazumdar, Maitreyi

2017-01-01

Neural tube defects contribute to severe morbidity and mortality in children and adults; however, they are largely preventable through maternal intake of folic acid before and during early pregnancy. We examined the association between maternal prenatal folic acid supplement intake and risk of myelomeningocele (a severe and common type of neural tube defect) in the offspring. We performed secondary analysis using data from a case-control study conducted at Dhaka Community Hospital, Bangladesh between April and November of 2013. Cases and controls included children with and without myelomeningocele, respectively, and their mothers. Cases were identified from local hospitals and rural health clinics served by Dhaka Community Hospital. Controls were selected from pregnancy registries located in the same region as the cases, and matched (1:1) to cases by age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician with expertise in classifying neural tube defects. Maternal prenatal folic acid supplement intake was the main exposure of interest. We estimated crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression analysis. There were 53 pairs of matched cases and controls in our study. Overall, 51% of case mothers reported using folic acid supplements during pregnancy compared to 72% of control mothers (p = 0.03). Median plasma folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL among case and control mothers, respectively (p = 0.85). Maternal prenatal folic acid use significantly decreased the odds of myelomeningocele in the offspring (unadjusted OR = 0.42, 95% CI = 0.18-0.96). The association was slightly attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR = 0.43, 95% CI = 0.18-1.02). Our study confirms the protective association between maternal prenatal folic acid supplement use and myelomeningocele among children born in Bangladesh. Our findings point to an overall low folic acid supplement use and low plasma folate concentrations among women of reproductive age in Bangladesh. Mandatory fortification of staple foods with folic acid can address low folate status among women of child-bearing age, and prevent child morbidity and mortality associated with myelomeningocele in Bangladesh.

Optimal estimation and scheduling in aquifer management using the rapid feedback control method

NASA Astrophysics Data System (ADS)

Ghorbanidehno, Hojat; Kokkinaki, Amalia; Kitanidis, Peter K.; Darve, Eric

2017-12-01

Management of water resources systems often involves a large number of parameters, as in the case of large, spatially heterogeneous aquifers, and a large number of "noisy" observations, as in the case of pressure observation in wells. Optimizing the operation of such systems requires both searching among many possible solutions and utilizing new information as it becomes available. However, the computational cost of this task increases rapidly with the size of the problem to the extent that textbook optimization methods are practically impossible to apply. In this paper, we present a new computationally efficient technique as a practical alternative for optimally operating large-scale dynamical systems. The proposed method, which we term Rapid Feedback Controller (RFC), provides a practical approach for combined monitoring, parameter estimation, uncertainty quantification, and optimal control for linear and nonlinear systems with a quadratic cost function. For illustration, we consider the case of a weakly nonlinear uncertain dynamical system with a quadratic objective function, specifically a two-dimensional heterogeneous aquifer management problem. To validate our method, we compare our results with the linear quadratic Gaussian (LQG) method, which is the basic approach for feedback control. We show that the computational cost of the RFC scales only linearly with the number of unknowns, a great improvement compared to the basic LQG control with a computational cost that scales quadratically. We demonstrate that the RFC method can obtain the optimal control values at a greatly reduced computational cost compared to the conventional LQG algorithm with small and controllable losses in the accuracy of the state and parameter estimation.

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

PubMed

Amirian, E Susan; Scheurer, Michael E; Zhou, Renke; Wrensch, Margaret R; Armstrong, Georgina N; Lachance, Daniel; Olson, Sara H; Lau, Ching C; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Il'yasova, Dora; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Jenkins, Robert B; Bernstein, Jonine L; Merrell, Ryan T; Davis, Faith G; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Melin, Beatrice S; Bondy, Melissa L

2016-06-01

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

PubMed Central

Skibola, Christine F.; Darabi, Hatef; Conde, Lucia; Hjalgrim, Henrik; Kumar, Vikrant; Chang, Ellen T.; Rothman, Nathaniel; Cerhan, James R.; Brooks-Wilson, Angela R.; Rehnberg, Emil; Irwan, Ishak D.; Ryder, Lars P.; Brown, Peter N.; Bracci, Paige M.; Agana, Luz; Riby, Jacques; Cozen, Wendy; Davis, Scott; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Wang, Sophia S.; Slager, Susan L.; Fredericksen, Zachary S.; Novak, Anne J.; Kay, Neil E.; Habermann, Thomas M.; Armstrong, Bruce; Kricker, Anne; Milliken, Sam; Purdue, Mark P.; Vajdic, Claire M.; Boyle, Peter; Lan, Qing; Zahm, Shelia H.; Zhang, Yawei; Zheng, Tongzhang; Leach, Stephen; Spinelli, John J.; Smith, Martyn T.; Chanock, Stephen J.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Glimelius, Bengt; Melbye, Mads; Liu, Edison T.; Adami, Hans-Olov; Humphreys, Keith; Liu, Jianjun

2011-01-01

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL. PMID:21533074

Diet-related risk factors for gastric dilatation-volvulus in dogs of high-risk breeds.

PubMed

Raghavan, Malathi; Glickman, Nita; McCabe, George; Lantz, Gary; Glickman, Lawrence T

2004-01-01

A nested case-control study was conducted among 1634 dogs with complete diet information in a 5-year prospective study to determine diet-related risk factors for gastric dilatation-volvulus (GDV). Cases included 106 dogs that developed GDV; controls included 212 dogs without GDV that were frequency matched to cases by year of GDV onset. Proportionate energy consumed from major food types and from carbohydrates was determined. Dogs were categorized as consuming either a low volume or high volume of food based on the median number of cups of food fed per kg of body weight per meal. Dogs fed a larger volume of food per meal were at a significantly (P<0.05) increased risk of GDV, regardless of the number of meals fed daily. For both large- and giant-breed dogs, the risk of GDV was highest for dogs fed a larger volume of food once daily.

Large outbreak caused by methicillin resistant Staphylococcus pseudintermedius ST71 in a Finnish Veterinary Teaching Hospital--from outbreak control to outbreak prevention.

PubMed

Grönthal, Thomas; Moodley, Arshnee; Nykäsenoja, Suvi; Junnila, Jouni; Guardabassi, Luca; Thomson, Katariina; Rantala, Merja

2014-01-01

The purpose of this study was to describe a nosocomial outbreak caused by methicillin resistant Staphylococcus pseudintermedius (MRSP) ST71 SCCmec II-III in dogs and cats at the Veterinary Teaching Hospital of the University of Helsinki in November 2010 - January 2012, and to determine the risk factors for acquiring MRSP. In addition, measures to control the outbreak and current policy for MRSP prevention are presented. Data of patients were collected from the hospital patient record software. MRSP surveillance data were acquired from the laboratory information system. Risk factors for MRSP acquisition were analyzed from 55 cases and 213 controls using multivariable logistic regression in a case-control study design. Forty-seven MRSP isolates were analyzed by pulsed field gel electrophoresis and three were further analyzed with multi-locus sequence and SCCmec typing. Sixty-three MRSP cases were identified, including 27 infections. MRSPs from the cases shared a specific multi-drug resistant antibiogram and PFGE-pattern indicated clonal spread. Four risk factors were identified; skin lesion (OR = 6.2; CI95% 2.3-17.0, P = 0.0003), antimicrobial treatment (OR = 3.8, CI95% 1.0-13.9, P = 0.0442), cumulative number of days in the intensive care unit (OR = 1.3, CI95% 1.1-1.6, P = 0.0007) or in the surgery ward (OR = 1.1, CI95% 1.0-1.3, P = 0.0401). Tracing and screening of contact patients, enhanced hand hygiene, cohorting and barrier nursing, as well as cleaning and disinfection were used to control the outbreak. To avoid future outbreaks and spread of MRSP a search-and-isolate policy was implemented. Currently nearly all new MRSP findings are detected in screening targeted to risk patients on admission. Multidrug resistant MRSP is capable of causing a large outbreak difficult to control. Skin lesions, antimicrobial treatment and prolonged hospital stay increase the probability of acquiring MRSP. Rigorous control measures were needed to control the outbreak. We recommend the implementation of a search-and-isolate policy to reduce the burden of MRSP.

Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Barrett's Esophagus Methylation Profiles — EDRN Public Portal

Cancer.gov

We propose a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, we will perform a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers will select from their cohorts who have progressed to HGD or to adenocarcinoma of the esophagus ("progressors"), and who also donated samples prior to the development of cancer, when their histology was felt to be benign. These subjects will be compared to individuals who have been under endoscopic surveillance, but who have not progressed to HGD or EAC ("non-progressors"). Using this approach, we hope to identify promising markers for risk stratification in BE. We expect to be able to make successful application for a prospective study of markers identified in this case-control study.

Stability analysis via the concept of Lyapunov exponents: a case study in optimal controlled biped standing

NASA Astrophysics Data System (ADS)

Sun, Yuming; Wu, Christine Qiong

2012-12-01

Balancing control is important for biped standing. In spite of large efforts, it is very difficult to design balancing control strategies satisfying three requirements simultaneously: maintaining postural stability, improving energy efficiency and satisfying the constraints between the biped feet and the ground. In this article, a proportional-derivative (PD) controller is proposed for a standing biped, which is simplified as a two-link inverted pendulum with one additional rigid foot-link. The genetic algorithm (GA) is used to search for the control gain meeting all three requirements. The stability analysis of such a deterministic biped control system is carried out using the concept of Lyapunov exponents (LEs), based on which, the system stability, where the disturbance comes from the initial states, and the structural stability, where the disturbance comes from the PD gains, are examined quantitively in terms of stability region. This article contributes to the biped balancing control, more significantly, the method shown in the studied case of biped provides a general framework of systematic stability analysis for certain deterministic nonlinear dynamical systems.

Considerations of study design.

PubMed

Koretz, Ronald L

2007-12-01

Research projects attempt to answer specific questions. The particular study design that is selected will depend in large measure on the nature of the question and the time and resources available. There are 5 common categories of clinical questions; they relate to etiology, prognosis, utility of diagnostic tests, efficacy of proposed interventions, and cost of treatment in specific disease states. A number of study designs can be used. Case reports serve to memorialize unusual or novel aspects of diseases. Retrospective case series are useful for defining natural history. Case-control studies are used by epidemiologists to elucidate potential etiologies of diseases. Prospective cohort studies can be used to assess natural history or to assess potential disease etiologies. Controlled trials are designed to assess the efficacy of therapeutic interventions. Studies that define the sensitivity and specificity of diagnostic tests can be used to assess the utility of those tests. Economic analyses estimate the costs that particular diseases or therapies will require. Each of these study designs has limitations; with the exception of high-quality randomized trials, none of these study designs can establish a causative relationship between putative etiologic (or therapeutic) factors and disease (outcomes).

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

PubMed

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

2017-09-12

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

Statins and hip fracture risk in men: a population-based case-control study.

PubMed

Adams, Annette L; Shi, Jiaxiao M; Reynolds, Kristi; Haque, Reina; Cheetham, T Craig; Kawatkar, Aniket A; Fithian, Donald C; Jacobsen, Steven J

2015-11-01

To estimate the association between hydroxymethylglutaryl-CoA inhibitor (statin) use and hip fracture. We conducted a population-based case-control study. Cases were 6774 male enrollees in a large managed care organization, aged 45 or more years, with an incident hip fracture from 1997 to 2006. Controls without fracture (n = 6774) were matched to cases on age, race, and medical center. Electronic information on pharmaceutical use was used to identify the dispensing of statins from 1991 forward. Overall, 1884 (27.8%) cases and 2150 controls (31.7%) used a statin before index date (matched odds ratio [mOR] = 0.81, 95% confidence interval [CI] = 0.74-0.87). Adjustment for comorbidity burden strengthened the magnitude of the overall association (mOR = 0.68, CI = 0.62-0.74). The adjusted association was similar across age groups but was strongest among men aged 80 years or more (mOR = 0.62, CI = 0.54-0.71) and was most pronounced in African Americans (mOR = 0.43, CI = 0.28-0.64). Greater duration of statin use did not alter the odds ratios. These data add to the growing evidence of a potential protective effect of statin use on bone health. However, these results need to be replicated in a prospective study that can account for confounding by indication which may explain these findings. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure to genocide and risk of suicide in Rwanda: a population-based case-control study.

PubMed

Rubanzana, Wilson; Hedt-Gauthier, Bethany L; Ntaganira, Joseph; Freeman, Michael D

2015-02-01

In Rwanda, an estimated one million people were killed during the 1994 genocide, leaving the country shattered and social fabric destroyed. Large-scale traumatic events such as wars and genocides have been linked to endemic post-traumatic stress disorder, depression and suicidality. The study objective was to investigate whether the 1994 genocide exposure is associated with suicide in Rwanda. We conducted a population-based case-control study. Suicide victims were matched to three living controls for sex, age and residential location. Exposure was defined as being a genocide survivor, having suffered physical/sexual abuse in the genocide, losing a first-degree relative in the genocide, having been convicted for genocide crimes or having a first-degree relative convicted for genocide. From May 2011 to May 2013, 162 cases and 486 controls were enrolled countrywide. Information was collected from the police, local village administrators and family members. After adjusting for potential confounders, having been convicted for genocide crimes was a significant predictor for suicide (OR=17.3, 95% CI 3.4 to 88.1). Being a survivor, having been physically or sexually abused during the genocide, and having lost a first-degree family member to genocide were not significantly associated with suicide. These findings demonstrate that individuals convicted for genocide crimes are experiencing continued psychological disturbances that affect their social reintegration into the community even 20 years after the event. Given the large number of genocide perpetrators reintegrated after criminal courts and Gacaca traditional reconciling trials, suicide could become a serious public health burden if preventive remedial action is not identified. 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.

Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.

PubMed

Rostomyan, Liliya; Daly, Adrian F; Petrossians, Patrick; Nachev, Emil; Lila, Anurag R; Lecoq, Anne-Lise; Lecumberri, Beatriz; Trivellin, Giampaolo; Salvatori, Roberto; Moraitis, Andreas G; Holdaway, Ian; Kranenburg-van Klaveren, Dianne J; Chiara Zatelli, Maria; Palacios, Nuria; Nozieres, Cecile; Zacharin, Margaret; Ebeling, Tapani; Ojaniemi, Marja; Rozhinskaya, Liudmila; Verrua, Elisa; Jaffrain-Rea, Marie-Lise; Filipponi, Silvia; Gusakova, Daria; Pronin, Vyacheslav; Bertherat, Jerome; Belaya, Zhanna; Ilovayskaya, Irena; Sahnoun-Fathallah, Mona; Sievers, Caroline; Stalla, Gunter K; Castermans, Emilie; Caberg, Jean-Hubert; Sorkina, Ekaterina; Auriemma, Renata Simona; Mittal, Sachin; Kareva, Maria; Lysy, Philippe A; Emy, Philippe; De Menis, Ernesto; Choong, Catherine S; Mantovani, Giovanna; Bours, Vincent; De Herder, Wouter; Brue, Thierry; Barlier, Anne; Neggers, Sebastian J C M M; Zacharieva, Sabina; Chanson, Philippe; Shah, Nalini Samir; Stratakis, Constantine A; Naves, Luciana A; Beckers, Albert

2015-10-01

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases. © 2015 Society for Endocrinology.

Analgesics use and ESRD in younger age: a case-control study

PubMed Central

van der Woude, Fokke J; Heinemann, Lothar AJ; Graf, Helmut; Lewis, Michael; Moehner, Sabine; Assmann, Anita; Kühl-Habich, Doerthe

2007-01-01

Background An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design. Methods We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed. Results The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls. Conclusion We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated. PMID:18053232

BETASEQ: a powerful novel method to control type-I error inflation in partially sequenced data for rare variant association testing.

PubMed

Yan, Song; Li, Yun

2014-02-15

Despite its great capability to detect rare variant associations, next-generation sequencing is still prohibitively expensive when applied to large samples. In case-control studies, it is thus appealing to sequence only a subset of cases to discover variants and genotype the identified variants in controls and the remaining cases under the reasonable assumption that causal variants are usually enriched among cases. However, this approach leads to inflated type-I error if analyzed naively for rare variant association. Several methods have been proposed in recent literature to control type-I error at the cost of either excluding some sequenced cases or correcting the genotypes of discovered rare variants. All of these approaches thus suffer from certain extent of information loss and thus are underpowered. We propose a novel method (BETASEQ), which corrects inflation of type-I error by supplementing pseudo-variants while keeps the original sequence and genotype data intact. Extensive simulations and real data analysis demonstrate that, in most practical situations, BETASEQ leads to higher testing powers than existing approaches with guaranteed (controlled or conservative) type-I error. BETASEQ and associated R files, including documentation, examples, are available at http://www.unc.edu/~yunmli/betaseq

Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics.

PubMed

McCaw, J M; Glass, K; Mercer, G N; McVernon, J

2014-03-01

The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans.

Alcohol consumption and lung cancer risk in never smokers: a pooled analysis of case-control studies.

PubMed

García Lavandeira, José A; Ruano-Ravina, Alberto; Kelsey, Karl T; Torres-Durán, María; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Zapata, Maruxa; Abal-Arca, José; Vidal-García, Iria; Montero-Martínez, Carmen; Amenedo, Margarita; Castro-Añón, Olalla; Golpe-Gómez, Antonio; Guzmán-Taveras, Rosirys; Martínez, Cristina; Provencio, Mariano; Mejuto-Martí, María J; García-García, Silvia; Fernández-Villar, Alberto; Piñeiro, María; Barros-Dios, Juan M

2018-06-01

Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS. We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed. A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern. Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

Crohn's disease and early exposure to domestic refrigeration.

PubMed

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.

Crohn's Disease and Early Exposure to Domestic Refrigeration

PubMed Central

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Background Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Methodology/Principal Findings Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. Conclusion This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood. PMID:19177167

Lung Cancer and Occupation in a Population-based Case-Control Study

PubMed Central

Consonni, Dario; De Matteis, Sara; Lubin, Jay H.; Wacholder, Sholom; Tucker, Margaret; Pesatori, Angela Cecilia; Caporaso, Neil E.; Bertazzi, Pier Alberto; Landi, Maria Teresa

2010-01-01

The authors examined the relation between occupation and lung cancer in the large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. In 2002–2005 in the Lombardy region of northern Italy, 2,100 incident lung cancer cases and 2,120 randomly selected population controls were enrolled. Lifetime occupational histories (industry and job title) were coded by using standard international classifications and were translated into occupations known (list A) or suspected (list B) to be associated with lung cancer. Smoking-adjusted odds ratios and 95% confidence intervals were calculated with logistic regression. For men, an increased risk was found for list A (177 exposed cases and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and most occupations therein. No overall excess was found for list B with the exception of filling station attendants and bus and truck drivers (men) and launderers and dry cleaners (women). The authors estimated that 4.9% (95% confidence interval: 2.0, 7.8) of lung cancers in men were attributable to occupation. Among those in other occupations, risk excesses were found for metal workers, barbers and hairdressers, and other motor vehicle drivers. These results indicate that past exposure to occupational carcinogens remains an important determinant of lung cancer occurrence. PMID:20047975

Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study

PubMed Central

Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G.; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

2010-01-01

Context: Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Objective: Our objective was to evaluate the association between organic nitrates and hip fracture risk. Methods: A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991–2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Results: Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83–1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63–1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97–1.40). No association was found between duration of nitrate use and fracture risk. Conclusions: Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects. PMID:20130070

Use of organic nitrates and the risk of hip fracture: a population-based case-control study.

PubMed

Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

2010-04-01

Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Our objective was to evaluate the association between organic nitrates and hip fracture risk. A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk. Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.

Night work and breast cancer: a population-based case-control study in France (the CECILE study).

PubMed

Menegaux, Florence; Truong, Thérèse; Anger, Antoinette; Cordina-Duverger, Emilie; Lamkarkach, Farida; Arveux, Patrick; Kerbrat, Pierre; Févotte, Joëlle; Guénel, Pascal

2013-02-15

Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99-1.64]). Odds ratios were 1.35 [1.01-1.80] in women who worked on overnight shifts, 1.40 [1.01-1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01-2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13-3.35] in women employed in night work for >4 years before their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full-term pregnancy. Copyright © 2012 UICC.

Biosocial and other characteristics of the large bowel cancer patients in Belgrade (Yugoslavia).

PubMed

Jarebinski, M; Vlajinac, H; Adanja, B

1988-01-01

This paper presents the results of a comparative biosocial study between 186 patients with large bowel cancer and two groups of matched controls, each with 186 persons. One of these groups was from hospitalized patients, the other from the neighbourhood of the cancer patients. Bowel cancer patients and their controls were compared with regard to level of education, profession, physical activity in job, smoking habits, alcohol and coffee consumption and previous illnesses. The only parameters that were statistically different between cancer patients and both controls were haemorrhoids and use of laxatives, that were found to be increased in the cancer group. Higher education level, coffee consumption, polyposis, appendectomia were significantly more presented in bowel cancer patients but only in comparison to one control group. Out of the other diseases of the digestive tract, cases and controls differed with respect to cholecystitis, cholecystectomy and to diabetes.

Nonlinear time-series-based adaptive control applications

NASA Technical Reports Server (NTRS)

Mohler, R. R.; Rajkumar, V.; Zakrzewski, R. R.

1991-01-01

A control design methodology based on a nonlinear time-series reference model is presented. It is indicated by highly nonlinear simulations that such designs successfully stabilize troublesome aircraft maneuvers undergoing large changes in angle of attack as well as large electric power transients due to line faults. In both applications, the nonlinear controller was significantly better than the corresponding linear adaptive controller. For the electric power network, a flexible AC transmission system with series capacitor power feedback control is studied. A bilinear autoregressive moving average reference model is identified from system data, and the feedback control is manipulated according to a desired reference state. The control is optimized according to a predictive one-step quadratic performance index. A similar algorithm is derived for control of rapid changes in aircraft angle of attack over a normally unstable flight regime. In the latter case, however, a generalization of a bilinear time-series model reference includes quadratic and cubic terms in angle of attack.

A systematic review of occupational safety and health business cases.

PubMed

Verbeek, Jos; Pulliainen, Marjo; Kankaanpää, Eila

2009-12-01

Business cases are commonly developed as means to rationalize investment. We systematically reviewed 26 reported cases on occupational safety and health (OSH) interventions to assess if health and productivity arguments make a good business case. To be included in the review, studies had to analyze the costs and benefits, including productivity, of an OSH intervention at the enterprise level. We searched Medline and Embase for studies and used Google search in addition. Two reviewers independently selected studies and extracted data. The intervention profitability was calculated in euros (euro in 2008) as the first year's benefits minus the total intervention costs per worker. The payback period was calculated as the intervention costs divided by the first year's benefits. We found three ex-ante and 23 ex-post cases. In 20 cases, the study design was a before-after comparison without a control group. Generally a 100% reduction of injuries or sickness absence was assumed. In two cases, productivity and quality increases were very large. The main benefit was avoided sick leave. Depreciation or discounting was applied only in a minority of cases. The intervention profitability was negative in seven studies, up to euro 500 per employee in 12 studies and more than euro 500 per employee in seven studies. The payback period was less than half a year for 19 studies. Only a few studies included sensitivity analyses. Few ex-ante business cases for management decisions on OSH are reported. Guidelines for reporting and evaluation are needed. Business cases need more sound assumptions on the effectiveness of interventions and should incorporate greater uncertainty into their design. Ex-post evaluation should be based preferably on study designs that control for trends at a time different from that of the intervention.

A matched case-control study of convenience store robbery risk factors.

PubMed

Hendricks, S A; Landsittel, D P; Amandus, H E; Malcan, J; Bell, J

1999-11-01

Convenience store clerks have been shown to be at high risk for assault and homicide, mostly owing to robbery or robbery attempts. Although the literature consistently indicates that at least some environmental designs are effective deterrents of robbery, the significance of individual interventions and policies has differed across past studies. To address these issues, a matched case-control study of 400 convenience store robberies in three metropolitan areas of Virginia was conducted. Conditional logistic regression was implemented to evaluate the significance of various environmental designs and other factors possibly related to convenience store robbery. Findings indicate that numerous characteristics of the surrounding environment and population were significantly associated with convenience store robbery. Results also showed that, on a univariate level, most crime prevention factors were significantly associated with a lower risk for robbery. Using a forward selection process, a multivariate model, which included cash handling policy, bullet-resistant shielding, and numerous characteristics of the surrounding area and population, was identified. This study addressed numerous limitations of the previous literature by prospectively collecting extensive data on a large sample of diverse convenience stores and directly addressing the current theory on the robbers' selection of a target store through a matched case-control design.

Genome-Wide Association Study Reveals Greater Polygenic Loading for Schizophrenia in Cases With a Family History of Illness

PubMed Central

Bigdeli, Tim B.; Ripke, Stephan; Bacanu, Silviu-Alin; Lee, Sang Hong; Wray, Naomi R.; Gejman, Pablo V.; Rietschel, Marcella; Cichon, Sven; St Clair, David; Corvin, Aiden; Kirov, George; McQuillin, Andrew; Gurling, Hugh; Rujescu, Dan; Andreassen, Ole A.; Werge, Thomas; Blackwood, Douglas H.R.; Pato, Carlos N.; Pato, Michele T.; Malhotra, Anil K.; O’Donovan, Michael C.; Kendler, Kenneth S.; Fanous, Ayman H.

2018-01-01

Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke’s R2 = 0.0021; P = 0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031).We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies. PMID:26663532

Flexible system model reduction and control system design based upon actuator and sensor influence functions

NASA Technical Reports Server (NTRS)

Yam, Yeung; Johnson, Timothy L.; Lang, Jeffrey H.

1987-01-01

A model reduction technique based on aggregation with respect to sensor and actuator influence functions rather than modes is presented for large systems of coupled second-order differential equations. Perturbation expressions which can predict the effects of spillover on both the reduced-order plant model and the neglected plant model are derived. For the special case of collocated actuators and sensors, these expressions lead to the derivation of constraints on the controller gains that are, given the validity of the perturbation technique, sufficient to guarantee the stability of the closed-loop system. A case study demonstrates the derivation of stabilizing controllers based on the present technique. The use of control and observation synthesis in modifying the dimension of the reduced-order plant model is also discussed. A numerical example is provided for illustration.

The c.553G>T Genetic Variant of the APOA5 Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case-Control Studies.

PubMed

He, Hongjuan; Lei, Lei; Chen, Erfei; Dong, Jing; Zhang, Kejin; Yang, Jin

2016-12-01

To explore the association of the APOA5 gene c.553G>T polymorphism with hypertriglyceridemia (HTG) susceptibility and altered triglyceride levels. We searched the PubMed, Google Scholar, and CNKI databases for published studies relating to analyses of these associations. Case-control and comparative studies of the association between the APOA5 c.553G>T variant and altered triglyceride levels were included. In total, the meta-analysis involved 10 studies on HTG, which provided 2219 cases and 3401 controls. To measure the correlation between the c.553G>T polymorphism and HTG susceptibility, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The overall OR was calculated using a random-effects model. Compared with APOA5 c.553 GG carriers, c.553T carriers displayed an increased risk of HTG in the Asian population, with an overall random effects OR of 3.55 (95% CI: 2.46-5.13) in the dominant model. There was significant heterogeneity among the studies (P heterogeneity : Chi 2  = 45.80, I 2  = 75.98%), which may be largely explained by certain patient types. Both the sensitivity analysis and publication bias suggested that the overall result was acceptable. Subgroup analysis showed a large difference in serum triglyceride levels based on the c.553 G > T polymorphism in healthy individuals and HTG patients. APOA5 c.553T carriers exhibit higher triglyceride levels than GG carriers. Our results suggest that APOA5 c. 553T is an independent risk factor for HTG and increased triglyceride levels in the Asian population. APOA5 c. 553T could be employed as a genetic risk marker for HTG and increased triglyceride levels.

Risk factors in lateral epicondylitis (tennis elbow): a case-control study.

PubMed

Titchener, A G; Fakis, A; Tambe, A A; Smith, C; Hubbard, R B; Clark, D I

2013-02-01

Lateral epicondylitis is a common condition, but relatively little is known about its aetiology and associated risk factors. We have undertaken a large case-control study using The Health Improvement Network database to assess and quantify the relative contributions of some constitutional and environmental risk factors for lateral epicondylitis in the community. Our dataset included 4998 patients with lateral epicondylitis who were individually matched with a single control by age, sex, and general practice. The median age at diagnosis was 49 (interquartile range 42-56) years . Multivariate analysis showed that the risk factors associated with lateral epicondylitis were rotator cuff pathology (OR 4.95), De Quervain's disease (OR 2.48), carpal tunnel syndrome (OR 1.50), oral corticosteroid therapy (OR 1.68), and previous smoking history (OR 1.20). Diabetes mellitus, current smoking, trigger finger, rheumatoid arthritis, alcohol intake, and obesity were not found to be associated with lateral epicondylitis.

Characterizing a large outbreak of dengue fever in Guangdong Province, China.

PubMed

Xiao, Jian-Peng; He, Jian-Feng; Deng, Ai-Ping; Lin, Hua-Liang; Song, Tie; Peng, Zhi-Qiang; Wu, Xiao-Cheng; Liu, Tao; Li, Zhi-Hao; Rutherford, Shannon; Zeng, Wei-Lin; Li, Xing; Ma, Wen-Jun; Zhang, Yong-Hui

2016-05-03

Dengue cases have been reported each year for the past 25 years in Guangdong Province, China with a recorded historical peak in 2014. This study aims to describe the epidemiological characteristics of this large outbreak in order to better understand its epidemic factors and to inform control strategies. Data for clinically diagnosed and laboratory-confirmed dengue fever cases in 2014 were extracted from the China Notifiable Infectious Disease Reporting System. We analyzed the incidence and characteristics of imported and indigenous cases in terms of population, temporal and spatial distributions. A total of 45 224 dengue fever cases and 6 deaths were notified in Guangdong Province in 2014, with an incidence of 47.3 per 100 000 people. The elderly (65+ years) represented 11.7 % of total indigenous cases with the highest incidence (72.3 per 100 000). Household workers and the unemployed accounted for 23.1 % of indigenous cases. The majority of indigenous cases occurred in the 37(th) to 44(th) week of 2014 (September and October) and almost all (20 of 21) prefecture-level cities in Guangdong were affected. Compared to the non-Pearl River Delta Region, the Pearl River Delta Region accounted for the majority of dengue cases and reported cases earlier in 2014. Dengue virus serotypes 1 (DENV-1), 2 (DENV-2) and 3 (DENV-3) were detected and DENV-1 was predominant (88.4 %). Dengue fever is a serious public health problem and is emerging as a continuous threat in Guangdong Province. There is an urgent need to enhance dengue surveillance and control, especially for the high-risk populations in high-risk areas.

Metformin for primary colorectal cancer prevention in patients with diabetes: a case-control study in a US population.

PubMed

Sehdev, Amikar; Shih, Ya-Chen T; Vekhter, Benjamin; Bissonnette, Marc B; Olopade, Olufunmilayo I; Polite, Blase N

2015-04-01

Emerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, to the authors' knowledge, none of these studies was conducted in a US population. Because environmental factors such as Western diet and obesity are implicated in the causation of CRC, a large case-control study was performed to assess the effects of metformin on the incidence of CRC in a US population. MarketScan databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to 2 controls matched for age, sex, and geographical region were selected for each case. Metformin exposure was assessed by prescription tracking within the 12-month period before the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AORs). The mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P = 1.0). Approximately 60% of the study participants were male and 40% were female in each group. In the multivariable model, any metformin use was associated with a 15% reduction in the odds of CRC (AOR, 0.85; 95% confidence interval, 0.76-0.95 [P = .007]). After adjusting for health care use, the beneficial effect of metformin was reduced to 12% (AOR, 0.88; 95% confidence interval, 0.77-1.00 [P = .05]). The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure. Metformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States. © 2014 American Cancer Society.

Childhood hematologic cancer and residential proximity to oil and gas development.

PubMed

McKenzie, Lisa M; Allshouse, William B; Byers, Tim E; Bedrick, Edward J; Serdar, Berrin; Adgate, John L

2017-01-01

Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Participants were 0-24 years old, living in rural Colorado, and diagnosed with cancer between 2001-2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Overall, ALL cases 0-24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5-24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0-4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.

Disease-Concordant Twins Empower Genetic Association Studies.

PubMed

Tan, Qihua; Li, Weilong; Vandin, Fabio

2017-01-01

Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost. © 2016 John Wiley & Sons Ltd/University College London.

Maternal Residential Exposure to Agricultural Pesticides and Birth Defects in a 2003 to 2005 North Carolina Birth Cohort

EPA Science Inventory

Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agr...

Controlling the development of coherent structures in high speed jets and the resultant near field

NASA Astrophysics Data System (ADS)

Speth, Rachelle

This work uses Large-Eddy Simulations to examine the effect of actuator parameters and jet exit properties on the evolution of coherent structures and their impact on the near-acoustic field without and with control. For the controlled cases, Localized Arc Filament Plasma Actuators (LAFPAs) are considered, and modeled with a simple heating approach that successfully reproduces the main observations and trends of experiments. A parametric study is first conducted, using the flapping mode (m = +/-1), to investigate the sensitivity of the results to various actuator parameters including: actuator model temperature, actuator duty cycle, and excitation frequency. It is shown by considering a Mach 1.3 jet at Reynolds number of 1 x 106 that the response of the jet is relatively insensitive to actuator model temperature within the limits of the experimentally measured temperature values. Furthermore, duty cycles in the range of 20%--90% were observed to be effective in reproducing the characteristic coherent structures of the flapping mode. Next, jet flow parameters were explored to determine the control authority under different operating conditions. To begin, the effect of the laminar nozzle exit boundary layer thickness was examined by varying its value from essentially uniform flow to 25% of the diameter. In the absence of control, the distance between the nozzle lip and the initial appearance of breakdown is proportional to the boundary-layer thickness, which is consistent with theory and previous results obtained by other researchers at Mach 0.9. The second flow parameter studied was the effect of Reynolds number on a Mach 1.3 jet controlled by the flapping mode at an excitation Strouhal number of 0.3. The higher Reynolds number (Re=1,100,000) jet exhibited reduced control authority compared to the Re=100,000 jet. Like the effect of increasing the nozzle exit boundary layer thickness, increasing the Reynolds number cause a reduction in spreading on the flapping plane and an increase on the non-flapping plane. Therefore, these thicker layers and higher Reynolds number jets may require actuators with a higher energy input (i.e. higher duty cycle, higher actuator temperature, more actuators) to ensure the excitation of the flow instability. The final parameter studied is the effect of Mach number on the development and decay of large scale structures for no-control and control cases for Mach 0.9 and Mach 1.3 jets. For this exercise, the axisymmetric mode (m=0) was considered at excitation frequencies of St=0.05, 0.15, and 0.25, with emphasis on the evolution of coherent structures and their effects on the resultant near field pressure map. Without control, the two jets have similar shear layer growth until the end of the potential core length of the subsonic case, at which point the subsonic jet spreads at a higher rate. For the controlled cases, relatively larger streamwise hairpin vortices have been noted for the subsonic cases than the supersonic cases resulting in stronger entrainment of the ambient fluid. This increased entrainment in the subsonic cases causes a reduction in the normalized convective velocity resulting in similar normalized values to that of the supersonic cases. As the excitation frequency is increased, more hairpin vortices are present and the normalized convective velocity is reduced for both subsonic and supersonic cases. (Abstract shortened by ProQuest.).

Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011.

PubMed

Frank, C; Faber, M S; Askar, M; Bernard, H; Fruth, A; Gilsdorf, A; Hohle, M; Karch, H; Krause, G; Prager, R; Spode, A; Stark, K; Werber, D

2011-05-26

Since early May 2011, an increased incidence of haemolytic uraemic syndrome (HUS) and bloody diarrhoea related to infections with Shiga toxin-producing Escherichia coli (STEC) has been observed in Germany, with most cases in the north of the country. Cases reported from other European countries had travelled to this area. First results of a case–control study conducted in Hamburg suggest an association between the occurrence of disease and the consumption of raw tomatoes, cucumber and leaf salad.

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

PubMed

Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

2009-11-01

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2-yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.

Unmatched Case-Control Study on Late Presentation of HIV Infection in Santiago, Cape Verde (2004–2011)

PubMed Central

Moreira, António L.; Fronteira, Inês; Augusto, Gonçalo Figueiredo; Martins, Maria Rosario O.

2016-01-01

Access to free antiretroviral therapy (ART) in Sub-Saharan Africa has been steadily increasing over the past decade. However, the success of large-scale ART programmes depends on timely diagnosis and early initiation of HIV care. This study characterizes late presenters to HIV care in Santiago (Cape Verde) between 2004 and 2011, and identifies factors associated with late presentation for care. We defined late presentation as persons presenting to HIV care with a CD4 count below 350 cells/mm3. An unmatched case-control study was conducted using socio-demographic and behavioural data of 368 individuals (191 cases and 177 controls) collected through an interviewer-administered questionnaire, comparing HIV patients late and early presented to care. Logistic regression was performed to estimate odds ratio and 95% confidence intervals. Results show that 51.9% were late presenters for HIV. No differences were found in gender distribution, marital status, or access to health services between cases and controls. Participants who undertook an HIV test by doctor indication were more likely to present late compared with those who tested for HIV by their own initiative. Also, individuals taking less time to initiate ART are more likely to present late. This study highlights the need to better understand reasons for late presentation to HIV care in Cape Verde. People in older age groups should be targeted in future approaches focused on late presenters to HIV care. PMID:26999167

Unmatched Case-Control Study on Late Presentation of HIV Infection in Santiago, Cape Verde (2004-2011).

PubMed

Moreira, António L; Fronteira, Inês; Augusto, Gonçalo Figueiredo; Martins, Maria Rosario O

2016-03-15

Access to free antiretroviral therapy (ART) in Sub-Saharan Africa has been steadily increasing over the past decade. However, the success of large-scale ART programmes depends on timely diagnosis and early initiation of HIV care. This study characterizes late presenters to HIV care in Santiago (Cape Verde) between 2004 and 2011, and identifies factors associated with late presentation for care. We defined late presentation as persons presenting to HIV care with a CD4 count below 350 cells/mm³. An unmatched case-control study was conducted using socio-demographic and behavioural data of 368 individuals (191 cases and 177 controls) collected through an interviewer-administered questionnaire, comparing HIV patients late and early presented to care. Logistic regression was performed to estimate odds ratio and 95% confidence intervals. Results show that 51.9% were late presenters for HIV. No differences were found in gender distribution, marital status, or access to health services between cases and controls. Participants who undertook an HIV test by doctor indication were more likely to present late compared with those who tested for HIV by their own initiative. Also, individuals taking less time to initiate ART are more likely to present late. This study highlights the need to better understand reasons for late presentation to HIV care in Cape Verde. People in older age groups should be targeted in future approaches focused on late presenters to HIV care.

A case-control study of hormonal exposures as etiologic factors for ALS in women: Euro-MOTOR.

PubMed

Rooney, James P K; Visser, Anne E; D'Ovidio, Fabrizio; Vermeulen, Roel; Beghi, Ettore; Chio, Adriano; Veldink, Jan H; Logroscino, Giancarlo; van den Berg, Leonard H; Hardiman, Orla

2017-09-19

To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history, breastfeeding, contraceptive use, hormonal replacement therapy, and gynecologic surgical history, were recorded with a validated questionnaire. Logistic regression models adjusted for age, education, study site, smoking, alcohol, and physical activity were used to determine the association between female hormones and ALS risk. We included 653 patients and 1,217 controls. Oral contraceptive use was higher among controls (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.84), and a dose-response effect was apparent. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands (OR = 0.57, 95% CI 0.37-0.85). These findings were robust to sensitivity analysis, but there was some heterogeneity across study sites. This large case-control study across 3 different countries has demonstrated an association between exogenous estrogens and progestogens and reduced odds of ALS in women. These results are at variance with previous findings, which may be partly explained by differential regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the countries included. Our results indicate that hormonal factors may be important etiologic factors in ALS; however, a full understanding requires further investigation. © 2017 American Academy of Neurology.

Concordance of occupational and environmental exposure information elicited from patients with Alzheimer's disease and surrogate respondents

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

Chong, J.P.; Turpie, I.; Haines, T.

Identification of risk factors for Alzheimer's disease through the use of well designed case-control studies has been described as a research priority. Increasing recognition of the neurotoxic potential of many industrial chemicals such as organic solvents raises the question of the occupational and environmental contribution to the etiology of this high-priority health problem. The intention of this study was to develop and evaluate a methodology that could be used in a large scale case-control study of the occupational and environmental risk factors for dementia or a population-based surveillance system for neurotoxic disorders. The specific objectives of this study were tomore » investigate: (1) the reliability of exposure-eliciting, interviewer-administered questionnaires given to patients with Alzheimer's disease (SDAT); (2) the reliability of exposure-eliciting interviewer-administered questionnaires given to the family of patients with SDAT and the agreement with the responses of the patient or surrogate respondents; (3) the reliability and agreement of responses of age- and sex-matched control patients and their families selected from geriatric care institutions and the community, with respect to the same exposure-eliciting and interviewer-administered questionnaire; and (4) the reliability of agent-based exposure ascertainment by a single, trained rater. The results of the study demonstrate that occupational and environmental histories from which exposure information can be derived is most reliably elicited from job descriptions of cases and control subjects rather than job titles alone or detailed probes for potential neurotoxic exposures. This will necessitate the use of standardized interviewer-administered instruments to derive this information in case-control studies of Alzheimer's disease or population-based surveillance systems for occupational and environmental neurotoxicity.« less

Large-Scale Gene-Centric Analysis Identifies Novel Variants for Coronary Artery Disease

PubMed Central

2011-01-01

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes. PMID:21966275

Birth defects in relation to Bendectin use in pregnancy. II. Pyloric stenosis.

PubMed

Mitchell, A A; Schwingl, P J; Rosenberg, L; Louik, C; Shapiro, S

1983-12-01

To test the hypothesis that the use of Bendectin in pregnancy increases the risk of pyloric stenosis, we determined rates of antenatal Bendectin exposure among 325 infants with pyloric stenosis and among two control groups comprising infants with other defects; one consisted of 3,153 infants with other conditions, and the other, a subset of that group, consisted of 724 infants with defects that may have had their origins at any time in pregnancy. Comparisons between the cases and the two control series yielded estimated relative risks of 0.9 (95% confidence interval, 0.6 to 1.2) and 1.0 (0.7 to 1.4), respectively. The findings from this large case-control study suggest that Bendectin does not increase the risk of pyloric stenosis.

Marijuana smoking and the risk of head and neck cancer: pooled analysis in the INHANCE consortium.

PubMed

Berthiller, Julien; Lee, Yuan-Chin Amy; Boffetta, Paolo; Wei, Qingyi; Sturgis, Erich M; Greenland, Sander; Morgenstern, Hal; Zhang, Zuo-Feng; Lazarus, Philip; Muscat, Joshua; Chen, Chu; Schwartz, Stephen M; Eluf Neto, José; Wünsch Filho, Victor; Koifman, Sergio; Curado, Maria Paula; Matos, Elena; Fernandez, Leticia; Menezes, Ana; Daudt, Alexander W; Ferro, Gilles; Brennan, Paul; Hashibe, Mia

2009-05-01

Marijuana contains carcinogens similar to tobacco smoke and has been suggested by relatively small studies to increase the risk of head and neck cancer (HNC). Because tobacco is a major risk factor for HNC, large studies with substantial numbers of never tobacco users could help to clarify whether marijuana smoking is independently associated with HNC risk. We pooled self-reported interview data on marijuana smoking and known HNC risk factors on 4,029 HNC cases and 5,015 controls from five case-control studies within the INHANCE Consortium. Subanalyses were conducted among never tobacco users (493 cases and 1,813 controls) and among individuals who did not consume alcohol or smoke tobacco (237 cases and 887 controls). The risk of HNC was not elevated by ever marijuana smoking [odds ratio (OR), 0.88; 95% confidence intervals (95% CI), 0.67-1.16], and there was no increasing risk associated with increasing frequency, duration, or cumulative consumption of marijuana smoking. An increased risk of HNC associated with marijuana use was not detected among never tobacco users (OR, 0.93; 95% CI, 0.63-1.37; three studies) nor among individuals who did not drink alcohol and smoke tobacco (OR, 1.06; 95% CI, 0.47-2.38; two studies). Our results are consistent with the notion that infrequent marijuana smoking does not confer a risk of these malignancies. Nonetheless, because the prevalence of frequent marijuana smoking was low in most of the contributing studies, we could not rule out a moderately increased risk, particularly among subgroups without exposure to tobacco and alcohol.

A Meta-Analysis of the Association between DNMT1 Polymorphisms and Cancer Risk.

PubMed

Li, Hao; Liu, Jing-Wei; Sun, Li-Ping; Yuan, Yuan

2017-01-01

Previous studies have examined the associations of DNA methyltransferase 1 ( DNMT1 ) polymorphisms, including single nucleotide polymorphisms rs16999593 (T/C), rs2228611 (G/A), and rs2228612 (A/G), with cancer risk. However, the results are inconclusive. The aim of this meta-analysis is to elucidate the associations between DNMT1 polymorphisms and cancer susceptibility. The PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure databases were searched systematically to identify potentially eligible reports. Odd ratios and 95% confidence intervals were used to evaluate the strength of association between three DNMT1 polymorphisms and cancer risk. A total of 16 studies were finally included in the meta-analysis, namely, nine studies of 3378 cases and 4244 controls for rs16999593, 11 studies of 3643 cases and 3866 controls for rs2228611, and three studies of 1343 cases and 1309 controls for rs2228612. The DNMT1 rs2228612 (A/G) polymorphism was significantly related to cancer risk in the recessive model. The meta-analysis also suggested that DNMT1 rs16999593 (T/C) may be associated with gastric cancer, while rs2228611 (G/A) may be associated with breast cancer. In future research, large-scale and well-designed studies are required to verify these findings.

Dynamic test results for the CASES ground experiment

NASA Technical Reports Server (NTRS)

Bukley, Angelia P.; Patterson, Alan F.; Jones, Victoria L.

1993-01-01

The Controls, Astrophysics, and Structures Experiment in Space (CASES) Ground Test Facility (GTF) has been developed at Marshall Space Flight Center (MSFC) to provide a facility for the investigation of Controls/Structures Interaction (CSI) phenomena, to support ground testing of a potential shuttle-based CASES flight experiment, and to perform limited boom deployment and retraction dynamics studies. The primary objectives of the ground experiment are to investigate CSI on a test article representative of a Large Space Structure (LSS); provide a platform for Guest Investigators (GI's) to conduct CSI studies; to test and evaluate LSS control methodologies, system identification (ID) techniques, failure mode analysis; and to compare ground test predictions and flight results. The proposed CASES flight experiment consists of a 32 meter deployable/retractable boom at the end of which is an occulting plate. The control objective of the experiment is to maintain alignment of the tip plate (occulter) with a detector located at the base of the boom in the orbiter bay. The tip plate is pointed towards a star, the sun, or the galactic center to collect high-energy X-rays emitted by these sources. The tip plate, boom, and detector comprise a Fourier telescope. The occulting holes in the tip plate are approximately one millimeter in diameter making the alignment requirements quite stringent. Control authority is provided by bidirectional linear thrusters located at the boom tip and Angular Momentum Exchange Devices (AMED's) located at mid-boom and at the tip. The experiment embodies a number of CSI control problems including vibration suppression, pointing a long flexible structure, and disturbance rejection. The CASES GTF is representative of the proposed flight experiment with identical control objectives.

The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

PubMed Central

Sadetzki, Siegal; Langer, Chelsea Eastman; Bruchim, Revital; Kundi, Michael; Merletti, Franco; Vermeulen, Roel; Kromhout, Hans; Lee, Ae-Kyoung; Maslanyj, Myron; Sim, Malcolm R.; Taki, Masao; Wiart, Joe; Armstrong, Bruce; Milne, Elizabeth; Benke, Geza; Schattner, Rosa; Hutter, Hans-Peter; Woehrer, Adelheid; Krewski, Daniel; Mohipp, Charmaine; Momoli, Franco; Ritvo, Paul; Spinelli, John; Lacour, Brigitte; Delmas, Dominique; Remen, Thomas; Radon, Katja; Weinmann, Tobias; Klostermann, Swaantje; Heinrich, Sabine; Petridou, Eleni; Bouka, Evdoxia; Panagopoulou, Paraskevi; Dikshit, Rajesh; Nagrani, Rajini; Even-Nir, Hadas; Chetrit, Angela; Maule, Milena; Migliore, Enrica; Filippini, Graziella; Miligi, Lucia; Mattioli, Stefano; Yamaguchi, Naohito; Kojimahara, Noriko; Ha, Mina; Choi, Kyung-Hwa; Mannetje, Andrea ’t; Eng, Amanda; Woodward, Alistair; Carretero, Gema; Alguacil, Juan; Aragones, Nuria; Suare-Varela, Maria Morales; Goedhart, Geertje; Schouten-van Meeteren, A. Antoinette Y. N.; Reedijk, A. Ardine M. J.; Cardis, Elisabeth

2014-01-01

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case–control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10–24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people. PMID:25295243

Written violence policies and risk of physical assault against Minnesota educators.

PubMed

Feda, Denise M; Gerberich, Susan G; Ryan, Andrew D; Nachreiner, Nancy M; McGovern, Patricia M

2010-12-01

Few research studies on school violence policies use quantitative methods to evaluate the impact of policies on workplace violence. This study analyzed nine different written violence policies and their impact on work-related physical assault in educational settings. Data were from the Minnesota Educators' Study. This large, nested case control study included cases (n=372) who reported physical assaults within the last year, and controls (n=1116) who did not. Multivariate logistic regression analyses, using directed acyclic graphs, estimated risk of assault. Results of the adjusted multivariate model suggested decreased risks of physical assault were associated with the presence of policies regarding how to report sexual harassment, verbal abuse, and threat (OR 0.53; 95 per cent CI: 0.30-0.95); assurance of confidential reporting of events (OR 0.67; 95 per cent CI: 0.44-1.04); and zero tolerance for violence (OR 0.70; 95 per cent CI: 0.47-1.04).

Risk factors for type 2 diabetes mellitus among out-patients in Ho, the Volta regional capital of Ghana: a case-control study.

PubMed

Gudjinu, Horlali Yao; Sarfo, Bismark

2017-07-26

The prevalence of type 2 diabetes mellitus in developing countries like Ghana continues to rise. This study seeks to assess the risk factors of type 2 diabetes mellitus in a Ghanaian setting. An unmatched case-control study among patients receiving care at the out-patient departments of the two major hospitals in the Ho Municipality. Patients diagnosed with type 2 diabetes mellitus were recruited. Appropriate controls with similar ages who were also patients receiving care at the out-patient department of these hospitals were recruited. Both cases and controls were administered a questionnaire that comprises of standardized and validated tools. These tools include WHO STEPs instrument, general practice physical activity questionnaire and rapid eating and activity assessment for patients. Additionally, the research participants were made to undergo physical examinations for weight, height, waist circumference and laboratory testing of fasting venous blood to assess the biochemical factors of interest namely fasting blood glucose and fasting lipids. Analysis of data was done using STATA version 11. A total of 136 (48 cases and 88 controls) participants of which 95 [39 (81.25%) cases and 56 (63.64%) controls] respondents underwent laboratory testing for fasting blood glucose and fasting blood lipid (total cholesterol, HDL cholesterol and triglycerides). Participants were aged between 35 and 62 years. This study reveals a number of risk factors for type 2 diabetes mellitus. Individuals in the middle socio-economic class have a greater risk of developing type 2 diabetes mellitus with an OR of 5.03 (p < 0.003; 95% CI 1.71-14.74). Eating large quantities/servings of fruits per seating provides protection against development of type 2 diabetes mellitus. A low physical activity level is a valid determinant of type 2 diabetes mellitus irrespective of body mass index, socio-economic level or place of residence. Individuals within the middle socio-economic level, who are physically inactive and do not consume large amounts of fruit are at greatest risk of developing type 2 diabetes mellitus. Living in a rural setting is attendant with high levels of physical activity this tends to protect rural residents from type 2 diabetes mellitus. Physical activity level confounds the relationship between place of residence and development of type 2 diabetes mellitus. Local policies should be realigned to attract individual of the middle socio-economic level to live in rural areas where they are more likely to be both physically active and consume more fruits thus averting the risks of developing T2DM.

A large outbreak of scombroid fish poisoning associated with eating yellowfin tuna (Thunnus albacares) at a military mass catering in Dakar, Senegal.

PubMed

Demoncheaux, J-P; Michel, R; Mazenot, C; Duflos, G; Iacini, C; de Laval, F; Delaval, F; Saware, E M; Renard, J-C

2012-06-01

On 26 November 2010, an outbreak of scombroid fish poisoning occurred in the French Armed Forces in Dakar, Senegal. This chemical intoxication, due to high histamine concentration in fish, is often mistaken for an allergic reaction. A case-control study was undertaken including the 71 cases and 78 randomly selected controls among lunch attendees. The usual symptoms for scombroid fish poisoning were observed in cases, i.e. flushing (85.9%), headache (83.1%), rapid/weak pulse (59.1%) and diarrhoea (47.9%). Symptoms occurred from within a few minutes to up to 3 h following the meal. Most patients quickly recovered with antihistamine and/or symptomatic treatment. Tuna was the only food item positively associated with illness (odds ratio 36.3, 95% confidence interval 6.3-210.0), with the risk of illness increasing with the quantity of fish consumed. No bacterial contamination was found in leftover food, but histamine concentration in tuna was found to be 4900 mg/kg, almost 50-fold higher than the concentration allowed by European regulations. This report is unique because of the large size of the case series - to our knowledge, the largest event of scombroid fish poisoning ever reported - and the chemical and bacteriological analyses results obtained on leftover food.

Fifty years of stroke researches in India

PubMed Central

Banerjee, Tapas Kumar; Das, Shyamal Kumar

2016-01-01

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

Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias

PubMed Central

Verhoef, Petra; Dötsch-Klerk, Mariska; Lathrop, Mark; Xu, Peng; Nordestgaard, Børge G.; Holm, Hilma; Hopewell, Jemma C.; Saleheen, Danish; Tanaka, Toshihiro; Anand, Sonia S.; Chambers, John C.; Kleber, Marcus E.; Ouwehand, Willem H.; Yamada, Yoshiji; Elbers, Clara; Peters, Bas; Stewart, Alexandre F. R.; Reilly, Muredach M.; Thorand, Barbara; Yusuf, Salim; Engert, James C.; Assimes, Themistocles L.; Kooner, Jaspal; Danesh, John; Watkins, Hugh; Samani, Nilesh J.

2012-01-01

Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases). Conclusions The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors' Summary PMID:22363213

Effects of Reservoir Characteristics on Malaria and its vector Abundance: A Case Study of the Bongo District of Ghana

NASA Astrophysics Data System (ADS)

Ofosu, E.; Awuah, E.; Annor, F. O.

2009-04-01

In the seven (7) administrative zones of the Bongo District of the Upper East Region of Ghana, the occurrences of malaria and relative abundance of the principal malaria vector, Anopheles species, were studied as a function of the presence and characteristics of reservoirs during the rainy season. Case studies in the sub-Sahara Africa indicate that malaria transmission may increase decrease or remain largely unchanged as a consequence of reservoir presence. Analysis made, shows that the distance from reservoir to settlement and surface area of reservoirs significantly affected adult Anopheles mosquito abundance. Percentage of inhabitants using insecticide treated nets, livestock population density, human population density and Anopheles mosquito abundance significantly affected the occurrence of malaria. The results suggest that vector control targeted at reservoir characteristics and larval control, and supplemented by high patronage of insecticide treated nets may be an effective approach for epidemic malaria control in the Bongo District. Key Words: Bongo District, Reservoir, Anopheles species, Malaria, Vector abundance.

Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study.

PubMed

Derancourt, C; Bourdon-Lanoy, E; Grob, J-J; Guillaume, J-C; Bernard, P; Bastuji-Garin, S

2007-01-01

Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. To assess whether these lesions are clinical markers of past severe sunburn. A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data.

PubMed

Seidler, Andreas; Wagner, Mandy; Schubert, Melanie; Dröge, Patrik; Römer, Karin; Pons-Kühnemann, Jörn; Swart, Enno; Zeeb, Hajo; Hegewald, Janice

2016-11-01

Several studies point to an elevated risk for cardiovascular diseases induced by traffic noise. We examined the association between aircraft, road traffic and railway noise and heart failure or hypertensive heart disease (HHD) in a large case-control study. The study population consisted of individuals that were insured by three large statutory health insurance funds in the Rhine-Main area of Germany. Based on insurance claims and prescription data, 104,145 cases of heart failure or HHD diagnosed 2006-10 were identified and compared with 654,172 control subjects. Address-specific exposure to aircraft, road and railway traffic noise in 2005 was estimated. Odds Ratios were calculated using logistic regression analysis, adjusted for age, sex, local proportion of persons receiving unemployment benefits, and individual socioeconomic status (available for 39% of the individuals). A statistically significant linear exposure-risk relationship with heart failure or hypertensive heart disease was found for aircraft traffic noise (1.6% risk increase per 10dB increase in the 24-h continuous noise level; 95% CI 0.3-3.0%), road traffic noise (2.4% per 10dB; 95% CI 1.6-3.2%), and railway noise (3.1% per 10dB; 95% CI 2.2-4.1%). For individuals with 24-h continuous aircraft noise levels <40dB and nightly maximum aircraft noise levels exceeding 50dB six or more times, a significantly increased risk was observed. In general, risks of HHD were considerably higher than the risks of heart failure. Regarding the high prevalence of traffic noise from various sources, even low risk increases for frequent diseases are relevant for the population as a whole. Copyright © 2016 Elsevier GmbH. All rights reserved.

Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

PubMed

Parodi, Stefano; Merlo, Domenico Franco; Stagnaro, Emanuele

2017-04-01

Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflammatory potential of diet and risk of oral and pharyngeal cancer in a large case-control study from Italy.

PubMed

Shivappa, Nitin; Hébert, James R; Rosato, Valentina; Garavello, Werner; Serraino, Diego; La Vecchia, Carlo

2017-08-01

Diet and inflammation have been suggested to be important risk factors for oral and pharyngeal cancer. We examined the association between dietary inflammatory index (DII™) and oral and pharyngeal cancer in a large case-control study conducted between 1992 and 2009 in Italy. This study included 946 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,492 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a valid 78-item food frequency questionnaire and was adjusted for nonalcohol energy intake using the residual approach (E-DII™). Logistic regression models were used to estimate odds ratios (ORs), and 95% confidence intervals (CIs), adjusted for age, sex, non-alcohol energy intake, study center, year of interview, education, body mass index, tobacco smoking, and alcohol drinking. Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of oral and pharyngeal cancer, the OR being 1.80 (95% CI 1.36-2.38) for the highest versus the lowest DII quartile and 1.17 (95% CI 1.10-1.25) for a one-unit increase (8% of the DII range). When stratified by selected covariates, a stronger association was observed among women (OR quartile4 v.1 3.30, 95% CI 1.95-5.57). We also observed a stronger association for oral cancers and a strong combined effect of higher DII score and tobacco smoking or alcohol consumption on oral and pharyngeal cancer. These results indicate that the pro-inflammatory potential of the diet, as shown by higher DII scores, is associated with higher odds of oral and pharyngeal cancer. © 2017 UICC.

Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

PubMed

Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

2011-05-01

Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min < 7 for both sexes combined (5.13, 2.55-10.3). ORs close to unity were seen for parental age and birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

Attributes of long-term heavy cannabis users: a case-control study.

PubMed

Gruber, A J; Pope, H G; Hudson, J I; Yurgelun-Todd, D

2003-11-01

Although cannabis is the most widely used illicit drug in the United States, few recent American studies have examined the attributes of long-term heavy cannabis users. Using a case-control design, we obtained psychological and demographic measures on 108 individuals, age 30-55, who had smoked cannabis a mean of 18000 times and a minimum of 5000 times in their lives. We compared these heavy users to 72 age-matched control subjects who had smoked at least once, but no more than 50 times in their lives. We found no significant differences between the two groups on reported levels of income and education in their families of origin. However, the heavy users themselves reported significantly lower educational attainment (P < 0.001) and income (P = 0.003) than the controls, even after adjustment for a large number of potentially confounding variables. When asked to rate the subjective effects of cannabis on their cognition, memory, career, social life, physical health and mental health, large majorities of heavy users (66-90%) reported a 'negative effect'. On several measures of quality of life, heavy users also reported significantly lower levels of satisfaction than controls. Both objective and self-report measures suggest numerous negative features associated with long-term heavy cannabis use. Thus, it seems important to understand why heavy users continue to smoke regularly for years, despite acknowledging these negative effects. Such an understanding may guide the development of strategies to treat cannabis dependence.

German outbreak of Escherichia coli O104:H4 associated with sprouts.

PubMed

Buchholz, Udo; Bernard, Helen; Werber, Dirk; Böhmer, Merle M; Remschmidt, Cornelius; Wilking, Hendrik; Deleré, Yvonne; an der Heiden, Matthias; Adlhoch, Cornelia; Dreesman, Johannes; Ehlers, Joachim; Ethelberg, Steen; Faber, Mirko; Frank, Christina; Fricke, Gerd; Greiner, Matthias; Höhle, Michael; Ivarsson, Sofie; Jark, Uwe; Kirchner, Markus; Koch, Judith; Krause, Gérard; Luber, Petra; Rosner, Bettina; Stark, Klaus; Kühne, Michael

2011-11-10

A large outbreak of the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 occurred in Germany in May 2011. The source of infection was undetermined. We conducted a matched case-control study and a recipe-based restaurant cohort study, along with environmental, trace-back, and trace-forward investigations, to determine the source of infection. The case-control study included 26 case subjects with the hemolytic-uremic syndrome and 81 control subjects. The outbreak of illness was associated with sprout consumption in univariable analysis (matched odds ratio, 5.8; 95% confidence interval [CI], 1.2 to 29) and with sprout and cucumber consumption in multivariable analysis. Among case subjects, 25% reported having eaten sprouts, and 88% reported having eaten cucumbers. The recipe-based study among 10 groups of visitors to restaurant K included 152 persons, among whom bloody diarrhea or diarrhea confirmed to be associated with Shiga-toxin-producing E. coli developed in 31 (20%). Visitors who were served sprouts were significantly more likely to become ill (relative risk, 14.2; 95% CI, 2.6 to ∞). Sprout consumption explained 100% of cases. Trace-back investigation of sprouts from the distributor that supplied restaurant K led to producer A. All 41 case clusters with known trading connections could be explained by producer A. The outbreak strain could not be identified on seeds from the implicated lot. Our investigations identified sprouts as the most likely outbreak vehicle, underlining the need to take into account food items that may be overlooked during subjects' recall of consumption.

Possible association of first and high birth order of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E; Veszprémi, Béla

2014-08-01

In epidemiological studies at the estimation of risk factors in the origin of specified congenital abnormalities in general birth order (parity) is considered as confounder. The aim of this study was to analyze the possible association of first and high (four or more) birth order with the risk of congenital abnormalities in a population-based case-matched control data set. The large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with different isolated congenital abnormality and their 34,311 matched controls. First the distribution of birth order was compared of 24 congenital abnormality groups and their matched controls. In the second step the possible association of first and high birth order with the risk of congenital abnormalities was estimated. Finally some subgroups of neural-tube defects, congenital heart defects and abdominal wall's defects were evaluated separately. A higher risk of spina bifida aperta/cystica, esophageal atresia/stenosis and clubfoot was observed in the offspring of primiparous mothers. Of 24 congenital abnormality groups, 14 had mothers with larger proportion of high birth order. Ear defects, congenital heart defects, cleft lip± palate and obstructive defects of urinary tract had a linear trend from a lower proportion of first born cases to the larger proportion of high birth order. Birth order showed U-shaped distribution of neural-tube defects and clubfoot, i.e. both first and high birth order had a larger proportion in cases than in their matched controls. Birth order is a contributing factor in the origin of some isolated congenital abnormalities. The higher risk of certain congenital abnormalities in pregnant women with first or high birth order is worth considering in the clinical practice, e.g. ultrasound scanning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Parental occupational paint exposure and risk of childhood leukemia in the offspring: Findings from the Childhood Leukemia International Consortium

PubMed Central

Bailey, Helen D; Fritschi, Lin; Metayer, Catherine; Infante-Rivard, Claire; Magnani, Corrado; Petridou, Eleni; Roman, Eve; Spector, Logan G; Kaatsch, Peter; Clavel, Jacqueline; Milne, Elizabeth; Dockerty, John D; Glass, Deborah C; Lightfoot, Tracy; Miligi, Lucia; Rudant, Jérémie; Baka, Margarita; Rondelli, Roberto; Amigou, Alicia; Simpson, Jill; Kang, Alice; Moschovi, Maria; Schüz, Joachim

2014-01-01

Purpose It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. Methods We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. Results Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukaemia (ALL) was 0.93 (95% confidence interval (CI) 0.76, 1.14). Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukaemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47) respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. Conclusions Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed. PMID:25088805

Childhood leukaemia and distance from power lines in California: a population-based case-control study

PubMed Central

Crespi, Catherine M; Vergara, Ximena P; Hooper, Chris; Oksuzyan, Sona; Wu, Sheng; Cockburn, Myles; Kheifets, Leeka

2016-01-01

Background: Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. Methods: The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986–2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. Results: For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7–2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. Conclusions: Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated. PMID:27219016

Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

PubMed

Jacquez, Geoffrey M; Shi, Chen; Meliker, Jaymie R

2015-01-01

In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation. Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race. Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed. Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.

A large common-source outbreak of norovirus gastroenteritis in a hotel in Singapore, 2012.

PubMed

Raj, P; Tay, J; Ang, L W; Tien, W S; Thu, M; Lee, P; Pang, Q Y; Tang, Y L; Lee, K Y; Maurer-Stroh, S; Gunalan, V; Cutter, J; Goh, K T

2017-02-01

An outbreak of gastroenteritis affected 453 attendees (attack rate 28·5%) of six separate events held at a hotel in Singapore. Active case detection, case-control studies, hygiene inspections and microbial analysis of food, environmental and stool samples were conducted to determine the aetiology of the outbreak and the modes of transmission. The only commonality was the food, crockery and cutlery provided and/or handled by the hotel's Chinese banquet kitchen. Stool specimens from 34 cases and 15 food handlers were positive for norovirus genogroup II. The putative index case was one of eight norovirus-positive food handlers who had worked while they were symptomatic. Several food samples and remnants tested positive for Escherichia coli or high faecal coliforms, aerobic plate counts and/or total coliforms, indicating poor food hygiene. This large common-source outbreak of norovirus gastroenteritis was caused by the consumption of contaminated food and/or contact with contaminated crockery or cutlery provided or handled by the hotel's Chinese banquet kitchen.

Case-based Reasoning for Automotive Engine Performance Tune-up

NASA Astrophysics Data System (ADS)

Vong, C. M.; Huang, H.; Wong, P. K.

2010-05-01

The automotive engine performance tune-up is greatly affected by the calibration of its electronic control unit (ECU). The ECU calibration is traditionally done by trial-and-error method. This traditional method consumes a large amount of time and money because of a large number of dynamometer tests. To resolve this problem, case based reasoning (CBR) is employed, so that an existing and effective ECU setup can be adapted to fit another similar class of engines. The adaptation procedure is done through a more sophisticated step called case-based adaptation (CBA) [1, 2]. CBA is an effective knowledge management tool, which can interactively learn the expert adaptation knowledge. The paper briefly reviews the methodologies of CBR and CBA. Then the application to ECU calibration is described via a case study. With CBR and CBA, the efficiency of calibrating an ECU can be enhanced. A prototype system has also been developed to verify the usefulness of CBR in ECU calibration.

Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

PubMed

Stram, Daniel O; Leigh Pearce, Celeste; Bretsky, Phillip; Freedman, Matthew; Hirschhorn, Joel N; Altshuler, David; Kolonel, Laurence N; Henderson, Brian E; Thomas, Duncan C

2003-01-01

The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the Rh2 criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well. Copyright 2003 S. Karger AG, Basel

Renewable source controls for grid stability.

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

Byrne, Raymond Harry; Elliott, Ryan Thomas; Neely, Jason C.

2012-12-01

The goal of this study was to evaluate the small signal and transient stability of the Western Electric- ity Coordinating Council (WECC) under high penetrations of renewable energy, and to identify control technologies that would improve the system performance. The WECC is the regional entity responsible for coordinating and promoting bulk electric system reliability in the Western Interconnection. Transient stability is the ability of the power system to maintain synchronism after a large disturbance while small signal stability is the ability of the power system to maintain synchronism after a small disturbance. Tran- sient stability analysis usually focuses on themore » relative rotor angle between synchronous machines compared to some stability margin. For this study we employed generator speed relative to system speed as a metric for assessing transient stability. In addition, we evaluated the system transient response using the system frequency nadir, which provides an assessment of the adequacy of the primary frequency control reserves. Small signal stability analysis typically identi es the eigenvalues or modes of the system in response to a disturbance. For this study we developed mode shape maps for the di erent scenarios. Prony analysis was applied to generator speed after a 1.4 GW, 0.5 second, brake insertion at various locations. Six di erent WECC base cases were analyzed, including the 2022 light spring case which meets the renewable portfolio standards. Because of the di culty in identifying the cause and e ect relationship in large power system models with di erent scenarios, several simulations were run on a 7-bus, 5-generator system to isolate the e ects of di erent con gurations. Based on the results of the study, for a large power system like the WECC, incorporating frequency droop into wind/solar systems provides a larger bene t to system transient response than replacing the lost inertia with synthetic inertia. From a small signal stability perspective, the increase in renewable penetration results in subtle changes to the system modes. In gen- eral, mode frequencies increase slightly, and mode shapes remain similar. The system frequency nadir for the 2022 light spring case was slightly lower than the other cases, largely because of the reduced system inertia. However, the nadir is still well above the minimum load shedding frequency of 59.5 Hz. Finally, several discrepancies were identi ed between actual and reported wind penetration, and additional work on wind/solar modeling is required to increase the delity of the WECC models.« less

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

PubMed

Siddiq, Afshan; Couch, Fergus J; Chen, Gary K; Lindström, Sara; Eccles, Diana; Millikan, Robert C; Michailidou, Kyriaki; Stram, Daniel O; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M; Buring, Julie E; Buys, Saundra S; Campa, Daniele; Carpenter, Jane E; Chasman, Daniel I; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S; Czene, Kamila; Deming, Sandra L; Diasio, Robert B; Diver, W Ryan; Dunning, Alison M; Durcan, Lorraine; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M; Gerty, Susan M; Rodriguez-Gil, Jorge L; Giles, Graham G; van Gils, Carla H; Godwin, Andrew K; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N; Hopper, John L; Hu, Jennifer J; Huntsman, Scott; Ingles, Sue A; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B; John, Esther M; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N; Coetzee, Gerhard A; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G; McLean, Catriona A; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R; Montgomery, Grant W; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J; Palmer, Julie R; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F; Schmutzler, Rita K; Slager, Susan; Southey, Melissa C; Stevens, Kristen N; Sinn, Hans-Peter; Press, Michael F; Ross, Eric; Riboli, Elio; Ridker, Paul M; Schumacher, Fredrick R; Severi, Gianluca; Dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J; Thun, Michael J; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F; Hunter, David J; Henderson, Brian E; Chanock, Stephen J; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A; Vachon, Celine M

2012-12-15

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

PubMed Central

Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

2012-01-01

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. PMID:22976474

Behavioral characteristics of Internet gamblers who trigger corporate responsible gambling interventions.

PubMed

Gray, Heather M; LaPlante, Debi A; Shaffer, Howard J

2012-09-01

As the worldwide popularity of Internet gambling increases, concerns about the potential for gambling-related harm also increase. This paper reports the results of a study examining actual Internet gambling behavior during 10 years of play. We examined the electronic gambling records of subscribers (N=2,066) who triggered a responsible gaming alert system at a large international online gaming company. We compared these cases with control subscribers (N=2,066) who had the same amount of exposure to the Internet gambling service provider. We used discriminant function analysis to explore what aspects of gambling behavior distinguish cases from controls. Indices of the intensity of gambling activity (e.g., total number of bets made, number of bets per betting day) best distinguished cases from controls, particularly in the case of live-action sports betting. Control group players evidenced behavior similar to the population of players using this service. These results add to our understanding of behavioral markers for disordered Internet gambling and will aid in the development of behavior-based algorithms capable of predicting the presence and/or the onset of disordered Internet gambling. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Association of tagSNPs in the urokinase-plasminogen activator (PLAU) gene with Alzheimer's disease and associated quantitative traits.

PubMed

Ozturk, Ayla; Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

2007-01-05

The gene coding for urokinase-plasminogen activator (PLAU) is a strong biological and positional candidate gene for Alzheimer's disease (AD). Previously some studies have examined the role of common variation in the PLAU gene with AD risk but the results have been inconsistent and this inconsistency could have been due to the use of relatively small sample sizes. In this study we evaluated the distribution of four tagSNPs (rs2227562 in intron 5, rs2227564 in exon 6, rs2227571 in intron 9, and rs4065 in 3'UTR) in the PLAU gene in a large case-control study consisting of up to 1,000 AD patients and 697 white control subjects. We examined the role of these tagSNPs with AD risk and quantitative traits of AD, including age-at-onset (AAO), disease duration, and mini-mental state examination (MMSE) scores. The 3'UTR SNP revealed modest significant association with risk (OR = 0.71, 95% CI: 0.53-0.95; P = 0.02), AAO (P = 0.036) and disease duration (P = 0.04) of AD. In addition, the intron 9 SNP also revealed a significant association with AAO (P = 0.01) and disease duration (P = 0.006). Our data on a large number of AD cases and controls suggest that genetic variation in PLAU may affect the risk and AAO of AD.

Risk factors associated with deforming oral habits in children aged 5 to 11: a case-control study.

PubMed

Reyes Romagosa, Daniel Enrique; Paneque Gamboa, María Rosa; Almeida Muñiz, Yamilka; Quesada Oliva, Leticia María; Escalona Oliva, Damiana; Torres Naranjo, Sonia

2014-03-31

Dental and maxillofacial anomalies have multiple and complex causes. Most frequent among these are poor oral habits. A large number of children present with oral malocclusions, most of which are caused by deforming oral habits. It is important to learn about risk factors for this condition in order to institute preventive measures, early detection and treatment, and identification of low- and high-risk groups. To identify risk factors associated with deforming oral habits, which, if maintained over time, are responsible for occlusion defects, speech disorders, and can affect physical and emotional child development. A case-control study of children presenting with deforming oral habits in the municipality of Manzanillo in Granma province was conducted between January and August 2013. 540 children aged 5 to 11 were included of which 180 had deforming oral habits and were asked to fill out a survey to identify specific type of habits leading to malocclusion. The case group was composed of children with deforming habits, and the remaining 360 children without poor oral habits were the control group. Each case was randomly matched to two control cases. The children mothers were also surveyed to gather supplemental information. Children with deforming oral habits were mostly female. At age 10, onychophagia was the predominant oral deforming habit. Risk factors detected for these habits were sociobiological maternal and child variables such as low and high birth weight, maternal breastfeeding inexperience, and discord in the family. The study identified likely risk factors associated with deforming oral habits. These are discord in the family, birth weight, and lack of breastfeeding experience.

Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.

PubMed

Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

2014-11-01

Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship.

Novel genes identified in a high-density genome wide association study for nicotine dependence.

PubMed

Bierut, Laura Jean; Madden, Pamela A F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide F; Swan, Gary E; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Goate, Alison M; Hinrichs, Anthony L; Konvicka, Karel; Martin, Nicholas G; Montgomery, Grant W; Saccone, Nancy L; Saccone, Scott F; Wang, Jen C; Chase, Gary A; Rice, John P; Ballinger, Dennis G

2007-01-01

Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community.

Outbreak of Salmonella javiana infection at a children's hospital.

PubMed

Elward, Alexis; Grim, Autumn; Schroeder, Patricia; Kieffer, Patricia; Sellenriek, Patricia; Ferrett, Rhonda; Adams, Hilda Chaski; Phillips, Virginia; Bartow, Rhonda; Mays, Debra; Lawrence, Steven; Seed, Patrick; Holzmann-Pazgal, Galit; Polish, Louis; Leet, Terry; Fraser, Victoria

2006-06-01

To determine the source of an outbreak of Salmonella javiana infection. Case-control study. A total of 101 culture-confirmed cases and 540 epidemiologically linked cases were detected between May 26, 2003, and June 16, 2003, in hospital employees, patients, and visitors. Asymptomatic employees who had eaten in the hospital cafeteria between May 30 and June 4, 2003, and had had no gastroenteritis symptoms after May 1, 2003, were chosen as control subjects. A 235-bed academic tertiary care children's hospital. Isolates from 100 of 101 culture-confirmed cases had identical pulsed-field gel electrophoresis patterns. A foodhandler with symptoms of gastroenteritis was the presumed index subject. In multivariate analysis, case subjects were more likely than control subjects to have consumed items from the salad bar (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.3-12.1) and to have eaten in the cafeteria on May 28 (aOR, 9.4; 95% CI, 1.8-49.5), May 30 (aOR, 3.6; 95% CI, 1.0-12.7), and/or June 3 (aOR, 4.0; 95% CI, 1.4-11.3). Foodhandlers who worked while they had symptoms of gastroenteritis likely contributed to the propagation of the outbreak. This large outbreak was rapidly controlled through the use of an incident command center.

Federal Public Health Service: In Retrospect and Prospects

ERIC Educational Resources Information Center

Kolbe, Lloyd J.

2016-01-01

In this article, I offer a retrospective case study about my early, short-term work within the U.S. Office of the Assistant Secretary for Health and then my later, longer-term work within the U.S. Centers for Disease Control and Prevention, where I endeavored for two decades largely to help our nation's schools improve health and associated…

ADHD Expressive Writing Difficulties of ADHD Children: When Good Declarative Knowledge Is Not Sufficient

ERIC Educational Resources Information Center

Re, Anna Maria; Cornoldi, Cesare

2010-01-01

A large body of evidence shows that many of the academic difficulties Attention Deficit Hyperactivity Disorder (ADHD) children have may be related to their problems in executive control. However, the particular case of expressive writing has not been deeply explored. The present study examines the typical school exercise of writing a letter.…

Israel's "Planning and Grants Committee": A Case Study of Autonomy and Control in Higher Education.

ERIC Educational Resources Information Center

Iram, Yaacov

The higher education system in Israel is discussed, noting that tertiary education in that country makes a clear distinction between higher (university and academic) education and postsecondary education that is largely vocational. The Planning and Grants Committee (PGC) of the Council for Higher Education is responsible for the budgets of…

Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

PubMed Central

Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

2012-01-01

Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

Molecular Dynamics Studies of Proton Transport in Hydrogenase and Hydrogenase Mimics

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

Ginovska-Pangovska, Bojana; Raugei, Simone; Shaw, Wendy J.

2016-08-02

Protons are used throughout the biological world for a number of functions, from charge balance to energy carriers. Metalloenzymes use protons as energy carriers and control proton movement both temporally and spatially. Despite the interest and need for controlled proton movement in other systems, the scientific community has not been able to develop extensive general rules for developing synthetic proton pathways. In part this is due to the challenging nature of studying these large and complex molecules experimentally, although experiments have gleaned extensive critical insight. While computational methods are also challenging because of the large size of the molecules, theymore » have been critical in advancing our knowledge of proton movement through pathways, but even further, they have advanced our knowledge in how protonation and proton movement is correlated with large and small scale molecular motions and electron movement. These studies often complement experimental studies but provide insight and depth simply not possible in many cases in the absence of theory. In this chapter, we will discuss advances and methods used in understanding proton movement in hydrogenases.« less

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility.

PubMed

Fu, Lingyu; Jin, Lei; Yan, Lei; Shi, Jingpu; Wang, Hailong; Zhou, Bo; Wu, Xiaomei

2016-01-01

MicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach. A PubMed database search was conducted during August 2013 to identify case-control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software. Our meta-analysis of six case-control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI=0.642-1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR=0.911, 95% CI=0.710-1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR=0.616, 95% CI=0.384-0.981, (T vs. C allele) and OR=0.386, 95% CI=0.226-0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR=1.263, 95% CI=1.136-1.405, G vs. A allele). The present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations. Copyright © 2014. Published by Elsevier Inc.

Average properties of bidisperse bubbly flows

NASA Astrophysics Data System (ADS)

Serrano-García, J. C.; Mendez-Díaz, S.; Zenit, R.

2018-03-01

Experiments were performed in a vertical channel to study the properties of a bubbly flow composed of two distinct bubble size species. Bubbles were produced using a capillary bank with tubes with two distinct inner diameters; the flow through each capillary size was controlled such that the amount of large or small bubbles could be controlled. Using water and water-glycerin mixtures, a wide range of Reynolds and Weber number ranges were investigated. The gas volume fraction ranged between 0.5% and 6%. The measurements of the mean bubble velocity of each species and the liquid velocity variance were obtained and contrasted with the monodisperse flows with equivalent gas volume fractions. We found that the bidispersity can induce a reduction of the mean bubble velocity of the large species; for the small size species, the bubble velocity can be increased, decreased, or remain unaffected depending of the flow conditions. The liquid velocity variance of the bidisperse flows is, in general, bound by the values of the small and large monodisperse values; interestingly, in some cases, the liquid velocity fluctuations can be larger than either monodisperse case. A simple model for the liquid agitation for bidisperse flows is proposed, with good agreement with the experimental measurements.

Residential traffic noise exposure and vestibular schwannoma - a Danish case-control study.

PubMed

Roswall, Nina; Stangerup, Sven-Eric; Cayé-Thomasen, Per; Schüz, Joachim; Johansen, Christoffer; Jensen, Steen Solvang; Raaschou-Nielsen, Ole; Sørensen, Mette

2017-10-01

Few risk factors for sporadic vestibular schwannoma (VS) are known. Several studies have proposed an increased risk with occupational noise exposure, whereas no studies have investigated residential traffic noise exposure as a risk factor. The present study investigated if residential traffic noise was associated with vestibular schwannoma in a large, population-based Danish case-control study. We identified 1454 VS cases, age above 30 years at diagnosis, between 1990 and 2007. For each case, we selected two random population controls, matched on sex and year of birth. Road and railway traffic noise at the residence was calculated for all present and historical addresses between 1987 and index date. Associations between traffic noise and risk for VS were estimated using conditional logistic regression, adjusted for education, disposable personal income, cohabitation status, railway noise exposure, municipal population density, and municipal income. A two-year time-weighted mean road traffic noise exposure was associated with an adjusted odds ratio of 0.92 (0.82-1.03) for developing VS, per 10 dB increment. There was no clear trend in categorical analyses. Similarly, linear and categorical analyses of residential railway noise did not suggest an association. We found no interaction with demographics, year of diagnosis, individual and municipal socioeconomic variables, and railway noise exposure. The results did not differ by tumor side, spread or size. The present study does not suggest an association between residential traffic noise and VS.

A nested case-control study of predictors for tuberculosis recurrence in a large UK Centre.

PubMed

Rosser, Andrew; Richardson, Matthew; Wiselka, Martin J; Free, Robert C; Woltmann, Gerrit; Mukamolova, Galina V; Pareek, Manish

2018-02-27

Tuberculosis (TB) recurrence represents a challenge to control programs. In low incidence countries, the prevailing risk factors leading to recurrence are poorly characterised. We conducted a nested case-control study using the Leicester TB service TBIT database. Cases were identified from database notifications between 1994 and 2014. Controls had one episode and were matched to cases on a ratio of two to one by the date of notification. Multiple imputation was used to account for missing data. Multivariate conditional logistic regression analysis was employed to identify clinical, sociodemographic and TB specific risk factors for recurrence. From a cohort of 4628 patients, 82 TB recurrences occurred (1.8%). Nineteen of 82 patients had paired isolates with MIRU-VNTR strain type profiles available, of which 84% were relapses and 16% reinfections. On multivariate analysis, smoking (OR 3.8; p = 0.04), grade 3/4 adverse drug reactions (OR 5.6; p = 0.02), ethnicity 'Indian subcontinent' (OR 8.5; p = <0.01), ethnicity 'other' (OR 31.2; p = 0.01) and receipt of immunosuppressants (OR 6.8; p = <0.01) were independent predictors of TB recurrence. Within this UK setting, the rate of TB recurrence was low, predominantly due to relapse. The identification of an elevated recurrence risk amongst the ethnic group contributing most cases to the national TB burden presents an opportunity to improve individual and population health.

A large multi-pathogen gastroenteritis outbreak caused by drinking contaminated water from antique neighbourhood fountains, Erzurum city, Turkey, December 2012.

PubMed

Sezen, F; Aval, E; Ağkurt, T; Yilmaz, Ş; Temel, F; Güleşen, R; Korukluoğlu, G; Sucakli, M B; Torunoğlu, M A; Zhu, B-P

2015-03-01

We investigated a gastroenteritis outbreak in Erzurum city, Turkey in December 2012 to identify its cause and mode of transmission. We defined a probable case as onset of diarrhoea (⩾3 episodes/day) or vomiting, plus fever or nausea or abdominal pain during 19-27 December, 2012 in an Erzurum city resident. In a case-control study we compared exposures of 95 randomly selected probable cases and 95 neighbourhood-matched controls. We conducted bacterial culture and real-time multiplex PCR for identification of pathogens. During the week before illness onset, 72% of cases and 15% of controls only drank water from antique neighbourhood fountains; conversely, 16% of cases and 65% of controls only drank bottled or tap water (adjusted odds ratio 20, 95% confidence interval 4·6-84, after controlling for age and sex using conditional logistic regression). Of eight stool specimens collected, two were positive for Shigella sonnei, one for astrovirus, one for astrovirus and norovirus, and one for astrovirus and rotavirus. Water samples from the fountains had elevated total coliform (38-300/100 ml) and Escherichia coli (22-198/100 ml) counts. In conclusion, drinking contaminated fountain water caused this multi-pathogen outbreak. Residents should stop drinking water from these fountains, and clean water from the water treatment plant should be connected to the fountains.

Evaluation of logistic regression models and effect of covariates for case-control study in RNA-Seq analysis.

PubMed

Choi, Seung Hoan; Labadorf, Adam T; Myers, Richard H; Lunetta, Kathryn L; Dupuis, Josée; DeStefano, Anita L

2017-02-06

Next generation sequencing provides a count of RNA molecules in the form of short reads, yielding discrete, often highly non-normally distributed gene expression measurements. Although Negative Binomial (NB) regression has been generally accepted in the analysis of RNA sequencing (RNA-Seq) data, its appropriateness has not been exhaustively evaluated. We explore logistic regression as an alternative method for RNA-Seq studies designed to compare cases and controls, where disease status is modeled as a function of RNA-Seq reads using simulated and Huntington disease data. We evaluate the effect of adjusting for covariates that have an unknown relationship with gene expression. Finally, we incorporate the data adaptive method in order to compare false positive rates. When the sample size is small or the expression levels of a gene are highly dispersed, the NB regression shows inflated Type-I error rates but the Classical logistic and Bayes logistic (BL) regressions are conservative. Firth's logistic (FL) regression performs well or is slightly conservative. Large sample size and low dispersion generally make Type-I error rates of all methods close to nominal alpha levels of 0.05 and 0.01. However, Type-I error rates are controlled after applying the data adaptive method. The NB, BL, and FL regressions gain increased power with large sample size, large log2 fold-change, and low dispersion. The FL regression has comparable power to NB regression. We conclude that implementing the data adaptive method appropriately controls Type-I error rates in RNA-Seq analysis. Firth's logistic regression provides a concise statistical inference process and reduces spurious associations from inaccurately estimated dispersion parameters in the negative binomial framework.

National outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to mixed salad leaves, United Kingdom, 2016.

PubMed

Gobin, Maya; Hawker, Jeremy; Cleary, Paul; Inns, Thomas; Gardiner, Daniel; Mikhail, Amy; McCormick, Jacquelyn; Elson, Richard; Ready, Derren; Dallman, Tim; Roddick, Iain; Hall, Ian; Willis, Caroline; Crook, Paul; Godbole, Gauri; Tubin-Delic, Drazenka; Oliver, Isabel

2018-05-01

We investigated a large outbreak of Escherichia coli O157 in the United Kingdom (UK) with 165 cases between 31 May and 29 July 2016. No linked cases were reported in other countries. Cases were predominately female (n = 128) and adult (n = 150), 66 attended hospital and nine had features of haemorrhagic uraemic syndrome. A series of epidemiological studies (case-control, case-case, ingredients-based and venue-based studies) and supply chain investigations implicated mixed salad leaves from Supplier A as the likely outbreak vehicle. Whole genome sequencing (WGS) indicated a link with strains from the Mediterranean and informed the outbreak control team to request that Supplier A cease distributing salad leaves imported from Italy. Microbiological tests of samples of salad leaves from Supplier A were negative. We were unable to confirm the source of contamination or the contaminated constituent leaf although our evidence pointed to red batavia received from Italy as the most likely vehicle. Variations in Shiga toxin-producing E. coli surveillance and diagnosis may have prevented detection of cases outside the UK and highlights a need for greater standardisation. WGS was useful in targeting investigations, but greater coverage across Europe is needed to maximise its potential.

Large-scale optimal control of interconnected natural gas and electrical transmission systems

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

Chiang, Nai-Yuan; Zavala, Victor M.

2016-04-01

We present a detailed optimal control model that captures spatiotemporal interactions between gas and electric transmission networks. We use the model to study flexibility and economic opportunities provided by coordination. A large-scale case study in the Illinois system reveals that coordination can enable the delivery of significantly larger amounts of natural gas to the power grid. In particular, under a coordinated setting, gas-fired generators act as distributed demand response resources that can be controlled by the gas pipeline operator. This enables more efficient control of pressures and flows in space and time and overcomes delivery bottlenecks. We demonstrate that themore » additional flexibility not only can benefit the gas operator but can also lead to more efficient power grid operations and results in increased revenue for gas-fired power plants. We also use the optimal control model to analyze computational issues arising in these complex models. We demonstrate that the interconnected Illinois system with full physical resolution gives rise to a highly nonlinear optimal control problem with 4400 differential and algebraic equations and 1040 controls that can be solved with a state-of-the-art sparse optimization solver. (C) 2016 Elsevier Ltd. All rights reserved.« less

The Misconception of Case-Control Studies in the Plastic Surgery Literature: A Literature Audit.

PubMed

Hatchell, Alexandra C; Farrokhyar, Forough; Choi, Matthew

2017-06-01

Case-control study designs are commonly used. However, many published case-control studies are not true case-controls and are in fact mislabeled. The purpose of this study was to identify all case-control studies published in the top three plastic surgery journals over the past 10 years, assess which were truly case-control studies, clarify the actual design of the articles, and address common misconceptions. MEDLINE, Embase, and Web of Science databases were searched for case-control studies in the three highest-impact factor plastic surgery journals (2005 to 2015). Two independent reviewers screened the resulting titles, abstracts, and methods, if applicable, to identify articles labeled as case-control studies. These articles were appraised and classified as true case-control studies or non-case-control studies. The authors found 28 articles labeled as case-control studies. However, only six of these articles (21 percent) were truly case-control designs. Of the 22 incorrectly labeled studies, one (5 percent) was a randomized controlled trial, three (14 percent) were nonrandomized trials, two (9 percent) were prospective comparative cohort designs, 14 (64 percent) were retrospective comparative cohort designs, and two (9 percent) were cross-sectional designs. The mislabeling was worse in recent years, despite increases in evidence-based medicine awareness. The majority of published case-control studies are not in fact case-control studies. This misunderstanding is worsening with time. Most of these studies are actually comparative cohort designs. However, some studies are truly clinical trials and thus a higher level of evidence than originally proposed.

Body Weight and Breast Cancer: Nested Case-Control Study in Southern Brazil.

PubMed

Kops, Natália Luiza; Bessel, Marina; Caleffi, Maira; Ribeiro, Rodrigo Antonini; Wendland, Eliana Marcia

2018-04-28

Current studies have shown that fast weight gain may be more important than body mass index on the incidence of breast cancer. The aim of this study was to evaluate the association between body weight and breast cancer. This was a case-control study nested in a cohort of a breast cancer mammography screening program in Southern Brazil. A trained investigator administered a standardized interview to collect sociodemographic and clinical data, and body weight history (weight at menarche, at marriage, at first and last pregnancy, and at menopause). Current anthropometric measurements were also made. Fifty-seven women with cancer (66.7% postmenopausal) and 159 controls were included. Current age (60.3 ± 10.4 vs. 55.8 ± 8.4 years, P < .01), marital status (49.1% vs. 64.8% with a partner, P = .03), and physical activity (48.2% vs. 32.3% sedentary, P = .01) were significantly different between cases and controls, respectively. Odds ratio showed that age and current waist circumference were associated with postmenopausal cancer. No difference was found in relation to body weight at different stages of life. Women with social vulnerability recruited at a mammography screening program in Southern Brazil showed a large weight gain during life, but no significant differences were found in body weight between women with or without breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

The evaluation of the National Long Term Care Demonstration. 4. Case management under channeling.

PubMed Central

Phillips, B R; Kemper, P; Applebaum, R A

1988-01-01

The channeling demonstration involved provision of comprehensive case management and direct service expansion. This article considers the former. Under both models, comprehensive case management was implemented largely as intended; moreover, channeling substantially increased the receipt of comprehensive care management. However, channeling was not a pure test of the effect of comprehensive case management: roughly 10-20 percent of control group members received comparable case management services. This was particularly the case for the financial control model. Thus, the demonstration was not a test of case management compared to no case management; rather, it compared channeling case management to the existing community care system, which already was providing comprehensive case management to some of the population eligible for channeling. PMID:3130331

Metformin for Primary Colorectal Cancer Prevention in Diabetic Patients: A Case-Control Study in a US Population

PubMed Central

Sehdev, Amikar; Shih, Ya-Chen T.; Vekhter, Benjamin; Bissonnette, Marc; Olopade, Olufunmilayo I.; Polite, Blase

2016-01-01

Background Emerging evidence from observational studies suggests that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, none of these were conducted in a US population. Since environmental factors, such as Western diet and obesity, are implicated in the causation of CRC, we conducted a large case control study to assess the effects of metformin on CRC incidence in a US population. Methods MarketScan® databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to two controls matched for age, sex and geographical region, were selected for each case. Metformin exposure was assessed by prescription tracking in the 12 months period prior to the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AOR). Results The mean age of participants was 55 and 57 years in the control and case group, respectively (p=1.0). Sixty percent of the study participants were males and 40% were females in each group. In the multivariable model, any metformin use was associated with 15% reduced odds of CRC (AOR, 0.85, 95% confidence interval (CI), 0.76–0.95, p<0.007). After adjusting for health-care utilization the beneficial effect of metformin was reduced to 12% (AOR, 0.88, 95% CI, 0.77–1.00, p=0.05). The dose-response analyses showed no significant association with metformin dose, duration or total exposure. Conclusions Metformin use is associated with reduced risk of developing CRC among diabetic patients in the US population. PMID:25424411

Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database.

PubMed

Jobski, Kathrin; Behr, Sigrid; Garbe, Edeltraut

2011-09-01

Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.

Unprovoked seizures after traumatic brain injury: A population-based case-control study.

PubMed

Mahler, Benno; Carlsson, Sofia; Andersson, Tomas; Adelöw, Cecilia; Ahlbom, Anders; Tomson, Torbjörn

2015-09-01

To quantify the risk of unprovoked seizures after traumatic brain injury (TBI) METHODS: We used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case-control study, including 1,885 cases with incident unprovoked seizures from September 1, 2000 through August 31, 2008, together with 15,080 matched controls. Information of prior hospitalizations for TBI was obtained through record linkage with the Swedish National Inpatient Registry for the period 1980-2008. Relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail. After hospitalization for mild TBI, the RR was 2.0 (95% confidence interval [CI] 1.5-2.7). The RR was higher after brain contusion (5.9, 95% CI 2.4-15.0) or intracranial hemorrhage (ICH) (4.5, 95% CI 2.2-9.0), whereas a combination of both diagnoses led to a further sevenfold increase in RR (42.6, 95% CI 12.2-148.5). The risk was greatest during the first 6 months after severe TBI (RR 48.9, 95% CI 10.9-218.9) or mild TBI (RR 8.1, 95% CI 3.1-21.7), but was still elevated >10 years after any TBI. Herein we present a large population-based case-control study on TBI as a risk factor for unprovoked epileptic seizures, including cases of all ages with individually validated seizure diagnoses. The risk for epileptic seizures was substantially increased after TBI, especially during the first 6 months after the injury and in patients with a combination of ICH and brain contusion. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Risk of Psoriasis Following Terbinafine or Itraconazole Treatment for Onychomycosis: A Population-Based Case-Control Comparative Study.

PubMed

Chiu, Hsien-Yi; Chang, Wei-Lun; Tsai, Tsen-Fang; Tsai, Yi-Wen; Shiu, Ming-Neng

2018-03-01

Several case studies have reported an association between antifungal drug use and psoriasis risk. The objective of this study was to investigate the association between terbinafine/itraconazole exposure and psoriasis incidence. Among patients with onychomycosis in the Taiwan National Health Insurance Research Database, 3831 incident psoriasis cases were identified during 2004-2010 and compared with 3831 age- and sex-matched controls with the same look-back period. Multivariate conditional logistic regression was used for the analysis. The psoriasis cases were significantly more likely than matched controls to have used terbinafine or itraconazole (59.85 vs. 42.70%, respectively; p < 0.0001). After adjusting for potential confounders and cumulative duration of antifungal drug prescription, terbinafine/itraconazole use was associated with an increased psoriasis risk (adjusted odds ratio 1.33, 95% confidence interval 1.15-1.54). The association was stronger for more recent drug exposure (adjusted odds ratio 2.96, 95% confidence interval 2.25-3.90 for ≤ 90 days before the sampling date; adjusted odds ratio 1.04, 95% confidence interval 0.89-1.22 for > 360 days). In a comparison of patients receiving terbinafine or itraconazole only, psoriasis risk was higher for itraconazole (adjusted odds ratio 1.21, 95% confidence interval 1.05-1.40). This large population-based case-control analysis showed that exposure to terbinafine or itraconazole is associated with an increased risk of incident psoriasis. The finding of an increased psoriasis risk for antifungal drug users, particularly for itraconazole, deserves attention in clinical practice although further prospective studies are necessary to confirm our findings and clarify the biological mechanisms that underlie these associations.

ALS and the Military: A Population-Based Study in the Danish Registries

PubMed Central

Seals, Ryan M.; Kioumourtzoglou, Marianthi-Anna; Gredal, Ole; Hansen, Johnni; Weisskopf, Marc G.

2016-01-01

Background Prior studies have suggested that military service may be associated with the development of amyotrophic lateral sclerosis. We conducted a population-based case-control study in Denmark to assess whether occupation in the Danish military is associated with an increased risk of developing amyotrophic lateral sclerosis. Methods There were 3,650 incident cases of amyotrophic lateral sclerosis recorded in the Danish National Patient Registry between 1982 and 2009. Each case was matched to 100 age- and sex-matched population controls alive and free of amyotrophic lateral sclerosis on the date of the case diagnosis. Comprehensive occupational history was obtained from the Danish Pension Fund database, which began in 1964. Results 2.4% (n=8,922) of controls had a history of employment in the military prior to the index date. Military employees overall had an elevated rate of ALS (OR=1.3; 95% CI: 1.1-1.6). A ten-year increase in years employed by the military was associated with an odds ratio of 1.2 (95% CI: 1.0-1.4), and all quartiles of time employed were elevated. There was little suggestion of a pattern across calendar year of first employment, but there was some evidence that increasing age at first employment was associated with increased ALS rates. Rates were highest in the decade immediately following the end of employment (OR=1.6; 95% CI: 1.2-2.2). Conclusions In this large population-based case-control study, employment by the military is associated with increased rates of ALS. These findings are consistent with earlier findings that military service or employment may entail exposure to risk factors for ALS. PMID:26583610

Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK primary care case-control study.

PubMed

Downham, Christina; Visser, Elizabeth; Vickers, Mark; Counsell, Carl

2017-10-01

Infectious mononucleosis (IM) and vitamin D deficiency are both risk factors for multiple sclerosis (MS). We wished to establish if IM in the winter months when vitamin D levels are low may be a greater risk factor for MS than IM in the summer months. We identified all patients with MS diagnosed aged 16-60 in a large primary care database in the United Kingdom and matched each by age, sex, general practice and observation period with up to six controls. We identified a coded diagnosis of IM prior to the index date (date of diagnosis). Logistic regression was used to calculate the odds ratio for prior IM exposure in cases versus controls and for winter versus summer exposure in cases and controls with prior IM exposure. Based on 9247 cases and 55,033 matched controls (246 and 846 with prior IM respectively), IM was associated with the development of MS (OR 1.77, 95%CI 1.53-2.05) but there was no evidence that IM in the winter as opposed to summer was associated with developing MS (OR 1.09, 95%CI 0.72-1.66). We found no evidence that the season of IM influences the risk of subsequent MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk factors for severe acute malnutrition in children below 5 y of age in India: a case-control study.

PubMed

Mishra, Kirtisudha; Kumar, Praveen; Basu, Srikanta; Rai, Kiran; Aneja, Satinder

2014-08-01

To determine the possible risk factors for severe acute malnutrition (SAM) in children below 5 y admitted in a hospital in north India. This case-control study was conducted in a medical college hospital in children below 5 y of age. All cases of SAM (diagnosed as per WHO definition) between 6 and 59 mo of age were compared with age-matched controls with weight for height above -2SD of WHO 2006 growth standards. Data regarding socio-demographic parameters, feeding practices and immunization were compared between the groups by univariable and multivariable logistic regression models. A total of 76 cases and 115 controls were enrolled. Among the 14 factors compared, maternal illiteracy, daily family income less than Rs. 200, large family size, lack of exclusive breast feeding in first 6 mo, bottle feeding, administration of pre-lacteals, deprivation of colostrum and incomplete immunization were significant risk factors for SAM. Regarding complementary feeding, it was the consistency, rather than the age of initiation, frequency and variety which showed a significant influence on occurrence of SAM. Multivariate analysis revealed that the risk of SAM was independently associated with 6 factors, namely, illiteracy among mothers, incomplete immunization, practice of bottle feeding, consistency of complementary feeding, deprivation of colostrum and receipt of pre-lacteals at birth. The present study identifies certain risk factors which need to be focused on during health planning and policy making related to children with SAM in India.

Edge control in a computer controlled optical surfacing process using a heterocercal tool influence function.

PubMed

Hu, Haixiang; Zhang, Xin; Ford, Virginia; Luo, Xiao; Qi, Erhui; Zeng, Xuefeng; Zhang, Xuejun

2016-11-14

Edge effect is regarded as one of the most difficult technical issues in a computer controlled optical surfacing (CCOS) process. Traditional opticians have to even up the consequences of the two following cases. Operating CCOS in a large overhang condition affects the accuracy of material removal, while in a small overhang condition, it achieves a more accurate performance, but leaves a narrow rolled-up edge, which takes time and effort to remove. In order to control the edge residuals in the latter case, we present a new concept of the 'heterocercal' tool influence function (TIF). Generated from compound motion equipment, this type of TIF can 'transfer' the material removal from the inner place to the edge, meanwhile maintaining the high accuracy and efficiency of CCOS. We call it the 'heterocercal' TIF, because of the inspiration from the heterocercal tails of sharks, whose upper lobe provides most of the explosive power. The heterocercal TIF was theoretically analyzed, and physically realized in CCOS facilities. Experimental and simulation results showed good agreement. It enables significant control of the edge effect and convergence of entire surface errors in large tool-to-mirror size-ratio conditions. This improvement will largely help manufacturing efficiency in some extremely large optical system projects, like the tertiary mirror of the Thirty Meter Telescope.

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

PubMed

Mariampillai, Julian E; Eskås, Per Anders; Heimark, Sondre; Kjeldsen, Sverre E; Narkiewicz, Krzysztof; Mancia, Giuseppe

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus. Copyright © 2016 Elsevier Inc. All rights reserved.

A community-based, case-control study of childhood stroke risk associated with congenital heart disease

PubMed Central

Fox, Christine K.; Sidney, Stephen; Fullerton, Heather J.

2014-01-01

Background and Purpose A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based, case-control study. Methods From 2.5 million children (< 20 years) enrolled in a Northern California integrated healthcare plan, we identified ischemic and hemorrhagic strokes and randomly selected age and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed prior to stroke) and used conditional logistic regression to analyze stroke risk. Results CHD was identified in 15/412 cases (4%) versus 7/1,236 controls (0.6%). Children (28 days – 20 years) with CHD had 19-fold (Odds Ratio [OR] 19; 95% Confidence Interval [CI] 4.2, 83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold increased risk of stroke (OR 31; CI 4, 241 compared to controls). After excluding peri-operative strokes, a history of CHD surgery still increased childhood stroke risk (OR 13; CI 1.5, 114). The majority of children with stroke and CHD were outpatient at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD. Conclusions CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside of the peri-operative period, and would benefit from optimized long-term stroke prevention strategies. PMID:25516197

Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

PubMed

Oh, Sung-Hee; Kang, Hye-Young

2018-01-01

We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

PubMed

Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

2018-04-01

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

PubMed Central

Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

2010-01-01

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package. PMID:20838587

NFKB1 -94insertion/deletion ATTG polymorphism and cancer risk: Evidence from 50 case-control studies.

PubMed

Fu, Wen; Zhuo, Zhen-Jian; Chen, Yung-Chang; Zhu, Jinhong; Zhao, Zhang; Jia, Wei; Hu, Jin-Hua; Fu, Kai; Zhu, Shi-Bo; He, Jing; Liu, Guo-Chang

2017-02-07

Nuclear factor-kappa B1 (NF-κB1) is a pleiotropic transcription factor and key contributor to tumorigenesis in many types of cancer. Numerous studies have addressed the association of a functional insertion (I)/deletion (D) polymorphism (-94ins/delATTG, rs28362491) in the promoter region of NFKB1 gene with the risk of various types of cancer; however, their conclusions have been inconsistent. We therefore conducted a meta-analysis to reevaluate this association. PubMed, EMBASE, China National Knowledge infrastructure (CNKI), and WANFANG databases were searched through July 2016 to retrieve relevant studies. After careful assessment, 50 case-control studies, comprising 18,299 cases and 23,484 controls were selected. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to determine the strength of the association. The NFKB1 -94ins/delATTG polymorphism was associated with a decreased risk of overall cancer in the homozygote model (DD vs. II): OR = 0.75, 95% CI = 0.64-0.87); heterozygote model (ID vs. II): OR = 0.91, 95% CI = 0.83-0.99; recessive model (DD vs. ID/II): OR = 0.81, 95% CI = 0.71-0.91; dominant model (ID/DD vs. II): OR = 0.86, 95% CI = 0.78-0.95; and allele contrast model (D vs. I): OR = 0.88, 95% CI = 0.81-0.95). Subgroup and stratified analyses revealed decreased risks for lung cancer, nasopharyngeal carcinoma, prostate cancer, ovarian cancer, and oral squamous cell carcinoma, and this association held true also for Asians (especially Chinese subjects) in hospital-based studies, and in studies with quality scores less than nine. Well-designed, large-scale case-control studies are needed to confirm these results.

Association of Interleukin-1 gene clusters polymorphisms with primary open-angle glaucoma: a meta-analysis.

PubMed

Li, Junhua; Feng, Yifan; Sung, Mi Sun; Lee, Tae Hee; Park, Sang Woo

2017-11-28

Previous studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility. PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies. Five studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests. Based on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

PubMed

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; Chong, Dawn Q; Jensen, Majken K; Wu, Chunsen; Overvad, Kim; Kühn, Tilman; Barrdahl, Myrto; Melander, Olle; Jirström, Karin; Peeters, Petra H; Sieri, Sabina; Panico, Salvatore; Cross, Amanda J; Riboli, Elio; Van Guelpen, Bethany; Myte, Robin; Huerta, José María; Rodriguez-Barranco, Miguel; Quirós, José Ramón; Dorronsoro, Miren; Tjønneland, Anne; Olsen, Anja; Travis, Ruth; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Bonet, Catalina; Palli, Domenico; Janke, Jürgen; Lee, Young-Ae; Boeing, Heiner; Giovannucci, Edward L; Ogino, Shuji; Fuchs, Charles S; Rimm, Eric; Wu, Kana; Chan, Andrew T; Pischon, Tobias

2017-05-01

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Living on the wedge: female control of paternity in a cooperatively polyandrous cichlid

PubMed Central

Kohda, Masanori; Heg, Dik; Makino, Yoshimi; Takeyama, Tomohiro; Shibata, Jun-ya; Watanabe, Katsutoshi; Munehara, Hiroyuki; Hori, Michio; Awata, Satoshi

2009-01-01

Theories suggest that, in cooperatively breeding species, female control over paternity and reproductive output may affect male reproductive skew and group stability. Female paternity control may come about through cryptic female choice or female reproductive behaviour, but experimental studies are scarce. Here, we show a new form of female paternity control in a cooperatively polyandrous cichlid fish (Julidochromis transcriptus), in which females prefer wedge-shaped nesting sites. Wedge-shaped sites allowed females to manipulate the siring success of the group member males by spawning the clutch at the spot where the large males were just able to enter and fertilize the outer part of the clutch. Small males fertilized the inner part of the clutch, protected from the large aggressive males, leading to low male reproductive skew. Small males provided more brood care than large males. Multiple paternity induced both males to provide brood care and reduced female brood care accordingly. This is, to our knowledge, the first documented case in a species with external fertilization showing female mating behaviour leading to multiple male paternity and increased male brood care as a result. PMID:19726479

A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015.

PubMed

Kabwama, Steven Ndugwa; Bulage, Lilian; Nsubuga, Fred; Pande, Gerald; Oguttu, David Were; Mafigiri, Richardson; Kihembo, Christine; Kwesiga, Benon; Masiira, Ben; Okullo, Allen Eva; Kajumbula, Henry; Matovu, Joseph K B; Makumbi, Issa; Wetaka, Milton; Kasozi, Sam; Kyazze, Simon; Dahlke, Melissa; Hughes, Peter; Sendagala, Juliet Nsimire; Musenero, Monica; Nabukenya, Immaculate; Hill, Vincent R; Mintz, Eric; Routh, Janell; Gómez, Gerardo; Bicknese, Amelia; Zhu, Bao-Ping

2017-01-05

On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures. We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples. From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (OR M-H  = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (OR M-H  = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination. Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas.

Risk factors for testicular cancer: a case-control study in twins.

PubMed

Swerdlow, A J; De Stavola, B L; Swanwick, M A; Mangtani, P; Maconochie, N E

1999-06-01

Early life and anthropometric risk factors for testicular cancer were examined in a case-control study in England and Wales in which affected male twins were compared with their unaffected male co-twins. Questionnaire data was obtained for 60 twin pairs. Significantly raised risk of testicular cancer occurred in twins who had longer arms and legs than their co-twin. There was a significant excess of testicular cancer reported in non-twin brothers, as well as in twin brothers, of cases. Risk was also significantly raised in relation to cryptorchidism. The results on limb length suggest that factors, perhaps nutritional, affecting growth before puberty, may be causes of testicular cancer. The results on risk in brothers add to evidence of a large genetic component in aetiology of the tumour. The risk associated with cryptorchidism in the twins accords with the hypothesis that cryptorchidism is causally associated with testicular cancer because it is a cause of the malignancy, rather than because the same maternal factors experienced in utero cause both conditions.

Towards large-cohort comparative studies to define the factors influencing the gut microbial community structure of ASD patients

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

McDonald, Daniel; Hornig, Mady; Lozupone, Catherine

Differences in the gut microbiota have been reported between individuals with autism spectrum disorders (ASD) and neurotypical controls, although direct evidence that changes in the microbiome contribute to causing ASD has been scarce to date. Here we summarize some considerations of experimental design that can help untangle causality in this complex system. In particular, large cross-sectional studies that can factor out important variables such as diet, prospective longitudinal studies that remove some of the influence of interpersonal variation in the microbiome (which is generally high, especially in children), and studies transferring microbial communities into germ-free mice may be especially useful.more » Controlling for the effects of technical variables, which have complicated efforts to combine existing studies, is critical when biological effect sizes are small. Large citizen-science studies with thousands of participants such as the American Gut Project have been effective at uncovering subtle microbiome effects in self-collected samples and with self-reported diet and behavior data, and may provide a useful complement to other types of traditionally funded and conducted studies in the case of ASD, especially in the hypothesis generation phase.« less

Towards large-cohort comparative studies to define the factors influencing the gut microbial community structure of ASD patients

DOE PAGES

McDonald, Daniel; Hornig, Mady; Lozupone, Catherine; ...

2015-03-09

Differences in the gut microbiota have been reported between individuals with autism spectrum disorders (ASD) and neurotypical controls, although direct evidence that changes in the microbiome contribute to causing ASD has been scarce to date. Here we summarize some considerations of experimental design that can help untangle causality in this complex system. In particular, large cross-sectional studies that can factor out important variables such as diet, prospective longitudinal studies that remove some of the influence of interpersonal variation in the microbiome (which is generally high, especially in children), and studies transferring microbial communities into germ-free mice may be especially useful.more » Controlling for the effects of technical variables, which have complicated efforts to combine existing studies, is critical when biological effect sizes are small. Large citizen-science studies with thousands of participants such as the American Gut Project have been effective at uncovering subtle microbiome effects in self-collected samples and with self-reported diet and behavior data, and may provide a useful complement to other types of traditionally funded and conducted studies in the case of ASD, especially in the hypothesis generation phase.« less

Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype.

PubMed

Ognjanovic, S; Carozza, S E; Chow, E J; Fox, E E; Horel, S; McLaughlin, C C; Mueller, B A; Puumala, S; Reynolds, P; Von Behren, J; Spector, L

2010-01-05

Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare. Case-control studies formed by linking cancer and birth registries of California, Minnesota, New York, Texas and Washington, which included 583 RMS cases (363 embryonal and 85 alveolar RMS) and 57 966 randomly selected control subjects, were analysed using logistic regression. The associations of RMS (overall, and based on embryonal or alveolar histology) with birth weight across five 500 g categories (from 2000 to 4500 g) were examined using normal birth weight (2500-3999 g) as a reference. Large (>90th percentile) and small (<10th percentile) size for gestational age were calculated based on birth weight distributions in controls and were similarly examined. High birth weight increased the risk of embryonal RMS and RMS overall. Each 500 g increase in birth weight increased the risk of embryonal RMS (odds ratio (OR)=1.27, 95% confidence interval (CI)=1.14-1.42) and RMS overall (OR=1.18, 95% CI=1.09-1.29). Large size for gestational age also significantly increased the risk of embryonal RMS (OR=1.42, 95% CI=1.03-1.96). These data suggest a positive association between accelerated in utero growth and embryonal RMS, but not alveolar RMS. These results warrant cautious interpretation owing to the small number of alveolar RMS cases.

Surgical management of peptic ulcer disease today--indication, technique and outcome.

PubMed

Zittel, T T; Jehle, E C; Becker, H D

2000-03-01

The current surgical management of peptic ulcer disease and its outcome have been reviewed. Today, surgery for peptic ulcer disease is largely restricted to the treatment of complications. In peptic ulcer perforation, a conservative treatment trial can be given in selected cases. If laparotomy is necessary, simple closure is sufficient in the large majority of cases, and definitive ulcer surgery to reduce gastric acid secretion is no longer justified in these patients. Laparoscopic surgery for perforated peptic ulcer has failed to prove to be a significant advantage over open surgery. In bleeding peptic ulcers, definitive hemostasis can be achieved by endoscopic treatment in more than 90% of cases. In 1-2% of cases, immediate emergency surgery is necessary. Some ulcers have a high risk of re-bleeding, and early elective surgery might be advisable. Surgical bleeding control can be achieved by direct suture and extraluminal ligation of the gastroduodenal artery or by gastric resection. Benign gastric outlet obstruction can be controlled by endoscopic balloon dilatation in 70% of cases, but gastrojejunostomy or gastric resection are necessary in about 30% of cases. Elective surgery for peptic ulcer disease has been largely abandoned, and bleeding or obstructing ulcers can be managed safely by endoscopic treatment in most cases. However, surgeons will continue to encounter patients with peptic ulcer disease for emergency surgery. Currently, laparoscopic surgery has no proven advantage in peptic ulcer surgery.

Large Outbreak Caused by Methicillin Resistant Staphylococcus pseudintermedius ST71 in a Finnish Veterinary Teaching Hospital – From Outbreak Control to Outbreak Prevention

PubMed Central

Grönthal, Thomas; Moodley, Arshnee; Nykäsenoja, Suvi; Junnila, Jouni; Guardabassi, Luca; Thomson, Katariina; Rantala, Merja

2014-01-01

Introduction The purpose of this study was to describe a nosocomial outbreak caused by methicillin resistant Staphylococcus pseudintermedius (MRSP) ST71 SCCmec II-III in dogs and cats at the Veterinary Teaching Hospital of the University of Helsinki in November 2010 – January 2012, and to determine the risk factors for acquiring MRSP. In addition, measures to control the outbreak and current policy for MRSP prevention are presented. Methods Data of patients were collected from the hospital patient record software. MRSP surveillance data were acquired from the laboratory information system. Risk factors for MRSP acquisition were analyzed from 55 cases and 213 controls using multivariable logistic regression in a case-control study design. Forty-seven MRSP isolates were analyzed by pulsed field gel electrophoresis and three were further analyzed with multi-locus sequence and SCCmec typing. Results Sixty-three MRSP cases were identified, including 27 infections. MRSPs from the cases shared a specific multi-drug resistant antibiogram and PFGE-pattern indicated clonal spread. Four risk factors were identified; skin lesion (OR = 6.2; CI95% 2.3–17.0, P = 0.0003), antimicrobial treatment (OR = 3.8, CI95% 1.0–13.9, P = 0.0442), cumulative number of days in the intensive care unit (OR = 1.3, CI95% 1.1–1.6, P = 0.0007) or in the surgery ward (OR = 1.1, CI95% 1.0–1.3, P = 0.0401). Tracing and screening of contact patients, enhanced hand hygiene, cohorting and barrier nursing, as well as cleaning and disinfection were used to control the outbreak. To avoid future outbreaks and spread of MRSP a search-and-isolate policy was implemented. Currently nearly all new MRSP findings are detected in screening targeted to risk patients on admission. Conclusion Multidrug resistant MRSP is capable of causing a large outbreak difficult to control. Skin lesions, antimicrobial treatment and prolonged hospital stay increase the probability of acquiring MRSP. Rigorous control measures were needed to control the outbreak. We recommend the implementation of a search-and-isolate policy to reduce the burden of MRSP. PMID:25333798

Marital status, education, and risk of acute myocardial infarction in Mainland China: the INTER-HEART study.

PubMed

Hu, Bo; Li, Wei; Wang, Xingyu; Liu, Lisheng; Teo, Koon; Yusuf, Salim

2012-01-01

We investigated the effects of marital status and education on the risk of acute myocardial infarction (AMI) in a large-scale case-control study in China. This study was part of the INTER-HEART China case-control study. The main outcome measure was first AMI. Incident cases of AMI and control patients with no past history of heart disease were recruited. Controls were matching by age (±5 years) and sex. Marital status was combined into 2 categories: single and not single. Education level was classified into 2 categories: 8 years or less and more than 8 years. From 1999 to 2002, we recruited 2909 cases and 2947 controls from 17 cities. After adjustment for age, sex, BMI, psychosocial factors, lifestyle, other factors, and mutually for other risk factors, the odds ratio (OR) for AMI associated with being single was 1.51 (95% confidence interval: 1.18-1.93) overall, 1.19 (0.84-1.68; P = 0.072) in men and 2.00 (1.39-2.86; P < 0.0001) in women. The interaction of sex and marital status was statistically significant (P = 0.045). Compared with a high education level, a low education level increased the risk of AMI (1.45, 1.26-1.67); the odds ratios in men and women were 1.29 (1.09-1.52) and 1.55 (1.16-2.08), respectively. Single women with a low education level had a high risk of AMI (2.95, 1.99-4.37). Being single was consistently associated with an increased risk for AMI, particularly in women. In addition, as compared with high education level, low education level was associated with a higher risk of AMI in both men and women.

Cross-border-assisted reproduction: a qualitative account of UK travellers' experiences.

PubMed

Hudson, Nicky; Culley, Lorraine; Blyth, Eric; Norton, Wendy; Pacey, Allan; Rapport, Frances

2016-06-01

Surveys on patients' experiences of cross-border fertility treatment have reported a range of positive and challenging features. However, the number of such studies is limited, and there is no detailed qualitative account of the experiences of UK patients who travel overseas for fertility treatment. The present study used a cross-sectional, qualitative design and in-depth interviews. Fifty-one participants (41 women and 10 men, representing 41 treatment 'cases') participated in semi-structured interviews. The experiences reported were broadly positive with a large proportion of participants (39 cases, 95%) citing a favourable overall experience with only two cases (5%) reporting a more negative experience. Thematic analysis revealed 6 major categories and 20 sub-categories, which described the positive and challenging aspects of cross-border fertility travel. The positive aspects were represented by the categories: 'access', 'control' and 'care and respect'. The more challenging aspects were categorized as 'logistics and coordination of care', 'uncertainty' and 'cultural dissonance'. The study confirms findings from others that despite some challenges, there is a relatively high level of patient satisfaction with cross-border treatment with participants able to extend the boundaries of their fertility-seeking trajectories and in some cases, regain a sense of control over their treatment.

Tetanus toxoid immunization to reduce mortality from neonatal tetanus.

PubMed

Blencowe, Hannah; Lawn, Joy; Vandelaer, Jos; Roper, Martha; Cousens, Simon

2010-04-01

Neonatal tetanus remains an important and preventable cause of neonatal mortality globally. Large reductions in neonatal tetanus deaths have been reported following major increases in the coverage of tetanus toxoid immunization, yet the level of evidence for the mortality effect of tetanus toxoid immunization is surprisingly weak with only two trials considered in a Cochrane review. To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age. We conducted a systematic review of multiple databases. Standardized abstraction forms were used. Individual study quality and the overall quality of evidence were assessed using an adaptation of the GRADE approach. Meta-analyses were performed. Only one randomised controlled trial (RCT) and one well-controlled cohort study were identified, which met inclusion criteria for meta-analysis. Immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% [95% confidence interval (CI) 80-98%]. Additionally, another RCT with a case definition based on day of death, 3 case-control studies and 1 before-and-after study gave consistent results. Based on the consistency of the mortality data, the very large effect size and that the data are all from low/middle-income countries, the overall quality of the evidence was judged to be moderate. This review uses a standard approach to provide a transparent estimate of the high impact of tetanus toxoid immunization on neonatal tetanus.

[Cannabinoids in pain medicine].

PubMed

Karst, M

2018-06-07

The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit. The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The "Cannabis-als-Medizin-Gesetz" (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.

Dietary factors and the risk of testicular cancer.

PubMed

Bonner, Matthew R; McCann, Susan E; Moysich, Kirsten B

2002-01-01

The etiology of testicular cancer (TC) remains largely unknown. Few studies have investigated the role diet may play in the etiology of TC. We report on a hospital-based case-control study of TC and selected nutrients and food groups. Cases included 117 patients with primary, incident TC treated at Roswell Park Cancer Institute between 1982 and 1998. A total of 334 hospital controls were frequency matched on age to cases. Cases were categorized by histology (seminoma, nonseminoma, and mixed germ cell TC), and multinomial logistic regression and unconditional logistic regression were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) comparing each histological type with the controls. For nonseminoma and mixed germ cell TC, vitamin E intake was suggestive of reduced risk (OR = 0.51, 95% CI = 0.15-1.76 and OR = 0.36, 95% CI = 0.01-1.31, respectively); for seminoma, it was suggestive of an increased risk (OR = 2.94, 95% CI = 0.99-8.78). Fat intakes were not associated with nonseminoma or mixed germ cell risk; high saturated, animal, and total fat intakes were suggestive of an increase in risk of seminoma. Overall, diet was not associated with TC. However, risk seemed to differ by histology, suggesting that seminoma, nonseminoma, and mixed germ cell TC may have different etiologies. We suggest that future investigations should continue to stratify cases by histology.

Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population.

PubMed

Usala, Rachel L; Fernandez, Stephen J; Mete, Mihriye; Cowen, Laura; Shara, Nawar M; Barsony, Julianna; Verbalis, Joseph G

2015-08-01

The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia. This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million. Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na(+)) data or with Na(+) with a same-day blood glucose greater than 200 mg/dL were excluded. Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures. Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59-4.39; fracture: OR 4.61, 95% CI 4.15-5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81-3.33; fracture: OR 3.05, 95% CI 2.83-3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34-15.66; fracture: OR 11.21, 95% CI 8.81-14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na(+). These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

Using unmanned aerial vehicle (UAV) surveys and image analysis in the study of large surface-associated marine species: a case study on reef sharks Carcharhinus melanopterus shoaling behaviour.

PubMed

Rieucau, G; Kiszka, J J; Castillo, J C; Mourier, J; Boswell, K M; Heithaus, M R

2018-06-01

A novel image analysis-based technique applied to unmanned aerial vehicle (UAV) survey data is described to detect and locate individual free-ranging sharks within aggregations. The method allows rapid collection of data and quantification of fine-scale swimming and collective patterns of sharks. We demonstrate the usefulness of this technique in a small-scale case study exploring the shoaling tendencies of blacktip reef sharks Carcharhinus melanopterus in a large lagoon within Moorea, French Polynesia. Using our approach, we found that C. melanopterus displayed increased alignment with shoal companions when distributed over a sandflat where they are regularly fed for ecotourism purposes as compared with when they shoaled in a deeper adjacent channel. Our case study highlights the potential of a relatively low-cost method that combines UAV survey data and image analysis to detect differences in shoaling patterns of free-ranging sharks in shallow habitats. This approach offers an alternative to current techniques commonly used in controlled settings that require time-consuming post-processing effort. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Neurocognitive performance in family-based and case-control studies of schizophrenia.

PubMed

Gur, Ruben C; Braff, David L; Calkins, Monica E; Dobie, Dorcas J; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Gur, Raquel E

2015-04-01

Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

Campylobacteriosis in New Zealand: results of a case-control study.

PubMed

Eberhart-Phillips, J; Walker, N; Garrett, N; Bell, D; Sinclair, D; Rainger, W; Bates, M

1997-12-01

To identify and assess the contributions of major risk factors for campylobacteriosis in New Zealand. Case-control study. Home interviews were conducted over nine months using a standardised questionnaire to assess recent food consumption and other exposures. Four centres in New Zealand with high notification rates of campylobacter infections--Auckland, Hamilton, Wellington, and Christchurch. Case patients were 621 people notified between 1 June 1994 and 28 February 1995 as having campylobacter infection. Control subjects were selected randomly from telephone directories, and were matched 1:1 with case patients in relation to sex, age group, and home telephone prefix. Risk of campylobacteriosis was strongly associated with recent consumption of raw or undercooked chicken (matched odds ratio 4.52, 95% confidence interval 2.88, 7.10). There was also an increased risk with chicken eaten in restaurants (matched odds ratio 3.85; 2.52, 5.88). Recent consumption of baked or roasted chicken seemed to be protective. Campylobacteriosis was also associated with recent overseas travel, rainwater as a source of water at home, consumption of raw dairy products, and contact with puppies and cattle, particularly calves. Improperly cooked chicken seems to be associated with a large proportion of campylobacteriosis in New Zealand. Thorough cooking of chicken in homes and restaurants could reduce considerably the incidence of this disease.

Fluconazole use and birth defects in the National Birth Defects Prevention Study.

PubMed

Howley, Meredith M; Carter, Tonia C; Browne, Marilyn L; Romitti, Paul A; Cunniff, Christopher M; Druschel, Charlotte M

2016-05-01

Low-dose fluconazole is used commonly to treat vulvovaginal candidiasis, a condition occurring frequently during pregnancy. Conflicting information exists on the association between low-dose fluconazole use among pregnant women and the risk of major birth defects. We used data from the National Birth Defects Prevention Study to examine this association. The National Birth Defects Prevention Study is a multisite, population-based, case-control study that includes pregnancies with estimated delivery dates from 1997 to 2011. Information on fluconazole use in early pregnancy was collected by self-report from 31,645 mothers of birth defect cases and 11,612 mothers of unaffected controls. Adjusted odds ratios and 95% confidence intervals were estimated for birth defects with 5 or more exposed cases; crude odds ratios and exact 95% confidence intervals were estimated for birth defects with 3-4 exposed cases. Of the 43,257 mothers analyzed, 44 case mothers and 6 control mothers reported using fluconazole. Six exposed infants had cleft lip with cleft palate, 4 had an atrial septal defect, and each of the following defects had 3 exposed cases: hypospadias, tetralogy of Fallot, d-transposition of the great arteries, and pulmonary valve stenosis. Fluconazole use was associated with cleft lip with cleft palate (odds ratio = 5.53; confidence interval = 1.68-18.24) and d-transposition of the great arteries (odds ratio = 7.56; confidence interval = 1.22-35.45). The associations between fluconazole and both cleft lip with cleft palate and d-transposition of the great arteries are consistent with earlier published case reports but not recent epidemiologic studies. Despite the larger sample size of the National Birth Defects Prevention Study, fluconazole use was rare. Further investigation is needed in large studies, with particular emphasis on oral clefts and conotruncal heart defects. Copyright © 2016 Elsevier Inc. All rights reserved.

Acrylamide Hemoglobin Adduct Levels and Ovarian Cancer Risk: a nested case-control study

PubMed Central

Xie, Jing; Terry, Kathryn L.; Poole, Elizabeth M.; Wilson, Kathryn M.; Rosner, Bernard A.; Willett, Walter C.; Vesper, Hubert W.; Tworoger, Shelley S.

2013-01-01

Background Acrylamide is a probable human carcinogen formed during cooking of starchy foods. Two large prospective cohort studies of dietary acrylamide intake and ovarian cancer risk observed a positive association, although two other studies reported no association. Methods We measured acrylamide exposure using red blood cell acrylamide and glycidamide hemoglobin adducts among women in two large prospective cohorts: the Nurses’ Health Study and Nurses’ Health Study II. Between blood collection and 2010, we identified 263 incident cases of epithelial ovarian cancer, matching two controls per case. We used logistic regression models to examine the association between acrylamide exposure and ovarian cancer risk, adjusting for matching factors, family history of ovarian cancer, tubal ligation, oral contraceptive use, body mass index (BMI), parity, alcohol intake, smoking, physical activity, and caffeine intake. Results The multivariate-adjusted relative risk (RR) of ovarian cancer comparing the highest versus lowest tertile of total acrylamide adducts was 0.79 (95% CI: 0.50–1.24, P trend = 0.08). The comparable RR of ovarian cancer among non-smokers at blood draw was 0.85 (95% CI: 0.57–1.27, P trend =0.14). The association did not differ by tumor histology (serous invasive versus not), P for heterogeneity=0.41. Individual adduct types (acrylamide or glycidamide) were not associated with risk. Conclusions We observed no evidence that acrylamide exposure as measured by adducts to hemoglobin is associated with an increased risk of ovarian cancer. Impact Our finding indicates that acrylamide intake may not increase risk of ovarian cancer. PMID:23417989

Self-reported Ethnicity, Genetic Structure and the Impact of Population Stratification in a Multiethnic Study

PubMed Central

Wang, Hansong; Haiman, Christopher A.; Kolonel, Laurence N.; Henderson, Brian E.; Wilkens, Lynne R.; Le Marchand, Loïc; Stram, Daniel O.

2011-01-01

It is well-known that population substructure may lead to confounding in case-control association studies. Here, we examined genetic structure in a large racially and ethnically diverse sample consisting of 5 ethnic groups of the Multiethnic Cohort study (African Americans, Japanese Americans, Latinos, European Americans and Native Hawaiians) using 2,509 SNPs distributed across the genome. Principal component analysis on 6,213 study participants, 18 Native Americans and 11 HapMap III populations revealed 4 important principal components (PCs): the first two separated Asians, Europeans and Africans, and the third and fourth corresponded to Native American and Native Hawaiian (Polynesian) ancestry, respectively. Individual ethnic composition derived from self-reported parental information matched well to genetic ancestry for Japanese and European Americans. STRUCTURE-estimated individual ancestral proportions for African Americans and Latinos are consistent with previous reports. We quantified the East Asian (mean 27%), European (mean 27%) and Polynesian (mean 46%) ancestral proportions for the first time, to our knowledge, for Native Hawaiians. Simulations based on realistic settings of case-control studies nested in the Multiethnic Cohort found that the effect of population stratification was modest and readily corrected by adjusting for race/ethnicity or by adjusting for top PCs derived from all SNPs or from ancestry informative markers; the power of these approaches was similar when averaged across causal variants simulated based on allele frequencies of the 2,509 genotyped markers. The bias may be large in case-only analysis of gene by gene interactions but it can be corrected by top PCs derived from all SNPs. PMID:20499252

Risk of Extrapyramidal Adverse Events With Aripiprazole.

PubMed

Etminan, Mahyar; Procyshyn, Ric M; Samii, Ali; Carleton, Bruce C

2016-10-01

Aripiprazole is a unique atypical antipsychotic with partial agonist activity on the dopamine-2 (D2) receptor. This unique pharmacological profile of aripiprazole was thought to lead to a lower incidence of extrapyramidal symptoms (EPSs). However, recent case reports have alluded to an increase in the risk of EPS in aripiprazole users compared with nonusers of the drug. No epidemiologic studies to date have quantified this risk. We conducted a pharmacoepidemiologic study composed of a nested case-control study using a large health claims database (IMS Health) in the United States. In the nested case-control analysis, there were 5242 cases of EPS with 50,532 corresponding controls in the entire cohort. The odds ratio (OR) for EPS among those with any prescription of aripiprazole was 5.38 (95% confidence interval [CI], 3.03-9.57). The OR was lower among those taking 2 to 3 prescriptions (OR, 2.9; 95% CI, 1.07-7.85) but increased in those receiving greater than 4 prescriptions (OR, 8.64; 95% CI, 2.63-28.38). All risk periods were compared with those of subjects who had not used aripiprazole or other antipsychotics. For the secondary outcome of dyskinesia, the risk for aripiprazole was 8.50 (95% CI, 8.53-2.27-31.97) compared with that of nonusers. In conclusion, we found an increase in the risk of EPS and dyskinesias among users of aripiprazole.

Campylobacteriosis in New Zealand: results of a case-control study.

PubMed Central

Eberhart-Phillips, J; Walker, N; Garrett, N; Bell, D; Sinclair, D; Rainger, W; Bates, M

1997-01-01

STUDY OBJECTIVE: To identify and assess the contributions of major risk factors for campylobacteriosis in New Zealand. DESIGN: Case-control study. Home interviews were conducted over nine months using a standardised questionnaire to assess recent food consumption and other exposures. SETTING: Four centres in New Zealand with high notification rates of campylobacter infections--Auckland, Hamilton, Wellington, and Christchurch. PARTICIPANTS: Case patients were 621 people notified between 1 June 1994 and 28 February 1995 as having campylobacter infection. Control subjects were selected randomly from telephone directories, and were matched 1:1 with case patients in relation to sex, age group, and home telephone prefix. RESULTS: Risk of campylobacteriosis was strongly associated with recent consumption of raw or undercooked chicken (matched odds ratio 4.52, 95% confidence interval 2.88, 7.10). There was also an increased risk with chicken eaten in restaurants (matched odds ratio 3.85; 2.52, 5.88). Recent consumption of baked or roasted chicken seemed to be protective. Campylobacteriosis was also associated with recent overseas travel, rainwater as a source of water at home, consumption of raw dairy products, and contact with puppies and cattle, particularly calves. CONCLUSIONS: Improperly cooked chicken seems to be associated with a large proportion of campylobacteriosis in New Zealand. Thorough cooking of chicken in homes and restaurants could reduce considerably the incidence of this disease. PMID:9519133

Outcomes Associated with In-Center Nocturnal Hemodialysis from a Large Multicenter Program

PubMed Central

Wang, Weiling; Lester, Keith; Ofsthun, Norma; Lazarus, J. Michael; Hakim, Raymond M.

2010-01-01

Background and objectives: The objective of this study was to evaluate epidemiology and outcomes of a large in-center nocturnal hemodialysis (INHD) program. Design, setting, participants, & measurements: This case-control study compared patients who were on thrice-weekly INHD from 56 Fresenius Medical Care, North America facilities with conventional hemodialysis patients from 244 facilities within the surrounding geographic area. All INHD cases and conventional hemodialysis control subjects who were active as of January 1, 2007, were followed until December 31, 2007, for evaluation of mortality and hospitalization. Results: As of January 1, 2007, 655 patients had been on INHD for 51 ± 73 d. Patients were younger, there were more male and black patients, and vintage was longer, but they had less diabetes compared with 15,334 control subjects. Unadjusted hazard ratio was 0.59 for mortality and 0.76 for hospitalization. After adjustment for case mix and access type, only hospitalization remained significant. Fewer INHD patients were hospitalized (48 versus 59%) with a normalized rate of 9.6 versus 13.5 hospital days per patient-year. INHD patients had greater interdialytic weight gains but lower BP. At baseline, hemoglobin values were similar, whereas albumin and phosphorus values favored INHD. Mean equilibrated Kt/V was higher in INHD patients related to longer treatment time, despite lower blood and dialysate flow rates. Conclusions: Patients who were on INHD exhibited excellent quality indicators, with better survival and lower hospitalization rates. The relative contributions of patient selection versus effect of therapy on outcomes remain to be elucidated in prospective clinical trials. PMID:19965529

Large Deletions at the SHOX Locus in the Pseudoautosomal Region Are Associated with Skeletal Atavism in Shetland Ponies

PubMed Central

Rafati, Nima; Andersson, Lisa S.; Mikko, Sofia; Feng, Chungang; Raudsepp, Terje; Pettersson, Jessica; Janecka, Jan; Wattle, Ove; Ameur, Adam; Thyreen, Gunilla; Eberth, John; Huddleston, John; Malig, Maika; Bailey, Ernest; Eichler, Evan E.; Dalin, Göran; Chowdary, Bhanu; Andersson, Leif; Lindgren, Gabriella; Rubin, Carl-Johan

2016-01-01

Skeletal atavism in Shetland ponies is a heritable disorder characterized by abnormal growth of the ulna and fibula that extend the carpal and tarsal joints, respectively. This causes abnormal skeletal structure and impaired movements, and affected foals are usually killed. In order to identify the causal mutation we subjected six confirmed Swedish cases and a DNA pool consisting of 21 control individuals to whole genome resequencing. We screened for polymorphisms where the cases and the control pool were fixed for opposite alleles and observed this signature for only 25 SNPs, most of which were scattered on genome assembly unassigned scaffolds. Read depth analysis at these loci revealed homozygosity or compound heterozygosity for two partially overlapping large deletions in the pseudoautosomal region (PAR) of chromosome X/Y in cases but not in the control pool. One of these deletions removes the entire coding region of the SHOX gene and both deletions remove parts of the CRLF2 gene located downstream of SHOX. The horse reference assembly of the PAR is highly fragmented, and in order to characterize this region we sequenced bacterial artificial chromosome (BAC) clones by single-molecule real-time (SMRT) sequencing technology. This considerably improved the assembly and enabled size estimations of the two deletions to 160−180 kb and 60−80 kb, respectively. Complete association between the presence of these deletions and disease status was verified in eight other affected horses. The result of the present study is consistent with previous studies in humans showing crucial importance of SHOX for normal skeletal development. PMID:27207956

Childhood hematologic cancer and residential proximity to oil and gas development

PubMed Central

McKenzie, Lisa M.; Allshouse, William B.; Byers, Tim E.; Bedrick, Edward J.; Serdar, Berrin; Adgate, John L.

2017-01-01

Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors. PMID:28199334

Understanding Rapid Changes in Phase Partitioning between Cloud Liquid and Ice in Stratiform Mixed-Phase Clouds: An Arctic Case Study

DOE PAGES

Kalesse, Heike; de Boer, Gijs; Solomon, Amy; ...

2016-11-23

Understanding phase transitions in mixed-phase clouds is of great importance because the hydrometeor phase controls the lifetime and radiative effects of clouds. These cloud radiative effects have a crucial impact on the surface energy budget and thus on the evolution of the ice cover, in high altitudes. For a springtime low-level mixed-phase stratiform cloud case from Barrow, Alaska, a unique combination of instruments and retrieval methods is combined with multiple modeling perspectives to determine key processes that control cloud phase partitioning. The interplay of local cloud-scale versus large-scale processes is considered. Rapid changes in phase partitioning were found to bemore » caused by several main factors. Some major influences were the large-scale advection of different air masses with different aerosol concentrations and humidity content, cloud-scale processes such as a change in the thermodynamical coupling state, and local-scale dynamics influencing the residence time of ice particles. Other factors such as radiative shielding by a cirrus and the influence of the solar cycle were found to only play a minor role for the specific case study (11–12 March 2013). Furthermore, for an even better understanding of cloud phase transitions, observations of key aerosol parameters such as profiles of cloud condensation nucleus and ice nucleus concentration are desirable.« less

Understanding Rapid Changes in Phase Partitioning between Cloud Liquid and Ice in Stratiform Mixed-Phase Clouds: An Arctic Case Study

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

Kalesse, Heike; de Boer, Gijs; Solomon, Amy

Understanding phase transitions in mixed-phase clouds is of great importance because the hydrometeor phase controls the lifetime and radiative effects of clouds. These cloud radiative effects have a crucial impact on the surface energy budget and thus on the evolution of the ice cover, in high altitudes. For a springtime low-level mixed-phase stratiform cloud case from Barrow, Alaska, a unique combination of instruments and retrieval methods is combined with multiple modeling perspectives to determine key processes that control cloud phase partitioning. The interplay of local cloud-scale versus large-scale processes is considered. Rapid changes in phase partitioning were found to bemore » caused by several main factors. Some major influences were the large-scale advection of different air masses with different aerosol concentrations and humidity content, cloud-scale processes such as a change in the thermodynamical coupling state, and local-scale dynamics influencing the residence time of ice particles. Other factors such as radiative shielding by a cirrus and the influence of the solar cycle were found to only play a minor role for the specific case study (11–12 March 2013). Furthermore, for an even better understanding of cloud phase transitions, observations of key aerosol parameters such as profiles of cloud condensation nucleus and ice nucleus concentration are desirable.« less

Ethical implications of excessive cluster sizes in cluster randomised trials.

PubMed

Hemming, Karla; Taljaard, Monica; Forbes, Gordon; Eldridge, Sandra M; Weijer, Charles

2018-02-20

The cluster randomised trial (CRT) is commonly used in healthcare research. It is the gold-standard study design for evaluating healthcare policy interventions. A key characteristic of this design is that as more participants are included, in a fixed number of clusters, the increase in achievable power will level off. CRTs with cluster sizes that exceed the point of levelling-off will have excessive numbers of participants, even if they do not achieve nominal levels of power. Excessively large cluster sizes may have ethical implications due to exposing trial participants unnecessarily to the burdens of both participating in the trial and the potential risks of harm associated with the intervention. We explore these issues through the use of two case studies. Where data are routinely collected, available at minimum cost and the intervention poses low risk, the ethical implications of excessively large cluster sizes are likely to be low (case study 1). However, to maximise the social benefit of the study, identification of excessive cluster sizes can allow for prespecified and fully powered secondary analyses. In the second case study, while there is no burden through trial participation (because the outcome data are routinely collected and non-identifiable), the intervention might be considered to pose some indirect risk to patients and risks to the healthcare workers. In this case study it is therefore important that the inclusion of excessively large cluster sizes is justifiable on other grounds (perhaps to show sustainability). In any randomised controlled trial, including evaluations of health policy interventions, it is important to minimise the burdens and risks to participants. Funders, researchers and research ethics committees should be aware of the ethical issues of excessively large cluster sizes in cluster trials. © 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.

A case-control study of risk factors for equine influenza spread onto horse premises during the 2007 epidemic in Australia.

PubMed

Firestone, Simon M; Schemann, Kathrin A; Toribio, Jenny-Ann L M L; Ward, Michael P; Dhand, Navneet K

2011-06-01

The 2007 epidemic of equine influenza in Australia provided an opportunity to investigate the effectiveness of on-farm biosecurity measures in preventing the spread of a novel pathogen in a largely naive population. We conducted a case-control study of 200 horse premises from highly affected regions of the state of New South Wales (NSW), to investigate risk factors for the spread of equine influenza onto horse premises, specifically, non-compliance with biosecurity measures recommended to horse owners by the relevant animal health authority, the NSW Department of Primary Industries. The study was restricted to cases occurring during the first seven weeks of the epidemic, a period prior to vaccination and the relaxation of some movement restrictions. Case and control premises were selected from a laboratory testing dataset and interviews were conducted with horse owners and managers on premises between July and November 2009. The proximity of premises to the nearest infected premises was the factor most strongly associated with case status. Case premises were more likely than control premises to be within 5 km and beyond 10 km of an infected premises. Having a footbath in place on the premises before any horses were infected was associated with a nearly four-fold reduction in odds of infection (odds ratio=0.27; 95% confidence interval: 0.09, 0.83). This protective association may have reflected overall premises biosecurity standards related to the fomite transmission of equine influenza. Compliance with certain on-farm biosecurity practices seemingly prevented horses on premises in high risk areas being infected with equine influenza during the 2007 outbreak in Australia. In future outbreaks, in addition to broader disease control measures, on-farm biosecurity practices should be adopted by horse owners and managers to prevent equine influenza spread. Copyright © 2011 Elsevier B.V. All rights reserved.

Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies.

PubMed

Thorsen, Jonathan; Brejnrod, Asker; Mortensen, Martin; Rasmussen, Morten A; Stokholm, Jakob; Al-Soud, Waleed Abu; Sørensen, Søren; Bisgaard, Hans; Waage, Johannes

2016-11-25

There is an immense scientific interest in the human microbiome and its effects on human physiology, health, and disease. A common approach for examining bacterial communities is high-throughput sequencing of 16S rRNA gene hypervariable regions, aggregating sequence-similar amplicons into operational taxonomic units (OTUs). Strategies for detecting differential relative abundance of OTUs between sample conditions include classical statistical approaches as well as a plethora of newer methods, many borrowing from the related field of RNA-seq analysis. This effort is complicated by unique data characteristics, including sparsity, sequencing depth variation, and nonconformity of read counts to theoretical distributions, which is often exacerbated by exploratory and/or unbalanced study designs. Here, we assess the robustness of available methods for (1) inference in differential relative abundance analysis and (2) beta-diversity-based sample separation, using a rigorous benchmarking framework based on large clinical 16S microbiome datasets from different sources. Running more than 380,000 full differential relative abundance tests on real datasets with permuted case/control assignments and in silico-spiked OTUs, we identify large differences in method performance on a range of parameters, including false positive rates, sensitivity to sparsity and case/control balances, and spike-in retrieval rate. In large datasets, methods with the highest false positive rates also tend to have the best detection power. For beta-diversity-based sample separation, we show that library size normalization has very little effect and that the distance metric is the most important factor in terms of separation power. Our results, generalizable to datasets from different sequencing platforms, demonstrate how the choice of method considerably affects analysis outcome. Here, we give recommendations for tools that exhibit low false positive rates, have good retrieval power across effect sizes and case/control proportions, and have low sparsity bias. Result output from some commonly used methods should be interpreted with caution. We provide an easily extensible framework for benchmarking of new methods and future microbiome datasets.

Development of an Outdoor Temperature-Based Control Algorithm for Residential Mechanical Ventilation Control

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

Less, Brennan; Walker, Iain; Tang, Yihuan

2014-06-01

Smart ventilation systems use controls to ventilate more during those periods that provide either an energy or IAQ advantage (or both) and less during periods that provide a dis advantage. Using detailed building simulations, this study addresses one of the simplest and lowest cost types of smart controllers —outdoor temperature- based control. If the outdoor temperature falls below a certain cut- off, the fan is simply turned off. T he main principle of smart ventilation used in this study is to shift ventilation from time periods with large indoor -outdoor temperature differences, to periods where these differences are smaller, andmore » their energy impacts are expected to be less. Energy and IAQ performance are assessed relative to a base case of a continuously operated ventilation fan sized to comply with ASHRAE 62.2-2013 whole house ventilation requirements. In order to satisfy 62.2-2013, annual pollutant exposure must be equivalent between the temperature controlled and continuous fan cases. This requires ventilation to be greater than 62.2 requirements when the ventilation system operates. This is achieved by increasing the mechanical ventilation system air flow rates.« less

Lower limb biomechanics during running in individuals with achilles tendinopathy: a systematic review

PubMed Central

2011-01-01

Background Abnormal lower limb biomechanics is speculated to be a risk factor for Achilles tendinopathy. This study systematically reviewed the existing literature to identify, critique and summarise lower limb biomechanical factors associated with Achilles tendinopathy. Methods We searched electronic bibliographic databases (Medline, EMBASE, Current contents, CINAHL and SPORTDiscus) in November 2010. All prospective cohort and case-control studies that evaluated biomechanical factors (temporospatial parameters, lower limb kinematics, dynamic plantar pressures, kinetics [ground reaction forces and joint moments] and muscle activity) associated with mid-portion Achilles tendinopathy were included. Quality of included studies was evaluated using the Quality Index. The magnitude of differences (effect sizes) between cases and controls was calculated using Cohen's d (with 95% CIs). Results Nine studies were identified; two were prospective and the remaining seven case-control study designs. The quality of 9 identified studies was varied, with Quality Index scores ranging from 4 to 15 out of 17. All studies analysed running biomechanics. Cases displayed increased eversion range of motion of the rearfoot (d = 0.92 and 0.67 in two studies), reduced maximum lower leg abduction (d = -1.16), reduced ankle joint dorsiflexion velocity (d = -0.62) and reduced knee flexion during gait (d = -0.90). Cases also demonstrated a number of differences in dynamic plantar pressures (primarily the distribution of the centre of force), ground reaction forces (large effects for timing variables) and also showed reduced peak tibial external rotation moment (d = -1.29). Cases also displayed differences in the timing and amplitude of a number of lower limb muscles but many differences were equivocal. Conclusions There are differences in lower limb biomechanics between those with and without Achilles tendinopathy that may have implications for the prevention and management of the condition. However, the findings need to be interpreted with caution due to the limited quality of a number of the included studies. Future well-designed prospective studies are required to confirm these findings. PMID:21619710

Simulation and optimal control of wind-farm boundary layers

NASA Astrophysics Data System (ADS)

Meyers, Johan; Goit, Jay

2014-05-01

In large wind farms, the effect of turbine wakes, and their interaction leads to a reduction in farm efficiency, with power generated by turbines in a farm being lower than that of a lone-standing turbine by up to 50%. In very large wind farms or `deep arrays', this efficiency loss is related to interaction of the wind farms with the planetary boundary layer, leading to lower wind speeds at turbine level. Moreover, for these cases it has been demonstrated both in simulations and wind-tunnel experiments that the wind-farm energy extraction is dominated by the vertical turbulent transport of kinetic energy from higher regions in the boundary layer towards the turbine level. In the current study, we investigate the use of optimal control techniques combined with Large-Eddy Simulations (LES) of wind-farm boundary layer interaction for the increase of total energy extraction in very large `infinite' wind farms. We consider the individual wind turbines as flow actuators, whose energy extraction can be dynamically regulated in time so as to optimally influence the turbulent flow field, maximizing the wind farm power. For the simulation of wind-farm boundary layers we use large-eddy simulations in combination with actuator-disk and actuator-line representations of wind turbines. Simulations are performed in our in-house pseudo-spectral code SP-Wind that combines Fourier-spectral discretization in horizontal directions with a fourth-order finite-volume approach in the vertical direction. For the optimal control study, we consider the dynamic control of turbine-thrust coefficients in an actuator-disk model. They represent the effect of turbine blades that can actively pitch in time, changing the lift- and drag coefficients of the turbine blades. Optimal model-predictive control (or optimal receding horizon control) is used, where the model simply consists of the full LES equations, and the time horizon is approximately 280 seconds. The optimization is performed using a nonlinear conjugate gradient method, and the gradients are calculated by solving the adjoint LES equations. We find that the extracted farm power increases by approximately 20% when using optimal model-predictive control. However, the increased power output is also responsible for an increase in turbulent dissipation, and a deceleration of the boundary layer. Further investigating the energy balances in the boundary layer, it is observed that this deceleration is mainly occurring in the outer layer as a result of higher turbulent energy fluxes towards the turbines. In a second optimization case, we penalize boundary-layer deceleration, and find an increase of energy extraction of approximately 10%. In this case, increased energy extraction is balanced by a reduction in of turbulent dissipation in the boundary layer. J.M. acknowledges support from the European Research Council (FP7-Ideas, grant no. 306471). Simulations were performed on the computing infrastructure of the VSC Flemish Supercomputer Center, funded by the Hercules Foundation and the Flemish Government.

Active local control of propeller-aircraft run-up noise.

PubMed

Hodgson, Murray; Guo, Jingnan; Germain, Pierre

2003-12-01

Engine run-ups are part of the regular maintenance schedule at Vancouver International Airport. The noise generated by the run-ups propagates into neighboring communities, disturbing the residents. Active noise control is a potentially cost-effective alternative to passive methods, such as enclosures. Propeller aircraft generate low-frequency tonal noise that is highly compatible with active control. This paper presents a preliminary investigation of the feasibility and effectiveness of controlling run-up noise from propeller aircraft using local active control. Computer simulations for different configurations of multi-channel active-noise-control systems, aimed at reducing run-up noise in adjacent residential areas using a local-control strategy, were performed. These were based on an optimal configuration of a single-channel control system studied previously. The variations of the attenuation and amplification zones with the number of control channels, and with source/control-system geometry, were studied. Here, the aircraft was modeled using one or two sources, with monopole or multipole radiation patterns. Both free-field and half-space conditions were considered: for the configurations studied, results were similar in the two cases. In both cases, large triangular quiet zones, with local attenuations of 10 dB or more, were obtained when nine or more control channels were used. Increases of noise were predicted outside of these areas, but these were minimized as more control channels were employed. By combining predicted attenuations with measured noise spectra, noise levels after implementation of an active control system were estimated.

Optimized PID control of depth of hypnosis in anesthesia.

PubMed

Padula, Fabrizio; Ionescu, Clara; Latronico, Nicola; Paltenghi, Massimiliano; Visioli, Antonio; Vivacqua, Giulio

2017-06-01

This paper addresses the use of proportional-integral-derivative controllers for regulating the depth of hypnosis in anesthesia by using propofol administration and the bispectral index as a controlled variable. In fact, introducing an automatic control system might provide significant benefits for the patient in reducing the risk for under- and over-dosing. In this study, the controller parameters are obtained through genetic algorithms by solving a min-max optimization problem. A set of 12 patient models representative of a large population variance is used to test controller robustness. The worst-case performance in the considered population is minimized considering two different scenarios: the induction case and the maintenance case. Our results indicate that including a gain scheduling strategy enables optimal performance for induction and maintenance phases, separately. Using a single tuning to address both tasks may results in a loss of performance up to 102% in the induction phase and up to 31% in the maintenance phase. Further on, it is shown that a suitably designed low-pass filter on the controller output can handle the trade-off between the performance and the noise effect in the control variable. Optimally tuned PID controllers provide a fast induction time with an acceptable overshoot and a satisfactory disturbance rejection performance during maintenance. These features make them a very good tool for comparison when other control algorithms are developed. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls

PubMed Central

Il’yasova, Dora; McCarthy, Bridget; Marcello, Jennifer; Schildkraut, Joellen M.; Moorman, Patricia G.; Krishnamachari, Bhuma; Ali-Osman, Francis; Bigner, Darell D.; Davis, Faith

2009-01-01

Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema and glioma risk using sibling, friend, and clinic-based controls. This analysis included 388 incident glioma cases and 80 sibling, 191 friend, and 177 clinic-based controls. Each subject’s medical history was assessed via a web-based or telephone survey. Odds ratios (ORs) and their 95% confidence intervals for the associations with allergies, asthma, eczema, and the overall number of these conditions were calculated from conditional (for sibling and friend controls) and unconditional (for clinic-based controls) logistic models. Allergies were consistently inversely associated with the glioma: ORs were 0.53 (95% CI, 0.15–1.84), 0.54 (95% CI, 0.28–1.07), and 0.34 (95% CI, 0.23–0.50) with sibling, friend, and clinic-based controls, respectively. Asthma showed an inverse association only in the comparison with sibling controls (OR=0.43; 95% CI, 0.19–1.00). Eczema showed an inverse association only in the comparison with friend controls (OR=0.42; 95% CI, 0.15–1.18). The overall number of these conditions (ordinal score 0, 1, 2, 3) was inversely associated with glioma: The risk decreased 31–45% with each addition of an atopic condition. These estimates were the most stable when different control groups were considered. Comparing the prevalence of these conditions in the three control groups with published data, we note that clinic-based controls generally better approximate the prevalence data for population-based groups. These controls appear to present a reasonable choice for clinic-centered case-control studies. PMID:19336556

Brief Report: Syndromes in Autistic Children in a Finnish Birth Cohort

ERIC Educational Resources Information Center

Timonen-Soivio, Laura; Vanhala, Raija; Malm, Heli; Hinkka-Yli-Salomäki, Susanna; Gissler, Mika; Brown, Alan; Sourander, Andre

2016-01-01

We studied the association between specific congenital syndromes and autism spectrum disorders (ASD) in the large Finnish Register material. Our data include all children diagnosed with ASD (n = 4441) according to Finnish Hospital Discharge Register in 1987-2000. Four controls per each case were matched to sex, birthplace, date of birth (±30 days)…

Ketamine for cancer pain: what is the evidence?

PubMed

Jonkman, Kelly; van de Donk, Tine; Dahan, Albert

2017-06-01

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy. While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit. Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

CMDR based differential evolution identifies the epistatic interaction in genome-wide association studies.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Lin, Yu-Da

2017-08-01

Detecting epistatic interactions in genome-wide association studies (GWAS) is a computational challenge. Such huge numbers of single-nucleotide polymorphism (SNP) combinations limit the some of the powerful algorithms to be applied to detect the potential epistasis in large-scale SNP datasets. We propose a new algorithm which combines the differential evolution (DE) algorithm with a classification based multifactor-dimensionality reduction (CMDR), termed DECMDR. DECMDR uses the CMDR as a fitness measure to evaluate values of solutions in DE process for scanning the potential statistical epistasis in GWAS. The results indicated that DECMDR outperforms the existing algorithms in terms of detection success rate by the large simulation and real data obtained from the Wellcome Trust Case Control Consortium. For running time comparison, DECMDR can efficient to apply the CMDR to detect the significant association between cases and controls amongst all possible SNP combinations in GWAS. DECMDR is freely available at https://goo.gl/p9sLuJ . chuang@isu.edu.tw or e0955767257@yahoo.com.tw. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Adaptive attitude control and momentum management for large-angle spacecraft maneuvers

NASA Technical Reports Server (NTRS)

Parlos, Alexander G.; Sunkel, John W.

1992-01-01

The fully coupled equations of motion are systematically linearized around an equilibrium point of a gravity gradient stabilized spacecraft, controlled by momentum exchange devices. These equations are then used for attitude control system design of an early Space Station Freedom flight configuration, demonstrating the errors caused by the improper approximation of the spacecraft dynamics. A full state feedback controller, incorporating gain-scheduled adaptation of the attitude gains, is developed for use during spacecraft on-orbit assembly or operations characterized by significant mass properties variations. The feasibility of the gain adaptation is demonstrated via a Space Station Freedom assembly sequence case study. The attitude controller stability robustness and transient performance during gain adaptation appear satisfactory.

Bias due to differential participation in case-control studies and review of available approaches for adjustment.

PubMed

Aigner, Annette; Grittner, Ulrike; Becher, Heiko

2018-01-01

Low response rates in epidemiologic research potentially lead to the recruitment of a non-representative sample of controls in case-control studies. Problems in the unbiased estimation of odds ratios arise when characteristics causing the probability of participation are associated with exposure and outcome. This is a specific setting of selection bias and a realistic hazard in many case-control studies. This paper formally describes the problem and shows its potential extent, reviews existing approaches for bias adjustment applicable under certain conditions, compares and applies them. We focus on two scenarios: a characteristic C causing differential participation of controls is linked to the outcome through its association with risk factor E (scenario I), and C is additionally a genuine risk factor itself (scenario II). We further assume external data sources are available which provide an unbiased estimate of C in the underlying population. Given these scenarios, we (i) review available approaches and their performance in the setting of bias due to differential participation; (ii) describe two existing approaches to correct for the bias in both scenarios in more detail; (iii) present the magnitude of the resulting bias by simulation if the selection of a non-representative sample is ignored; and (iv) demonstrate the approaches' application via data from a case-control study on stroke. The bias of the effect measure for variable E in scenario I and C in scenario II can be large and should therefore be adjusted for in any analysis. It is positively associated with the difference in response rates between groups of the characteristic causing differential participation, and inversely associated with the total response rate in the controls. Adjustment in a standard logistic regression framework is possible in both scenarios if the population distribution of the characteristic causing differential participation is known or can be approximated well.

Medication Use in Pregnancy in Relation to the Risk of Isolated Clubfoot in Offspring

PubMed Central

Werler, Martha M.; Yazdy, Mahsa M.; Kasser, James R.; Mahan, Susan T.; Meyer, Robert E.; Anderka, Marlene; Druschel, Charlotte M.; Mitchell, Allen A.

2014-01-01

Clubfoot, a common major structural malformation, develops early in gestation. Epidemiologic studies have identified higher risks among boys, first-born children, and babies with a family history of clubfoot, but studies of risks associated with maternal exposures are lacking. We conducted the first large-scale, population-based, case-control study of clubfoot with detailed information on maternal medication use in pregnancy. Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina during 2007–2011. Cases were 646 mothers of children with clubfoot without other major structural malformations (i.e., isolated clubfoot); controls were mothers of 2,037 children born without major malformations. Mothers were interviewed within 12 months of delivery about medication use, including product, timing, and frequency. Odds ratios were estimated for exposure to 27 medications in pregnancy months 2–4 after adjustment for study site, infant sex, first-born status, body mass index (weight (kg)/height (m)2), and smoking. Odds ratios were less than 1.20 for 14 of the medications; of the remainder, most odds ratios were only slightly elevated (range, 1.21–1.66), with wide confidence intervals. The use of antiviral drugs was more common in clubfoot cases than in controls (odds ratio = 4.22, 95% confidence interval: 1.52, 11.73). Most of these results are new findings and require confirmation in other studies. PMID:24824985

Noncultured keratinocyte/melanocyte cosuspension: effect on reepithelialization and repigmentation--a randomized, placebo-controlled study.

PubMed

Back, Christopher; Dearman, Bronwyn; Li, Amy; Neild, Tim; Greenwood, John E

2009-01-01

Randomized controlled trials in the literature investigating the efficacy of noncultured keratinocyte/melanocyte suspensions are scarce; however, the advocates of such techniques press the value of their application based largely on case studies and anecdote. Caucasian patients with burn hypopigmentation seldom request cosmetic revision making worthwhile clinical trials difficult so that informal case treatments with new therapies generate anecdotal results. A randomized, placebo-controlled trial was carried out to evaluate whether cosuspensions of noncultured skin cells are capable of (1) decreasing the time to reepithelialization and (2) reestablishing pigmentation in vitiligo leukoderma following epidermal/superficial dermal ablation (in the knowledge that a positive result would make the technique likely to be successful in burn hypopigmentation). Vitiligo is common and is socially more debilitating such that suitable trial subjects for new therapies from this pool are more forthcoming. This study demonstrated that suspensions of noncultured keratinocytes and melanocytes do not decrease the time to epithelialization of superficial partial thickness wounds compared with controls. It also suggested that the achievement, quality, and duration of any pigmentation were unpredictable and largely disappointing. Some pigmentation was recorded in placebo-treated areas indicating an effect of the method of epidermal ablation in these patients. These findings have mandated a complete review of the use of these techniques in burn care at the Royal Adelaide Hospital; they have been omitted from surgical protocols where the aim of use was to speed reepithelialization. Their infrequent use in burns hypopigmentation will continue contingent on the successful repigmentation of a test patch.

Assessing impacts of introduced aquatic species: Grass carp in large systems

NASA Astrophysics Data System (ADS)

Bain, Mark B.

1993-03-01

Introduced species have created environmental benefits and unanticipated disasters so a priori assessments of species introductions are needed for environmental management. A checklist for assessing impacts of introduced species was developed from studies of introduced species and recommendations for planning introductions. Sterile, triploid grass carp ( Ctenopharyngodon idella) are just beginning to be used as a biocontrol agent for the management of aquatic vegetation in open waterways. Potential impacts of grass carp in open systems were identified by reviewing grass carp biology relative to the impact assessment checklist. The potential consequences of introduced grass carp were reviewed for one case study. The case study demonstrated that conclusions about potential impacts and monitoring needs can be made despite incomplete information and uncertainty. Indicators of environmental impact and vulnerability of host systems were grouped into six categories: population control, hybridization, diseases and parasites, habitat alterations, biological effects, and management issues. Triploid grass carp can significantly alter habitat and biological resources through the secondary effects of reductions in aquatic vegetation. Potential impacts and significant uncertainties involve fish dispersions from plant control areas, inability to control vegetation loss, loss of diverse plant communities and their dependent species, and conflicts with human use of the water resource. Adequate knowledge existed to assess most potential consequences of releasing large numbers of triploid grass carp in Guntersville Reservoir, Alabama. However, the assessment of potential impacts indicated that moderate, incremental stockings combined with monitoring of vegetation and biological resources are necessary to control the effects of grass carp and achieve desirable, intermediate plant densities.

Investigating Strategies to Increase Persistence and Success Rates among Anatomy & Physiology Students: A Case Study at Austin Community College District

NASA Astrophysics Data System (ADS)

Vedartham, Padmaja B.

Snap-through buckling provides an intricate force-displacement relationship for study. With the possibility for multiple limit points and pitchfork bifurcations and large regions of instability, experimental validation of numerical analysis can become difficult. This requires stabilization of unstable static equilibria, for which limited prior research exists. For all but the simplest cases, more than one actuator is needed, increasing the complexity of the experiment to the point of intractability without a control system. In this thesis, the necessary conditions for stabilization of a buckled beam with pinned boundaries under transverse loading were determined. By combining various nonlinear solution methods, a control system was created that could stabilize any branch of the force-displacement response. Experimental traversal of an unstable branch are presented along with other unstable static equilibrium configurations. The control system had numerical limitations, losing convergence near singular points. The groundwork for experimental stabilization was validated and demonstrated.

POSITIVE AND NEGATIVE PSYCHOLOGICAL CORRELATES, GENDER SPECIFIC AND TRADITIONAL FACTORS FOR FIRST ONSET ANGINA IN A SAMPLE OF PAKISTANI WOMEN.

PubMed

Rafique, Rafia; Anjum, Afifa

2015-01-01

Coronary Heart Disease (CHD) occurs to a greater extent in developed than developing countries like Pakistan. Our understanding of risk factors leading to this disease in women, are largely derived from studies carried out on samples obtained from developed countries. Since prevalence of CHD in Pakistan is growing, it seems pertinent to infer risk and protective factors prevalent within the Pakistani women. This case control study investigated the role of psychological, traditional and gender specific risk and protective factors for Angina in a sample of Pakistani women aged between 35-65 years. Female patients admitted with first episode of Angina fulfilling the study inclusion/exclusion criteria were recruited within the first three days of stay in the hospital. One control per case matched on age was recruited. Translated versions of standardized tools: Life Orientation Test (LOT), The Hope Scale, Subjective Happiness Scale and Depression, Anxiety and Stress Scale (DASS) were used to measure the psychological variables. Information on medical conditions like diabetes, hypertension, family history of IHD, presence and absence of menopause and use of oral contraceptive pills was obtained from the participants. Body Mass Index for cases and controls was calculated separately with the help of height and weight recorded for the participants. Multivariate logistic regression analyses revealed that depression, anxiety and stress are risk factors, were as optimism and hope are protective predictors of Angina. 64% and 85% of variance in Angina were attributed to psychological factors. Menopause, diabetes and hypertension are significantly associated with the risk of Angina, explaining 37% and 49% of variance in Angina. The study provides evidence for implementation of gender specific risk assessment and preventive strategies for Angina. The study gives directions for large scale prospective, epidemiological, longitudinal as well as interventional studies, to be tailored for indigenous population and secondly development and standardization of measures to appraise psychological factors of Angina prevalent within the Pakistani population.

Differences in risk factors for 2nd and 3rd degree hypospadias in the National Birth Defects Prevention Study

PubMed Central

in 't Woud, Sander Groen; van Rooij, Iris A.L.M.; van Gelder, Marleen M.H.J.; Olney, Richard S.; Carmichael, Suzan L.; Roeleveld, Nel; Reefhuis, Jennita

2015-01-01

Background Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case-control study, we compared risk factors for second and third degree hypospadias. Methods A wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected via computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center. Results In total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history. Conclusions Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between 2nd and 3rd degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype. PMID:25181604

Military Service, Deployments, and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology

PubMed Central

Beard, John D.; Engel, Lawrence S.; Richardson, David B.; Gammon, Marilie D.; Baird, Coleen; Umbach, David M.; Allen, Kelli D.; Stanwyck, Catherine L.; Keller, Jean; Sandler, Dale P.; Schmidt, Silke; Kamel, Freya

2016-01-01

Background Factors underlying a possible excess of amyotrophic lateral sclerosis (ALS) among military veterans remain unidentified. Limitations of previous studies on this topic include reliance on ALS mortality as a surrogate for ALS incidence, low statistical power, and sparse information on military-related factors. Objectives We evaluated associations between military-related factors and ALS using data from a case-control study of U.S. military veterans. Methods From 2005 to 2010, we identified medical record-confirmed ALS cases via the National Registry of Veterans with ALS and controls via the Veterans Benefits Administration’s Beneficiary Identification and Records Locator System database. In total, we enrolled 621 cases and 958 frequency-matched controls in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study. We collected information on military service and deployments and 39 related exposures. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We used inverse probability weighting to adjust for potential bias from confounding, missing covariate data, and selection arising from a case group that disproportionately included long-term survivors and a control group that may or may not differ from U.S. military veterans at large. Results The odds of ALS did not differ for veterans of the Air Force, Army, Marines, and Navy. We found higher odds of ALS for veterans whose longest deployment was World War II or the Korean War and a positive trend with total years of all deployments (OR = 1.27; 95% CI: 1.06, 1.52). ALS was positively associated with exposure to herbicides for military purposes, nasopharyngeal radium, personal pesticides, exhaust from heaters or generators, high-intensity radar waves, contaminated food, explosions within one mile, herbicides in the field, mixing and application of burning agents, burning agents in the field, and Agent Orange in the field, with ORs between 1.50 and 7.75. Conclusions Although our results need confirmation, they are potentially important given the large number of U.S. military veterans, and they provide clues to potential factors underlying the apparent increase of ALS in veteran populations. PMID:26923711

Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis etiology.

PubMed

Beard, John D; Engel, Lawrence S; Richardson, David B; Gammon, Marilie D; Baird, Coleen; Umbach, David M; Allen, Kelli D; Stanwyck, Catherine L; Keller, Jean; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

2016-05-01

Factors underlying a possible excess of amyotrophic lateral sclerosis (ALS) among military veterans remain unidentified. Limitations of previous studies on this topic include reliance on ALS mortality as a surrogate for ALS incidence, low statistical power, and sparse information on military-related factors. We evaluated associations between military-related factors and ALS using data from a case-control study of U.S. military veterans. From 2005 to 2010, we identified medical record-confirmed ALS cases via the National Registry of Veterans with ALS and controls via the Veterans Benefits Administration's Beneficiary Identification and Records Locator System database. In total, we enrolled 621 cases and 958 frequency-matched controls in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study. We collected information on military service and deployments and 39 related exposures. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We used inverse probability weighting to adjust for potential bias from confounding, missing covariate data, and selection arising from a case group that disproportionately included long-term survivors and a control group that may or may not differ from U.S. military veterans at large. The odds of ALS did not differ for veterans of the Air Force, Army, Marines, and Navy. We found higher odds of ALS for veterans whose longest deployment was World War II or the Korean War and a positive trend with total years of all deployments (OR=1.27; 95% CI: 1.06, 1.52). ALS was positively associated with exposure to herbicides for military purposes, nasopharyngeal radium, personal pesticides, exhaust from heaters or generators, high-intensity radar waves, contaminated food, explosions within one mile, herbicides in the field, mixing and application of burning agents, burning agents in the field, and Agent Orange in the field, with ORs between 1.50 and 7.75. Although our results need confirmation, they are potentially important given the large number of U.S. military veterans, and they provide clues to potential factors underlying the apparent increase of ALS in veteran populations. Published by Elsevier Ltd.

The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial.

PubMed

Anders, Katherine L; Indriani, Citra; Ahmad, Riris Andono; Tantowijoyo, Warsito; Arguni, Eggi; Andari, Bekti; Jewell, Nicholas P; Rances, Edwige; O'Neill, Scott L; Simmons, Cameron P; Utarini, Adi

2018-05-31

Dengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field. The study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km 2 study area was subdivided into 24 contiguous clusters, allocated randomly 1:1 to receive Wolbachia deployments or no intervention. We use a novel epidemiological study design, the cluster-randomised test-negative design trial, in which dengue cases and arbovirus-negative controls are sampled concurrently from among febrile patients presenting to a network of primary care clinics, with case or control status classified retrospectively based on the results of laboratory diagnostic testing. Efficacy is estimated from the odds ratio of Wolbachia exposure distribution (probability of living in a Wolbachia-treated area) among virologically confirmed dengue cases compared to test-negative controls. A secondary per-protocol analysis allows for individual Wolbachia exposure levels to be assessed to account for movements outside the cluster and the heterogeneity in local Wolbachia prevalence among treated clusters. The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings. ClinicalTrials.gov, identifier: NCT03055585 . Registered on 14 February 2017.

Vitamins and abdominal aortic aneurysm.

PubMed

Takagi, Hisato; Umemoto, Takuya

2017-02-01

To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E supplementation may not reduce AAA incidence.

What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders?

PubMed

Fornito, Alex; Bullmore, Edward T

2010-05-01

Resting-state functional MRI (rs-fMRI) is an increasingly popular technique for studying brain dysfunction in psychiatric patients, and is widely assumed to measure intrinsic properties of functional brain organization. Here, we review rs-fMRI studies of psychiatric populations and consider how recent evidence concerning the neuronal basis, behavioural relevance, and the stability of rs-fMRI measures can inform and constrain interpretation of findings obtained using case-control designs. A range of rs-fMRI measures have been applied to different patient groups, although the findings have not always been consistent. The large-scale organization of rs-fMRI networks is robust and reproducible, and rs-fMRI measures show correlations with behavioural phenotypes relevant to psychiatry. However, evidence that such measures are also influenced by preceding psychological states and contexts, as well as individual variations in physiological arousal, may help to explain inconsistent findings in case-control comparisons. rs-fMRI measures show both stable and dynamic properties, the nature of which are only beginning to be uncovered. As such, interpreting significant differences between patients and controls on rs-fMRI measures as evidence for alterations in intrinsic functional brain organization should be done cautiously. Better understanding of the relationship between stable and transient aspects of spontaneous brain dynamics will be necessary to constrain interpretation of case-control studies and inform pathophysiological models.

Air Pollution and Pulmonary Tuberculosis: A Nested Case-Control Study among Members of a Northern California Health Plan.

PubMed

Smith, Geneé S; Van Den Eeden, Stephen K; Garcia, Cynthia; Shan, Jun; Baxter, Roger; Herring, Amy H; Richardson, David B; Van Rie, Annelies; Emch, Michael; Gammon, Marilie D

2016-06-01

Ecologic analyses, case-case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. We conducted a case-control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant's residence. In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. In this first, to our knowledge, U.S. nested case-control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761-768; http://dx.doi.org/10.1289/ehp.1408166.

Till receipts--a new approach for investigating outbreaks? Evaluation during a large Salmonella Enteritidis phage type 14b outbreak in a North West London takeaway restaurant, September 2009.

PubMed

Zenner, D; Zoellner, J; Charlett, A; Marmairis, W; Lane, C; Chow, J Y

2014-07-10

Selecting suitable controls for outbreak investigations is often difficult and if done inappropriately will lead to biased inferences. Till receipts and other sales records are frequently available on food premises, but their applicability has not been fully explored. Using data from an investigation into a Salmonella outbreak affecting 66 individuals exposed in a London takeaway restaurant, this study aimed to evaluate the use of till receipts to assess associations between sales and illness. Cases identified through local case-finding were subjected to a standardised exposure questionnaire. Till receipts over the time period when cases arose were analysed. Estimated food exposures from sales were compared to case reported exposures and till receipts analysis showed strong association between illness and consumption of rotisserie chicken (odds ratio (OR): 2.75; confidence interval (CI): 1.7-4.5). Chicken sales immediately prior to food consumption for cases were compared to two control periods in an ecological case-crossover design. On average there was an estimated increase of 3.7 (CI: 2.2-5.2) extra chickens sold in the hour immediately prior to the consumption in the cases (p<0.0001) and the risk of becoming ill at busy times increased by 5% with each additional chicken quarter sold per hour (OR: 1.05; CI: 1.03-1.08). Microbiological and environmental investigations revealed Salmonella Enteritidis phage type (PT)14b in all available cases' stool samples, two environmental samples and leftover chicken from the takeaway. The feasibility of this novel approach to obtain exposure information in the population at risk has been demonstrated, and its limitations are discussed. Further validation is required, comparing results with those in a concurrent classic case-control study.

Applying the 15 Public Health Emergency Preparedness Capabilities to Support Large-Scale Tuberculosis Investigations in Complex Congregate Settings

PubMed Central

Toren, Katelynne Gardner; Elsenboss, Carina; Narita, Masahiro

2017-01-01

Public Health—Seattle and King County, a metropolitan health department in western Washington, experiences rates of tuberculosis (TB) that are 1.6 times higher than are state and national averages. The department’s TB Control Program uses public health emergency management tools and capabilities sustained with Centers for Disease Control and Prevention grant funding to manage large-scale complex case investigations. We have described 3 contact investigations in large congregate settings that the TB Control Program conducted in 2015 and 2016. The program managed the investigations using public health emergency management tools, with support from the Preparedness Program. The 3 investigations encompassed medical evaluation of more than 1600 people, used more than 100 workers, identified nearly 30 individuals with latent TB infection, and prevented an estimated 3 cases of active disease. These incidents exemplify how investments in public health emergency preparedness can enhance health outcomes in traditional areas of public health. PMID:28892445

Argentine Population Genetic Structure: Large Variance in Amerindian Contribution

PubMed Central

Seldin, Michael F.; Tian, Chao; Shigeta, Russell; Scherbarth, Hugo R.; Silva, Gabriel; Belmont, John W.; Kittles, Rick; Gamron, Susana; Allevi, Alberto; Palatnik, Simon A.; Alvarellos, Alejandro; Paira, Sergio; Caprarulo, Cesar; Guillerón, Carolina; Catoggio, Luis J.; Prigione, Cristina; Berbotto, Guillermo A.; García, Mercedes A.; Perandones, Carlos E.; Pons-Estel, Bernardo A.; Alarcon-Riquelme, Marta E.

2011-01-01

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies. PMID:17177183

Interplay Between Childhood Physical Abuse and Familial Risk in the Onset of Psychotic Disorders

PubMed Central

Fisher, Helen L.; McGuffin, Peter; Boydell, Jane; Fearon, Paul; Craig, Thomas K.; Dazzan, Paola; Morgan, Kevin; Doody, Gillian A.; Jones, Peter B.; Leff, Julian; Murray, Robin M.; Morgan, Craig

2014-01-01

Background: Childhood abuse is considered one of the main environmental risk factors for the development of psychotic symptoms and disorders. However, this association could be due to genetic factors influencing exposure to such risky environments or increasing sensitivity to the detrimental impact of abuse. Therefore, using a large epidemiological case-control sample, we explored the interplay between a specific form of childhood abuse and family psychiatric history (a proxy for genetic risk) in the onset of psychosis. Methods: Data were available on 172 first presentation psychosis cases and 246 geographically matched controls from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire and occurrence of psychotic and affective disorders in first degree relatives with the Family Interview for Genetic Studies. Results: Parental psychosis was more common among psychosis cases than unaffected controls (adjusted OR = 5.96, 95% CI: 2.09–17.01, P = .001). Parental psychosis was also associated with physical abuse from mothers in both cases (OR = 3.64, 95% CI: 1.06–12.51, P = .040) and controls (OR = 10.93, 95% CI: 1.03–115.90, P = .047), indicative of a gene-environment correlation. Nevertheless, adjusting for parental psychosis did not measurably impact on the abuse-psychosis association (adjusted OR = 3.31, 95% CI: 1.22–8.95, P = .018). No interactions were found between familial liability and maternal physical abuse in determining psychosis caseness. Conclusions: This study found no evidence that familial risk accounts for associations between childhood physical abuse and psychotic disorder nor that it substantially increases the odds of psychosis among individuals reporting abuse. PMID:24399191

Interplay between childhood physical abuse and familial risk in the onset of psychotic disorders.

PubMed

Fisher, Helen L; McGuffin, Peter; Boydell, Jane; Fearon, Paul; Craig, Thomas K; Dazzan, Paola; Morgan, Kevin; Doody, Gillian A; Jones, Peter B; Leff, Julian; Murray, Robin M; Morgan, Craig

2014-11-01

Childhood abuse is considered one of the main environmental risk factors for the development of psychotic symptoms and disorders. However, this association could be due to genetic factors influencing exposure to such risky environments or increasing sensitivity to the detrimental impact of abuse. Therefore, using a large epidemiological case-control sample, we explored the interplay between a specific form of childhood abuse and family psychiatric history (a proxy for genetic risk) in the onset of psychosis. Data were available on 172 first presentation psychosis cases and 246 geographically matched controls from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire and occurrence of psychotic and affective disorders in first degree relatives with the Family Interview for Genetic Studies. Parental psychosis was more common among psychosis cases than unaffected controls (adjusted OR = 5.96, 95% CI: 2.09-17.01, P = .001). Parental psychosis was also associated with physical abuse from mothers in both cases (OR = 3.64, 95% CI: 1.06-12.51, P = .040) and controls (OR = 10.93, 95% CI: 1.03-115.90, P = .047), indicative of a gene-environment correlation. Nevertheless, adjusting for parental psychosis did not measurably impact on the abuse-psychosis association (adjusted OR = 3.31, 95% CI: 1.22-8.95, P = .018). No interactions were found between familial liability and maternal physical abuse in determining psychosis caseness. This study found no evidence that familial risk accounts for associations between childhood physical abuse and psychotic disorder nor that it substantially increases the odds of psychosis among individuals reporting abuse. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study.

PubMed

Dominguez, Angela; Salleras, Lluis; Fedson, David S; Izquierdo, Conchita; Ruiz, Laura; Ciruela, Pilar; Fenoll, Asuncion; Casal, Julio

2005-05-01

Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study. We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination. Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period. Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.

Maternal consumption of coffee and tea during pregnancy and risk of childhood brain tumors: results from an Australian case-control study.

PubMed

Greenop, Kathryn R; Miller, Margaret; Attia, John; Ashton, Lesley J; Cohn, Richard; Armstrong, Bruce K; Milne, Elizabeth

2014-10-01

The causes of childhood brain tumors (CBT) are largely unknown, but gestational diet may influence this risk. The aim of this analysis was to investigate whether maternal coffee or tea consumption during pregnancy was associated with the risk of CBT. The Australian Study of the Causes of Childhood Brain Tumours was a population-based, Australian case-control study conducted between 2005 and 2010. Case children were recruited from 10 pediatric oncology centers and control children by nationwide random-digit dialing, frequency matched to cases on the basis of age, sex and state of residence. Coffee and tea intake were assessed using a food frequency questionnaire. Data on coffee and tea consumption during pregnancy were available from 293 case mothers and 726 control mothers. Odds ratios (ORs) and confidence intervals (CIs) were calculated using multivariable unconditional logistic regression. There was little evidence of an association between gestational consumption of any coffee (OR 1.23, 95% CI 0.92, 1.64) or tea (OR 1.00, 95% CI 0.74, 1.36) and CBT risk. Among children aged under 5 years, the OR for any coffee consumption during pregnancy was 1.76 (95% CI 1.09, 2.84) and for ≥2 cups per day during pregnancy was 2.52 (95% CI 1.26, 5.04). There was little evidence that associations with coffee or tea intake differed by parental smoking status. These results suggest a positive association between coffee intake ≥2 cups per day and risk of CBT in younger children, although some estimates are imprecise. There was no association between maternal tea drinking and risk of CBT.

Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study.

PubMed

Stark, Klaus; Reinhard, Wibke; Neureuther, Katharina; Wiedmann, Silke; Sedlacek, Kamil; Baessler, Andrea; Fischer, Marcus; Weber, Stefan; Kaess, Bernhard; Erdmann, Jeanette; Schunkert, Heribert; Hengstenberg, Christian

2008-04-09

Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population.

An entropy-based statistic for genomewide association studies.

PubMed

Zhao, Jinying; Boerwinkle, Eric; Xiong, Momiao

2005-07-01

Efficient genotyping methods and the availability of a large collection of single-nucleotide polymorphisms provide valuable tools for genetic studies of human disease. The standard chi2 statistic for case-control studies, which uses a linear function of allele frequencies, has limited power when the number of marker loci is large. We introduce a novel test statistic for genetic association studies that uses Shannon entropy and a nonlinear function of allele frequencies to amplify the differences in allele and haplotype frequencies to maintain statistical power with large numbers of marker loci. We investigate the relationship between the entropy-based test statistic and the standard chi2 statistic and show that, in most cases, the power of the entropy-based statistic is greater than that of the standard chi2 statistic. The distribution of the entropy-based statistic and the type I error rates are validated using simulation studies. Finally, we apply the new entropy-based test statistic to two real data sets, one for the COMT gene and schizophrenia and one for the MMP-2 gene and esophageal carcinoma, to evaluate the performance of the new method for genetic association studies. The results show that the entropy-based statistic obtained smaller P values than did the standard chi2 statistic.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

PubMed

Tran, K T; McMenamin, Ú C; Hicks, B; Murchie, P; Thrift, A P; Coleman, H G; Iversen, L; Johnston, B T; Lee, A J; Cardwell, C R

2018-05-09

Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research. © 2018 John Wiley & Sons Ltd.

Characteristics of boys with the so-called true undescended testis diagnosed at the third postnatal month--a population-based case-control study.

PubMed

Mavrogenis, Stelios; Urbán, Robert; Czeizel, Andrew E

2015-07-01

Undescended testis (cryptorchidism) is a common congenital abnormality of male genital organs diagnosed at birth followed with frequent postnatal descensus. However, the so-called isolated true undescended testis (ITUT) diagnosed at the third postnatal month seems to be an independent defect-entity, and this hypothesis was planned to confirm or reject in the study. The evaluation of birth outcomes and maternal socio-demographic data of cases with ITUT in the population-based large dataset of the Hungarian Congenital Abnormality Registry. There was a higher rate of preterm birth and particularly of low birthweight in 2052 cases with ITUT compared to 24,814 population male controls without any defects. The rate of twins was not higher in cases with older mothers, higher birth order and lower socio-economic status. The comparison of data of boys with undescended testis diagnosed at birth found in the previous study and with ITUT in this study confirmed our hypothesis. Undescended testis can be differentiated into two subgroups: boys with frequent postnatal descensus mainly after preterm delivery and boys with ITUT without postnatal testis descensus with frequent intrauterine growth restriction, older mothers with higher birth order and low socio-economic status.

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

2015-06-05

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46 450 cases and 42 461 controls from the breast cancer association consortium

PubMed Central

Milne, Roger L.; Herranz, Jesús; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P.; Zamora, M. Pilar; Arias-Perez, José Ignacio; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Wang, Qin; Bolla, Manjeet K.; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Li, Jingmei; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Clarke, Christina A.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Chenevix-Trench, Georgia; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Dunning, Alison M.; Shah, Mitul; Guénel, Pascal; Truong, Thérèse; Sanchez, Marie; Mulot, Claire; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J.; Hollestelle, Antoinette; Collée, J. Margriet; Jager, Agnes; Cox, Angela; Brock, Ian W.; Reed, Malcolm W.R.; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Dumont, Martine; Soucy, Penny; Dörk, Thilo; Bogdanova, Natalia V.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Fasching, Peter A.; Häberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Mariani, Paolo; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Lambrechts, Diether; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Pharoah, Paul D.P.; Hall, Per; Benítez, Javier; Malats, Núria; Easton, Douglas F.

2014-01-01

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome. PMID:24242184

A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium.

PubMed

Milne, Roger L; Herranz, Jesús; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P; Zamora, M Pilar; Arias-Perez, José Ignacio; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Wang, Qin; Bolla, Manjeet K; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Li, Jingmei; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Clarke, Christina A; Hopper, John L; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Chenevix-Trench, Georgia; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Wang, Xianshu; Olson, Janet E; Vachon, Celine; Purrington, Kristen; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Dunning, Alison M; Shah, Mitul; Guénel, Pascal; Truong, Thérèse; Sanchez, Marie; Mulot, Claire; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; Collée, J Margriet; Jager, Agnes; Cox, Angela; Brock, Ian W; Reed, Malcolm W R; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Dumont, Martine; Soucy, Penny; Dörk, Thilo; Bogdanova, Natalia V; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Fasching, Peter A; Häberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Mariani, Paolo; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Lambrechts, Diether; Yesilyurt, Betul T; Floris, Giuseppe; Leunen, Karin; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen-Dale, Anne-Lise; García-Closas, Montserrat; Chanock, Stephen J; Lissowska, Jolanta; Figueroa, Jonine D; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Couch, Fergus J; Toland, Amanda E; Yannoukakos, Drakoulis; Pharoah, Paul D P; Hall, Per; Benítez, Javier; Malats, Núria; Easton, Douglas F

2014-04-01

Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70,917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46,450 breast cancer cases and 42,461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

Risk Factors for Measles Virus Infection Among Adults During a Large Outbreak in Postelimination Era in Mongolia, 2015.

PubMed

Hagan, José E; Takashima, Yoshihiro; Sarankhuu, Amarzaya; Dashpagma, Otgonbayar; Jantsansengee, Baigalmaa; Pastore, Roberta; Nyamaa, Gunregjav; Yadamsuren, Buyanjargal; Mulders, Mick N; Wannemuehler, Kathleen A; Anderson, Raydel; Bankamp, Bettina; Rota, Paul; Goodson, James L

2017-12-05

In 2015, a large nationwide measles outbreak occurred in Mongolia, with very high incidence in the capital city of Ulaanbaatar and among young adults. We conducted an outbreak investigation including a matched case-control study of risk factors for laboratory-confirmed measles among young adults living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in the capital city of Ulaanbaatar, were matched with 2-3 neighborhood controls. Conditional logistic regression was used to estimate adjusted matched odds ratios (aMORs) for risk factors, with 95% confidence intervals. During March 1-September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases were confirmed. Independent risk factors for measles included being unvaccinated (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02). This large, nationwide outbreak shortly after verification of elimination had high incidence among young adults, particularly those born outside the national capital. In addition, findings indicated that nosocomial transmission within health facilities helped amplify the outbreak. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The case-control design in veterinary sciences: A survey.

PubMed

Cullen, Jonah N; Sargeant, Jan M; Makielski, Kelly M; O'Connor, Annette M

2016-11-01

The case-control study design is deceptively simple. However, many design considerations influence the estimated effect measure. An investigation of case-control studies in the human health literature suggested that some of these considerations are not described in reports of case-control studies. Our hypothesis was that the majority of veterinary studies labeled as case-controls would be incident density designs, and many would not interpret the effect measure obtained from those studies as the rate ratio rather than the odds ratio. Reference databases were searched for author-designated case-control studies. A survey of 100 randomly selected studies was conducted to examine the different design options described and estimated effect measures. Of the 100 author-identified case-control studies, 83 assessed an exposure-outcome association and, of those, only 54 (65.1%) sampled the study population based on an outcome and would thus be considered case-control designs. Twelve studies were incidence density designs but none used this terminology. Of the studies that reported an odds ratio as the effect measure, none reported on additional considerations that would have enabled a more interpretable result. This survey indicated many case-control-labeled studies were not case-control designs and among case-control studies, key design aspects were not often described. The absence of information about study design elements and underlying assumptions in case-control studies limits the ability to establish the effect measured by the study and the evidentiary value of the study might be underestimated. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of patients with gout: elaboration of a questionnaire for epidemiological studies.

PubMed

Richette, P; Clerson, P; Bouée, S; Chalès, G; Doherty, M; Flipo, R M; Lambert, C; Lioté, F; Poiraud, T; Schaeverbeke, T; Bardin, T

2015-09-01

In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France. 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.

Space-Time Analysis of Testicular Cancer Clusters Using Residential Histories: A Case-Control Study in Denmark

PubMed Central

Sloan, Chantel D.; Nordsborg, Rikke B.; Jacquez, Geoffrey M.; Raaschou-Nielsen, Ole; Meliker, Jaymie R.

2015-01-01

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population. PMID:25756204

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

PubMed

Sloan, Chantel D; Nordsborg, Rikke B; Jacquez, Geoffrey M; Raaschou-Nielsen, Ole; Meliker, Jaymie R

2015-01-01

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

An Integrated Approach to Damage Accommodation in Flight Control

NASA Technical Reports Server (NTRS)

Boskovic, Jovan D.; Knoebel, Nathan; Mehra, Raman K.; Gregory, Irene

2008-01-01

In this paper we present an integrated approach to in-flight damage accommodation in flight control. The approach is based on Multiple Models, Switching and Tuning (MMST), and consists of three steps: In the first step the main objective is to acquire a realistic aircraft damage model. Modeling of in-flight damage is a highly complex problem since there is a large number of issues that need to be addressed. One of the most important one is that there is strong coupling between structural dynamics, aerodynamics, and flight control. These effects cannot be studied separately due to this coupling. Once a realistic damage model is available, in the second step a large number of models corresponding to different damage cases are generated. One possibility is to generate many linear models and interpolate between them to cover a large portion of the flight envelope. Once these models have been generated, we will implement a recently developed-Model Set Reduction (MSR) technique. The technique is based on parameterizing damage in terms of uncertain parameters, and uses concepts from robust control theory to arrive at a small number of "centered" models such that the controllers corresponding to these models assure desired stability and robustness properties over a subset in the parametric space. By devising a suitable model placement strategy, the entire parametric set is covered with a relatively small number of models and controllers. The third step consists of designing a Multiple Models, Switching and Tuning (MMST) strategy for estimating the current operating regime (damage case) of the aircraft, and switching to the corresponding controller to achieve effective damage accommodation and the desired performance. In the paper present a comprehensive approach to damage accommodation using Model Set Design,MMST, and Variable Structure compensation for coupling nonlinearities. The approach was evaluated on a model of F/A-18 aircraft dynamics under control effector damage, augmented by nonlinear cross-coupling terms and a structural dynamics model. The proposed approach achieved excellent performance under severe damage effects.

Designed for Learning: A Case Study in Rethinking Teaching and Learning for a Large First Year Class

ERIC Educational Resources Information Center

Goldacre, Lisa; Bolt, Susan; Lambiris, Michael

2013-01-01

This paper presents a case study in which the principles of scholarship were applied to designing an approach to learning suitable for large classes. While this case study describes an Australian first year Business Law unit, the findings presented in this paper would be relevant to a wide range of teachers faced with large enrollments in first…

Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

PubMed

Parodi, Stefano; Santi, Irene; Marani, Enza; Casella, Claudia; Puppo, Antonella; Garrone, Elsa; Fontana, Vincenzo; Stagnaro, Emanuele

2016-03-01

Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

Genotyping and inflated type I error rate in genome-wide association case/control studies

PubMed Central

Sampson, Joshua N; Zhao, Hongyu

2009-01-01

Background One common goal of a case/control genome wide association study (GWAS) is to find SNPs associated with a disease. Traditionally, the first step in such studies is to assign a genotype to each SNP in each subject, based on a statistic summarizing fluorescence measurements. When the distributions of the summary statistics are not well separated by genotype, the act of genotype assignment can lead to more potential problems than acknowledged by the literature. Results Specifically, we show that the proportions of each called genotype need not equal the true proportions in the population, even as the number of subjects grows infinitely large. The called genotypes for two subjects need not be independent, even when their true genotypes are independent. Consequently, p-values from tests of association can be anti-conservative, even when the distributions of the summary statistic for the cases and controls are identical. To address these problems, we propose two new tests designed to reduce the inflation in the type I error rate caused by these problems. The first algorithm, logiCALL, measures call quality by fully exploring the likelihood profile of intensity measurements, and the second algorithm avoids genotyping by using a likelihood ratio statistic. Conclusion Genotyping can introduce avoidable false positives in GWAS. PMID:19236714

Analyzing simulation-based PRA data through traditional and topological clustering: A BWR station blackout case study

DOE PAGES

Maljovec, D.; Liu, S.; Wang, B.; ...

2015-07-14

Here, dynamic probabilistic risk assessment (DPRA) methodologies couple system simulator codes (e.g., RELAP and MELCOR) with simulation controller codes (e.g., RAVEN and ADAPT). Whereas system simulator codes model system dynamics deterministically, simulation controller codes introduce both deterministic (e.g., system control logic and operating procedures) and stochastic (e.g., component failures and parameter uncertainties) elements into the simulation. Typically, a DPRA is performed by sampling values of a set of parameters and simulating the system behavior for that specific set of parameter values. For complex systems, a major challenge in using DPRA methodologies is to analyze the large number of scenarios generated,more » where clustering techniques are typically employed to better organize and interpret the data. In this paper, we focus on the analysis of two nuclear simulation datasets that are part of the risk-informed safety margin characterization (RISMC) boiling water reactor (BWR) station blackout (SBO) case study. We provide the domain experts a software tool that encodes traditional and topological clustering techniques within an interactive analysis and visualization environment, for understanding the structures of such high-dimensional nuclear simulation datasets. We demonstrate through our case study that both types of clustering techniques complement each other for enhanced structural understanding of the data.« less

Alcohol consumption and PSA-detected prostate cancer risk—A case-control nested in the ProtecT study

PubMed Central

Zuccolo, Luisa; Lewis, Sarah J; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Smith, George Davey

2013-01-01

Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; pdifference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. What's new? Alcohol is not an established risk factor for prostate cancer; however, the current work suggests that heavy drinking could cause a small increase in risk of the more aggressive forms. If the results are confirmed to be causal, prostate cancer risk will be added to the many long-term health risks of heavy drinking, and public health strategies will then also reduce high-risk, poorer prognosis prostate cancer. The authors also found that heavy drinkers have lower PSA levels, suggesting that heavy alcohol consumption could be used as a marker to identify men in whom some cancers might be missed. PMID:23024014

[Application of nested case-control study on safe evaluation of post-marketing traditional Chinese medicine injection].

PubMed

Xiao, Ying; Zhao, Yubin; Xie, Yanming

2011-10-01

The nested case-control study design (or the case-control in a cohort study) is described here as a new study design used in safe evaluation of post-marketing traditional Chinese medicine injection. In the nested case-control study, cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case. For many research questions, the nested case-control design potentially offers impressive reductions in costs and efforts of data collection and analysis compared with the full cohort approach, with relatively minor loss in statistical efficiency. The nested case-control design is particularly advantageous for studies in safe evaluation of post-marketing traditional Chinese medicine injection. Some examples of the application of nested case-control study were given.

Literature Review: Herbal Medicine Treatment after Large-Scale Disasters.

PubMed

Takayama, Shin; Kaneko, Soichiro; Numata, Takehiro; Kamiya, Tetsuharu; Arita, Ryutaro; Saito, Natsumi; Kikuchi, Akiko; Ohsawa, Minoru; Kohayagawa, Yoshitaka; Ishii, Tadashi

2017-01-01

Large-scale natural disasters, such as earthquakes, tsunamis, volcanic eruptions, and typhoons, occur worldwide. After the Great East Japan earthquake and tsunami, our medical support operation's experiences suggested that traditional medicine might be useful for treating the various symptoms of the survivors. However, little information is available regarding herbal medicine treatment in such situations. Considering that further disasters will occur, we performed a literature review and summarized the traditional medicine approaches for treatment after large-scale disasters. We searched PubMed and Cochrane Library for articles written in English, and Ichushi for those written in Japanese. Articles published before 31 March 2016 were included. Keywords "disaster" and "herbal medicine" were used in our search. Among studies involving herbal medicine after a disaster, we found two randomized controlled trials investigating post-traumatic stress disorder (PTSD), three retrospective investigations of trauma or common diseases, and seven case series or case reports of dizziness, pain, and psychosomatic symptoms. In conclusion, herbal medicine has been used to treat trauma, PTSD, and other symptoms after disasters. However, few articles have been published, likely due to the difficulty in designing high quality studies in such situations. Further study will be needed to clarify the usefulness of herbal medicine after disasters.

Large multistate outbreak of norovirus gastroenteritis associated with frozen strawberries, Germany, 2012.

PubMed

Bernard, H; Faber, M; Wilking, H; Haller, S; Höhle, M; Schielke, A; Ducomble, T; Siffczyk, C; Merbecks, S S; Fricke, G; Hamouda, O; Stark, K; Werber, D

2014-02-27

From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions in five federal states reported nearly 11,000 cases of gastroenteritis. They were predominantly schools and childcare facilities and were supplied almost exclusively by one large catering company. The analytical epidemiological studies consistently identified dishes containing strawberries as the most likely vehicle, with estimated odds ratios ranging from 2.6 to 45.4. The dishes had been prepared in different regional kitchens of the catering company and were served in the schools two days before the peaks of the respective outbreaks. All affected institutions had received strawberries of one lot, imported frozen from China. The outbreak vehicle was identified within a week, which led to a timely recall and prevented more than half of the lot from reaching the consumer. This outbreak exemplifies the risk of large outbreaks in the era of global food trade. It underlines the importance of timely surveillance and epidemiological outbreak investigations for food safety.

[The case-case-time-control study design].

PubMed

Wang, Jing; Zhuo, Lin; Zhan, Siyan

2014-12-01

Although the 'self-matched case-only studies' (such as the case-cross-over or self-controlled case-series method) can control the time-invariant confounders (measured or unmeasured) through design of the study, however, they can not control those confounders that vary with time. A bidirectional case-crossover design can be used to adjust the exposure-time trends. In the areas of pharmaco-epidemiology, illness often influence the future use of medications, making a bidirectional study design problematic. Suissa's case-time-control design combines the case-crossover and the case-control design which could adjust for exposure-trend bias, but the control group may reintroduce selection bias, if the matching does not go well. We propose a "case-case-time-control" design which is an extension of the case-time-control design. However, rather than using a sample of external controls, we choose those future cases as controls for current cases to counter the bias that arising from temporal trends caused by exposure to the target of interest. In the end of this article we will discuss the strength and limitations of this design based on an applied example.

Health and Development of Children Born after Assisted Reproductive Technology and Sub-Fertility Compared to Naturally Conceived Children: Data from a National Study

PubMed Central

Sutcliffe, Alastair G.; Melhuish, Edward; Barnes, Jacqueline; Gardiner, Julian

2014-01-01

In a non-matched case-control study using data from two large national cohort studies, we investigated whether indicators of child health and development up to 7 years of age differ between children conceived using assisted reproductive technology (ART), children born after sub-fertility (more than 24 months of trying for conception) and other children. Information on ART use/sub-fertility was available for 23,649 children. There were 227 cases (children conceived through ART) and two control groups: 783 children born to sub-fertile couples, and 22,639 children born to couples with no fertility issues. In models adjusted for social and demographic factors there were significant differences between groups in rate of hospital admissions before the children were 9 months old (P=0.029), with the ART group showing higher rates of hospital admission than the no fertility issues control group, the sub-fertile control group being intermediate between the two. Children born after ART had comparable health and development beyond 9 months of age to their naturally conceived peers. This applied to the whole sample and to a sub-sample of children from deprived neighborhoods. PMID:24711911

Incomplete sanitation of a meat grinder and ingestion of raw ground beef: contributing factors to a large outbreak of Salmonella typhimurium infection.

PubMed

Roels, T H; Frazak, P A; Kazmierczak, J J; Mackenzie, W R; Proctor, M E; Kurzynski, T A; Davis, J P

1997-10-01

Consumers in the United States continue to eat raw or undercooked foods of animal origin despite public health warnings following several well-publicized outbreaks. We investigated an outbreak of Salmonella serotype Typhimurium infection in 158 patients in Wisconsin during the 1994 Christmas holiday period. To determine the vehicle and source of the outbreak, we conducted cohort and case-control studies, and environmental investigations in butcher shop A. Eating raw ground beef purchased from butcher shop A was the only item significantly associated with illness [cohort study: relative risk = 5.8, 95% confidence interval (CI) = 1.5-21.8; case control study: odds ratio = 46.2, 95% CI = 3.8-2751]. Inadequate cleaning and sanitization of the meat grinder in butcher shop A likely resulted in sustained contamination of ground beef during an 8-day interval. Consumer education, coupled with hazard reduction efforts at multiple stages in the food processing chain, will continue to play an important role in the control of foodborne illness.

Incomplete sanitation of a meat grinder and ingestion of raw ground beef: contributing factors to a large outbreak of Salmonella typhimurium infection.

PubMed Central

Roels, T. H.; Frazak, P. A.; Kazmierczak, J. J.; Mackenzie, W. R.; Proctor, M. E.; Kurzynski, T. A.; Davis, J. P.

1997-01-01

Consumers in the United States continue to eat raw or undercooked foods of animal origin despite public health warnings following several well-publicized outbreaks. We investigated an outbreak of Salmonella serotype Typhimurium infection in 158 patients in Wisconsin during the 1994 Christmas holiday period. To determine the vehicle and source of the outbreak, we conducted cohort and case-control studies, and environmental investigations in butcher shop A. Eating raw ground beef purchased from butcher shop A was the only item significantly associated with illness [cohort study: relative risk = 5.8, 95% confidence interval (CI) = 1.5-21.8; case control study: odds ratio = 46.2, 95% CI = 3.8-2751]. Inadequate cleaning and sanitization of the meat grinder in butcher shop A likely resulted in sustained contamination of ground beef during an 8-day interval. Consumer education, coupled with hazard reduction efforts at multiple stages in the food processing chain, will continue to play an important role in the control of foodborne illness. PMID:9363010

Making the business case for enhanced depression care: the National Institute of Mental Health-harvard Work Outcomes Research and Cost-effectiveness Study.

PubMed

Wang, Philip S; Simon, Gregory E; Kessler, Ronald C

2008-04-01

Explore the business case for enhanced depression care and establish a return on investment rationale for increased organizational involvement by employer-purchasers. Literature review, focused on the National Institute of Mental Health-sponsored Work Outcomes Research and Cost-effectiveness Study. This randomized controlled trial compared telephone outreach, care management, and optional psychotherapy to usual care among depressed workers in large national corporations. By 12 months, the intervention significantly improved depression outcomes, work retention, and hours worked among the employed. Results of the Work Outcomes Research and Cost-effectiveness Study trial and other studies suggest that enhanced depression care programs represent a human capital investment opportunity for employers.

Crash risk factors for interstate large trucks in North Carolina.

PubMed

Teoh, Eric R; Carter, Daniel L; Smith, Sarah; McCartt, Anne T

2017-09-01

Provide an updated examination of risk factors for large truck involvements in crashes resulting in injury or death. A matched case-control study was conducted in North Carolina of large trucks operated by interstate carriers. Cases were defined as trucks involved in crashes resulting in fatal or non-fatal injury, and one control truck was matched on the basis of location, weekday, time of day, and truck type. The matched-pair odds ratio provided an estimate of the effect of various driver, vehicle, or carrier factors. Out-of-service (OOS) brake violations tripled the risk of crashing; any OOS vehicle defect increased crash risk by 362%. Higher historical crash rates (fatal, injury, or all crashes) of the carrier were associated with increased risk of crashing. Operating on a short-haul exemption increased crash risk by 383%. Antilock braking systems reduced crash risk by 65%. All of these results were statistically significant at the 95% confidence level. Other safety technologies also showed estimated benefits, although not statistically significant. With the exception of the finding that short-haul exemption is associated with increased crash risk, results largely bolster what is currently known about large truck crash risk and reinforce current enforcement practices. Results also suggest vehicle safety technologies can be important in lowering crash risk. This means that as safety technology continues to penetrate the fleet, whether from voluntary usage or government mandates, reductions in large truck crashes may be achieved. Practical application: Results imply that increased enforcement and use of crash avoidance technologies can improve the large truck crash problem. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

Genetic variations in the Dravidian population of South West coast of India: Implications in designing case-control studies.

PubMed

D'Cunha, Anitha; Pandit, Lekha; Malli, Chaithra

2017-06-01

Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and <1 per cent variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

SOS1 gene polymorphisms are associated with gestational diabetes mellitus in a Chinese population: Results from a nested case-control study in Taiyuan, China.

PubMed

Chen, Qiong; Yang, Hailan; Feng, Yongliang; Zhang, Ping; Wu, Weiwei; Li, Shuzhen; Thompson, Brian; Wang, Xin; Peng, Tingting; Wang, Fang; Xie, Bingjie; Guo, Pengge; Li, Mei; Wang, Ying; Zhao, Nan; Wang, Suping; Zhang, Yawei

2018-03-01

Gestational diabetes mellitus is a growing public health concern due to its large disease burden; however, the underlying pathophysiology remains unclear. Therefore, we examined the relationship between 107 single-nucleotide polymorphisms in insulin signalling pathway genes and gestational diabetes mellitus risk using a nested case-control study. The SOS1 rs7598922 GA and AA genotype were statistically significantly associated with reduced gestational diabetes mellitus risk ( p trend  = 0.0006) compared with GG genotype. At the gene level, SOS1 was statistically significantly associated with gestational diabetes mellitus risk after adjusting for multiple comparisons. Moreover, AGGA and GGGG haplotypes in SOS1 gene were associated with reduced risk of gestational diabetes mellitus. Our study provides evidence for an association between the SOS1 gene and risk of gestational diabetes mellitus; however, its role in the pathogenesis of gestational diabetes mellitus will need to be verified by further studies.

Different occupations associated with amyotrophic lateral sclerosis: is diesel exhaust the link?

PubMed

Pamphlett, Roger; Rikard-Bell, Anna

2013-01-01

The cause of sporadic amyotrophic lateral sclerosis (SALS) remains unknown. We attempted to find out if occupational exposure to toxicants plays a part in the pathogenesis of this disease. In an Australia-wide case-control study we compared the lifetime occupations of 611 SALS and 775 control individuals. Occupations were coded using country-specific as well as international classifications. The risk of SALS for each occupation was calculated with odds ratios using logistic regression. In addition, the literature was searched for possible toxicant links between our findings and previously-reported occupational associations with SALS. Male occupations in our study that required lower skills and tasks tended to have increased risks of SALS, and conversely, those occupations that required higher skills and tasks had decreased risks of SALS. Of all the occupations, only truck drivers, where exposure to diesel exhaust is common, maintained an increased risk of SALS throughout all occupational groups. Another large case-control study has also found truck drivers to be at risk of SALS, and almost two-thirds of occupations, as well as military duties, that have previously been associated with SALS have potential exposure to diesel exhaust. In conclusion, two of the largest case-control studies of SALS have now found that truck drivers have an increased risk of SALS. Since exposure to diesel exhaust is common in truck drivers, as well as in other occupations that have been linked to SALS, exposure to this toxicant may underlie some of the occupations that are associated with SALS.

Psychological autopsy study comparing suicide decedents, suicide ideators, and propensity score matched controls: results from the study to assess risk and resilience in service members (Army STARRS).

PubMed

Nock, M K; Dempsey, C L; Aliaga, P A; Brent, D A; Heeringa, S G; Kessler, R C; Stein, M B; Ursano, R J; Benedek, D

2017-11-01

The suicide rate has increased significantly among US Army soldiers over the past decade. Here we report the first results from a large psychological autopsy study using two control groups designed to reveal risk factors for suicide death among soldiers beyond known sociodemographic factors and the presence of suicide ideation. Informants were next-of-kin and Army supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched on known sociodemographic risk factors for suicide and Army history variables, and 118 control soldiers who reported suicide ideation in the past year. Results revealed that most (79.3%) soldiers who died by suicide have a prior mental disorder; mental disorders in the prior 30-days were especially strong risk factors for suicide death. Approximately half of suicide decedents tell someone that they are considering suicide. Virtually all of the risk factors identified in this study differed between suicide cases and propensity-score-matched controls, but did not significantly differ between suicide cases and suicide ideators. The most striking difference between suicides and ideators was the presence in the former of an internalizing disorder (especially depression) and multi-morbidity (i.e. 3+ disorders) in the past 30 days. Most soldiers who die by suicide have identifiable mental disorders shortly before their death and tell others about their suicidal thinking, suggesting that there are opportunities for prevention and intervention. However, few risk factors distinguish between suicide ideators and decedents, pointing to an important direction for future research.

LSS systems planning and performance program

NASA Technical Reports Server (NTRS)

Mckenna, Victoria Jones; Dendy, Michael J.; Naumann, Charles B.; Rice, Sally A.; Weathers, John M.

1993-01-01

This report describes, using viewgraphs, the Marshall Space Flight Center's Large Space Structures Ground Test Facilities located in building 4619. Major topics include the Active Control Evaluation of Systems (ACES) Laboratory; the Control-Structures Interaction/Controls, Astrophysics, and Structures Experiment in Space (CSI/CASES); Advanced Development Facility; and the ACES Guest Investigator Program.

Incentives and control in primary health care: findings from English pay-for-performance case studies.

PubMed

McDonald, Ruth; Harrison, Stephen; Checkland, Kath

2008-01-01

The authors' aim was to investigate mechanisms and perceptions of control following the implementation of a new "pay-for-performance" contract (the new General Medical Services, or GMS, contract) in general practice. This article was based on an in-depth qualitative case study approach in two general practices in England. A distinction is emerging amongst ostensibly equal partners between those general practitioners conducting and those subject to surveillance. Attitudes towards the contract were largely positive, although discontent was higher in the practice which employed a more intensive surveillance regime and greater amongst nurses than doctors. The sample was small and opportunistic. Further research is required to examine the longer-term effects as new contractual arrangements evolve. Increased surveillance and feedback mechanisms associated with new pay-for-performance schemes have the potential to constrain and shape clinical practice. The paper highlights the emergence of new tensions within and between existing professional groupings.

Abatacept as a successful therapy for myositis—a case-based review.

PubMed

Kerola, Anne M; Kauppi, Markku J

2015-03-01

Only limited evidence exists on the therapeutic potential of biologic agents in the treatment of myositis. We present a brief review of the literature on off-label experiences of biologic agents in myositis, with a special interest in abatacept. Rituximab has been indicated to be beneficial and well tolerated in one large randomized controlled trial and many smaller studies. Initial data on tumour necrosis factor (TNF) inhibitors are conflicting. There are only a few case reports and mechanistic studies on the treatment of myositis with other biologics, including alemtuzumab, anakinra, tocilizumab and abatacept. We report a patient with severe myositis overlap syndrome, manifesting also as rheumatoid arthritis, peripheral vasculitis and interstitial lung disease. Her myositis was refractory to many conventional and biologic therapies but was well controlled with abatacept. This suggests that abatacept might be a beneficial option for the treatment of refractory myositis and that clinical trials are needed to further investigate its efficacy.

Control-oriented modelization of a satellite with large flexible appendages and use of worst-case analysis to verify robustness to model uncertainties of attitude control

NASA Astrophysics Data System (ADS)

Gasbarri, Paolo; Monti, Riccardo; Campolo, Giovanni; Toglia, Chiara

2012-12-01

The design of large space structures (LSS) requires the use of design and analysis tools that include different disciplines. For such a kind of spacecrafts it is in fact mandatory that mechanical design and guidance navigation and control (GNC) design are developed within a common framework. One of the key-points in the development of LSS is related to the dynamic phenomena. These phenomena usually lead to two different interpretations. The former one is related to the overall motion of the spacecraft, i.e., the motion of the centre of gravity and motion around the centre of gravity. The latter one is related to the local motion of the elastic elements that leads to oscillations. These oscillations have in turn a disturbing effect on the motion of the spacecraft. From an engineering perspective, the structural model of flexible spacecrafts is generally obtained via FEM involving thousands of degrees of freedom (DOFs). Many of them are not significant from the attitude control point of view. One of the procedures to reduce the structural DOFs is tied to the modal decomposition technique. In the present paper a technique to develop a control-oriented structural model will be proposed. Starting from a detailed FE model of the spacecraft and using a special modal condensation approach, a continuous model is defined. With this transformation the number of DOFs necessary to study the coupled elastic/rigid dynamic is reduced. The final dynamic model will be suitable for the control design implementation. In order to properly design a satellite controller, it is important to recall that the characteristic parameters of the satellite are uncertain. The effect that uncertainties have on control performance must be investigated. A possible solution is that, after the attitude controller is designed on the nominal model, a Verification and Validation (V&V) process is performed to guarantee a correct functionality under a large number of scenarios. The V&V process can be very lengthy and expensive: difficulty and cost do increase because of the overall system dimension that depends on the number of uncertainties. Uncertain parameters have to be parametrically investigated to determine robust performance of the control laws via gridding approaches. In particular in this paper we propose to consider two methods: (i) a conventional Monte Carlo analysis, and (ii) a worst-case analysis, i.e., an optimization process to find an estimation of the true worst-case behaviour. Both techniques allow to verify that the design is robust enough to meet the system performance specification in case of uncertainties.

A case report of evaluating a large-scale health systems improvement project in an uncontrolled setting: a quality improvement initiative in KwaZulu-Natal, South Africa.

PubMed

Mate, Kedar S; Ngidi, Wilbroda Hlolisile; Reddy, Jennifer; Mphatswe, Wendy; Rollins, Nigel; Barker, Pierre

2013-11-01

New approaches are needed to evaluate quality improvement (QI) within large-scale public health efforts. This case report details challenges to large-scale QI evaluation, and proposes solutions relying on adaptive study design. We used two sequential evaluative methods to study a QI effort to improve delivery of HIV preventive care in public health facilities in three districts in KwaZulu-Natal, South Africa, over a 3-year period. We initially used a cluster randomised controlled trial (RCT) design. During the RCT study period, tensions arose between intervention implementation and evaluation design due to loss of integrity of the randomisation unit over time, pressure to implement changes across the randomisation unit boundaries, and use of administrative rather than functional structures for the randomisation. In response to this loss of design integrity, we switched to a more flexible intervention design and a mixed-methods quasiexperimental evaluation relying on both a qualitative analysis and an interrupted time series quantitative analysis. Cluster RCT designs may not be optimal for evaluating complex interventions to improve implementation in uncontrolled 'real world' settings. More flexible, context-sensitive evaluation designs offer a better balance of the need to adjust the intervention during the evaluation to meet implementation challenges while providing the data required to evaluate effectiveness. Our case study involved HIV care in a resource-limited setting, but these issues likely apply to complex improvement interventions in other settings.

Selection of actuator locations for static shape control of large space structures by heuristic integer programing

NASA Technical Reports Server (NTRS)

Haftka, R. T.; Adelman, H. M.

1984-01-01

Orbiting spacecraft such as large space antennas have to maintain a highly accurate space to operate satisfactorily. Such structures require active and passive controls to mantain an accurate shape under a variety of disturbances. Methods for the optimum placement of control actuators for correcting static deformations are described. In particular, attention is focused on the case were control locations have to be selected from a large set of available sites, so that integer programing methods are called for. The effectiveness of three heuristic techniques for obtaining a near-optimal site selection is compared. In addition, efficient reanalysis techniques for the rapid assessment of control effectiveness are presented. Two examples are used to demonstrate the methods: a simple beam structure and a 55m space-truss-parabolic antenna.

A Framework for the Design of Service Systems

NASA Astrophysics Data System (ADS)

Tan, Yao-Hua; Hofman, Wout; Gordijn, Jaap; Hulstijn, Joris

We propose a framework for the design and implementation of service systems, especially to design controls for long-term sustainable value co-creation. The framework is based on the software support tool e3-control. To illustrate the framework we use a large-scale case study, the Beer Living Lab, for simplification of customs procedures in international trade. The BeerLL shows how value co-creation can be achieved by reduction of administrative burden in international beer export due to electronic customs. Participants in the BeerLL are Heineken, IBM and Dutch Tax & Customs.

Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

PubMed Central

Wang, Yufei; McKay, James D.; Rafnar, Thorunn; Wang, Zhaoming; Timofeeva, Maria; Broderick, Peter; Zong, Xuchen; Laplana, Marina; Wei, Yongyue; Han, Younghun; Lloyd, Amy; Delahaye-Sourdeix, Manon; Chubb, Daniel; Gaborieau, Valerie; Wheeler, William; Chatterjee, Nilanjan; Thorleifsson, Gudmar; Sulem, Patrick; Liu, Geoffrey; Kaaks, Rudolf; Henrion, Marc; Kinnersley, Ben; Vallée, Maxime; LeCalvez-Kelm, Florence; Stevens, Victoria L.; Gapstur, Susan M.; Chen, Wei V.; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Krokan, Hans E.; Gabrielsen, Maiken Elvestad; Skorpen, Frank; Vatten, Lars; Njølstad, Inger; Chen, Chu; Goodman, Gary; Benhamou, Simone; Vooder, Tonu; Valk, Kristjan; Nelis, Mari; Metspalu, Andres; Lener, Marcin; Lubiński, Jan; Johansson, Mattias; Vineis, Paolo; Agudo, Antonio; Clavel-Chapelon, Francoise; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Khaw, Kay-Tee; Johansson, Mikael; Weiderpass, Elisabete; Tjønneland, Anne; Riboli, Elio; Lathrop, Mark; Scelo, Ghislaine; Albanes, Demetrius; Caporaso, Neil E.; Ye, Yuanqing; Gu, Jian; Wu, Xifeng; Spitz, Margaret R.; Dienemann, Hendrik; Rosenberger, Albert; Su, Li; Matakidou, Athena; Eisen, Timothy; Stefansson, Kari; Risch, Angela; Chanock, Stephen J.; Christiani, David C.; Hung, Rayjean J.; Brennan, Paul; Landi, Maria Teresa; Houlston, Richard S.; Amos, Christopher I.

2014-01-01

We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants of BRCA2-K3326X (rs11571833; odds ratio [OR]=2.47, P=4.74×10−20) and of CHEK2-I157T (rs17879961; OR=0.38 P=1.27×10−13). We also showed an association between common variation at 3q28 (TP63; rs13314271; OR=1.13, P=7.22×10−10) and lung adenocarcinoma previously only reported in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants having substantive effects on cancer risk from pre-existing GWAS data. PMID:24880342

Automatic detection of tweets reporting cases of influenza like illnesses in Australia

PubMed Central

2015-01-01

Early detection of disease outbreaks is critical for disease spread control and management. In this work we investigate the suitability of statistical machine learning approaches to automatically detect Twitter messages (tweets) that are likely to report cases of possible influenza like illnesses (ILI). Empirical results obtained on a large set of tweets originating from the state of Victoria, Australia, in a 3.5 month period show evidence that machine learning classifiers are effective in identifying tweets that mention possible cases of ILI (up to 0.736 F-measure, i.e. the harmonic mean of precision and recall), regardless of the specific technique implemented by the classifier investigated in the study. PMID:25870759

[Impact of screening and treatment of low systemic blood flow in the prevention of severe intraventricular haemorrhage and/or death in pre-term infants].

PubMed

Oulego Erroz, Ignacio; Alonso Quintela, Paula; Jiménez Gonzalez, Aquilina; Terroba Seara, Sandra; Rodríguez Blanco, Silvia; Rosón Varas, María; Castañón López, Leticia

2018-04-02

To assess the effect of a protocolised intervention for low systemic blood flow (SBF) in the occurrence of severe intraventricular haemorrhage (IVH) or death in pre-term infants. A study with a quasi-experimental design with retrospective controls was conducted on pre-term infants of less than 30weeks of gestational age, born between January 2016 and July 2017, who were consecutively included in the intervention period. The control cohort included pre-term infants (born between January 2013 and December 2015) matched by gestational age, birth weight, and gender (two controls for each case). The cases of low SBF diagnosed according to functional echocardiography during the study period received dobutamine (5-10μg/kg/min) for 48hours. The study included 29 cases (intervention period) and 54 controls (pre-intervention period). Ten out of 29 (34.5%) infants received dobutamine for low SBF during the intervention period, with 3/29 (10.3%) cases of severe IVH and/or death compared to 17/54 (31.5%) in the control cohort (p=.032). There was an independent association between the intervention and a decreased occurrence of severe IVH/death after adjusting for confounding factors both in the logistic regression model [OR 0.11 (95%CI: 0.01-0.65), p=.015], as well as in the sensitivity analysis using inverse probability of treatment weighting [OR 0.23 (95%CI: 0.09-0.56); p=.001]. In this study with retrospective controls, a protocolised screening, and treatment for low SBF was associated with a decreased occurrence of severe IVH or death in preterm infants. Large, adequately powered trials, are needed in order to determine whether postnatal interventions directed at low SBF can improve neurological outcomes. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Smoke-Free Airlines and the Role of Organized Labor: A Case Study

PubMed Central

Pan, Jocelyn; Barbeau, Elizabeth M.; Levenstein, Charles; Balbach, Edith D.

2005-01-01

Labor unions play an important role in debates about smoke-free worksites. We investigated the role of flight attendants and their unions in creating smoke-free air travel. We used case study methodology to search tobacco industry documents and labor union periodicals and to interview key informants (i.e., people identified as having first-hand information and experience in the campaign to make airlines smoke free). We then compared findings across these data sources. Tobacco industry strategies against the establishment of smoke-free worksites failed in the case of airlines, largely because of the efforts of flight attendants and their unions. Other factors contributed to the failure but likely would have been insufficient to derail industry efforts without strong stands by the flight attendants. This case illustrates the potential for successful partnerships between unions and tobacco control policy advocates when developing smoke-free worksite policies. PMID:15727966

Smoke-free airlines and the role of organized labor: a case study.

PubMed

Pan, Jocelyn; Barbeau, Elizabeth M; Levenstein, Charles; Balbach, Edith D

2005-03-01

Labor unions play an important role in debates about smoke-free worksites. We investigated the role of flight attendants and their unions in creating smoke-free air travel. We used case study methodology to search tobacco industry documents and labor union periodicals and to interview key informants (i.e., people identified as having first-hand information and experience in the campaign to make airlines smoke free). We then compared findings across these data sources. Tobacco industry strategies against the establishment of smoke-free worksites failed in the case of airlines, largely because of the efforts of flight attendants and their unions. Other factors contributed to the failure but likely would have been insufficient to derail industry efforts without strong stands by the flight attendants. This case illustrates the potential for successful partnerships between unions and tobacco control policy advocates when developing smoke-free worksite policies.

Clostridium difficile in the Military Population

DTIC Science & Technology

2016-08-05

association between race and infection . This is similar to the Buchner and associates case- control study; which noted an increase in occurrence of C...sustained within a hospital , additional persons infected with C. difficile are needed10. Acute appendicitis ranking first among diagnoses for hospitalized ...Buchner AM, Sonnenberg A. Epidemiology of Clostridium difficile infection in a large population of hospitalized US military veterans. Dig Dis Sci

Does Household Gun Access Increase the Risk of Attempted Suicide?: Evidence from a National Sample of Adolescents

ERIC Educational Resources Information Center

Watkins, Adam M.; Lizotte, Alan J.

2013-01-01

The aim of this research is to assess if home firearm access increases the risk of nonfatal suicidal attempts among adolescents. Such a gun focus has largely been limited to case-control studies on completed suicides. This line of research has found that household gun access increases the risk of suicide due to features of available firearms…

Trends in Segregation of Hispanic Students in Major School Districts Having Large Hispanic Enrollment. Ethnographic Case Studies, Volume II. Final Report.

ERIC Educational Resources Information Center

Aspira, Inc., New York, NY.

School desegregation did not lead to greater understanding of the Hispanic community by white educational personnel in two school districts analyzed to document the desegregation process and the impact of school desegregation on the Hispanic community. Each district was in a white-controlled, tri-ethnic community in its second year of successful…

Variable-Speed Induction Motor Drives for Aircraft Environmental Control Compressors

NASA Technical Reports Server (NTRS)

Mildice, J. W.; Hansen, I. G.; Schreiner, K. E.; Roth, M. E.

1996-01-01

New, more-efficient designs for aircraft jet engines are not capable of supplying the large quantities of bleed air necessary to provide pressurization and air conditioning for the environmental control systems (ECS) of the next generation of large passenger aircraft. System analysis and engineering have determined that electrically-driven ECS can help to maintain the improved fuel efficiencies; and electronic controllers and induction motors are now being developed in a NASA/NPD SBIR Program to drive both types of ECS compressors. Previous variable-speed induction motor/controller system developments and publications have primarily focused on field-oriented control, with large transient reserve power, for maximum acceleration and optimum response in actuator and robotics systems. The application area addressed herein is characterized by slowly-changing inputs and outputs, small reserve power capability for acceleration, and optimization for maximum efficiency. This paper therefore focuses on the differences between this case and the optimum response case, and shows the development of this new motor/controller approach. It starts with the creation of a new set of controller requirements. In response to those requirements, new control algorithms are being developed and implemented in an embedded computer, which is integrated into the motor controller closed loop. Buffered logic outputs are used to drive the power switches in a resonant-technology, power processor/motor-controller, at switching/resonant frequencies high enough to support efficient high-frequency induction motor operation at speeds up to 50,000-RPA

Does Exposure to Agricultural Chemicals Increase the Risk of Prostate Cancer among Farmers?

PubMed Central

Parent, Marie-Élise; Désy, Marie; Siemiatycki, Jack

2009-01-01

Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980’s, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. Subjects were interviewed about their occupation histories, and a team of industrial hygienists assigned their past exposures using a checklist of some 300 chemicals. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. We created a pool of 183 controls combining the patients with cancers at sites other than the prostate and the population controls. We then estimated the odds ratio for prostate cancer associated with exposure to each of 10 agricultural chemicals, i.e., pesticides, arsenic compounds, acetic acid, gasoline engine emissions, diesel engine emissions, polycyclic aromatic hydrocarbons from petroleum, lubricating oils and greases, alkanes with ≥18 carbons, solvents, and mononuclear aromatic hydrocarbons. Based on a model adjusting for age, ethnicity, education, and respondent status, there was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides [odds ratio (OR)=2.3, 95% confidence interval (CI) 1.1–5.1], as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions (OR=5.7, 95% CI 1.2–26.5). The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need further confirmation in larger samples. PMID:19753293

Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study.

PubMed

Yao, Song; Sucheston, Lara E; Millen, Amy E; Johnson, Candace S; Trump, Donald L; Nesline, Mary K; Davis, Warren; Hong, Chi-Chen; McCann, Susan E; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B; O'Connor, Tracey L; Ambrosone, Christine B

2011-02-28

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

PubMed Central

Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

2011-01-01

Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women. PMID:21386992

Large outbreak of verocytotoxin-producing Escherichia coli O157 infection in visitors to a petting farm in South East England, 2009

PubMed Central

IHEKWEAZU, C.; CARROLL, K.; ADAK, B.; SMITH, G.; PRITCHARD, G. C.; GILLESPIE, I. A.; VERLANDER, N. Q.; HARVEY-VINCE, L.; REACHER, M.; EDEGHERE, O.; SULTAN, B.; COOPER, R.; MORGAN, G.; KINROSS, P. T. N.; BOXALL, N. S.; IVERSEN, A.; BICKLER, G.

2012-01-01

SUMMARY In the summer of 2009, an outbreak of verocytotoxigenic Escherichia coli O157 (VTEC O157) was identified in visitors to a large petting farm in South East England. The peak attack rate was 6/1000 visitors, and highest in those aged <2 years (16/1000). We conducted a case-control study with associated microbiological investigations, on human, animal and environmental samples. We identified 93 cases; 65 primary, 13 secondary and 15 asymptomatic. Cases were more likely to have visited a specific barn, stayed for prolonged periods and be infrequent farm visitors. The causative organism was identified as VTEC O157 PT21/28 with the same VNTR profile as that isolated in faecal specimens from farm animals and the physical environment, mostly in the same barn. Contact with farm livestock, especially ruminants, should be urgently reviewed at the earliest suspicion of a farm-related VTEC O157 outbreak and appropriate risk management procedures implemented without delay. PMID:22093751

Large outbreak of verocytotoxin-producing Escherichia coli O157 infection in visitors to a petting farm in South East England, 2009.

PubMed

Ihekweazu, C; Carroll, K; Adak, B; Smith, G; Pritchard, G C; Gillespie, I A; Verlander, N Q; Harvey-Vince, L; Reacher, M; Edeghere, O; Sultan, B; Cooper, R; Morgan, G; Kinross, P T N; Boxall, N S; Iversen, A; Bickler, G

2012-08-01

In the summer of 2009, an outbreak of verocytotoxigenic Escherichia coli O157 (VTEC O157) was identified in visitors to a large petting farm in South East England. The peak attack rate was 6/1000 visitors, and highest in those aged <2 years (16/1000). We conducted a case-control study with associated microbiological investigations, on human, animal and environmental samples. We identified 93 cases; 65 primary, 13 secondary and 15 asymptomatic. Cases were more likely to have visited a specific barn, stayed for prolonged periods and be infrequent farm visitors. The causative organism was identified as VTEC O157 PT21/28 with the same VNTR profile as that isolated in faecal specimens from farm animals and the physical environment, mostly in the same barn. Contact with farm livestock, especially ruminants, should be urgently reviewed at the earliest suspicion of a farm-related VTEC O157 outbreak and appropriate risk management procedures implemented without delay.

Neurocognitive performance in family-based and case-control studies of schizophrenia

PubMed Central

Gur, Ruben C.; Braff, David L.; Calkins, Monica E.; Dobie, Dorcas J.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Gur, Raquel E.

2014-01-01

Background Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs. PMID:25432636

National outbreak of Salmonella serotype saintpaul infections: importance of Texas restaurant investigations in implicating jalapeño peppers.

PubMed

Mody, Rajal K; Greene, Sharon A; Gaul, Linda; Sever, Adrianne; Pichette, Sarah; Zambrana, Ingrid; Dang, Thi; Gass, Angie; Wood, René; Herman, Karen; Cantwell, Laura B; Falkenhorst, Gerhard; Wannemuehler, Kathleen; Hoekstra, Robert M; McCullum, Isaac; Cone, Amy; Franklin, Lou; Austin, Jana; Delea, Kristin; Behravesh, Casey Barton; Sodha, Samir V; Yee, J Christopher; Emanuel, Brian; Al-Khaldi, Sufian F; Jefferson, Val; Williams, Ian T; Griffin, Patricia M; Swerdlow, David L

2011-02-23

In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination.

National Outbreak of Salmonella Serotype Saintpaul Infections: Importance of Texas Restaurant Investigations in Implicating Jalapeño Peppers

PubMed Central

Mody, Rajal K.; Greene, Sharon A.; Gaul, Linda; Sever, Adrianne; Pichette, Sarah; Zambrana, Ingrid; Dang, Thi; Gass, Angie; Wood, René; Herman, Karen; Cantwell, Laura B.; Falkenhorst, Gerhard; Wannemuehler, Kathleen; Hoekstra, Robert M.; McCullum, Isaac; Cone, Amy; Franklin, Lou; Austin, Jana; Delea, Kristin; Behravesh, Casey Barton; Sodha, Samir V.; Yee, J. Christopher; Emanuel, Brian; Al-Khaldi, Sufian F.; Jefferson, Val; Williams, Ian T.; Griffin, Patricia M.; Swerdlow, David L.

2011-01-01

Background In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. Methodology/Principal Findings We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2–386; Restaurant B: mOR, 13; 95% CI 1.3–infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. Conclusions/Significance Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination. PMID:21373185

Possible association between different congenital abnormalities and use of different sulfonamides during pregnancy.

PubMed

Czeizel, Andrew E; Puhó, Erzsébet; Sørensen, Henrik T; Olsen, Jørn

2004-06-01

The objective of the study presented here was to check the debated human teratogenic potential of sulfonamide drugs. Five different sulfonamides such as sulfamethazine, sulfathiourea, sulfamethoxypyridazine, sulfamethoxydiazine and the combination of sulfamethazine-sulfathiourea-sulfamethoxypyridazine were differentiated. Cases with congenital abnormalities were compared with their matched controls without congenital abnormalities in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 newborn infants without any congenital abnormalities (control group), 163 (0.4%) had mothers who were treated with the sulfonamides studied during pregnancy, while of 22,843 cases with congenital abnormalities, 140 (0.6%) had mothers who were treated with the sulfonamides studied during pregnancy. The analysis of cases and matched controls indicated a higher rate of cardiovascular malformation (adjusted prevalence odds ratios [POR] with 95% CI: 3.5, 1.9-6.4) and clubfoot (adjusted POR with 95% CI: 2.6, 1.1-6.2) in infants born to mothers with sulfonamide treatment in the second and third months of pregnancy. The detailed analysis of different sulfonamides showed a possible association between cardiovascular malformations (adjusted POR with 95%; CI: 6.5, 2.6-15.9), particularly ventricular septal defect (17.1, 1.3-141.1) and sulfamethoxydiazine during the second and third months of pregnancy. In addition, a possible association was found between clubfoot and sulfathiourea, both during the entire pregnancy (adjusted POR with 95% CI: 2.3, 1.2-4.3) and in the second and third months of gestation (3.9, 1.1-13.8). Thus, maternal treatment of sulfamethoxydiazine may cause ventricular septal defect, while sulfathiourea may induce clubfoot; however, further studies are needed to verify or reject these associations.

Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study.

PubMed

Parent, Marie-Elise; Turner, Michelle C; Lavoué, Jérôme; Richard, Hugues; Figuerola, Jordi; Kincl, Laurel; Richardson, Lesley; Benke, Geza; Blettner, Maria; Fleming, Sarah; Hours, Martine; Krewski, Daniel; McLean, David; Sadetzki, Siegal; Schlaefer, Klaus; Schlehofer, Brigitte; Schüz, Joachim; Siemiatycki, Jack; van Tongeren, Martie; Cardis, Elisabeth

2017-08-25

Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.

Controls on Water Use for Thermoelectric Generation: Case Study Texas, U.S.

PubMed Central

2013-01-01

Large-scale U.S. dependence on thermoelectric (steam electric) generation requiring water for cooling underscores the need to understand controls on this water use. The study objective was to quantify water consumption and withdrawal for thermoelectric generation, identifying controls, using Texas as a case study. Water consumption for thermoelectricity in Texas in 2010 totaled ∼0.43 million acre feet (maf; 0.53 km3), accounting for ∼4% of total state water consumption. High water withdrawals (26.2 maf, 32.3 km3) mostly reflect circulation between ponds and power plants, with only two-thirds of this water required for cooling. Controls on water consumption include (1) generator technology/thermal efficiency and (2) cooling system, resulting in statewide consumption intensity for natural gas combined cycle generators with mostly cooling towers (0.19 gal/kWh) being 63% lower than that of traditional coal, nuclear, or natural gas steam turbine generators with mostly cooling ponds (0.52 gal/kWh). The primary control on water withdrawals is cooling system, with ∼2 orders of magnitude lower withdrawals for cooling towers relative to once-through ponds statewide. Increases in natural gas combined cycle plants with cooling towers in response to high production of low-cost natural gas has greatly reduced water demand for thermoelectric cooling since 2000. PMID:23937226

Controls on water use for thermoelectric generation: case study Texas, US.

PubMed

Scanlon, Bridget R; Reedy, Robert C; Duncan, Ian; Mullican, William F; Young, Michael

2013-10-01

Large-scale U.S. dependence on thermoelectric (steam electric) generation requiring water for cooling underscores the need to understand controls on this water use. The study objective was to quantify water consumption and withdrawal for thermoelectric generation, identifying controls, using Texas as a case study. Water consumption for thermoelectricity in Texas in 2010 totaled ∼0.43 million acre feet (maf; 0.53 km(3)), accounting for ∼4% of total state water consumption. High water withdrawals (26.2 maf, 32.3 km(3)) mostly reflect circulation between ponds and power plants, with only two-thirds of this water required for cooling. Controls on water consumption include (1) generator technology/thermal efficiency and (2) cooling system, resulting in statewide consumption intensity for natural gas combined cycle generators with mostly cooling towers (0.19 gal/kWh) being 63% lower than that of traditional coal, nuclear, or natural gas steam turbine generators with mostly cooling ponds (0.52 gal/kWh). The primary control on water withdrawals is cooling system, with ∼2 orders of magnitude lower withdrawals for cooling towers relative to once-through ponds statewide. Increases in natural gas combined cycle plants with cooling towers in response to high production of low-cost natural gas has greatly reduced water demand for thermoelectric cooling since 2000.

Operational and Strategic Controlling Tools in Microenterprises - Case Study

NASA Astrophysics Data System (ADS)

Konsek-Ciechońska, Justyna

2017-12-01

Globalisation and increasing requirements of the environment cause the executives and supervisors to search for more and more perfect solutions, allowing them to streamline and improve the effectiveness of company operations. One of such tools, used more and more often, is controlling, the role of which has substantially increased in the recent years. It is already implemented not only in large companies with foreign capital, but also in increasingly smaller entities, which begin to notice the positive effects of the implications of the principles and tools of controlling - both operational and strategic. The purpose of the article is to demonstrate the practical side of controlling tools that can be used for the purposes of operations conducted by microenterprises.

Sustainer electric propulsion system application for spacecraft attitude control

NASA Astrophysics Data System (ADS)

Obukhov, V. A.; Pokryshkin, A. I.; Popov, G. A.; Yashina, N. V.

2010-07-01

Application of electric propulsion system (EPS) requires spacecraft (SC) equipping with large solar panels (SP) for the power supply to electric propulsions. This makes the problem of EPS-equipped SC control at the insertion stage more difficult to solve than in the case of SC equipped with chemical engines, because in addition to the SC attitude control associated with the mission there appears necessity in keeping SP orientation to Sun that is necessary for generation of electric power sufficient for the operation of service systems, purpose-oriented equipment, and EPS. The theoretical study of the control problem is the most interesting for a non-coplanar transfer from high elliptic orbit (HEO) to geostationary orbit (GSO).

Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.

PubMed

Nelson, Elliot C; Lynskey, Michael T; Heath, Andrew C; Wray, Naomi; Agrawal, Arpana; Shand, Fiona L; Henders, Anjali K; Wallace, Leanne; Todorov, Alexandre A; Schrage, Andrew J; Madden, Pamela A F; Degenhardt, Louisa; Martin, Nicholas G; Montgomery, Grant W

2014-01-01

Genes encoding the opioid receptors (OPRM1, OPRD1 and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes and yielded inconsistent results. Participants for the current investigation included 1459 heroin-dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls) and 531 controls ascertained from economically disadvantaged neighborhoods in proximity to the maintenance clinics. A total of 136 OPRM1, OPRD1 and OPRK1 SNPs were genotyped in this sample. After controlling for admixture with principal components analysis, our comparison of cases to non-dependent controls found four OPRD1 SNPs in fairly high linkage disequilibrium for which adjusted P values remained significant (e.g. rs2236857; OR 1.25; P=2.95×10(-4) ) replicating a previously reported association. A post hoc analysis revealed that the two SNP (rs2236857 and rs581111) GA haplotype in OPRD1 is associated with greater risk (OR 1.68; P=1.41×10(-5) ). No OPRM1 or OPRK1 SNPs reached more than nominal significance. Comparisons of cases to neighborhood controls reached only nominal significance. Our results replicate a prior report providing strong evidence implicating OPRD1 SNPs and, in particular, the two SNP (rs2236857 and rs581111) GA haplotype in liability for heroin dependence. Support was not found for similar association involving either OPRM1 or OPRK1 SNPs. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering.

PubMed

Roy, Monika; Benedict, Kaitlin; Deak, Eszter; Kirby, Miles A; McNiel, Jena T; Sickler, Carrie J; Eckardt, Eileen; Marx, Ruth K; Heffernan, Richard T; Meece, Jennifer K; Klein, Bruce S; Archer, John R; Theurer, Joan; Davis, Jeffrey P; Park, Benjamin J

2013-09-01

Blastomycosis is a potentially life-threatening infection caused by the soil-based dimorphic fungus Blastomyces dermatitidis, which is endemic throughout much of the Midwestern United States. We investigated an increase in reported cases of blastomycosis that occurred during 2009-2010 in Marathon County, Wisconsin. Case detection was conducted using the Wisconsin Electronic Disease Surveillance System (WEDSS). WEDSS data were used to compare demographic, clinical, and exposure characteristics between outbreak-related and historical case patients, and to calculate blastomycosis incidence rates. Because initial mapping of outbreak case patients' homes and recreational sites demonstrated unusual neighborhood and household case clustering, we conducted a 1:3 matched case-control study to identify factors associated with being in a geographic cluster. Among the 55 patients with outbreak-related cases, 33 (70%) were hospitalized, 2 (5%) died, 30 (55%) had cluster-related cases, and 20 (45%) were Hmong. The overall incidence increased significantly since 2005 (average 11% increase per year, P < .001), and incidence during 2005-2010 was significantly higher among Asians than non-Asians (2010 incidence: 168 vs 13 per 100 000 population). Thirty of the outbreak cases grouped into 5 residential clusters. Outdoor activities were not risk factors for blastomycosis among cluster case patients or when comparing outbreak cases to historical cases. This outbreak of blastomycosis, the largest ever reported, was characterized by unique household and neighborhood clustering likely related to multifocal environmental sources. The reasons for the large number of Hmong affected are unclear, but may involve genetic predisposition.

A recurrent 16p12.1 microdeletion suggests a two-hit model for severe developmental delay

PubMed Central

Girirajan, Santhosh; Rosenfeld, Jill A.; Cooper, Gregory M.; Antonacci, Francesca; Siswara, Priscillia; Itsara, Andy; Vives, Laura; Walsh, Tom; McCarthy, Shane E.; Baker, Carl; Mefford, Heather C.; Kidd, Jeffrey M.; Browning, Sharon R.; Browning, Brian L.; Dickel, Diane E.; Levy, Deborah L.; Ballif, Blake C.; Platky, Kathryn; Farber, Darren M.; Gowans, Gordon C.; Wetherbee, Jessica J.; Asamoah, Alexander; Weaver, David D.; Mark, Paul R.; Dickerson, Jennifer; Garg, Bhuwan P.; Ellingwood, Sara A.; Smith, Rosemarie; Banks, Valerie C.; Smith, Wendy; McDonald, Marie T.; Hoo, Joe J.; French, Beatrice N.; Hudson, Cindy; Johnson, John P.; Ozmore, Jillian R.; Moeschler, John B.; Surti, Urvashi; Escobar, Luis F.; El-Kechen, Dima; Gorski, Jerome L.; Kussman, Jennifer; Salbert, Bonnie; Lacassie, Yves; Biser, Alisha; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Deardorff, Matthew A.; Shaikh, Tamim H.; Haan, Eric; Friend, Kathryn L.; Fichera, Marco; Romano, Corrado; Gécz, Jozef; deLisi, Lynn E.; Sebat, Jonathan; King, Mary-Claire; Shaffer, Lisa G.; Eichler, Evan E.

2010-01-01

We report the identification of a recurrent 520-kbp 16p12.1 microdeletion significantly associated with childhood developmental delay. The microdeletion was detected in 20/11,873 cases vs. 2/8,540 controls (p=0.0009, OR=7.2) and replicated in a second series of 22/9,254 cases vs. 6/6,299 controls (p=0.028, OR=2.5). Most deletions were inherited with carrier parents likely to manifest neuropsychiatric phenotypes (p=0.037, OR=6). Probands were more likely to carry an additional large CNV when compared to matched controls (10/42 cases, p=5.7×10-5, OR=6.65). Clinical features of cases with two mutations were distinct from and/or more severe than clinical features of patients carrying only the co-occurring mutation. Our data suggest a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity suggests that this two-hit model may be more generally applicable to neuropsychiatric disease. PMID:20154674

Evaluation of US rear underride guard regulation for large trucks using real-world crashes.

PubMed

Brumbelow, Matthew L; Blanar, Laura

2010-11-01

Current requirements for rear underride guards on large trucks are set by the National Highway Traffic Safety Administration in Federal Motor Vehicle Safety Standards (FMVSS) 223 and 224. The standards have been in place since 1998, but their adequacy has not been evaluated apart from two series of controlled crash tests. The current study used detailed reviews of real-world crashes from the Large Truck Crash Causation Study to assess the ability of guards that comply with certain aspects of the regulation to mitigate passenger vehicle underride. It also evaluated the dangers posed by underride of large trucks that are exempt from guard requirements. For the 115 cases meeting the inclusion criteria, coded data, case narratives, photographs, and measurements were used to examine the interaction between study vehicles. The presence and type of underride guard was determined, and its performance in mitigating underride was categorized. Overall, almost one-half of the passenger vehicles had underride damage classified as severe or catastrophic. These vehicles accounted for 23 of the 28 in which occupants were killed. For the cases involving trailers with underride guards compliant with one or both FMVSS, guard deformation or complete failure was frequent and most commonly due to weak attachments, buckling of the trailer chassis, or bending of the lateral end of the guard under narrow overlap loading. Most of the truck units studied qualified for at least one of the FMVSS exemptions. The two largest groups were trailers with small wheel setbacks and single-unit straight trucks. Dump trucks represented a particularly hazardous category of straight truck. The current study suggests several weaknesses in the rear underride guard regulation. The standard allows too much ground clearance, the quasi-static test conditions allow guard designs that fail in narrow overlap crashes, and certifying guards independent of trailers leads to systems with inadequate attachment and chassis strength. Additionally, the regulation should be expanded to cover a higher percentage of the large truck fleet.

Evidence of Recessive Alzheimer Disease Loci in a Caribbean Hispanic Data Set

PubMed Central

Ghani, Mahdi; Sato, Christine; Lee, Joseph H.; Reitz, Christiane; Moreno, Danielle; Mayeux, Richard; St George-Hyslop, Peter; Rogaeva, Ekaterina

2014-01-01

IMPORTANCE The search for novel Alzheimer disease (AD) genes or pathologic mutations within known AD loci is ongoing. The development of array technologies has helped to identify rare recessive mutations among long runs of homozygosity (ROHs), in which both parental alleles are identical. Caribbean Hispanics are known to have an elevated risk for AD and tend to have large families with evidence of inbreeding. OBJECTIVE To test the hypothesis that the late-onset AD in a Caribbean Hispanic population might be explained in part by the homozygosity of unknown loci that could harbor recessive AD risk haplotypes or pathologic mutations. DESIGN We used genome-wide array data to identify ROHs (>1 megabase) and conducted global burden and locus-specific ROH analyses. SETTING A whole-genome case-control ROH study. PARTICIPANTS A Caribbean Hispanic data set of 547 unrelated cases (48.8% with familial AD) and 542 controls collected from a population known to have a 3-fold higher risk of AD vs non-Hispanics in the same community. Based on a Structure program analysis, our data set consisted of African Hispanic (207 cases and 192 controls) and European Hispanic (329 cases and 326 controls) participants. EXPOSURE Alzheimer disease risk genes. MAIN OUTCOMES AND MEASURES We calculated the total and mean lengths of the ROHs per sample. Global burden measurements among autosomal chromosomes were investigated in cases vs controls. Pools of overlapping ROH segments (consensus regions) were identified, and the case to control ratio was calculated for each consensus region. We formulated the tested hypothesis before data collection. RESULTS In total, we identified 17 137 autosomal regions with ROHs. The mean length of the ROH per person was significantly greater in cases vs controls (P = .0039), and this association was stronger with familial AD (P = .0005). Among the European Hispanics, a consensus region at the EXOC4 locus was significantly associated with AD even after correction for multiple testing (empirical P value 1 [EMP1], .0001; EMP2, .002; 21 AD cases vs 2 controls). Among the African Hispanic subset, the most significant but nominal association was observed for CTNNA3, a well-known AD gene candidate (EMP1, .002; 10 AD cases vs 0 controls). CONCLUSIONS AND RELEVANCE Our results show that ROHs could significantly contribute to the etiology of AD. Future studies would require the analysis of larger, relatively inbred data sets that might reveal novel recessive AD genes. The next step is to conduct sequencing of top significant loci in a subset of samples with overlapping ROHs. PMID:23978990

The Effectiveness of Lecture-Integrated, Web-Supported Case Studies in Large Group Teaching

ERIC Educational Resources Information Center

Azzawi, May; Dawson, Maureen M.

2007-01-01

The effectiveness of lecture-integrated and web-supported case studies in supporting a large and academically diverse group of undergraduate students was evaluated in the present study. Case studies and resource (web)-based learning were incorporated as two complementary interactive learning strategies into the traditional curriculum. A truncated…

Handedness and the risk of glioma.

PubMed

Miller, Briana; Peeri, Noah C; Nabors, Louis Burt; Creed, Jordan H; Thompson, Zachary J; Rozmeski, Carrie M; LaRocca, Renato V; Chowdhary, Sajeel; Olson, Jeffrey J; Thompson, Reid C; Egan, Kathleen M

2018-05-01

Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case-control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.

Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct.

PubMed

Strong, C; Anderton, B H; Perry, R H; Perry, E K; Ince, P G; Lovestone, S

1995-01-01

The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. AD pathology is characterised by both amyloid deposition and abnormal phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic processes of senile plaques, and also in neuropil threads dispersed throughout the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low density of tangles, and large amounts of PHF-tau were present in AD cases. This study demonstrates that abnormally phosphorylated PHF-tau is only present where tangles are found and not in SDLT cases without tangles or with only occasional tangles. It is concluded that Lewy body dementias are distinct at a molecular level from AD.

A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006.

PubMed

Kendall, G M; Little, M P; Wakeford, R; Bunch, K J; Miles, J C H; Vincent, T J; Meara, J R; Murphy, M F G

2013-01-01

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

Absenteeism due to mental health problems and systems for return to work: an internet-based unmatched case-control study.

PubMed

Doki, Shotaro; Sasahara, Shinichiro; Hirai, Yasuhito; Oi, Yuichi; Matsuzaki, Ichiyo

2016-11-01

The aim of this study was to investigate the risk factors for absenteeism due to mental health problems with regard to company characteristics and systems for return to work in Japan. This was an Internet-based unmatched case-control study. Two hundred and fifty-eight workers who experienced over 28 days of sick leave due to mental health problems (cases) and 258 workers who have not taken sick leave (controls) were recruited. Company characteristics and the awareness and presence of systems for return to work were analysed as indicators of absenteeism. A total of 501 workers were included in the analysis. Females were less likely to experience absenteeism when adjustments were made for both the awareness and presence of systems [odds ratio (OR) = 0.51 and 0.41, respectively]. Large companies showed an increased risk of having absentee workers than small companies. The awareness of a gradual resumption system and the presence of a sick pay system were related to absenteeism (OR = 2.75 and 2.40, respectively). The awareness and presence of systems for return to work are related to the long-term absenteeism. The predictors of sex and company size are also related to the experience of the long-term absenteeism. To understand the effect of systems for return to work on absenteeism due to mental problems, further studies are needed.

Associations between trans fatty acid consumption and colon cancer among Whites and African Americans in the North Carolina colon cancer study I.

PubMed

Vinikoor, Lisa C; Satia, Jessie A; Schroeder, Jane C; Millikan, Robert C; Martin, Christopher F; Ibrahim, Joseph G; Sandler, Robert S

2009-01-01

Disparities in incidence and mortality rates of colon cancer exist between Whites and African Americans. Prior studies examined the association between trans fatty acid consumption and colorectal cancer, but none assessed this possible relationship within a large study population of African Americans and Whites. Using data from a population-based, case-control study in North Carolina, we investigated this association with attention to possible racial differences. Cases and matched controls were queried on demographic characteristics, lifestyle factors, medical history, and diet. Cases reported higher daily consumption (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5) compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy-adjusted trans fatty acid consumption was not associated with colon cancer. Compared to participants in the lowest quartile of consumption, those in the highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval 0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African Americans. No association was found between increased consumption of trans fatty acid and specific tumor location (proximal or distal colon). In conclusion, trans fatty acid consumption is not associated with colon cancer and does not contribute to disparities in colon cancer rates.

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV--a case-control study from eastern Uganda.

PubMed

Muhamadi, Lubega; Tumwesigye, Nazarius Mbona; Kadobera, Daniel; Marrone, Gaetano; Wabwire-Mangen, Fred; Pariyo, George; Peterson, Stefan; Ekström, Anna Mia

2011-01-01

Although WHO recommends starting antiretroviral treatment at a CD4 count of 350 cells/[µ]L, many Ugandan districts still struggle with large proportions of clients initiating ART very late at CD4<50 cells/[µ]L. This study seeks to establish crucial risk factors for very late ART initiation in eastern Uganda. All adult HIV-infected clients on ART in Iganga who enrolled between 2005 and 2009 were eligible for this case-control study. Clients who started ART at CD4 cell count of <50 cells/[µ]L (very late initiators) were classified as cases and 50-200 cells/[µ]L (late initiators) as control subjects. A total of 152 cases and 202 controls were interviewed. Multivariate analyses were performed to calculate adjusted odds ratios and 95% confidence intervals. Reported health system-related factors associated with very late ART initiation were stock-outs of antiretroviral drugs stock-outs (affecting 70% of the cases and none of the controls), competition from traditional/spiritual healers (AOR 7.8, 95 CI% 3.7-16.4), and lack of pre-ARV care (AOR 4.6, 95% CI: 2.3-9.3). Men were 60% more likely and subsistence farmers six times more likely (AOR 6.3, 95% CI: 3.1-13.0) to initiate ART very late. Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility. ART services should be more affordable, accessible and user-friendly to make them more attractive than traditional healers.

Safety Case Development as an Information Modelling Problem

NASA Astrophysics Data System (ADS)

Lewis, Robert

This paper considers the benefits from applying information modelling as the basis for creating an electronically-based safety case. It highlights the current difficulties of developing and managing large document-based safety cases for complex systems such as those found in Air Traffic Control systems. After a review of current tools and related literature on this subject, the paper proceeds to examine the many relationships between entities that can exist within a large safety case. The paper considers the benefits to both safety case writers and readers from the future development of an ideal safety case tool that is able to exploit these information models. The paper also introduces the idea that the safety case has formal relationships between entities that directly support the safety case argument using a methodology such as GSN, and informal relationships that provide links to direct and backing evidence and to supporting information.

Hemoglobin E and Glucose-6-Phosphate Dehydrogenase Deficiency and Plasmodium falciparum Malaria in the Chittagong Hill Districts of Bangladesh.

PubMed

Shannon, Kerry L; Ahmed, Sabeena; Rahman, Hafizur; Prue, Chai S; Khyang, Jacob; Ram, Malathi; Haq, M Zahirul; Chowdhury, Ashish; Akter, Jasmin; Glass, Gregory E; Shields, Timothy; Nyunt, Myaing M; Khan, Wasif A; Sack, David A; Sullivan, David J

2015-08-01

Hemoglobin E is largely confined to south and southeast Asia. The association between hemoglobin E (HbE) and malaria is less clear than that of hemoglobin S and C. As part of a malaria study in the Chittagong Hill Districts of Bangladesh, an initial random sample of 202 individuals showed that 39% and 49% of Marma and Khyang ethnic groups, respectively, were positive for either heterozygous or homozygous hemoglobin E. In this group, 6.4% were also found to be severely deficient and 35% mildly deficient for glucose-6-phosphate dehydrogenase (G6PD). In a separate Plasmodium falciparum malaria case-uninfected control study, the odds of having homozygous hemoglobin E (HbEE) compared with normal hemoglobin (HbAA) were higher among malaria cases detected by passive surveillance than age and location matched uninfected controls (odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.07-46.93). The odds of heterozygous hemoglobin E (HbAE) compared with HbAA were similar between malaria cases and uninfected controls (OR = 0.71, 95% CI = 0.42-1.19). No association by hemoglobin type was found in the initial parasite density or the proportion parasite negative after 2 days of artemether/lumefantrine treatment. HbEE, but not HbAE status was associated with increased passive case detection of malaria. © The American Society of Tropical Medicine and Hygiene.

A robust and high-performance queue management controller for large round trip time networks

NASA Astrophysics Data System (ADS)

Khoshnevisan, Ladan; Salmasi, Farzad R.

2016-05-01

Congestion management for transmission control protocol is of utmost importance to prevent packet loss within a network. This necessitates strategies for active queue management. The most applied active queue management strategies have their inherent disadvantages which lead to suboptimal performance and even instability in the case of large round trip time and/or external disturbance. This paper presents an internal model control robust queue management scheme with two degrees of freedom in order to restrict the undesired effects of large and small round trip time and parameter variations in the queue management. Conventional approaches such as proportional integral and random early detection procedures lead to unstable behaviour due to large delay. Moreover, internal model control-Smith scheme suffers from large oscillations due to the large round trip time. On the other hand, other schemes such as internal model control-proportional integral and derivative show excessive sluggish performance for small round trip time values. To overcome these shortcomings, we introduce a system entailing two individual controllers for queue management and disturbance rejection, simultaneously. Simulation results based on Matlab/Simulink and also Network Simulator 2 (NS2) demonstrate the effectiveness of the procedure and verify the analytical approach.

Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease.

PubMed

Lygirou, Vasiliki; Latosinska, Agnieszka; Makridakis, Manousos; Mullen, William; Delles, Christian; Schanstra, Joost P; Zoidakis, Jerome; Pieske, Burkert; Mischak, Harald; Vlahou, Antonia

2018-04-17

Cardiovascular disease (CVD) describes the pathological conditions of the heart and blood vessels. Despite the large number of studies on CVD and its etiology, its key modulators remain largely unknown. To this end, we performed a comprehensive proteomic analysis of blood plasma, with the scope to identify disease-associated changes after placing them in the context of existing knowledge, and generate a well characterized dataset for further use in CVD multi-omics integrative analysis. LC-MS/MS was employed to analyze plasma from 32 subjects (19 cases of various CVD phenotypes and 13 controls) in two steps: discovery (13 cases and 8 controls) and test (6 cases and 5 controls) set analysis. Following label-free quantification, the detected proteins were correlated to existing plasma proteomics datasets (plasma proteome database; PPD) and functionally annotated (Cytoscape, Ingenuity Pathway Analysis). Differential expression was defined based on identification confidence (≥ 2 peptides per protein), statistical significance (Mann-Whitney p value ≤ 0.05) and a minimum of twofold change. Peptides detected in at least 50% of samples per group were considered, resulting in a total of 3796 identified proteins (838 proteins based on ≥ 2 peptides). Pathway annotation confirmed the functional relevance of the findings (representation of complement cascade, fibrin clot formation, platelet degranulation, etc.). Correlation of the relative abundance of the proteins identified in the discovery set with their reported concentrations in the PPD was significant, confirming the validity of the quantification method. The discovery set analysis revealed 100 differentially expressed proteins between cases and controls, 39 of which were verified (≥ twofold change) in the test set. These included proteins already studied in the context of CVD (such as apolipoprotein B, alpha-2-macroglobulin), as well as novel findings (such as low density lipoprotein receptor related protein 2 [LRP2], protein SZT2) for which a mechanism of action is suggested. This proteomic study provides a comprehensive dataset to be used for integrative and functional studies in the field. The observed protein changes reflect known CVD-related processes (e.g. lipid uptake, inflammation) but also novel hypotheses for further investigation including a potential pleiotropic role of LPR2 but also links of SZT2 to CVD.

Polymorphism of SMAD7 gene (rs2337104) and risk of colorectal cancer in an Iranian population: a case-control study

PubMed Central

Akbari, Zahra; Safari-Alighiarloo, Nahid; Taleghani, Mohammad Yaghoob; Mirfakhar, Farzaneh Sadat; Asadzadeh Aghdaei, Hamid; Vahedi, Mohsen; Irani Shemirani, Atena; Nazemalhosseini-Mojarad, Ehsan; Zali, Mohammad Reza

2014-01-01

Aim: The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 (Mothers Against Decantaplegic Homolog 7) gene (rs2337104) on the risk of colorectal cancer (CRC) and clinicopathological features in an Iranian population. Background: SMAD7 has been identified as an antagonist of transforming growth factor beta (TGF-b)-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. Patients and methods: This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinicopathological features was investigated. Results: Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism (rs2337104) and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls (OR=1.705, 95% CI= 0.916–3.172). Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients (P>0.05). Conclusion: For the first time, this study results revealed that this SMAD7 polymorphism couldn’t be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results. PMID:25289133

Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank.

PubMed

Gan, Wei; Walters, Robin G; Holmes, Michael V; Bragg, Fiona; Millwood, Iona Y; Banasik, Karina; Chen, Yiping; Du, Huaidong; Iona, Andri; Mahajan, Anubha; Yang, Ling; Bian, Zheng; Guo, Yu; Clarke, Robert J; Li, Liming; McCarthy, Mark I; Chen, Zhengming

2016-07-01

Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations. The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a population-based China Kadoorie Biobank (CKB) study of 93,000 Chinese adults, including >7,100 diabetes cases. Association signals were directionally consistent between CKB and the original discovery GWAS: of 56 variants passing quality control, 48 showed the same direction of effect (binomial test, p = 2.3 × 10(-8)). We observed a consistent overall trend towards lower risk variant effect sizes in CKB than in case-control samples of GWAS meta-analyses (mean 19-22% decrease in log odds, p ≤ 0.0048), likely to reflect correction of both 'winner's curse' and spectrum bias effects. The association with risk of diabetes of a genetic risk score, based on lead variants at 25 loci considered to act through beta cell function, demonstrated significant interactions with several measures of adiposity (BMI, waist circumference [WC], WHR and percentage body fat [PBF]; all p interaction < 1 × 10(-4)), with a greater effect being observed in leaner adults. Our study provides further evidence of shared genetic architecture for type 2 diabetes between Europeans and East Asians. It also indicates that even very large GWAS meta-analyses may be vulnerable to substantial inflation of effect size estimates, compared with those observed in large-scale population-based cohort studies. Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access .

Neural control and transient analysis of the LCL-type resonant converter

NASA Astrophysics Data System (ADS)

Zouggar, S.; Nait Charif, H.; Azizi, M.

2000-07-01

This paper proposes a generalised inverse learning structure to control the LCL converter. A feedforward neural network is trained to act as an inverse model of the LCL converter then both are cascaded such that the composed system results in an identity mapping between desired response and the LCL output voltage. Using the large signal model, we analyse the transient output response of the controlled LCL converter in the case of large variation of the load. The simulation results show the efficiency of using neural networks to regulate the LCL converter.

Clostridium perfringens in London, July 2009: two weddings and an outbreak.

PubMed

Eriksen, J; Zenner, D; Anderson, S R; Grant, K; Kumar, D

2010-06-24

Food poisoning outbreaks caused by Clostridium perfringens enterotoxin occur occasionally in Europe but have become less common in recent years. This paper presents the microbiological and epidemiological results of a large C. perfringens outbreak occurring simultaneously at two weddings that used the same caterer. The outbreak involved several London locations and required coordination across multiple agencies. A case-control study (n=134) was carried out to analyse possible associations between the food consumed and becoming ill. Food, environmental and stool samples were tested for common causative agents, including enterotoxigenic C. perfringens. The clinical presentation and the epidemiological findings were compatible with C. perfringens food poisoning and C. perfringens enterotoxin was detected in stool samples from two cases. The case-control study found statistically significant associations between becoming ill and eating either a specific chicken or lamb dish prepared by the same food handler of the implicated catering company. A rapid outbreak investigation with preliminary real-time results and the successful collaboration between the agencies and the caterer led to timely identification and rectification of the failures in the food handling practices.

Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003.

PubMed

Tavani, Alessandra; La Vecchia, Carlo

2004-10-01

The literature from 1990 to 2003 on the relation between coffee, decaffeinated coffee, tea and colorectal cancer risk has been reviewed. For the relation with coffee, three cohort (517 total cases) and nine case-control studies (7555 cases) analysed colon cancer; three cohort (307 cases) and four case-control studies (2704 cases) rectal cancer; six case-control studies (854 cases) colorectal cancer. For colon cancer most case-control studies found risk estimates below unity; the results are less clear for cohort studies. No relation emerged for rectal cancer. A meta-analysis, including five cohort and twelve case-control studies, reported a pooled relative risk of 0.76 (significant). Any methodological artefact is unlikely to account for the consistent inverse association in different countries and settings. Plausible biological explanations include coffee-related reductions of cholesterol, bile acids and neutral sterol secretion in the colon; antimutagenic properties of selected coffee components; increased colonic motility. Decaffeinated coffee was not related to either colon or rectal cancer in three case-control studies. No overall association between tea and either colon or rectal cancer risk emerged in seven cohort (1756 total cases of colon, 759 of rectal and 60 of colorectal cancer) and 12 case-control studies (8058 cases of colon, 4865 of rectal, 604 of colorectal cancer).

GSTT1 and GSTM1 gene polymorphisims in sarcoidosis.

PubMed

Coskun, Funda; Karkucak, Mutlu; Yilmaz, Dilber; Yakut, Tahsin; Uzaslan, Esra

2016-10-07

Sarcoidosis is a granulomatous disease of unknown cause, which affects all systems, especially the lungs and the lymphatic system. Genetic and environmental factors are held accountable for the etiology. Based on the general opinion, sarcoidosis develops after exposure to a specific environmental agent by genetically susceptible individuals.  The present study aimed to evaluate the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in the patients with sarcoidosis. The present study included 78 patients; 38 patients with histopathologically verified sarcoidosis and 40 control subjects. Multiplex PCR method was used to determine the GSTT1 and GSTM1 gene polymorphisms. The genotype was determined based on the bands formed in the agarose gel electrophoresis. The statistical analysis was done using the chi-square test. The positive/negative genotype rates were 79%/21% and 53%/47%, respectively in the case group for the GSTT1 and GSTM1 gene polymorphisms, whereas the positive/negative genotype rates were 77%/23% and 55%/45% in the control group. There was no statistically significant difference in the positive and negative genotypes compared with the case group and the control group for the GSTT1 and GSTM1 gene polymorphisms (p > 0.05). The results from the present study suggest that there is not any association with the control group for the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in patients with sarcoidosis, and this result should be supported by large-scale studies because of the limited number of cases in the present study.

HIV and Childhood Disability: A Case-Controlled Study at a Paediatric Antiretroviral Therapy Centre in Lilongwe, Malawi

PubMed Central

Devendra, Akash; Makawa, Atupele; Kazembe, Peter N.; Calles, Nancy R.; Kuper, Hannah

2013-01-01

Background As paediatric antiretroviral therapy (ART) is rapidly scaled up in Southern Africa, Human Immunodeficiency Virus (HIV) infection is becoming a chronic illness. Children growing up with HIV may begin to encounter disabilities. The relationship between HIV, disability and the need for rehabilitation has added an additional element that needs to be addressed by paediatric HIV treatment programmes. Study Objectives 1) Estimate the prevalence of disabilities in HIV-infected and HIV-uninfected children in Lilongwe, Malawi. 2) Examine types of disability and associated clinical and socio-demographic factors. 3) Identify needs, opportunities and barriers for rehabilitation in Malawi. Methods A case-controlled study of 296 HIV-infected children aged 2–9 years attending an ART centre in Lilongwe (cases) and their uninfected siblings (controls) was conducted. Disability was assessed using the WHO Ten Question Screen (TQS). Socio-demographic and clinical data were collected using a parent-proxy questionnaire and medical records. Results Of 296 case and control pairs recruited, 33% (98) versus 7% (20) screened positive for a disability (OR 8.4, 4.4–15.7) respectively. Of these 98 HIV-infected cases, 6%, 36%, 33%, 53%, 46% and 6% had a vision, hearing; physical, learning/comprehension, speech or seizure-related disability respectively and 51% had multiple coexisting disabilities. HIV-infected cases with a disability were more likely to be WHO stage III or IV at enrolment (71% vs. 52%, OR 2.7, 1.5–4.2), to have had TB (58% vs. 39%, OR 2.3, 1.4–3.8) and to have below-average school grades (18% vs. 2%, OR 11.1, 2.2–54.6) than those without. Sixty-seven percent of cases with a disability had never attended any rehabilitative service. Twenty-nine percent of caregivers reported facing stigma and discrimination because of the child’s disability. Conclusion This study reveals the magnitude of disability among HIV-infected children and the large unmet need for rehabilitation services. This expanding issue demands further investigation to provide an evidence base for holistic care for disabled children living with HIV. PMID:24391869

Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable.

PubMed

Broderick, Joseph P; Viscoli, Catherine M; Brott, Thomas; Kernan, Walter N; Brass, Lawrence M; Feldmann, Edward; Morgenstern, Lewis B; Wilterdink, Janet Lee; Horwitz, Ralph I

2003-06-01

To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.

Interactive large-group teaching in a dermatology course.

PubMed

Ochsendorf, F R; Boehncke, W-H; Sommerlad, M; Kaufmann, R

2006-12-01

This is a prospective study to find out whether an interactive large-group case-based teaching approach combined with small-group bedside teaching improves student satisfaction and learning outcome in a practical dermatology course. During two consecutive terms a rotating system of large-group interactive case-study-method teaching with two tutors (one content expert, one process facilitator) and bedside teaching with randomly appointed tutors was evaluated with a nine-item questionnaire and multiple-choice test performed at the beginning and the end of the course (n = 204/231 students evaluable). The results of three different didactic approaches utilized over the prior year served as a control. The interactive course was rated significantly better (p < 0.0001) than the standard course with regard to all items. The aggregate mark given by the students for the whole course was 1.58-0.61 (mean +/- SD, range 1 (good)-5 (poor)). This was significantly better than the standard course (p < 0.0001) and not different from small-group teaching approaches. The mean test results in the final examination improved significantly (p < 0.01). The combination of large-group interactive teaching and small-group bedside teaching was well accepted, improved the learning outcome, was rated as good as a small-group didactic approach and needed fewer resources in terms of personnel.

Combining epidemiology and biomechanics in sports injury prevention research: a new approach for selecting suitable controls.

PubMed

Finch, Caroline F; Ullah, Shahid; McIntosh, Andrew S

2011-01-01

Several important methodological issues need to be considered when designing sports injury case-control studies. Major design goals for case-control studies include the accounting for prior injury risk exposure, and optimal definitions of both cases and suitable controls are needed to ensure this. This article reviews methodological aspects of published sports injury case-control studies, particularly with regard to the selection of controls. It argues for a new approach towards selecting controls for case-control studies that draws on an interface between epidemiological and biomechanical concepts. A review was conducted to identify sport injury case-control studies published in the peer-review literature during 1985-2008. Overall, 32 articles were identified, of which the majority related to upper or lower extremity injuries. Matching considerations were used for control selection in 16 studies. Specific mention of application of biomechanical principles in the selection of appropriate controls was absent from all studies, including those purporting to evaluate the benefits of personal protective equipment to protect against impact injury. This is a problem because it could lead to biased conclusions, as cases and controls are not fully comparable in terms of similar biomechanical impact profiles relating to the injury incident, such as site of the impact on the body. The strength of the conclusions drawn from case-control studies, and the extent to which results can be generalized, is directly influenced by the definition and recruitment of cases and appropriate controls. Future studies should consider the interface between epidemiological and biomechanical concepts when choosing appropriate controls to ensure that proper adjustment of prior exposure to injury risk is made. To provide necessary guidance for the optimal selection of controls in case-control studies of interventions to prevent sports-related impact injury, this review outlines a new case-control selection strategy that reflects the importance of biomechanical considerations, which ensures that controls are selected based on the presence of the same global injury mechanism as the cases. To summarize, the general biomechanical principles that should apply to the selection of controls in future case-control studies are as follows: (i) each control must have been exposed to the same global injury mechanism as the case, (e.g. head impact, fall onto outstretched arm); and (ii) intrinsic (individual) factors (e.g. age, sex, skill level) that might modify the person's response to the relevant biomechanical loads are adjusted when either selecting the controls or are in the analysis phase. The same considerations for control selection apply to other study designs such as matched cohort studies or case-crossover studies.

Exome sequencing supports a de novo mutational paradigm for schizophrenia

PubMed Central

Xu, Bin; Roos, J. Louw; Dexheimer, Phillip; Boone, Braden; Plummer, Brooks; Levy, Shawn; Gogos, Joseph A.; Karayiorgou, Maria

2011-01-01

Despite high heritability, a large fraction of cases with schizophrenia do not have a family history of the disease (sporadic cases). Here, we examine the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exome of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 patients affecting 40 genes including a potentially disruptive mutation in DGCR2, a gene removed by the recurrent schizophrenia-predisposing 22q11.2 microdeletion. Comparison to rare inherited variants revealed that the identified de novo mutations show a large excess of nonsynonymous changes in cases, as well as a greater potential to affect protein structure and function. Our analysis reveals a major role of de novo mutations in schizophrenia and also a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. PMID:21822266

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

PubMed

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

2013-04-01

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

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

PubMed Central

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

2013-01-01

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

Morphological processes in permeable sediment traps with check dams

NASA Astrophysics Data System (ADS)

Schwindt, S.; Franca, M. J.; Schleiss, A. J.

2017-12-01

Sediment traps serve for the retention of sediment in the case of major floods, but the retention of sediment is not wanted up to smaller frequent floods which are important to the morphodynamics of rivers. A new concept for the sediment traps that enables sediment transfer for frequent floods and safely retains sediment in the case of important floods was recently developed and experimentally tested. The tests were performed using a standardized hydrograph and different barrier types for the mechanically or hydraulically controlled retention of sediments. The deposition pattern was measured at the end of every experimental run using a motion sensing camera. These measurements show that the shape of the deposits varies as a function of the retention control type (mechanical or hydraulic) and particularly as a function of the barrier height. Deposits were large when a high barrier was applied that was not overflown, and when both control types were combined. The deposition slope was shallow in the case of the high barrier, steeper for combined controls and steepest when mechanical control only was tested. The study enables a better understanding for the optimization of the shape of artificial deposition areas upstream of partially permeable check dams to enhance the tradeoff between eco-morphological and economical aspects of flood protection.

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

PubMed

Bisanzio, Donal; Mutuku, Francis; LaBeaud, Angelle D; Mungai, Peter L; Muinde, Jackson; Busaidy, Hajara; Mukoko, Dunstan; King, Charles H; Kitron, Uriel

2015-12-01

Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system. Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM). Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012. The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

Intracranial haemorrhage and use of selective serotonin reuptake inhibitors

PubMed Central

de Abajo, Francisco J; Jick, Hershel; Derby, Laura; Jick, Susan; Schmitz, Stephen

2000-01-01

Aims In the past few years an increasing number of bleeding disorders have been reported in association with the use of selective serotonin reuptake inhibitors (SSRIs), including serious cases of intracranial haemorrhage, raising concerns about the safety of this class of drugs. The present study was performed to test the hypothesis of an increased risk of intracranial haemorrhage associated with the use of SSRIs. Methods We carried out a case-control study nested in a cohort of antidepressants users with the UK-based General Practice Research Database (GPRD) as the primary source of information. The study cohort encompassed subjects aged between 18 and 79 years who received a first-time prescription for any antidepressant from January, 1990 to October, 1997. Patients with presenting conditions or treatments that could be associated with an increased risk of intracranial haemorrhage were excluded from the cohort. Patients were followed-up until the occurrence of an idiopathic intracranial haemorrhage. Up to four controls per case, matched on age, sex, calendar time and practice were randomly selected from the study cohort. We estimated adjusted odds ratios and 95% confidence intervals of intracranial haemorrhage with current use of SSRIs and other antidepressants as compared with nonuse using conditional logistic regression. Results We identified 65 cases of idiopathic intracranial haemorrhage and 254 matched controls. Current exposure to SSRIs was ascertained in 7 cases (10.8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of 0.8 (0.3,2.3). The estimate for ‘other antidepressants’ was 0.7 (0.3,1.6). The effect measures were not modified by gender or age. No effect related to dose or treatment duration was detected. The risk estimates did not change according to the location of bleeding (intracerebral or subarachnoid). Conclusions Our results are not compatible with a major increased risk of intracranial haemorrhage among users of SSRIs or other antidepressants at large. However, smaller but still relevant increased risks cannot be ruled out. PMID:10886117

Nested case–control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage

PubMed Central

Sharpe, C R; Collet, J-P; McNutt, M; Belzile, E; Boivin, J-F; Hanley, J A

2000-01-01

We carried out a nested case–control study to measure the rate ratio (RR) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug (NSAID) use. The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970. Four controls/case, matched on age and sampling time, were randomly selected. Dispensing rates during successive time periods characterized NSAID exposure. RRs associated with exposure during each period were adjusted for exposure during the others. Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing samples of subjects accrued from mid-1991 to mid-1995. We accrued 5882 cases and 23 517 controls. Increasing NSAID exposure 2–5 years preceding diagnosis was associated with a trend towards a decreasing RR (P -trend = 0.003); for the highest exposure level RR = 0.76, 95% confidence interval 0.63–0.92. This protective effect could not be attributed to confounding by other determinants. In analyses involving only the cases, NSAID exposure 2–5 and 6–10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour (> 5 cm diameter) or distant metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis. © 2000 Cancer Research Campaign PMID:10883678

Myocardial infarction in Swedish subway drivers.

PubMed

Bigert, Carolina; Klerdal, Kristina; Hammar, Niklas; Gustavsson, Per

2007-08-01

Particulate matter in urban air is associated with the risk of myocardial infarction in the general population. Very high levels of airborne particles have been detected in the subway system of Stockholm, as well as in several other large cities. This situation has caused concern for negative health effects among subway staff. The aim of this study was to investigate whether there is an increased incidence of myocardial infarction among subway drivers. Data from a population-based case-control study of men aged 40-69 in Stockholm County in 1976-1996 were used. The study included all first events of myocardial infarction in registers of hospital discharges and deaths. The controls were selected randomly from the general population. National censuses were used for information on occupation. Altogether, 22 311 cases and 131 496 controls were included. Among these, 54 cases and 250 controls had worked as subway drivers. The relative risk of myocardial infarction among subway drivers was not increased. It was 0.92 [95% confidence interval (95% CI) 0.68-1.25] when the subway drivers were compared with other manual workers and 1.06 (95% CI 0.78-1.43) when the subway drivers were compared with all other gainfully employed men. Subgroup analyses indicated no influence on the risk of myocardial infarction from the duration of employment, latency time, or time since employment stopped. Subway drivers in Stockholm do not have a higher incidence of myocardial infarction than other employed persons.

The impact of ordinate scaling on the visual analysis of single-case data.

PubMed

Dart, Evan H; Radley, Keith C

2017-08-01

Visual analysis is the primary method for detecting the presence of treatment effects in graphically displayed single-case data and it is often referred to as the "gold standard." Although researchers have developed standards for the application of visual analysis (e.g., Horner et al., 2005), over- and underestimation of effect size magnitude is not uncommon among analysts. Several characteristics have been identified as potential contributors to these errors; however, researchers have largely focused on characteristics of the data itself (e.g., autocorrelation), paying less attention to characteristics of the graphic display which are largely in control of the analyst (e.g., ordinate scaling). The current study investigated the impact that differences in ordinate scaling, a graphic display characteristic, had on experts' accuracy in judgments regarding the magnitude of effect present in single-case percentage data. 32 participants were asked to evaluate eight ABAB data sets (2 each presenting null, small, moderate, and large effects) along with three iterations of each (32 graphs in total) in which only the ordinate scale was manipulated. Results suggest that raters are less accurate in their detection of treatment effects as the ordinate scale is constricted. Additionally, raters were more likely to overestimate the size of a treatment effect when the ordinate scale was constricted. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Case Study Effectiveness in a Team-Teaching and General-Education Environment

ERIC Educational Resources Information Center

Olorunnisola, Anthony A.; Ramasubramanian, Srividya; Russill, Chris; Dumas, Josephine

2003-01-01

This paper examines the effectiveness of the case study method in a team-teaching environment designed to augment a large capstone communications course that satisfies general education requirements. Results from a survey revealed that the use of case study enhanced the otherwise missing connection between the large lecture and the recitation…

The impact of changes in tobacco control funding on healthcare expenditures in California, 2012-2016.

PubMed

Max, Wendy; Sung, Hai-Yen; Lightwood, James

2013-05-01

This study presents estimates of the impact of changes in California tobacco control funding on healthcare expenditures for 2012-2016 under four funding scenarios. Smoking prevalence is projected using a cointegrated time series regression model. Smoking-attributable healthcare expenditures are estimated with econometric models that use a prevalence-based annual cost approach and an excess cost methodology. If tobacco control spending in California remains at the current level of 5 cents per pack (base case), smoking prevalence will increase from 12.2% in 2011 to 12.7% in 2016. If funding is cut in half, smoking prevalence will increase to 12.9% in 2016 and smoking-attributable healthcare expenditures will be $307 million higher over this time period than in the base case. If the tobacco tax is increased by $1.00 per pack with 20 cents per pack allocated to tobacco control, smoking prevalence will fall to 10.4% in 2016 and healthcare expenditures between 2012 and 2016 will be $3.3 billion less than in the base case. If funding is increased to the Centers for Disease Control and Prevention recommended level, smoking prevalence will fall to 10.6% in 2016 and there will be savings in healthcare expenditures of $4.7 billion compared to the base case due to the large reduction in heavy smoking prevalence. California's highly successful tobacco control program will become less effective over time because inflation is eroding the 5 cents per pack currently allocated to tobacco control activities. More aggressive action needs to be taken to reduce smoking prevalence and healthcare expenditures in the future.

Methodology Series Module 2: Case-control Studies.

PubMed

Setia, Maninder Singh

2016-01-01

Case-Control study design is a type of observational study. In this design, participants are selected for the study based on their outcome status. Thus, some participants have the outcome of interest (referred to as cases), whereas others do not have the outcome of interest (referred to as controls). The investigator then assesses the exposure in both these groups. The investigator should define the cases as specifically as possible. Sometimes, definition of a disease may be based on multiple criteria; thus, all these points should be explicitly stated in case definition. An important aspect of selecting a control is that they should be from the same 'study base' as that of the cases. We can select controls from a variety of groups. Some of them are: General population; relatives or friends; and hospital patients. Matching is often used in case-control control studies to ensure that the cases and controls are similar in certain characteristics, and it is a useful technique to increase the efficiency of the study. Case-Control studies can usually be conducted relatively faster and are inexpensive - particularly when compared with cohort studies (prospective). It is useful to study rare outcomes and outcomes with long latent periods. This design is not very useful to study rare exposures. Furthermore, they may also be prone to certain biases - selection bias and recall bias.

Design and implementation of multichannel global active structural acoustic control for a device casing

NASA Astrophysics Data System (ADS)

Mazur, Krzysztof; Wrona, Stanislaw; Pawelczyk, Marek

2018-01-01

The paper presents the idea and discussion on implementation of multichannel global active noise control systems. As a test plant an active casing is used. It has been developed by the authors to reduce device noise directly at the source by controlling vibration of its casing. To provide global acoustic effect in the whole environment, where the device operates, it requires a number of secondary sources and sensors for each casing wall, thus making the whole active control structure complicated, i.e. with a large number of interacting channels. The paper discloses all details concerning hardware setup and efficient implementation of control algorithms for the multichannel case. A new formulation is presented to introduce the distributed version of the Switched-error Filtered-reference Least Mean Squares (FXLMS) algorithm together with adaptation rate enhancement. The convergence rate of the proposed algorithm is compared with original Multiple-error FXLMS. A number of hints followed from many years of authors' experience on microprocessor control systems design and signal processing algorithms optimization are presented. They can be used for various active control and signal processing applications, both for academic research and commercialization.

Molecular inversion probe assay.

PubMed

Absalan, Farnaz; Ronaghi, Mostafa

2007-01-01

We have described molecular inversion probe technologies for large-scale genetic analyses. This technique provides a comprehensive and powerful tool for the analysis of genetic variation and enables affordable, large-scale studies that will help uncover the genetic basis of complex disease and explain the individual variation in response to therapeutics. Major applications of the molecular inversion probes (MIP) technologies include targeted genotyping from focused regions to whole-genome studies, and allele quantification of genomic rearrangements. The MIP technology (used in the HapMap project) provides an efficient, scalable, and affordable way to score polymorphisms in case/control populations for genetic studies. The MIP technology provides the highest commercially available multiplexing levels and assay conversion rates for targeted genotyping. This enables more informative, genome-wide studies with either the functional (direct detection) approach or the indirect detection approach.

Case-control studies in neurosurgery.

PubMed

Nesvick, Cody L; Thompson, Clinton J; Boop, Frederick A; Klimo, Paul

2014-08-01

Observational studies, such as cohort and case-control studies, are valuable instruments in evidence-based medicine. Case-control studies, in particular, are becoming increasingly popular in the neurosurgical literature due to their low cost and relative ease of execution; however, no one has yet systematically assessed these types of studies for quality in methodology and reporting. The authors performed a literature search using PubMed/MEDLINE to identify all studies that explicitly identified themselves as "case-control" and were published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Each paper was evaluated for 22 descriptive variables and then categorized as having either met or missed the basic definition of a case-control study. All studies that evaluated risk factors for a well-defined outcome were considered true case-control studies. The authors sought to identify key features or phrases that were or were not predictive of a true case-control study. Those papers that satisfied the definition were further evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The search detected 67 papers that met the inclusion criteria, of which 32 (48%) represented true case-control studies. The frequency of true case-control studies has not changed with time. Use of odds ratios (ORs) and logistic regression (LR) analysis were strong positive predictors of true case-control studies (for odds ratios, OR 15.33 and 95% CI 4.52-51.97; for logistic regression analysis, OR 8.77 and 95% CI 2.69-28.56). Conversely, negative predictors included focus on a procedure/intervention (OR 0.35, 95% CI 0.13-0.998) and use of the word "outcome" in the Results section (OR 0.23, 95% CI 0.082-0.65). After exclusion of nested case-control studies, the negative correlation between focus on a procedure/intervention and true case-control studies was strengthened (OR 0.053, 95% CI 0.0064-0.44). There was a trend toward a negative association between the use of survival analysis or Kaplan-Meier curves and true case-control studies (OR 0.13, 95% CI 0.015-1.12). True case-control studies were no more likely than their counterparts to use a potential study design "expert" (OR 1.50, 95% CI 0.57-3.95). The overall average STROBE score was 72% (range 50-86%). Examples of reporting deficiencies were reporting of bias (28%), missing data (55%), and funding (44%). The results of this analysis show that the majority of studies in the neurosurgical literature that identify themselves as "case-control" studies are, in fact, labeled incorrectly. Positive and negative predictors were identified. The authors provide several recommendations that may reverse the incorrect and inappropriate use of the term "case-control" and improve the quality of design and reporting of true case-control studies in neurosurgery.

Circulating 25-Hydroxyvitamin D and Risk of Kidney Cancer

PubMed Central

Gallicchio, Lisa; Moore, Lee E.; Stevens, Victoria L.; Ahn, Jiyoung; Albanes, Demetrius; Hartmuller, Virginia; Setiawan, V. Wendy; Helzlsouer, Kathy J.; Yang, Gong; Xiang, Yong-Bing; Shu, Xiao-Ou; Snyder, Kirk; Weinstein, Stephanie J.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Cai, Qiuyin; Campbell, David S.; Chen, Yu; Chow, Wong-Ho; Horst, Ronald L.; Kolonel, Laurence N.; McCullough, Marjorie L.; Purdue, Mark P.; Koenig, Karen L.

2010-01-01

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of ≥75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically. PMID:20562187

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

PubMed Central

Vonkeman, Harald E; Fernandes, Robert W; van der Palen, Job; van Roon, Eric N; van de Laar, Mart AFJ

2007-01-01

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications. PMID:17521422

Risk Factors for Human Immunodeficiency Virus Infection among Brazilian Blood Donors; a Multicenter Case-Control Study Using Audio Computer-Assisted Structured-Interviews

PubMed Central

de Almeida-Neto, Cesar; Goncalez, Thelma T.; Birch, Rebecca Jeffries; de Carvalho, Silvia Maia F.; Capuani, Ligia; Leão, Silvana Carneiro; Miranda, Carolina; Rocha, Pedro Capuani; Carneiro-Proietti, Anna Barbara; Johnson, Bryce R.; Wright, David J.; Murphy, Edward L.; Custer, Brian

2013-01-01

Background Although risk factors for HIV infection are known, it is important for blood centers to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed. Methods A case-control study was conducted at large public blood centers located in four major cities between April 2009 – March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western Blot confirmation. Audio computer-assisted structured-interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs). Results There were 341 cases, including 47 with recently-acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV-positive person (adjusted odds ratio (AOR) 11.3, 95% CI [4.1, 31.7]) and being an IVDU or sexual partner of an IVDU (AOR 4.65 [1.8, 11.7]). For female blood donors, additional risk factors were having male sex partners who also are MSM (AOR 13.5 [3.1, 59.8]), and having unprotected sex with multiple sexual partners (AOR 5.19 [2.1, 12.9]). The primary risk factor for male blood donors was MSM activity (AOR 21.6 [8.8, 52.9.]). Behaviors associated with recently-acquired HIV were being a MSM or sex partner of MSM (13.82, [4.7, 40.3]), and IVDU (11.47, [3.0, 43.2]). Conclusion Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centers is inadequate. PMID:23517235

Lung cancer risk and consumption of vegetables and fruit: an evaluation based on a systematic review of epidemiological evidence from Japan.

PubMed

Wakai, Kenji; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Sasazuki, Shizuka; Shimazu, Taichi; Sawada, Norie; Inoue, Manami; Tsugane, Shoichiro

2011-05-01

Clinical trials of β-carotene supplementation and recent large-scale prospective studies have called into question the protective effects of vegetable and fruit consumption against lung cancer. To re-assess this issue, we reviewed data from Japanese epidemiological studies. Original data were obtained from searches of MEDLINE and the Japana Centra Revuo Medicina (Ichushi) database. The associations were assessed based on their magnitude and the strength of the evidence, together with their biological plausibility as previously evaluated by the International Agency for Research on Cancer. We identified six cohort studies and four case-control studies on the consumption of vegetables and/or fruit. We focused on fruit and green-yellow vegetables as food items, as they were included in more of the studies, and insufficient data were available on other types of vegetables. Among the three cohort and two case-control studies that reported on green-yellow vegetables, only one of each study type showed a weak inverse association between lung cancer risk and their consumption. Two of the four cohort studies and one (or possibly two) of the four case-control studies demonstrated a weak inverse correlation between lung cancer risk and fruit consumption. Meta-analysis for fruit consumption revealed a summary relative risk that was significantly smaller than unity. Our analysis of the Japanese epidemiological data showed that fruit consumption possibly decreased the risk of lung cancer, but found insufficient evidence of a link with vegetable consumption. Further prospective studies should assess the effects of consuming these food groups.

Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants

PubMed Central

Sharma, R; Kraemer, DF; Torrazza, RM; Mai, V; Neu, J; Shuster, JJ; Hudak, ML

2015-01-01

OBJECTIVE Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN We used a case–control design to match each case of NEC in our study population of infants born at <33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION In contrast to previous studies, our case–control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC. PMID:25144159

A boundedness result for the direct heuristic dynamic programming.

PubMed

Liu, Feng; Sun, Jian; Si, Jennie; Guo, Wentao; Mei, Shengwei

2012-08-01

Approximate/adaptive dynamic programming (ADP) has been studied extensively in recent years for its potential scalability to solve large state and control space problems, including those involving continuous states and continuous controls. The applicability of ADP algorithms, especially the adaptive critic designs has been demonstrated in several case studies. Direct heuristic dynamic programming (direct HDP) is one of the ADP algorithms inspired by the adaptive critic designs. It has been shown applicable to industrial scale, realistic and complex control problems. In this paper, we provide a uniformly ultimately boundedness (UUB) result for the direct HDP learning controller under mild and intuitive conditions. By using a Lyapunov approach we show that the estimation errors of the learning parameters or the weights in the action and critic networks remain UUB. This result provides a useful controller convergence guarantee for the first time for the direct HDP design. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Clinical Significance of Eosinophils in the Amniotic Fluid in Preterm Labor

PubMed Central

ROMERO, ROBERTO; KUSANOVIC, JUAN PEDRO; GOMEZ, RICARDO; LAMONT, RONALD; BYTAUTIENE, EGLE; GARFIELD, ROBERT E.; MITTAL, POOJA; HASSAN, SONIA S.; YEO, LAMI

2012-01-01

Objective White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity. Methods This retrospective case-control study included women who presented with preterm labor and intact membranes between 24 and 34 weeks of gestation. Patients underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Cytologic studies included amniotic fluid white blood cell count and differential, which was performed on cytocentrifuged specimens. Patients with microbial invasion of the amniotic cavity and/or a white blood cell count >20 cells/mm3 were excluded from the study. Cases were defined as women in whom the differential contained >20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count ≤20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics. Results The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32–37.3 weeks vs. 38.0 weeks, IQR 35–40 weeks, respectively; p=0.018]. The prevalence of preterm delivery ≤35 weeks was higher among patients who had >20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p=0.029]. Similar results were observed for delivery at <37 weeks [Cases: 70% (7/10) vs. Controls: 36% (18/50); p=0.046]. Conclusions Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction. PMID:19900034

Selective mutism and anxiety: a review of the current conceptualization of the disorder.

PubMed

Sharp, William G; Sherman, Colleen; Gross, Alan M

2007-01-01

Selective mutism (SM) is a rare and interesting condition that has been associated with a wide variety of childhood psychiatric conditions. Historically viewed as more of an oddity than a distinct diagnostic entity, early conceptualizations of the condition were based largely on case studies that tended to link SM with oppositional behavior. More recently, controlled studies have enhanced our understanding of SM. This review summarizes the current conceptualization of SM, highlighting evidence supporting the notion that SM is an anxiety-related condition.

Maternal syphilis and accomplishing sexual partner treatment: still a huge gap.

PubMed

Dallé, Jessica; Baumgarten, Vanessa Z; Ramos, Mauro C; Jimenez, Mirela F; Acosta, Lisiane; Bumaguin, Daniela B; Antonello, Vicente S

2017-08-01

Congenital syphilis (CS) is a preventable epidemic disease for which control is hindered by socioeconomic and health system issues. Inadequately treated maternal syphilis (MaS) commonly has serious adverse obstetric outcomes. This study - which is a cross-sectional study in a Brazilian large urban public Mother and Child hospital, making use of secondary data - evaluated the occurrence of treatment of sexual partners (SP) among women with MaS. The results showed that 771 MaS cases were identified from 2007 to 2014. No information on SP treatment was available in 570 (73.9%) cases. Of the 201 cases presenting information, 25 (12.4%) SP were treated. Out of 164 women having six or more prenatal visits, 25 (15.2%) SP received treatment. Data analyzed biennially have shown a growing trend of cases without collected information, ranging from 27.2% in 2007-2008 to 87.5% in 2013-2014. No linear trend in proportions of treated SP (maximum 7.4% SP treated) was found. Thus, in this study, it has been concluded that the proportion of SP adequately treated was consistently low, and the quality of information deteriorated during the studied period. Prenatal care per se, as provided, was not effective in delivering adequate treatment of SP. Creative integrated services with SP active participation are greatly needed if CS is to be controlled.

Case-Control Studies of Sporadic Enteric Infections: A Review and Discussion of Studies Conducted Internationally from 1990 to 2009

PubMed Central

Fullerton, Kathleen E.; Scallan, Elaine; Kirk, Martyn D.; Mahon, Barbara E.; Angulo, Frederick J.; de Valk, Henriette; van Pelt, Wilfrid; Gauci, Charmaine; Hauri, Anja M.; Majowicz, Shannon; O’Brien, Sarah J.

2015-01-01

Epidemiologists have used case-control studies to investigate enteric disease outbreaks for many decades. Increasingly, case-control studies are also used to investigate risk factors for sporadic (not outbreak-associated) disease. While the same basic approach is used, there are important differences between outbreak and sporadic disease settings that need to be considered in the design and implementation of the case-control study for sporadic disease. Through the International Collaboration on Enteric Disease “Burden of Illness” Studies (the International Collaboration), we reviewed 79 case-control studies of sporadic enteric infections caused by nine pathogens that were conducted in 22 countries and published from 1990 through to 2009. We highlight important methodological and study design issues (including case definition, control selection, and exposure assessment) and discuss how approaches to the study of sporadic enteric disease have changed over the last 20 years (e.g., making use of more sensitive case definitions, databases of controls, and computer-assisted interviewing). As our understanding of sporadic enteric infections grows, methods and topics for case-control studies are expected to continue to evolve; for example, advances in understanding of the role of immunity can be used to improve control selection, the apparent protective effects of certain foods can be further explored, and case-control studies can be used to provide population-based measures of the burden of disease. PMID:22443481

Increased CNV-Region deletions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects in the ADNI sample

PubMed Central

Guffanti, Guia; Torri, Federica; Rasmussen, Jerod; Clark, Andrew P.; Lakatos, Anita; Turner, Jessica A.; Fallon, James H.; Saykin, Andrew J.; Weiner, Michael; Vawter, Marquis P.; Knowles, James A.; Potkin, Steven G.; Macciardi, Fabio

2014-01-01

We investigated the genome-wide distribution of CNVs in the Alzheimer's disease (AD) Neuroimaging Initiative (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large heterozygous deletions in cases (p-value < 0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p = 0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and confirmed our main findings with genome re-sequencing of selected patients and controls. The functional pathway analysis of the genes putatively affected by deletions of CNV-Regions reveals enrichment of genes implicated in axonal guidance, cell–cell adhesion, neuronal morphogenesis and differentiation. Our findings support the role of CNVs in AD, and suggest an association between large deletions and the development of cognitive impairment PMID:23583670

Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene.

PubMed

Silvestri, Valentina; Zelli, Veronica; Valentini, Virginia; Rizzolo, Piera; Navazio, Anna Sara; Coppa, Anna; Agata, Simona; Oliani, Cristina; Barana, Daniela; Castrignanò, Tiziana; Viel, Alessandra; Russo, Antonio; Tibiletti, Maria Grazia; Zanna, Ines; Masala, Giovanna; Cortesi, Laura; Manoukian, Siranoush; Azzollini, Jacopo; Peissel, Bernard; Bonanni, Bernardo; Peterlongo, Paolo; Radice, Paolo; Palli, Domenico; Giannini, Giuseppe; Chillemi, Giovanni; Montagna, Marco; Ottini, Laura

2017-01-01

Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation-negative MBC cases. Germ-line DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high-risk, BRCA1/2 mutation-negative MBC cases from an Italian multicenter study of MBC. A case-control series of 433 BRCA1/2 mutation-negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study. WES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N-acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutation-negative MBC cases. NAT1 c.97C>T was not found in the case-control series. These results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation-negative families with multiple MBC and FBC cases. Cancer 2017;123:210-218. © 2016 American Cancer Society. © 2016 American Cancer Society.

A Study of the Impact of Thirteen Celebrity Suicides on Subsequent Suicide Rates in South Korea from 2005 to 2009

PubMed Central

Fu, King-wa; Chan, C. H.

2013-01-01

A number of ecological studies have found a pattern of increasing suicide rates after suicides of several Asian entertainment celebrities. However, the finding may be subject to positive outcome bias where cases with no perceived impact may be routinely excluded. In this study, we deploy interrupted time-series analysis using ARIMA transfer function models to investigate systematically the impact of thirteen celebrity suicides on subsequent suicide rates in South Korea. We find that three out of eleven cases were found to be followed by a significant increase in suicide rate, while controlling for seasonality, secular trends, and unemployment rates. Such significant increases could last for nine weeks. Non-significance cases may be attributable to the small amount of media coverage, the “displacement” effect of preceding case, and the negative connotation of celebrity deaths. We therefore conclude that whether or not the impacts were detected may be largely conditioned by various contextual factors. Current evidence based on ecological studies is insufficient to draw a firm conclusion. Further studies using multiple approaches should be developed. PMID:23342026

Binational outbreak of Guillain-Barré syndrome associated with Campylobacter jejuni infection, Mexico and USA, 2011.

PubMed

Jackson, B R; Zegarra, J Alomía; López-Gatell, H; Sejvar, J; Arzate, F; Waterman, S; Núñez, A Sánchez; López, B; Weiss, J; Cruz, R Quintero; Murrieta, D Y López; Luna-Gierke, R; Heiman, K; Vieira, A R; Fitzgerald, C; Kwan, P; Zárate-Bermúdez, M; Talkington, D; Hill, V R; Mahon, B

2014-05-01

In June 2011, a cluster of suspected cases of Guillain-Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May-21 July 2011, exceeding the expected number of cases (n = 1-2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5-∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.

Marital Status, Education, and Risk of Acute Myocardial Infarction in Mainland China: The INTER-HEART Study

PubMed Central

Hu, Bo; Li, Wei; Wang, Xingyu; Liu, Lisheng; Teo, Koon; Yusuf, Salim

2012-01-01

Background We investigated the effects of marital status and education on the risk of acute myocardial infarction (AMI) in a large-scale case-control study in China. Methods This study was part of the INTER-HEART China case-control study. The main outcome measure was first AMI. Incident cases of AMI and control patients with no past history of heart disease were recruited. Controls were matching by age (±5 years) and sex. Marital status was combined into 2 categories: single and not single. Education level was classified into 2 categories: 8 years or less and more than 8 years. Results From 1999 to 2002, we recruited 2909 cases and 2947 controls from 17 cities. After adjustment for age, sex, BMI, psychosocial factors, lifestyle, other factors, and mutually for other risk factors, the odds ratio (OR) for AMI associated with being single was 1.51 (95% confidence interval: 1.18–1.93) overall, 1.19 (0.84–1.68; P = 0.072) in men and 2.00 (1.39–2.86; P < 0.0001) in women. The interaction of sex and marital status was statistically significant (P = 0.045). Compared with a high education level, a low education level increased the risk of AMI (1.45, 1.26–1.67); the odds ratios in men and women were 1.29 (1.09–1.52) and 1.55 (1.16–2.08), respectively. Single women with a low education level had a high risk of AMI (2.95, 1.99–4.37). Conclusions Being single was consistently associated with an increased risk for AMI, particularly in women. In addition, as compared with high education level, low education level was associated with a higher risk of AMI in both men and women. PMID:22245707

Long-term mobile phone use and brain tumor risk.

PubMed

Lönn, Stefan; Ahlbom, Anders; Hall, Per; Feychting, Maria

2005-03-15

Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified all cases aged 20-69 years who were diagnosed with glioma or meningioma during 2000-2002 in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.

Esophageal varices on computed tomography and subsequent variceal hemorrhage.

PubMed

Somsouk, Ma; To'o, Katherine; Ali, Mujtaba; Vittinghoff, Eric; Yeh, Benjamin M; Yee, Judy; Monto, Alex; Inadomi, John M; Aslam, Rizwan

2014-04-01

Endoscopy is recommended to screen for esophageal varices in patients with cirrhosis. The objective of this study was to identify features on abdominal CT imaging associated variceal hemorrhage (VH). A case-control study was performed among patients with cirrhosis who had a CT scan. Consecutive patients who experienced VH were included as cases, and patients without VH served as controls. Two radiologists recorded the maximal esophageal varix diameter in addition to other measures of portal hypertension at CT. The most powerful CT parameter associated with VH was the esophageal varix diameter (5.8 vs. 2.7 mm, p < 0.001; adjusted OR 1.84 per mm, p = 0.009). 63% of individuals with VH had a maximal varix diameter ≥5 mm compared to 7.5% of cirrhotic patients without VH (p < 0.001). In contrast, the proportion of individuals whose largest varix was <3 mm was 7.4% among VH cases compared to 54.7% among controls (p = 0.001). The varix diameter powerfully discriminated those with and without VH (C-statistic 0.84). A large esophageal varix diameter is strongly associated with subsequent VH. A threshold of <3 and ≥5 mm appears to identify patients with cirrhosis at low and high risk for hemorrhage.

Bioavailable serum estradiol may alter radiation risk of postmenopausal breast cancer: a nested case-control study.

PubMed

Grant, Eric J; Cologne, John B; Sharp, Gerald B; Eguchi, Hidetaka; Stevens, Richard G; Izumi, Shizue; Kim, Young-Min; Berrington de González, Amy; Ohishi, Waka; Nakachi, Kei

2018-02-01

Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE 2 ). A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis. Radiation exposure, higher levels of bE 2 , testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE 2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE 2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE 2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

Rapid effective trace-back capability value: a case study of foot-and-mouth in the Texas High Plains.

PubMed

Hagerman, Amy D; Ward, Michael P; Anderson, David P; Looney, J Chris; McCarl, Bruce A

2013-07-01

In this study our aim was to value the benefits of rapid effective trace-back capability-based on a livestock identification system - in the event of a foot and mouth disease (FMD) outbreak. We simulated an FMD outbreak in the Texas High Plains, an area of high livestock concentration, beginning in a large feedlot. Disease spread was simulated under different time dependent animal tracing scenarios. In the specific scenario modeled (incursion of FMD within a large feedlot, detection within 14 days and 90% effective tracing), simulation suggested that control costs of the outbreak significantly increase if tracing does not occur until day 10 as compared to the baseline of tracing on day 2. In addition, control costs are significantly increased if effectiveness were to drop to 30% as compared to the baseline of 90%. Results suggest potential benefits from rapid effective tracing in terms of reducing government control costs; however, a variety of other scenarios need to be explored before determining in which situations rapid effective trace-back capability is beneficial. Copyright © 2012 Elsevier B.V. All rights reserved.

Inverse Association between Glucose‒6‒Phosphate Dehydrogenase Deficiency and Hepatocellular Carcinoma

PubMed

Dore, Maria Pina; Vidili, Gianpaolo; Marras, Giuseppina; Assy, Silas; Pes, Giovanni Mario

2018-04-27

Background: Studies in experimental models and humans suggest that glucose‒6‒phosphate dehydrogenase (G6PD) deficiency, an inherited condition, may be inversely related to hepatocellular carcinoma (HCC). We tested this hypothesis in a large cohort of Sardinian patients. Methods: A case-control study was performed using data from 11,143 records of patients who underwent upper endoscopy between 2002 and 2017. Gender, age, G6PD status and information regarding the presence of HCC, were recorded. Cases (HCC positive) and controls (HCC negative) were compared for the presence of G6PD deficiency adjusting for major HCC risk factors using logistic regression. Results: Overall, 114 HCC cases and 11,029 controls were identified. G6PD deficiency was detected in 11.5% of study participants, and was associated with a reduced risk of HCC [odds ratio (OR); 0.451; 95% confidence interval (CI), 0.207−0.982] after adjusting for all covariates. Factors significantly associated with HCC were cirrhosis (OR, 23.30; 95% CI, 11.48−47.25), diabetes (OR, 2.396; 95% CI, 1.449−3.963), among infection hepatitis HBV with an OR of 2.326, age ≥65 years (OR, 1.941; 95% CI, 1.234−2.581) and male gender (OR, 1.611; 95% CI, 1.006−3.081). Conclusions: Our study revealed a significant inverse association between G6PD deficiency and risk of HCC. These findings need to be confirmed in further studies. Creative Commons Attribution License

Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.

PubMed

Green, Elaine K; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Grozeva, Detelina; Fraser, Christine; Richards, Alexander L; Moran, Jennifer L; Purcell, Shaun; Sklar, Pamela; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Craddock, Nick; Jones, Lisa; Jones, Ian R

2017-12-01

Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10 -5 for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.31 (p-value, 4.37 × 10 -8 ). This locus did not reach genome-wide significance in bipolar disorder or schizophrenia large Psychiatric Genomic Consortium datasets, suggesting that it may represent a relatively specific genetic risk for the bipolar subtype of schizoaffective disorder. © 2017 Wiley Periodicals, Inc.