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

Case Studies in Modelling, Control in Food Processes.

PubMed

Glassey, J; Barone, A; Montague, G A; Sabou, V

This chapter discusses the importance of modelling and control in increasing food process efficiency and ensuring product quality. Various approaches to both modelling and control in food processing are set in the context of the specific challenges in this industrial sector and latest developments in each area are discussed. Three industrial case studies are used to demonstrate the benefits of advanced measurement, modelling and control in food processes. The first case study illustrates the use of knowledge elicitation from expert operators in the process for the manufacture of potato chips (French fries) and the consequent improvements in process control to increase the consistency of the resulting product. The second case study highlights the economic benefits of tighter control of an important process parameter, moisture content, in potato crisp (chips) manufacture. The final case study describes the use of NIR spectroscopy in ensuring effective mixing of dry multicomponent mixtures and pastes. Practical implementation tips and infrastructure requirements are also discussed.

Nonlinear multivariable design by total synthesis. [of gas turbine engine control systems

NASA Technical Reports Server (NTRS)

Sain, M. K.; Peczkowski, J. L.

1982-01-01

The Nominal Design Problem (NDP) is extended to nonlinear cases, and a new case study of robust feedback synthesis for gas turbine control design is presented. The discussion of NDP extends and builds on earlier Total Synthesis Problem theory and ideas. Some mathematical preliminaries are given in which a bijection from a set S onto a set T is considered, with T admitting the structure of an F-vector space. NDP is then discussed for a nonlinear plant, and nonlinear nominal design is defined and characterized. The design of local controllers for a turbojet and the scheduling of these controls into a global control are addressed.

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

Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies

PubMed Central

dos Santos, Rafael G.; Bouso, José Carlos; Hallak, Jaime E. C.

2017-01-01

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake. PMID:28540034

Childhood risk factors in Korean women with anorexia nervosa: two sets of case-control studies with retrospective comparisons.

PubMed

Kim, Youl-Ri; Heo, Si Young; Kang, Heechan; Song, Ki Jun; Treasure, Janet

2010-11-01

The aim of this study was to investigate the characteristics of the risk factors for anorexia nervosa (AN) in Korean women. Two sets of case-control comparisons were conducted, in which 52 women with lifetime AN from Seoul, S. Korea, were compared with 108 Korean healthy controls and also with 42 women with lifetime AN from the UK in terms of their childhood risk factors. A questionnaire designed to conduct a retrospective assessment of the childhood risk factors was administered to all participants. The Korean AN women were more likely to report premorbid anxiety, perfectionism, and emotional undereating and were less likely to report having supportive figures in their childhood than the Korean healthy controls. There were no overall differences in the childhood risk factors between the Korean and British women with AN. Premorbid anxiety, perfectionism, less social support, and emotional undereating merit attention as risk factors in Korean AN. The current results are informative, but an epidemiologically robust prospective case-control study would be needed to validate these findings. © 2009 by Wiley Periodicals, Inc.

An Algorithm for Creating Virtual Controls Using Integrated and Harmonized Longitudinal Data.

PubMed

Hansen, William B; Chen, Shyh-Huei; Saldana, Santiago; Ip, Edward H

2018-06-01

We introduce a strategy for creating virtual control groups-cases generated through computer algorithms that, when aggregated, may serve as experimental comparators where live controls are difficult to recruit, such as when programs are widely disseminated and randomization is not feasible. We integrated and harmonized data from eight archived longitudinal adolescent-focused data sets spanning the decades from 1980 to 2010. Collectively, these studies examined numerous psychosocial variables and assessed past 30-day alcohol, cigarette, and marijuana use. Additional treatment and control group data from two archived randomized control trials were used to test the virtual control algorithm. Both randomized controlled trials (RCTs) assessed intentions, normative beliefs, and values as well as past 30-day alcohol, cigarette, and marijuana use. We developed an algorithm that used percentile scores from the integrated data set to create age- and gender-specific latent psychosocial scores. The algorithm matched treatment case observed psychosocial scores at pretest to create a virtual control case that figuratively "matured" based on age-related changes, holding the virtual case's percentile constant. Virtual controls matched treatment case occurrence, eliminating differential attrition as a threat to validity. Virtual case substance use was estimated from the virtual case's latent psychosocial score using logistic regression coefficients derived from analyzing the treatment group. Averaging across virtual cases created group estimates of prevalence. Two criteria were established to evaluate the adequacy of virtual control cases: (1) virtual control group pretest drug prevalence rates should match those of the treatment group and (2) virtual control group patterns of drug prevalence over time should match live controls. The algorithm successfully matched pretest prevalence for both RCTs. Increases in prevalence were observed, although there were discrepancies between live and virtual control outcomes. This study provides an initial framework for creating virtual controls using a step-by-step procedure that can now be revised and validated using other prevention trial data.

Open cycle ocean thermal energy conversion steam control and bypass system

DOEpatents

Wittig, J. Michael; Jennings, Stephen J.

1980-01-01

Two sets of hinged control doors for regulating motive steam flow from an evaporator to a condenser alternatively through a set of turbine blades in a steam bypass around the turbine blades. The evaporator has a toroidal shaped casing situated about the turbine's vertical axis of rotation and an outlet opening therein for discharging motive steam into an annular steam flow path defined between the turbine's radially inner and outer casing structures. The turbine blades extend across the steam flow path intermediate the evaporator and condenser. The first set of control doors is arranged to prevent steam access to the upstream side of the turbine blades and the second set of control doors acts as a bypass around the blades so as to maintain equilibrium between the evaporator and condenser during non-rotation of the turbine. The first set of control doors preferably extend, when closed, between the evaporator casing and the turbine's outer casing and, when open, extend away from the axis of rotation. The second set of control doors preferably constitute a portion of the turbine's outer casing downstream from the blades when closed and extend, when open, toward the axis of rotation. The first and second sets of control doors are normally held in the open and closed positions respectively by locking pins which may be retracted upon detecting an abnormal operating condition respectively to permit their closing and opening and provide steam flow from the evaporator to the condenser.

Employing Case Study Methodology in Special Educational Settings

ERIC Educational Resources Information Center

Rouse, Angelise M.

2016-01-01

In general, case studies are a preferred strategy when "how" or "why" questions are being posed, when the investigator has little control over events, and when the focus is on a contemporary phenomenon within some real-life context (Yin, 2009). This article will examine the advantages and disadvantages of employing case study…

Association Study of Prostate Cancer Susceptibility Variants with Risks of Invasive Ovarian, Breast, and Colorectal Cancer

PubMed Central

Song, Honglin; Koessler, Thibaud; Ahmed, Shahana; Ramus, Susan J.; Kjaer, Susanne Krüger; DiCioccio, Richard A.; Wozniak, Eva; Hogdall, Estrid; Whittemore, Alice S.; McGuire, Valerie; Ponder, Bruce A.J.; Turnbull, Clare; Hines, Sarah; Rahman, Nazneen; Eeles, Rosalind A.; Easton, Douglas F.; Gayther, Simon A.; Dunning, Alison M.; Pharoah, Paul D.P.

2009-01-01

Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; Ptrend = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor allele OR, 0.95; 95% CI, 0.91-0.99; Ptrend = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies. PMID:18974127

Nosocomial infection control in healthcare settings: Protection against emerging infectious diseases.

PubMed

Fu, Chuanxi; Wang, Shengyong

2016-04-12

The Middle East respiratory syndrome (MERS) outbreak in Korea in 2015 may be attributable to poor nosocomial infection control procedures implemented. Strict infection control measures were taken in the hospital where an imported case with MERS was treated in southern China and 53 health care workers were confirmed to be MERS-CoV negative. Infection control in healthcare settings, in which patients with emerging infectious diseases such as MERS, Ebola virus disease, and the severe acute respiratory syndrome (SARS) are diagnosed and treated, are often imperfect. When it comes to emerging or unknown infectious diseases, before the imported case was finally identified or community transmission was reported, cases have often occurred in clusters in healthcare settings. Nosocomial infection control measures should be further strengthened among the workers and inpatients in designated healthcare settings that accommodate suspected cases suffering from emerging or unknown infectious diseases.

Health-related quality of life of irritable bowel syndrome patients in different cultural settings

PubMed Central

Faresjö, Åshild; Anastasiou, Foteini; Lionis, Christos; Johansson, Saga; Wallander, Mari-Ann; Faresjö, Tomas

2006-01-01

Background Persons with Irritable bowel syndrome (IBS) are seriously affected in their everyday life. The effect across different cultural settings of IBS on their quality of life has been little studied. The aim was to compare health-related quality of life (HRQOL) of individuals suffering from IBS in two different cultural settings; Crete, Greece and Linköping, Sweden. Methods This study is a sex and age-matched case-control study, with n = 30 Cretan IBS cases and n = 90 Swedish IBS cases and a Swedish control group (n = 300) randomly selected from the general population. Health-related quality of life, measured by SF-36 and demographics, life style indicators and co-morbidity, was measured. Results Cretan IBS cases reported lower HRQOL on most dimensions of SF-36 in comparison to the Swedish IBS cases. Significant differences were found for the dimensions mental health (p < 0.0001) and general health (p = 0.05) even after adjustments for educational level and co-morbidity. Women from Crete with IBS scored especially low on the dimensions general health (p = 0.009) and mental health (p < 0.0001) in comparison with Swedish women with IBS. The IBS cases, from both sites, reported significantly lower scores on all HRQOL dimensions in comparison with the Swedish control group. Conclusion The results from this study tentatively support that the claim that similar individuals having the same disease, e.g. IBS, but living in different cultural environments could perceive their disease differently and that the disease might affect their everyday life and quality of life in a different way. The Cretan population, and especially women, are more seriously affected mentally by their disease than Swedish IBS cases. Coping with IBS in everyday life might be more problematic in the Cretan environment than in the Swedish setting. PMID:16566821

Systematic investigation of the relationship between high myopia and polymorphisms of the MMP2, TIMP2, and TIMP3 genes by a DNA pooling approach.

PubMed

Leung, Kim Hung; Yiu, Wai Chi; Yap, Maurice K H; Ng, Po Wah; Fung, Wai Yan; Sham, Pak Chung; Yip, Shea Ping

2011-06-01

This study examined the relationship between high myopia and three myopia candidate genes--matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase-2 and -3 (TIMP2 and TIMP3)--involved in scleral remodeling. Recruited for the study were unrelated adult Han Chinese who were high myopes (spherical equivalent, ≤ -6.0 D in both eyes; cases) and emmetropes (within ±1.0 D in both eyes; controls). Sample set 1 had 300 cases and 300 controls, and sample set 2 had 356 cases and 354 controls. Forty-nine tag single-nucleotide polymorphisms (SNPs) were selected from these candidate genes. The first stage was an initial screen of six case pools and six control pools constructed from sample set 1, each pool consisting of 50 distinct subjects of the same affection status. In the second stage, positive SNPs from the first stage were confirmed by genotyping individual samples forming the DNA pools. In the third stage, positive SNPs from stage 2 were replicated, with sample set 2 genotyped individually. Of the 49 SNPs screened by DNA pooling, three passed the lenient threshold of P < 0.10 (nested ANOVA) and were followed up by individual genotyping. Of the three SNPs genotyped, two TIMP3 SNPs were found to be significantly associated with high myopia by single-marker or haplotype analysis. However, the initial positive results could not be replicated by sample set 2. MMP2, TIPM2, and TIMP3 genes were not associated with high myopia in this Chinese sample and hence are unlikely to play a major role in the genetic susceptibility to high myopia.

Breast Reference Set Application: GeorgeTuszynski-Temple (2012) — EDRN Public Portal

Cancer.gov

As recommended by the review committee, we will analyze 30 invasive cancer cases and 30 benign controls from the EDRN breast reference set. Cases and controls should be selected that are Caucasian and post-menopausal. It is suggested that the Caucasian cases and controls match as closely as possible in regards to age and body mass index.

Quantifying the economic benefits of prevention in a healthcare setting with severe financial constraints: the case of hypertension control.

PubMed

Athanasakis, Kostas; Kyriopoulos, Ilias-Ioannis; Boubouchairopoulou, Nadia; Stergiou, George S; Kyriopoulos, John

2015-01-01

Hypertension significantly contributes to the increased cardiovascular morbidity and mortality, thus leading to rising healthcare costs. The objective of this study was to quantify the clinical and economic benefits of optimal systolic blood pressure (SBP), in a setting under severe financial constraints, as in the case of Greece. Hence, a Markov model projecting 10-year outcomes and costs was adopted, in order to compare two scenarios. The first one depicted the "current setting", where all hypertensives in Greece presented an average SBP of 164 mmHg, while the second scenario namely "optimal SBP control" represented a hypothesis in which the whole population of hypertensives would achieve optimal SBP (i.e. <140 mmHg). Cardiovascular events' occurrence was estimated for four sub-models (according to gender and smoking status). Costs were calculated from the Greek healthcare system's perspective (discounted at a 3% annual rate). Findings showed that compared to the "current setting", universal "optimal SBP control" could, within a 10-year period, reduce the occurrence of non-fatal events and deaths, by 80 and 61 cases/1000 male smokers; 59 and 37 cases/1000 men non-smokers; whereas the respective figures for women were 69 and 57 cases/1000 women smokers; and accordingly, 52 and 28 cases/1000 women non-smokers. Considering health expenditures, they could be reduced by approximately €83 million per year. Therefore, prevention of cardiovascular events through BP control could result in reduced morbidity, thereby in substantial cost savings. Based on clinical and economic outcomes, interventions that promote BP control should be a health policy priority.

Impact of Export Control and Technology Transfer Regimes: International Perspectives

DTIC Science & Technology

2012-01-07

major national security and public policy issue. Exploring the ITAR environment through a set of case studies was the central idea in a project...cover) was based on a survey of UK stakeholders. The results were unambiguous and striking. Our British partners conclude ITAR is a good idea gone...ITAR) regime is a major national security and public policy issue. Exploring the ITAR environment through a set of case studies was the central idea

Better cancer biomarker discovery through better study design.

PubMed

Rundle, Andrew; Ahsan, Habibul; Vineis, Paolo

2012-12-01

High-throughput laboratory technologies coupled with sophisticated bioinformatics algorithms have tremendous potential for discovering novel biomarkers, or profiles of biomarkers, that could serve as predictors of disease risk, response to treatment or prognosis. We discuss methodological issues in wedding high-throughput approaches for biomarker discovery with the case-control study designs typically used in biomarker discovery studies, especially focusing on nested case-control designs. We review principles for nested case-control study design in relation to biomarker discovery studies and describe how the efficiency of biomarker discovery can be effected by study design choices. We develop a simulated prostate cancer cohort data set and a series of biomarker discovery case-control studies nested within the cohort to illustrate how study design choices can influence biomarker discovery process. Common elements of nested case-control design, incidence density sampling and matching of controls to cases are not typically factored correctly into biomarker discovery analyses, inducing bias in the discovery process. We illustrate how incidence density sampling and matching of controls to cases reduce the apparent specificity of truly valid biomarkers 'discovered' in a nested case-control study. We also propose and demonstrate a new case-control matching protocol, we call 'antimatching', that improves the efficiency of biomarker discovery studies. For a valid, but as yet undiscovered, biomarker(s) disjunctions between correctly designed epidemiologic studies and the practice of biomarker discovery reduce the likelihood that true biomarker(s) will be discovered and increases the false-positive discovery rate. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Simulation study of the ROMPS robot control system

NASA Technical Reports Server (NTRS)

Nguyen, Charles C.; Liu, HUI-I.

1994-01-01

This is a report presenting the progress of a research grant funded by NASA for work performed from June 1, 1993 to August 1, 1993. The report deals with the Robot Operated Material Processing System (ROMPS). It presents results of a computer simulation study conducted to investigate the performance of the control systems controlling the azimuth, elevation, and radial axes of the ROMPS and its gripper. Four study cases are conducted. The first case investigates the control of free motion of the three areas. In the second case, the compliant motion in the elevation axis with the wrist compliant device is studied in terms of position accuracy and impact forces. The third case focuses on the behavior of the control system in controlling the robot motion along the radial axis when pulling the pallet out of the rack. In the fourth case, the compliant motion of the gripper grasping a solid object under the effect of the gripper passive compliance is studied in terms of position accuracy and contact forces. For each of the above cases, a set of PIR gains will be selected to optimize the controller performance and computer simulation results will be presented and discussed.

Case Studies of Action Research in Various Adult Education Settings.

ERIC Educational Resources Information Center

Kuhne, Gary W.; Weirauch, Drucie; Fetterman, David J.; Mearns, Raiana M.; Kalinosky, Kathy; Cegles, Kathleen A.; Ritchey, Linda

1997-01-01

Six case studies illustrate action research in adult education: faculty development in a museum, participation in a church congregation, retention of literacy volunteers in a corrections center, learner participation in a homeless shelter, technology innovation in a university, and infection control in a hospital. (SK)

The Importance of Geodetically Controlled Data Sets: THEMIS Controlled Mosaics of Mars, a Case Study

NASA Astrophysics Data System (ADS)

Fergason, R. L.; Weller, L.

2018-04-01

Accurate image registration is necessary to answer questions that are key to addressing fundamental questions about our universe. To provide such a foundational product for Mars, we have geodetically controlled and mosaicked THEMIS IR images.

Quantifying the impact of selection bias caused by nonparticipation in a case-control study of mobile phone use.

PubMed

Vrijheid, Martine; Richardson, Lesley; Armstrong, Bruce K; Auvinen, Anssi; Berg, Gabriele; Carroll, Matthew; Chetrit, Angela; Deltour, Isabelle; Feychting, Maria; Giles, Graham G; Hours, Martine; Iavarone, Ivano; Lagorio, Susanna; Lönn, Stefan; McBride, Mary; Parent, Marie-Elise; Sadetzki, Siegal; Salminen, Tina; Sanchez, Marie; Schlehofer, Birgitte; Schüz, Joachim; Siemiatycki, Jack; Tynes, Tore; Woodward, Alistair; Yamaguchi, Naohito; Cardis, Elisabeth

2009-01-01

To quantitatively assess the impact of selection bias caused by nonparticipation in a multinational case-control study of mobile phone use and brain tumor. Non-response questionnaires (NRQ) were completed by a sub-set of nonparticipants. Selection bias factors were calculated based on the prevalence of mobile phone use reported by nonparticipants with NRQ data, and on scenarios of hypothetical exposure prevalence for other nonparticipants. Regular mobile phone use was reported less frequently by controls and cases who completed the NRQ (controls, 56%; cases, 50%) than by those who completed the full interview (controls, 69%; cases, 66%). This relationship was consistent across study centers, sex, and age groups. Lower education and more recent start of mobile phone use were associated with refusal to participate. Bias factors varied between 0.87 and 0.92 in the most plausible scenarios. Refusal to participate in brain tumor case-control studies seems to be related to less prevalent use of mobile phones, and this could result in a downward bias of around 10% in odds ratios for regular mobile phone use. The use of simple selection bias estimation methods in case-control studies can give important insights into the extent of any bias, even when nonparticipant information is incomplete.

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

SPORE/EDRN/PRE-PLCO Ovarian Phase II Validation Study — EDRN Public Portal

Cancer.gov

Create a new set of phase II specimens (160 cases with pre-operative bloods representing major histologic types and including 80 early-staged and 80 late-staged cases, 160 controls with benign disease, 480 general population controls, and a small set of serial Samples collected either at least 3 months apart, but not more than 6 months apart OR between 10 months apart and no more than 14 months apart in 40 healthy controls) will be used to evaluate markers identified in preliminary work. The top 5-10 markers, plus an expanded panel of Luminex markers, will comprise a “working consensus panel” for subsequent analysis in PLCO specimens.

Case-control study on uveal melanoma (RIFA): rational and design

PubMed Central

Schmidt-Pokrzywniak, Andrea; Jöckel, Karl-Heinz; Bornfeld, Norbert; Stang, Andreas

2004-01-01

Background Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. Methods/Design We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding. PMID:15318944

Genetic characterization of Shigella spp. isolated from diarrhoeal and asymptomatic children.

PubMed

Ghosh, Santanu; Pazhani, Gururaja P; Niyogi, Swapan Kumar; Nataro, James P; Ramamurthy, Thandavarayan

2014-07-01

Phenotypic and genetic characteristics of Shigella spp. isolated from diarrhoeal and asymptomatic children aged up to 5 years were analysed in this study. In total, 91 and 17 isolates were identified from diarrhoeal (case) and asymptomatic (control) children, respectively. All the isolates were tested for antimicrobial resistance, the presence of integrons, plasmid-mediated quinolone resistance (PMQR), virulence-associated genes and Shigella pathogenicity island (SH-PAI). The majority of the Shigella spp. from cases (68.1%) and controls (82.3%) were found to be resistant to fluoroquinolones. Integron carriage was detected more in cases (76.9%) than in controls (35.5%). Atypical class 1 integron was detected exclusively in Shigella flexneri from cases but not from the controls. PMQR genes such as aac(6')-Ib-cr and qnrS1 were detected in 82.4 and 14.3% of the isolates from cases and in 53 and 17.6% in controls, respectively. Shigella isolates from cases as well as from controls were positive for the invasive plasmid antigen H-encoding gene ipaH. The other virulence genes such as virF, sat, setA, setB, sen and ial were detected in Shigella isolates in 80.2, 49.4, 27.4, 27.4, 80.2 and 79.1% of cases and in 64.7, 52.9, 17.6, 17.6, 64.7 and 64.7% of controls, respectively. The entire SH-PAI was detected in S. flexneri serotype 2a from cases and controls. In an isolate from a control child, the SH-PAI was truncated. Integrons, PMQR and virulence-encoding genes were detected more frequently in cases than in controls. In diarrhoea endemic areas, asymptomatic carriers may play a crucial role in the transmission of multidrug-resistant Shigella spp. with all the putative virulence genes. © 2014 The Authors.

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.

Analysis of binary responses with outcome-specific misclassification probability in genome-wide association studies.

PubMed

Rekaya, Romdhane; Smith, Shannon; Hay, El Hamidi; Farhat, Nourhene; Aggrey, Samuel E

2016-01-01

Errors in the binary status of some response traits are frequent in human, animal, and plant applications. These error rates tend to differ between cases and controls because diagnostic and screening tests have different sensitivity and specificity. This increases the inaccuracies of classifying individuals into correct groups, giving rise to both false-positive and false-negative cases. The analysis of these noisy binary responses due to misclassification will undoubtedly reduce the statistical power of genome-wide association studies (GWAS). A threshold model that accommodates varying diagnostic errors between cases and controls was investigated. A simulation study was carried out where several binary data sets (case-control) were generated with varying effects for the most influential single nucleotide polymorphisms (SNPs) and different diagnostic error rate for cases and controls. Each simulated data set consisted of 2000 individuals. Ignoring misclassification resulted in biased estimates of true influential SNP effects and inflated estimates for true noninfluential markers. A substantial reduction in bias and increase in accuracy ranging from 12% to 32% was observed when the misclassification procedure was invoked. In fact, the majority of influential SNPs that were not identified using the noisy data were captured using the proposed method. Additionally, truly misclassified binary records were identified with high probability using the proposed method. The superiority of the proposed method was maintained across different simulation parameters (misclassification rates and odds ratios) attesting to its robustness.

All set! Evidence of simultaneous attentional control settings for multiple target colors.

PubMed

Irons, Jessica L; Folk, Charles L; Remington, Roger W

2012-06-01

Although models of visual search have often assumed that attention can only be set for a single feature or property at a time, recent studies have suggested that it may be possible to maintain more than one attentional control setting. The aim of the present study was to investigate whether spatial attention could be guided by multiple attentional control settings for color. In a standard spatial cueing task, participants searched for either of two colored targets accompanied by an irrelevantly colored distractor. Across five experiments, results consistently showed that nonpredictive cues matching either target color produced a significant spatial cueing effect, while irrelevantly colored cues did not. This was the case even when the target colors could not be linearly separated from irrelevantly cue colors in color space, suggesting that participants were not simply adopting one general color set that included both target colors. The results could not be explained by intertrial priming by previous targets, nor could they be explained by a single inhibitory set for the distractor color. Overall, the results are most consistent with the maintenance of multiple attentional control settings.

Accounting for control mislabeling in case-control biomarker studies.

PubMed

Rantalainen, Mattias; Holmes, Chris C

2011-12-02

In biomarker discovery studies, uncertainty associated with case and control labels is often overlooked. By omitting to take into account label uncertainty, model parameters and the predictive risk can become biased, sometimes severely. The most common situation is when the control set contains an unknown number of undiagnosed, or future, cases. This has a marked impact in situations where the model needs to be well-calibrated, e.g., when the prediction performance of a biomarker panel is evaluated. Failing to account for class label uncertainty may lead to underestimation of classification performance and bias in parameter estimates. This can further impact on meta-analysis for combining evidence from multiple studies. Using a simulation study, we outline how conventional statistical models can be modified to address class label uncertainty leading to well-calibrated prediction performance estimates and reduced bias in meta-analysis. We focus on the problem of mislabeled control subjects in case-control studies, i.e., when some of the control subjects are undiagnosed cases, although the procedures we report are generic. The uncertainty in control status is a particular situation common in biomarker discovery studies in the context of genomic and molecular epidemiology, where control subjects are commonly sampled from the general population with an established expected disease incidence rate.

Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes.

PubMed

Zachry, Woodie M; Doan, Quynhchau D; Clewell, Jerry D; Smith, Brien J

2009-03-01

Although antiepileptic drugs (AEDs) with multisource generic alternatives are becoming more prevalent, no case-control studies have been published examining multisource medication use and epilepsy-related outcomes. This study evaluated the association between inpatient/emergency epilepsy care and the occurrence of a recent switch in AED formulation. A case-control analysis was conducted utilizing the Ingenix LabRx Database. Eligible patients were 12-64 years of age, received >or=145 days of AEDs in the preindex period, had continuous eligibility for 6 months preindex, and no prior inpatient/emergency care. Cases received care between 7/1/2006 and 12/31/2006 in an ambulance, emergency room, or inpatient hospital with a primary epilepsy diagnosis. Controls had a primary epilepsy diagnosis in a physician's office during the same period. The index date was the earliest occurrence of care in each respective setting. Cases and controls were matched 1:3 by epilepsy diagnosis and age. Odds of a switch between "A-rated" AEDs within 6 months prior to index were calculated. Cases (n = 416) had 81% greater odds of having had an A-rated AED formulation switch [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.25 to 2.63] relative to controls (n = 1248). There were no significant differences between groups regarding demographics or diagnosis. Significant differences were found with regard to medical coverage type (case Medicaid = 4.6%, control Medicaid = 1.8%, p = 0.002). Post hoc analysis results excluding Medicaid recipients remained significant and concordant with the original analysis. This analysis found an association between patients receiving epilepsy care in an emergency or inpatient setting and the recent occurrence of AED formulation switching involving A-rated generics.

Identification and medical utilization of incident cases of alcohol dependence: A population-based case-control study.

PubMed

Pan, Chun-Hung; Li, Min-Shan; Yang, Tien-Wey; Huang, Ming-Chyi; Su, Sheng-Shiang; Hung, Yen-Ni; Chen, Chiao-Chicy; Kuo, Chian-Jue

2018-05-05

Patients with alcohol dependence (AD) often seek help from medical professionals due to alcohol-related diseases, but the overall distribution of medical specialties identifying new AD cases is unclear. We investigated how such cases were identified and how medical resources were utilized before the identification of AD in a nationwide cohort. We enrolled a population-based cohort (N = 1,000,000) using the National Health Insurance Research Database of Taiwan; 8181 cases with incident AD were retrieved between January 1, 2000, and December 31, 2010. For this nested case-control study, four controls were matched for age and sex with each case based on risk-set sampling. We measured various dimensions of medical utilization before AD was diagnosed, including department visited, physical comorbidity, and medication used. Conditional logistic regression was used for estimating the variables associated with AD. Patients living in less urbanized areas who were unemployed were more likely to develop AD. The highest proportions (34.2%) of AD cases were identified in the internal medicine department, followed by the emergency (22.3%) and psychiatry (18.7%) departments. AD patients had a higher risk of comorbid chronic hepatic disease (adjusted RR = 2.72, p < 0.001) before identification of AD than controls. AD patients also had greater numbers of hospital admissions than controls, including non-psychiatric and psychiatric hospitalizations. Outpatient visit numbers were similar for AD patients and controls. The findings indicate that clinicians providing care in diverse medical settings should be prepared to screen for unhealthy alcohol use and to mitigate its detrimental effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk Factors for Border Malaria in a Malaria Elimination Setting: A Retrospective Case-Control Study in Yunnan, China

PubMed Central

Xu, Jian-Wei; Liu, Hui; Zhang, Yu; Guo, Xiang-Rui; Wang, Jia-Zhi

2015-01-01

A retrospective case-control study was conducted to identify risk factors for border malaria in a malaria elimination setting of Yunnan Province, China. The study comprised 214 cases and 428 controls. The controls were individually matched to the cases on the basis of residence, age, and gender. In addition, statistical associations are based on matched analyses. The frequencies of imported, male, adult, and vivax malaria cases were respectively 201 (93.9%), 194 (90.7%), 210 (98.1%), and 176 (82.2%). Overnight stay in Myanmar within the prior month was independently associated with malaria infection (odds ratio [OR] 159.5, 95% confidence interval [CI] 75.1–338.9). In particular, stays in lowland and foothill (OR 5.5, 95% CI 2.5–11.8) or mid-hill (OR 42.8, 95% CI 5.1–319.8) areas, or near streamlets (OR 15.3, 95% CI 4.3–55.2) or paddy field or pools (OR10.1, 95% CI 4.4–55.8) were found to be independently associated with malaria. Neither forest exposure nor use of vector control measures was associated with malaria. In conclusion, travel to lowland and foothill or mid-hill hyperendemic areas, especially along the waterside in Myanmar, was found to be the highest risk factor for malaria. In considering the limitations of the study, further investigations are needed to identify the major determinants of malaria risk and develop new strategies for malaria elimination on China-Myanmar border. PMID:25601994

Optimal selection of markers for validation or replication from genome-wide association studies.

PubMed

Greenwood, Celia M T; Rangrej, Jagadish; Sun, Lei

2007-07-01

With reductions in genotyping costs and the fast pace of improvements in genotyping technology, it is not uncommon for the individuals in a single study to undergo genotyping using several different platforms, where each platform may contain different numbers of markers selected via different criteria. For example, a set of cases and controls may be genotyped at markers in a small set of carefully selected candidate genes, and shortly thereafter, the same cases and controls may be used for a genome-wide single nucleotide polymorphism (SNP) association study. After such initial investigations, often, a subset of "interesting" markers is selected for validation or replication. Specifically, by validation, we refer to the investigation of associations between the selected subset of markers and the disease in independent data. However, it is not obvious how to choose the best set of markers for this validation. There may be a prior expectation that some sets of genotyping data are more likely to contain real associations. For example, it may be more likely for markers in plausible candidate genes to show disease associations than markers in a genome-wide scan. Hence, it would be desirable to select proportionally more markers from the candidate gene set. When a fixed number of markers are selected for validation, we propose an approach for identifying an optimal marker-selection configuration by basing the approach on minimizing the stratified false discovery rate. We illustrate this approach using a case-control study of colorectal cancer from Ontario, Canada, and we show that this approach leads to substantial reductions in the estimated false discovery rates in the Ontario dataset for the selected markers, as well as reductions in the expected false discovery rates for the proposed validation dataset. Copyright 2007 Wiley-Liss, Inc.

Highly Efficient Design-of-Experiments Methods for Combining CFD Analysis and Experimental Data

NASA Technical Reports Server (NTRS)

Anderson, Bernhard H.; Haller, Harold S.

2009-01-01

It is the purpose of this study to examine the impact of "highly efficient" Design-of-Experiments (DOE) methods for combining sets of CFD generated analysis data with smaller sets of Experimental test data in order to accurately predict performance results where experimental test data were not obtained. The study examines the impact of micro-ramp flow control on the shock wave boundary layer (SWBL) interaction where a complete paired set of data exist from both CFD analysis and Experimental measurements By combining the complete set of CFD analysis data composed of fifteen (15) cases with a smaller subset of experimental test data containing four/five (4/5) cases, compound data sets (CFD/EXP) were generated which allows the prediction of the complete set of Experimental results No statistical difference were found to exist between the combined (CFD/EXP) generated data sets and the complete Experimental data set composed of fifteen (15) cases. The same optimal micro-ramp configuration was obtained using the (CFD/EXP) generated data as obtained with the complete set of Experimental data, and the DOE response surfaces generated by the two data sets were also not statistically different.

Quantum thermodynamics with local control

NASA Astrophysics Data System (ADS)

Lekscha, J.; Wilming, H.; Eisert, J.; Gallego, R.

2018-02-01

We investigate the limitations that emerge in thermodynamic tasks as a result of having local control only over the components of a thermal machine. These limitations are particularly relevant for devices composed of interacting many-body systems. Specifically, we study protocols of work extraction that employ a many-body system as a working medium whose evolution can be driven by tuning the on-site Hamiltonian terms. This provides a restricted set of thermodynamic operations, giving rise to alternative bounds for the performance of engines. Our findings show that those limitations in control render it, in general, impossible to reach Carnot efficiency; in its extreme ramification it can even forbid to reach a finite efficiency or finite work per particle. We focus on the one-dimensional Ising model in the thermodynamic limit as a case study. We show that in the limit of strong interactions the ferromagnetic case becomes useless for work extraction, while the antiferromagnetic case improves its performance with the strength of the couplings, reaching Carnot in the limit of arbitrary strong interactions. Our results provide a promising connection between the study of quantum control and thermodynamics and introduce a more realistic set of physical operations well suited to capture current experimental scenarios.

Measles: effect of a two-dose vaccination programme in Catalonia, Spain.

PubMed Central

Godoy, P.; Domínguez, A.; Salleras, L.

1999-01-01

The study reports incidences of measles in Catalonia, Spain, as detected by surveillance, and analyses the specific characteristics of the outbreaks reported for the period 1986-95. Incidences per 100,000 inhabitants were calculated for the period 1971-95. The following variables were studied: year of presentation, number of cases, median age, transmission setting, cases with a record of vaccination and preventable cases. Associations between variables were determined using odds ratios (OR). The incidence of measles declined from 306.3 cases in 1971 to 30.9 in 1995. A total of 50 outbreaks were investigated. The outbreaks that occurred in the last two years of the study had a higher likelihood of having a transmission setting other than primary school (OR = 3.9); a median case age > 10 years (OR = 7.2); and fewer than 6 cases (OR = 2.3). The characteristics of recent outbreaks, marked by a rise both in transmission outside the primary-school setting and in median age, indicate the need for the introduction of a specific vaccination programme at the end of adolescence in addition to control of school-related outbreaks. PMID:10083711

Computer-Aided System Engineering and Analysis (CASE/A) Programmer's Manual, Version 5.0

NASA Technical Reports Server (NTRS)

Knox, J. C.

1996-01-01

The Computer Aided System Engineering and Analysis (CASE/A) Version 5.0 Programmer's Manual provides the programmer and user with information regarding the internal structure of the CASE/A 5.0 software system. CASE/A 5.0 is a trade study tool that provides modeling/simulation capabilities for analyzing environmental control and life support systems and active thermal control systems. CASE/A has been successfully used in studies such as the evaluation of carbon dioxide removal in the space station. CASE/A modeling provides a graphical and command-driven interface for the user. This interface allows the user to construct a model by placing equipment components in a graphical layout of the system hardware, then connect the components via flow streams and define their operating parameters. Once the equipment is placed, the simulation time and other control parameters can be set to run the simulation based on the model constructed. After completion of the simulation, graphical plots or text files can be obtained for evaluation of the simulation results over time. Additionally, users have the capability to control the simulation and extract information at various times in the simulation (e.g., control equipment operating parameters over the simulation time or extract plot data) by using "User Operations (OPS) Code." This OPS code is written in FORTRAN with a canned set of utility subroutines for performing common tasks. CASE/A version 5.0 software runs under the VAX VMS(Trademark) environment. It utilizes the Tektronics 4014(Trademark) graphics display system and the VTIOO(Trademark) text manipulation/display system.

Optimal intervention strategies for cholera outbreak by education and chlorination

NASA Astrophysics Data System (ADS)

Bakhtiar, Toni

2016-01-01

This paper discusses the control of infectious diseases in the framework of optimal control approach. A case study on cholera control was studied by considering two control strategies, namely education and chlorination. We distinct the former control into one regarding person-to-person behaviour and another one concerning person-to-environment conduct. Model are divided into two interacted populations: human population which follows an SIR model and pathogen population. Pontryagin maximum principle was applied in deriving a set of differential equations which consists of dynamical and adjoin systems as optimality conditions. Then, the fourth order Runge-Kutta method was exploited to numerically solve the equation system. An illustrative example was provided to assess the effectiveness of the control strategies toward a set of control scenarios.

Estimating the influenza vaccine effectiveness against medically attended influenza in clinical settings: a hospital-based case-control study with a rapid diagnostic test in Japan.

PubMed

Suzuki, Motoi; Yoshimine, Hiroyuki; Harada, Yoshitaka; Tsuchiya, Naho; Shimada, Ikumi; Ariyoshi, Koya; Inoue, Kenichiro

2013-01-01

Influenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting. A prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records. Between December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures. The test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.

A 2cM genome-wide scan of European Holstein cattle affected by classical BSE

PubMed Central

2010-01-01

Background Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with variations in transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism (SNP) markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic. Results Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set of paired cases with controls. The family set comprises half-sibling progeny from six sires. The progeny from four of these sires had previously been scanned with microsatellite markers. The results obtained from the current analysis of the family set yielded both some supporting and new results compared with those obtained in the earlier study. The results revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease. These results confirm a region previously reported on chromosome 20, and identify additional regions on chromosomes 2, 14, 16, 21 and 28. This study did not identify a significant association near the PRNP in the family sample set. The only association found in the PRNP region was in the case-control sample set and this was not significant after multiple test correction. The genome scan of the case-control animals did not identify any associations that passed a stringent genome-wide significance threshold. Conclusions Several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. Further investigation of loci on chromosomes 2, 14, 16, 20, 21 and 28 will be required to uncover any biological significance underlying these marker associations. PMID:20350325

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population.

PubMed

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population*

PubMed Central

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)AA+AG: 0.654, 95% confidence interval (CI): 0.406–1.055; P=0.082), rs4233532 (ORCC: 1.667, 95% CI: 0.967–2.876; ORCT: 1.435, 95% CI: 0.998–2.063; P=0.077), and rs2881930 (ORCC: 0.263, 95% CI: 0.095–0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (ORAA+AG: 1.233, 95% CI: 0.903–1.683), rs4233532 (ORCC: 0.892, 95% CI: 0.640–1.243; ORCT: 1.134, 95% CI: 0.897–1.433), and rs2881930 (ORCC: 1.096, 95% CI: 0.620–1.938; ORCT: 1.009, 95% CI: 0.801–1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319–2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC. PMID:23303631

Case-control vaccine effectiveness studies: Data collection, analysis and reporting results.

PubMed

Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

2017-06-05

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. Published by Elsevier Ltd.

Risk factors for childhood burns: a case-control study of Ghanaian children.

PubMed Central

Forjuoh, S N; Guyer, B; Strobino, D M; Keyl, P M; Diener-West, M; Smith, G S

1995-01-01

STUDY OBJECTIVE--To study risk factors for childhood burns in order to identify possible preventive strategies. DESIGN--Case-control design with pair matching of controls to cases in relation to age, sex, and area of residence. The cases and controls were identified by a community based, multisite survey. The effects of host and socioenvironmental variables reported by mothers were investigated in a multivariate analysis using conditional logistic regression. SETTING--A developing country setting the Ashanti Region in Ghana. PARTICIPANTS--These comprised 610 cases aged 0-5 years who had been burned (as evidenced by a visible scar) and 610 controls with no burn history. MAIN RESULTS--The presence of a pre-existing impairment in a child was the strongest risk factor in this population (OR = 6.71; 95% CI 2.78, 16.16). Other significant risk factor included: sibling death from a burn (OR = 4.41; 95% CI 1.16, 16.68); history of burn in a sibling (OR = 1.79; 95% CI 1.24, 2.58); and storage of a flammable substance in the home (OR = 1.51; 95% CI 1.03; 2.21). Maternal education had a protective effect against childhood burns, although this effect was not strong (OR = 0.76; 95% CI 0.55, 1.05). CONCLUSIONS--Community programmes to ensure adequate child supervision and general child wellbeing, particularly for those with impairments, as well as parental education about burns are recommended, to reduce childhood burns in this region of Ghana. The public should bed advised against storing flammable substances in the home. PMID:7798049

Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings.

PubMed

Chen, Hongda; Knebel, Phillip; Brenner, Hermann

2016-07-01

Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation. A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting. In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting. Validation of early detection markers of cancer in a true screening setting is important to limit the number of false-positive findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Laryngospasm during emergency department ketamine sedation: a case-control study.

PubMed

Green, Steven M; Roback, Mark G; Krauss, Baruch

2010-11-01

The objective of this study was to assess predictors of emergency department (ED) ketamine-associated laryngospasm using case-control techniques. We performed a matched case-control analysis of a sample of 8282 ED ketamine sedations (including 22 occurrences of laryngospasm) assembled from 32 prior published series. We sequentially studied the association of each of 7 clinical variables with laryngospasm by assigning 4 controls to each case while matching for the remaining 6 variables. We then used univariate statistics and conditional logistic regression to analyze the matched sets. We found no statistical association of age, dose, oropharyngeal procedure, underlying physical illness, route, or coadministered anticholinergics with laryngospasm. Coadministered benzodiazepines showed a borderline association in the multivariate but not univariate analysis that was considered anomalous. This case-control analysis of the largest available sample of ED ketamine-associated laryngospasm did not demonstrate evidence of association with age, dose, or other clinical factors. Such laryngospasm seems to be idiosyncratic, and accordingly, clinicians administering ketamine must be prepared for its rapid identification and management. Given no evidence that they decrease the risk of laryngospasm, coadministered anticholinergics seem unnecessary.

Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling

PubMed Central

2014-01-01

Background The aim of this discovery study was the identification of peptide serum biomarkers for detecting biliary tract cancer (BTC) using samples from healthy volunteers and benign cases of biliary disease as control groups. This work was based on the hypothesis that cancer-specific exopeptidases exist and that their activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation. Methods This case control study used a semi-automated platform incorporating polypeptide extraction linked to matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) to profile 92 patient serum samples. Predictive models were generated to test a validation serum set from BTC cases and healthy volunteers. Results Several peptide peaks were found that could significantly differentiate BTC patients from healthy controls and benign biliary disease. A predictive model resulted in a sensitivity of 100% and a specificity of 93.8% in detecting BTC in the validation set, whilst another model gave a sensitivity of 79.5% and a specificity of 83.9% in discriminating BTC from benign biliary disease samples in the training set. Discriminatory peaks were identified by tandem MS as fragments of abundant clotting proteins. Conclusions Serum MALDI MS peptide signatures can accurately discriminate patients with BTC from healthy volunteers. PMID:24495412

Evaluation of Cox's model and logistic regression for matched case-control data with time-dependent covariates: a simulation study.

PubMed

Leffondré, Karen; Abrahamowicz, Michal; Siemiatycki, Jack

2003-12-30

Case-control studies are typically analysed using the conventional logistic model, which does not directly account for changes in the covariate values over time. Yet, many exposures may vary over time. The most natural alternative to handle such exposures would be to use the Cox model with time-dependent covariates. However, its application to case-control data opens the question of how to manipulate the risk sets. Through a simulation study, we investigate how the accuracy of the estimates of Cox's model depends on the operational definition of risk sets and/or on some aspects of the time-varying exposure. We also assess the estimates obtained from conventional logistic regression. The lifetime experience of a hypothetical population is first generated, and a matched case-control study is then simulated from this population. We control the frequency, the age at initiation, and the total duration of exposure, as well as the strengths of their effects. All models considered include a fixed-in-time covariate and one or two time-dependent covariate(s): the indicator of current exposure and/or the exposure duration. Simulation results show that none of the models always performs well. The discrepancies between the odds ratios yielded by logistic regression and the 'true' hazard ratio depend on both the type of the covariate and the strength of its effect. In addition, it seems that logistic regression has difficulty separating the effects of inter-correlated time-dependent covariates. By contrast, each of the two versions of Cox's model systematically induces either a serious under-estimation or a moderate over-estimation bias. The magnitude of the latter bias is proportional to the true effect, suggesting that an improved manipulation of the risk sets may eliminate, or at least reduce, the bias. Copyright 2003 JohnWiley & Sons, Ltd.

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome

PubMed Central

2013-01-01

Background Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Methods Two previously published blood gene expression data sets – the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members) – were analyzed. All individuals of each dataset were projected to biological pathways, and each sample’s Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Results Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Conclusions Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression signal, and showed that outlier groups were distinct for each implicated pathway. Moreover, our results suggest that by seeking heterogeneity, pathway-based outlier analysis can reveal expression signals that are not apparent when considering only shared group differences. PMID:24063311

A case-control study of syphilis among men who have sex with men in New York City: association With HIV infection.

PubMed

Paz-Bailey, Gabriela; Meyers, Andrea; Blank, Susan; Brown, James; Rubin, Steve; Braxton, Jim; Zaidi, Akbar; Schafzin, Josh; Weigl, Susan; Markowitz, Laurie E

2004-10-01

The objective of this study was to determine factors associated with syphilis among men who report sex with other men in New York City. DESIGN, SETTING AND STUDY SUBJECTS: We conducted a case-control study among 88 men who reported sex with men in the previous year, 18 to 55 years old and diagnosed with primary or secondary syphilis during 2001; and 176 control subjects frequently matched by age and type of health provider. HIV prevalence among syphilis cases was 48% compared with 15% among control subjects (P <0.001). Variables associated with syphilis in a multivariate model were HIV infection (odds ratio [OR], 7.3; 95% confidence interval [CI], 3.5-15.4), income >$30,000 per year (OR, 2.7; CI, 1.4-5.2), and barebacking (OR, 2.6; CI, 1.4-4.8). The median time since HIV diagnosis for HIV-positive was 6 years for cases and 7 years for control subjects (P = 0.70). Among HIV-infected participants, syphilis cases were more likely than control subjects to report being on antiretroviral therapy (69% vs. 44%, P = 0.05) and to report having undetectable viral load (58% vs. 24%, P = 0.02). HIV infection was strongly associated with syphilis in this study. High-risk behavior reported by both cases and control subjects indicates the potential for increased HIV transmission.

Test Cases for the Benchmark Active Controls: Spoiler and Control Surface Oscillations and Flutter

NASA Technical Reports Server (NTRS)

Bennett, Robert M.; Scott, Robert C.; Wieseman, Carol D.

2000-01-01

As a portion of the Benchmark Models Program at NASA Langley, a simple generic model was developed for active controls research and was called BACT for Benchmark Active Controls Technology model. This model was based on the previously-tested Benchmark Models rectangular wing with the NACA 0012 airfoil section that was mounted on the Pitch and Plunge Apparatus (PAPA) for flutter testing. The BACT model had an upper surface spoiler, a lower surface spoiler, and a trailing edge control surface for use in flutter suppression and dynamic response excitation. Previous experience with flutter suppression indicated a need for measured control surface aerodynamics for accurate control law design. Three different types of flutter instability boundaries had also been determined for the NACA 0012/PAPA model, a classical flutter boundary, a transonic stall flutter boundary at angle of attack, and a plunge instability near M = 0.9. Therefore an extensive set of steady and control surface oscillation data was generated spanning the range of the three types of instabilities. This information was subsequently used to design control laws to suppress each flutter instability. There have been three tests of the BACT model. The objective of the first test, TDT Test 485, was to generate a data set of steady and unsteady control surface effectiveness data, and to determine the open loop dynamic characteristics of the control systems including the actuators. Unsteady pressures, loads, and transfer functions were measured. The other two tests, TDT Test 502 and TDT Test 5 18, were primarily oriented towards active controls research, but some data supplementary to the first test were obtained. Dynamic response of the flexible system to control surface excitation and open loop flutter characteristics were determined during Test 502. Loads were not measured during the last two tests. During these tests, a database of over 3000 data sets was obtained. A reasonably extensive subset of the data sets from the first two tests have been chosen for Test Cases for computational comparisons concentrating on static conditions and cases with harmonically oscillating control surfaces. Several flutter Test Cases from both tests have also been included. Some aerodynamic comparisons with the BACT data have been made using computational fluid dynamics codes at the Navier-Stokes level (and in the accompanying chapter SC). Some mechanical and active control studies have been presented. In this report several Test Cases are selected to illustrate trends for a variety of different conditions with emphasis on transonic flow effects. Cases for static angles of attack, static trailing-edge and upper-surface spoiler deflections are included for a range of conditions near those for the oscillation cases. Cases for trailing-edge control and upper-surface spoiler oscillations for a range of Mach numbers, angle of attack, and static control deflections are included. Cases for all three types of flutter instability are selected. In addition some cases are included for dynamic response measurements during forced oscillations of the controls on the flexible mount. An overview of the model and tests is given, and the standard formulary for these data is listed. Some sample data and sample results of calculations are presented. Only the static pressures and the first harmonic real and imaginary parts of the pressures are included in the data for the Test Cases, but digitized time histories have been archived. The data for the Test Cases are also available as separate electronic files.

The prevalence and virulence characteristics of enteroaggregative Escherichia coli at an urgent-care clinic in the USA: a case-control study.

PubMed

Cennimo, David; Abbas, Atif; Huang, David B; Chiang, Tom

2009-04-01

This case-control study examined the prevalence of enteroaggregative Escherichia coli (EAEC), its genes and elicited inflammatory response, and the stool characteristics of adult patients with and without acute diarrhoeal illness presenting to an urgent-care clinic in the USA. A total of 1004 individual stool specimens (253 from patients with acute diarrhoeal illness and 751 from patients without diarrhoeal illness) were collected between 1 June 2003 and 30 June 2008. EAEC was identified as the sole cause of acute diarrhoeal illness in 6 % (n=15) of patients and in 2 % (n=15) without diarrhoeal illness. Control patients (n=15) were similar to case patients (n=15) for age, gender and co-morbidities. The EAEC genes aggR, aap, aat, astA and/or set1A were identified more frequently in case patients compared with control patients (P <0.05). aggR-positive EAEC elicited higher levels of interleukin (IL)-1ra, IL-6, IL-8 and tumour necrosis factor-alpha compared with aggR-negative EAEC during co-incubation with HCT-8 cells. Patients with EAEC diarrhoea and isolates with the genes aggR, aap, aatA, astA or set1A had stools characterized by gross mucus and the presence of faecal leukocytes (P <0.05). These results indicate that EAEC is a potential cause of acute diarrhoeal illness affecting patients presenting to an acute-care clinic in the USA and suggest that aggR, aap, aatA, astA and set1A may be markers for virulence.

Childhood Leukemia and 50 Hz Magnetic Fields: Findings from the Italian SETIL Case-Control Study

PubMed Central

Salvan, Alberto; Ranucci, Alessandra; Lagorio, Susanna; Magnani, Corrado

2015-01-01

We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0–10 years at diagnosis in 1998–2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24–48 h), in the child’s bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 μT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 μT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 μT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk. PMID:25689995

Association between age and high-risk human papilloma virus in Mexican oral cancer patients.

PubMed

González-Ramírez, I; Irigoyen-Camacho, M E; Ramírez-Amador, V; Lizano-Soberón, M; Carrillo-García, A; García-Carrancá, A; Sánchez-Pérez, Y; Méndez-Martínez, R; Granados-García, M; Ruíz-Godoy, Lm; García-Cuellar, Cm

2013-11-01

Studies reporting low prevalence of HPV in OSCC with declining age at presentation are increasing. The aim of this study was to determine the prevalence of HPV in a group of OSCC cases and controls in a Mexican population. The matched case-control study included 80 OSCC cases and 320 controls. HPV/DNA presence was evaluated through PCR amplification using three sets of consensus primers for the L1 gene. A conditional logistic regression analysis was carried out for the matched OSCC cases and controls. Interactions between risk factors and OCSS were tested in the construction process of the models. HPV prevalence was 5% in OSCC cases and 2.5% in controls. HPV-detected types were 16, 18 and 56. According to conditional logistics regression model, an association was detected between HR-HPV and OSCC. All HR-HPV-positive OSCC cases corresponded to young patients (<45 years), non-smokers and non-alcohol drinkers. The HR-HPV can be a contributing factor to oral carcinogenesis, especially in younger individuals without known risk factors such as tobacco and alcohol. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Legionnaires' disease outbreak in an automobile engine manufacturing plant.

PubMed

Fry, Alicia M; Rutman, Miai; Allan, Terry; Scaife, Heidi; Salehi, Ellen; Benson, Robert; Fields, Barry; Nowicki, Scott; Parrish, Mary Kay; Carpenter, Joseph; Brown, Ellen; Lucas, Claressa; Horgan, Timothy; Koch, Elizabeth; Besser, Richard E

2003-03-15

We investigated 4 cases of legionnaires' disease (LD) reported among workers at an Ohio automotive plant in March 2001. A "confirmed" case of LD was defined as x-ray-confirmed pneumonia and a confirmatory laboratory test. A "possible" case of LD was defined as elevated titers of antibody and respiratory symptoms. Legionella pneumophila serogroup 1 (LP1) was isolated from 1 case patient. Legionella was isolated from 18 (9%) of 197 environmental samples; 3 isolates were LP1 but did not match the case isolate. We conducted a case-control study; 17 case patients with confirmed or possible LD and 86 control subjects (workers with low antibody titers and without symptoms) were enrolled. Visiting a specific cleaning line (odds ratio, [OR], 7.29; 95% confidence interval [CI], 2.31-23.00) and working in the cleaning region of the plant (OR, 3.22; 95% CI, 1.11-9.38) were associated with LD. LD can be transmitted in industrial settings in which aerosols are produced. Clinicians should consider LD when treating persons from these settings for pneumonia.

New ideas for shallow gas well control

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

Bourgoyne, A.T.; Kelly, O.A.; Sandoz, C.L.

1996-06-01

Flow from an unexpected shallow gas sand is one of the most difficult well control problems faced by oil and gas well operators during drilling operations. Current well control practice for bottom-supported marine rigs usually calls for shutting in the well when a kick is detected, if sufficient casing has been set to keep any flow underground. However, when shallow gas is encountered, casing may not be set deep enough to keep the underground flow from broaching to surface near the platform foundations. Once the flow reaches surface, craters are sometimes formed which can lead to loss of the rigmore » and associated marine structures. This short article overviews an ongoing study by Louisiana State University of the breakdown resistance of shallow marine sediments, using leak-off test data and geotechnical reports provided by Unocal. Such study is important for improving the characterization of shallow marine sediments to allow more reliable shallow casing designs, as the authors will conclude. This study has already proven that sediment failure mechanisms that lead to cratering have been poorly understood. In addition, there has been considerable uncertainty as to the best choices of well design parameters and well control contingency plans that will minimize risks associated with a shallow gas flow.« less

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

Buckdahn, Rainer, E-mail: Rainer.Buckdahn@univ-brest.fr; Li, Juan, E-mail: juanli@sdu.edu.cn; Ma, Jin, E-mail: jinma@usc.edu

In this paper we study the optimal control problem for a class of general mean-field stochastic differential equations, in which the coefficients depend, nonlinearly, on both the state process as well as of its law. In particular, we assume that the control set is a general open set that is not necessary convex, and the coefficients are only continuous on the control variable without any further regularity or convexity. We validate the approach of Peng (SIAM J Control Optim 2(4):966–979, 1990) by considering the second order variational equations and the corresponding second order adjoint process in this setting, and wemore » extend the Stochastic Maximum Principle of Buckdahn et al. (Appl Math Optim 64(2):197–216, 2011) to this general case.« less

Methodological Issues in Design and Analysis of a Matched Case-Control Study of a Vaccine’s Effectiveness

PubMed Central

Niccolai, Linda M.; Ogden, Lorraine G.; Muehlenbein, Catherine E.; Dziura, James D.; Vázquez, Marietta; Shapiro, Eugene D.

2007-01-01

Objective Case-control studies of the effectiveness of a vaccine are useful to answer important questions, such as the effectiveness of a vaccine over time, that usually are not addressed by pre-licensure clinical trials of the vaccine’s efficacy. This report describes methodological issues related to design and analysis that were used to determine the effects of time since vaccination and age at the time of vaccination. Study Design and Setting A matched case-control study of the effectiveness of varicella vaccine. Results Sampling procedures and conditional logistic regression models including interaction terms are described. Conclusion Use of these methods will allow investigators to assess the effects of a wide range of variables, such as time since vaccination and age at the time of vaccination, on the effectiveness of a vaccine. PMID:17938054

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.

PubMed

Elmore, James R; Obmann, Melissa A; Kuivaniemi, Helena; Tromp, Gerard; Gerhard, Glenn S; Franklin, David P; Boddy, Amy M; Carey, David J

2009-06-01

The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. A genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. This study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

PubMed

Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

2013-04-01

Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

An integrated methods study of the experiences of youth with severe disabilities in leisure activity settings: the importance of belonging, fun, and control and choice.

PubMed

King, Gillian; Gibson, Barbara E; Mistry, Bhavnita; Pinto, Madhu; Goh, Freda; Teachman, Gail; Thompson, Laura

2014-01-01

The aim was to examine the leisure activity setting experiences of two groups of youth with severe disabilities - those with complex continuing care (CCC) needs and those who have little functional speech and communicate using augmentative and alternative communication (AAC). Twelve youth took part in a mixed methods study, in which their experiences were ascertained using qualitative methods (observations, photo elicitation and interviews) and the measure of Self-Reported Experiences of Activity Settings (SEAS). Data integration occurred using a "following a thread" technique and case-by-case analysis. The analysis revealed several highly valued aspects of leisure activity setting experiences for youth, including engagement with others, enjoying the moment, and control and choice in selection and participation in activity settings. The findings provide preliminary insights into the nature of optimal activity settings for youth with severe disabilities, and the mediators of these experiences. Compared to other youth, the data illustrate both the commonalities of experiences and differences in the ways in which these experiences are attained. Implications for research concern the utility of mixed methods approaches in understanding the complex nature of participation experiences. Implications for clinical practice concern the importance of not assuming the nature of youths' experiences.

Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.

PubMed

Schwartz, Lauren M; Halloran, M Elizabeth; Rowhani-Rahbar, Ali; Neuzil, Kathleen M; Victor, John C

2017-01-03

The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Pattern-Based Design of Insider Threat Programs

DTIC Science & Technology

2014-12-01

also applied these models to develop best practices and technical controls for mitigating insider threat. In some cases of in- sider threat...departing insiders might take valuable IP with them. One set of practices and controls designed to reduce the risk of insider IP theft is based on case data...describing this set of practices and controls helps to balance the costs of monitoring employee behavior for suspicious actions against the risk of

Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

PubMed

Koster, Roelof; Mitra, Nandita; D'Andrea, Kurt; Vardhanabhuti, Saran; Chung, Charles C; Wang, Zhaoming; Loren Erickson, R; Vaughn, David J; Litchfield, Kevin; Rahman, Nazneen; Greene, Mark H; McGlynn, Katherine A; Turnbull, Clare; Chanock, Stephen J; Nathanson, Katherine L; Kanetsky, Peter A

2014-11-15

Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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.

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.

Job and industry classifications associated with sarcoidosis in A Case-Control Etiologic Study of Sarcoidosis (ACCESS).

PubMed

Barnard, Juliana; Rose, Cecile; Newman, Lee; Canner, Martha; Martyny, John; McCammon, Chuck; Bresnitz, Eddy; Rossman, Milt; Thompson, Bruce; Rybicki, Benjamin; Weinberger, Steven E; Moller, David R; McLennan, Geoffrey; Hunninghake, Gary; DePalo, Louis; Baughman, Robert P; Iannuzzi, Michael C; Judson, Marc A; Knatterud, Genell L; Teirstein, Alvin S; Yeager, Henry; Johns, Carol J; Rabin, David L; Cherniack, Reuben

2005-03-01

To determine whether specific occupations and industries may be associated with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) obtained occupational and environmental histories on 706 newly diagnosed sarcoidosis cases and matched controls. We used Standard Industrial Classification (SIC) and Standard Occupational Classification (SOC) to assess occupational contributions to sarcoidosis risk. Univariable analysis identified elevated risk of sarcoidosis for workers with industrial organic dust exposures, especially in Caucasian workers. Workers for suppliers of building materials, hardware, and gardening materials were at an increased risk of sarcoidosis as were educators. Work providing childcare was negatively associated with sarcoidosis risk. Jobs with metal dust or metal fume exposures were negatively associated with sarcoidosis risk, especially in Caucasian workers. In this study, we found that exposures in particular occupational settings may contribute to sarcoidosis risk.

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Alternative approaches to analytical designs in occupational injury epidemiology.

PubMed

Mittleman, M A; Maldonado, G; Gerberich, S G; Smith, G S; Sorock, G S

1997-08-01

In this paper, we discuss the theoretical framework upon which observational studies of occupational injuries are based. Following a general description of how causal effects are estimated, the challenges faced by researchers working in this area are outlined, with an emphasis on case-control studies. These challenges include defining the at-risk period for workers whose tasks change over time and whose hazard period may be very brief, evaluating the underreporting of both exposures and injuries, and considering the effects of multiple injuries per individual on study design and data analysis. We review both the theoretical and practical considerations in the design and conduct of traditional case-control studies, based on the collection of individual level data, as well as other approaches, such as using information culled from administrative and descriptive databases, and case-control studies in which the plant or work site is the unit of analysis. The case-crossover design is also reviewed and its utility for reducing confounding due to differences between individuals by self-matching is highlighted. While this design has not yet been applied to the work setting, its potential for increasing our understanding of the causes of acute-onset occupational injuries seems promising. Finally, a variety of hybrid designs are discussed, including combinations of case-control, case-crossover, and cohort designs.

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus

PubMed Central

Ho, Daniel W. H.; Yap, Maurice K. H.; Ng, Po Wah; Fung, Wai Yan; Yip, Shea Ping

2012-01-01

Background Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified. Methodology/Principal Findings Two independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent ≤ -8 dioptres and emmetropic controls by spherical equivalent within ±1.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on initial and replication studies, rs2009066 located in the crystallin beta A4 (CRYBA4) gene was identified to be the most significantly associated with high myopia (initial study: P = 0.02; replication study: P = 1.88e-4; meta-analysis: P = 1.54e-5) among all the SNPs tested. The association result survived correction for multiple comparisons. Under the allelic genetic model for the combined sample set, the odds ratio of the minor allele G was 1.41 (95% confidence intervals, 1.21-1.64). Conclusions/Significance A novel susceptibility gene (CRYBA4) was discovered for high myopia. Our study also signified the potential importance of appropriate gene prioritization in candidate selection. PMID:22792142

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

PubMed

Andersen, Allan M; Pietrzak, Robert H; Kranzler, Henry R; Ma, Li; Zhou, Hang; Liu, Xiaoming; Kramer, John; Kuperman, Samuel; Edenberg, Howard J; Nurnberger, John I; Rice, John P; Tischfield, Jay A; Goate, Alison; Foroud, Tatiana M; Meyers, Jacquelyn L; Porjesz, Bernice; Dick, Danielle M; Hesselbrock, Victor; Boerwinkle, Eric; Southwick, Steven M; Krystal, John H; Weissman, Myrna M; Levinson, Douglas F; Potash, James B; Gelernter, Joel; Han, Shizhong

2017-11-01

Major depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive. To examine whether AD and MDD overlap genetically, using a polygenic score approach. Association analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P < .05 to P ≤ .99 in each AD GWAS data set. Association between MDD PRS and AD. Participants analyzed included 788 cases (548 [69.5%] men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P = 1.7 × 10-6, R2 = 0.026; SAGE: best P = .001, R2 = 0.01; Yale-Penn: best P = .035, R2 = 0.0018; and NHRVS: best P = .004, R2 = 0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P = 3.3 × 10-9). In analyses adjusted for MDD status in 3 AD GWAS data sets, similar patterns of association were observed (COGA: best P = 7.6 × 10-6, R2 = 0.023; Yale-Penn: best P = .08, R2 = 0.0013; and NHRVS: best P = .006, R2 = 0.0072). After recalculating MDD PRS using MDD GWAS data sets without comorbid MDD-AD cases, significant evidence was observed for an association between the MDD PRS and AD in the meta-analysis of 3 GWAS AD samples without MDD cases (best P = .007). These results suggest that shared genetic susceptibility contributes modestly to MDD and AD comorbidity. Individuals with elevated polygenic risk for MDD may also be at risk for AD.

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.

Suppression of Bark Beetles and Protection of Pines in the Urban Environment: A Case Study

Treesearch

Jane Leslie Hayes; James R. Meeker; John L. Foltz; Brian L. Strom

1996-01-01

Southern pine beetles (SPB), and associated bark beetles, have long been recognized as major pests of southern forests. Tactics used for controlling infestations in conventional forest settings have not proven effective at achieving area-wide control, nor are they suitable for the control of infestations in high-value stands such as homesites or wildlife habitat areas...

A modified case-control study of cryptosporidiosis (using non-Cryptosporidium-infected enteric cases as controls) in a community setting.

PubMed

Pintar, K D M; Pollari, F; Waltner-Toews, D; Charron, D F; McEwen, S A; Fazil, A; Nesbitt, A

2009-12-01

Data from the first sentinel site (Waterloo Region, Ontario) of the Canadian Integrated Enteric Disease Surveillance System (C-EnterNet) were used in a secondary-based case-control study of laboratory-confirmed Cryptosporidium infections to study the role of various exposure factors. The incidence of cryptosporidiosis in Waterloo Region was almost double both the provincial and national rates. Persons ill with one of nine other enteric infections (amoebiasis, campylobacteriosis, cyclosporiasis, giardiasis, listeriosis, salmonellosis, shigellosis, verotoxigenic E. coli infections, yersiniosis) captured by the surveillance system were used as the control group. Of 1204 cases of enteric illness in the sentinel area between April 2005 and December 2007, 36 cases and 803 controls were selected after excluding outbreak and international travel-related cases. Univariable analyses (Pearson chi2 and Fisher's exact tests) and multivariable logistic regression were performed. Results of the multivariable analysis found that cryptosporidiosis was associated with swimming in a lake or river (OR 2.9, 95% CI 1.2-7.4), drinking municipal water (a potential surrogate for urban respondents vs. rural) (OR 2.4, 95% CI 1.04-5.7), and having a family member with a diarrhoeal illness (OR 2.9, 95% CI 1.3-6.4).

Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico.

PubMed

Falcón-Lezama, Jorge Abelardo; Santos-Luna, René; Román-Pérez, Susana; Martínez-Vega, Ruth Aralí; Herrera-Valdez, Marco Arieli; Kuri-Morales, Ángel Fernando; Adams, Ben; Kuri-Morales, Pablo Antonio; López-Cervantes, Malaquías; Ramos-Castañeda, José

2017-01-01

Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority's administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.

Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico

PubMed Central

Falcón-Lezama, Jorge Abelardo; Santos-Luna, René; Román-Pérez, Susana; Martínez-Vega, Ruth Aralí; Herrera-Valdez, Marco Arieli; Kuri-Morales, Ángel Fernando; Adams, Ben; Kuri-Morales, Pablo Antonio; López-Cervantes, Malaquías

2017-01-01

Introduction Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. Materials and methods We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. Results Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. Conclusions Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies. PMID:28225820

From orphan virus to pathogen: the path to the clinical lab.

PubMed

Li, Linlin; Delwart, Eric

2011-10-01

Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum can temporarily link symptoms with a recent infection. Neutralizing antibody detection require often difficult cell culture virus amplification. Antibody binding assays require proper antigen synthesis and positive control sera to set assay thresholds. High levels of viral genetic diversity within orphan viral groups, frequent co-infections, low or rare pathogenicity, and chronic virus shedding, can all complicate disease association studies. The limited availability of matched cases and controls sample sets from different age groups and geographic origins is a major block for estimating the pathogenic potential of recently characterized orphan viruses. Current limitations on the practical use of deep sequencing for viral diagnostics are listed.

Analysis of Clinical Cohort Data Using Nested Case-control and Case-cohort Sampling Designs. A Powerful and Economical Tool.

PubMed

Ohneberg, K; Wolkewitz, M; Beyersmann, J; Palomar-Martinez, M; Olaechea-Astigarraga, P; Alvarez-Lerma, F; Schumacher, M

2015-01-01

Sampling from a large cohort in order to derive a subsample that would be sufficient for statistical analysis is a frequently used method for handling large data sets in epidemiological studies with limited resources for exposure measurement. For clinical studies however, when interest is in the influence of a potential risk factor, cohort studies are often the first choice with all individuals entering the analysis. Our aim is to close the gap between epidemiological and clinical studies with respect to design and power considerations. Schoenfeld's formula for the number of events required for a Cox' proportional hazards model is fundamental. Our objective is to compare the power of analyzing the full cohort and the power of a nested case-control and a case-cohort design. We compare formulas for power for sampling designs and cohort studies. In our data example we simultaneously apply a nested case-control design with a varying number of controls matched to each case, a case cohort design with varying subcohort size, a random subsample and a full cohort analysis. For each design we calculate the standard error for estimated regression coefficients and the mean number of distinct persons, for whom covariate information is required. The formula for the power of a nested case-control design and the power of a case-cohort design is directly connected to the power of a cohort study using the well known Schoenfeld formula. The loss in precision of parameter estimates is relatively small compared to the saving in resources. Nested case-control and case-cohort studies, but not random subsamples yield an attractive alternative for analyzing clinical studies in the situation of a low event rate. Power calculations can be conducted straightforwardly to quantify the loss of power compared to the savings in the num-ber of patients using a sampling design instead of analyzing the full cohort.

Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data

PubMed Central

Randerson-Moor, Juliette A.; Taylor, John C.; Elliott, Faye; Chang, Yu-Mei; Beswick, Samantha; Kukalizch, Kairen; Affleck, Paul; Leake, Susan; Haynes, Sue; Karpavicius, Birute; Marsden, Jerry; Gerry, Edwina; Bale, Linda; Bertram, Chandra; Field, Helen; Barth, Julian; dos Santos Silva, Isabel; Swerdlow, Anthony; Kanetsky, Peter A.; Barrett, Jennifer H.; Bishop, D. Timothy; Bishop, Julia A. Newton

2009-01-01

We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D3 levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascertained cases and 402 controls from Leeds, UK. In a second Leeds case-control study (299 cases and 560 controls) the FokI T allele was associated with increased melanoma risk (OR 1.42, 95% CI 1.06-1.91, p=0.02). In a meta-analysis in conjunction with published data from other smaller data sets (total 3769 cases and 3636 controls), the FokI T allele was associated with increased melanoma risk (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.05-1.35), and the BsmI A allele was associated with a reduced risk (OR 0.81, 95% CI 0.72-0.92), in each instance under a parsimonious dominant model. In the first Leeds case-control comparison cases were more likely to have a higher body mass index (BMI) than controls (p=0.007 for linear trend). There was no evidence of a case-control difference in serum 25-hydroxyvitamin D3 levels. In 1043 incident cases from the first Leeds case-control study, a single estimation of serum 25-hydroxyvitamin D3 level taken at recruitment was inversely correlated with Breslow thickness (p=0.03 for linear trend). These data provide evidence to support the view that vitamin D and VDR may have a small but potentially important role in melanoma susceptibility, and putatively a greater role in disease progression. PMID:19615888

Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer.

PubMed

Tamura, Koji; Yu, Jun; Hata, Tatsuo; Suenaga, Masaya; Shindo, Koji; Abe, Toshiya; MacGregor-Das, Anne; Borges, Michael; Wolfgang, Christopher L; Weiss, Matthew J; He, Jin; Canto, Marcia Irene; Petersen, Gloria M; Gallinger, Steven; Syngal, Sapna; Brand, Randall E; Rustgi, Anil; Olson, Sara H; Stoffel, Elena; Cote, Michele L; Zogopoulos, George; Potash, James B; Goes, Fernando S; McCombie, Richard W; Zandi, Peter P; Pirooznia, Mehdi; Kramer, Melissa; Parla, Jennifer; Eshleman, James R; Roberts, Nicholas J; Hruban, Ralph H; Klein, Alison Patricia; Goggins, Michael

2018-05-01

To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of CPB1 and other genes encoding pancreatic secretory enzymes and known pancreatitis susceptibility genes ( PRSS1 , CPA1 , CTRC , and SPINK1 ) in a hospital series of pancreatic cancer cases and controls. Variants in CPB1 , CPA1 (encoding carboxypeptidase B1 and A1), and CTRC were evaluated in a second set of cases with familial pancreatic cancer and controls. More deleterious CPB1 variants, defined as having impaired protein secretion and induction of endoplasmic reticulum (ER) stress in transfected HEK 293T cells, were found in the hospital series of pancreatic cancer cases (5/986, 0.5%) than in controls (0/1,045, P = 0.027). Among familial pancreatic cancer cases, ER stress-inducing CPB1 variants were found in 4 of 593 (0.67%) vs. 0 of 967 additional controls ( P = 0.020), with a combined prevalence in pancreatic cancer cases of 9/1,579 vs. 0/2,012 controls ( P < 0.01). More ER stress-inducing CPA1 variants were also found in the combined set of hospital and familial cases with pancreatic cancer than in controls [7/1,546 vs. 1/2,012; P = 0.025; odds ratio, 9.36 (95% CI, 1.15-76.02)]. Overall, 16 (1%) of 1,579 pancreatic cancer cases had an ER stress-inducing CPA1 or CPB1 variant, compared with 1 of 2,068 controls ( P < 0.00001). No other candidate genes had statistically significant differences in variant prevalence between cases and controls. Our study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development.

An Evaluation of Mass Screening Using Fecal Occult Blood Test for Colorectal Cancer in Japan: A Case‐Control Study

PubMed Central

Hiwatashi, Nobuo; Morimoto, Tomizo; Fukao, Akira; Sato, Hirofusa; Sugahara, Nobuyuki; Hisamichi, Shigeru; Toyota, Takayoshi

1993-01-01

There is as yet no firm evidence showing that mass screening for colorectal cancer using fecal occult blood tests (FOBTs) reduces the mortality from this cancer. Therefore we evaluated the effectiveness of the screening by a case‐control study in Miyagi Prefecture, Japan. The study included as case subjects 28 individuals who had died from colorectal cancer and had had an opportunity to participate in the mass screening before the date of diagnosis as colorectal cancer, and 3 controls for each case subject randomly selected from residents who were alive on the date of death of case subjects and matched by sex, age (within 3 years) and living area using residential files. For each set, i.e., a case subject and 3 controls, screening histories before the date of the diagnosis of the case as colorectal cancer were examined. Both the case subjects and the controls who had participated in the screening at least once within 3 years before the date of diagnosis of the case were classified as “screened.” The 28 case subjects consisted of 12 males and 16 females (average age: 60.8 years). The odds ratio of death from colorectal cancer for the screened versus the non‐screened persons was 0.24 (95% confidence interval = 0.08–0.76) by the Mantel‐Haenszel method. The present study suggests that mass screening using FOBTs for colorectal cancer significantly reduces the mortality from this cancer epidemiologically. PMID:8276715

Genome-wide Association Study of Obsessive-Compulsive Disorder

PubMed Central

Stewart, S Evelyn; Yu, Dongmei; Scharf, Jeremiah M; Neale, Benjamin M; Fagerness, Jesen A; Mathews, Carol A; Arnold, Paul D; Evans, Patrick D; Gamazon, Eric R; Osiecki, Lisa; McGrath, Lauren; Haddad, Stephen; Crane, Jacquelyn; Hezel, Dianne; Illman, Cornelia; Mayerfeld, Catherine; Konkashbaev, Anuar; Liu, Chunyu; Pluzhnikov, Anna; Tikhomirov, Anna; Edlund, Christopher K; Rauch, Scott L; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, Stephan; Grabe, Hans-Jörgen; Lennertz, Leonard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A; Cook, Edwin H; Kennedy, James L; Rosenberg, David; Stein, Dan J; Hemmings, Sian MJ; Lochner, Christine; Azzam, Amin; Chavira, Denise A; Fournier, Eduardo; Garrido, Helena; Sheppard, Brooke; Umaña, Paul; Murphy, Dennis L; Wendland, Jens R; Veenstra-VanderWeele, Jeremy; Denys, Damiaan; Blom, Rianne; Deforce, Dieter; Van Nieuwerburgh, Filip; Westenberg, Herman GM; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripedes Constantino; Cappi, Carolina; Hounie, Ana G; Conceição do Rosário, Maria; Sampaio, Aline S; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatriz; Delorme, Richard; Leboyer, Marion; Pato, Carlos N; Pato, Michele T; Voyiaziakis, Emanuel; Heutink, Peter; Cath, Danielle C; Posthuma, Danielle; Smit, Jan H; Samuels, Jack; Bienvenu, O Joseph; Cullen, Bernadette; Fyer, Abby J; Grados, Marco A; Greenberg, Benjamin D; McCracken, James T; Riddle, Mark A; Wang, Ying; Coric, Vladimir; Leckman, James F; Bloch, Michael; Pittenger, Christopher; Eapen, Valsamma; Black, Donald W; Ophoff, Roel A; Strengman, Eric; Cusi, Daniele; Turiel, Maurizio; Frau, Francesca; Macciardi, Fabio; Gibbs, J Raphael; Cookson, Mark R; Singleton, Andrew; Hardy, John; Crenshaw, Andrew T; Parkin, Melissa A; Mirel, Daniel B; Conti, David V; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L; Jenike, Michael A; Knowles, James A; Cox, Nancy; Pauls, David L

2014-01-01

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

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.

A case-control study to investigate the association between exposure to benzene and deaths from leukaemia in oil refinery workers.

PubMed

Rushton, L; Alderson, M R

1981-01-01

All deaths with a mention of leukaemia on the death certificate, in men employed over a period of 25 years of 8 oil refineries in the U.K. were identified. The potential benzene exposure of these cases was compared with that of two sets of controls selected from the total refinery population. One set of controls was matched for refinery and year of birth, the other set was matched for refinery, year of birth nd length of service. No information was available on measurement of benzene in the work environment but a job history was obtained from refinery personnel records for all cases and controls. This was used to allocate each man to a benzene exposure level of "low", "medium", or "high". There was no overall excess of deaths from leukaemia when compared with the expectation from national rates. There was also no excess of cytological types of leukaemia which have been shown to be particularly associated with benzene exposure. However, the risk for those men with medium or high exposure relative to the risk for those with low benzene exposure approached a significance (P=0.05) when length of service was taken into account. If there were an increased risk of leukaemia due to benzene exposure, it could have only been one that affected a very small proportion of men within the refinery workforce.

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.

Potential Immunological Biomarkers for Detection of Mycobacterium tuberculosis Infection in a Setting Where M. tuberculosis Is Endemic, Ethiopia.

PubMed

Teklu, Takele; Kwon, Keehwan; Wondale, Biniam; HaileMariam, Milkessa; Zewude, Aboma; Medhin, Girmay; Legesse, Mengistu; Pieper, Rembert; Ameni, Gobena

2018-04-01

Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate Mycobacterium tuberculosis infection outcomes in a setting where it is endemic, Ethiopia. Whole blood from 90 participants was stimulated using the ESAT-6/CFP-10 antigen cocktail. The interferon gamma (IFN-γ)-based QuantiFERON diagnostic test was used to distinguish between LTBI and uninfected control cases. Forty cytokines/chemokines were detected from antigen-stimulated plasma supernatants (SPSs) and unstimulated plasma samples (UPSs) using human cytokine/chemokine antibody microarrays. Statistical tests allowed us to identify potential biomarkers that distinguish the TB, LTBI, and healthy control groups. As expected, the levels of IFN-γ in SPSs returned a high area under the receiver operating characteristic curve (AUC) value comparing healthy controls and LTBI cases (Z = 0.911; P < 0.001). The SPS data also indicated that interleukin 17 (IL-17) abundance discriminates LTBI from healthy controls (Z = 0.763; P = 0.001). RANTES and MIP-1β were significantly elevated in SPSs of TB-infected compared to healthy controls ( P < 0.05), while IL-12p40 and soluble tumor necrosis factor receptor II (sTNF-RII) were significantly increased in active TB cases compared to the combined LTBI and control groups ( P < 0.05). Interestingly, quantitative changes for RANTES were observed using both SPSs and UPSs, with P values of 0.013 and 0.012, respectively, in active TB versus LTBI cases and 0.001 and 0.002, respectively, in active TB versus healthy controls. These results encourage biomarker verification studies for IL-17 and RANTES. Combinations of these cytokines may complement IFN-γ measurements to diagnose LTBI and distinguish active TB from LTBI cases. Copyright © 2018 American Society for Microbiology.

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

PubMed

Chung, Philip; Currie, Brian; Guo, Yi; Talansky, Moshe; Brown, Shakara; Ostrowsky, Belinda

2014-10-01

Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high-risk antibiotics associated with CDI. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Case control study of rotavirus vaccine effectiveness in Portugal during 6 years of private market use.

PubMed

Marlow, Robin; Ferreira, Muriel; Cordeiro, Eugénio; Trotter, Caroline; Januário, Luis; Finn, Adam; Rodrigues, Fernanda

2015-05-01

Although recommended by the vaccine committee of the Portuguese Paediatric Society, rotavirus vaccines have not been included in the routine immunization schedule. They have been available privately since 2006 with estimated coverage reaching approximately 30%. However, unlike other European countries using the vaccine, sentinel surveillance has detected fluctuations but no clear trends in the rate of gastrointestinal disease presentations. In this study, we set out to establish the real world effectiveness of rotavirus immunization in this low vaccine coverage setting. We carried out a test-negative case control study on a population of children attending a regional pediatric hospital, between 2006 and 2012, with symptoms of acute gastroenteritis and producing a stool sample for routine rotavirus testing. We calculated exposure odds ratio (ratio of odds of antecedent vaccination among cases compared with controls) to derive vaccine effectiveness ([1 - adjusted odds ratio]/100) against both hospital attendance and admission. Vaccine effectiveness against attendance with rotavirus acute gastroenteritis was 83.7% (95% confidence interval: 73.9-89.8) and against hospital admission was 96.1% (95% confidence interval: 83.8-99.1). No significant difference between the 2 available vaccines was detected. Both rotavirus vaccines offer a high degree of individual protection in this population.

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

Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study

PubMed Central

Zmirou, D; Gauvin, S; Pin, I; Momas, I; Sahraoui, F; Just, J; Le Moullec, Y; Bremont, F; Cassadou, S; Reungoat, P; Albertini, M; Lauvergne, N; Chiron, M; Labbe, A

2004-01-01

Study objective: The Vesta project aims to assess the role of traffic related air pollution in the occurrence of childhood asthma. Design and setting: Case-control study conducted in five French metropolitan areas between 1998 and 2000. A set of 217 pairs of matched 4 to 14 years old cases and controls were investigated. An index of lifelong exposure to traffic exhausts was constructed, using retrospective information on traffic density close to all home and school addresses since birth; this index was also calculated for the 0–3 years age period to investigate the effect of early exposures. Main results: Adjusted on environmental tobacco smoke, personal and parental allergy, and several confounders, lifelong exposure was not associated with asthma. In contrast, associations before age of 3 were significant: odds ratios for tertiles 2 and 3 of the exposure index, relative to tertile 1, exhibited a positive trend (1.48 (95%CI = 0.7 to 3.0) and 2.28 (1.1 to 4.6)), with greater odds ratios among subjects with positive skin prick tests. Conclusions: These results suggest that traffic related pollutants might have contributed to the asthma epidemic that has taken place during the past decades among children. PMID:14684722

Stability analysis of multiple-robot control systems

NASA Technical Reports Server (NTRS)

Wen, John T.; Kreutz, Kenneth

1989-01-01

In a space telerobotic service scenario, cooperative motion and force control of multiple robot arms are of fundamental importance. Three paradigms to study this problem are proposed. They are distinguished by the set of variables used for control design. They are joint torques, arm tip force vectors, and an accelerated generalized coordinate set. Control issues related to each case are discussed. The latter two choices require complete model information, which presents practical modeling, computational, and robustness problems. Therefore, focus is on the joint torque control case to develop relatively model independent motion and internal force control laws. The rigid body assumption allows the motion and force control problems to be independently addressed. By using an energy motivated Lyapunov function, a simple proportional derivative plus gravity compensation type of motion control law is always shown to be stabilizing. The asymptotic convergence of the tracing error to zero requires the use of a generalized coordinate with the contact constraints taken into account. If a non-generalized coordinate is used, only convergence to a steady state manifold can be concluded. For the force control, both feedforward and feedback schemes are analyzed. The feedback control, if proper care has been taken, exhibits better robustness and transient performance.

Two-speed phacoemulsification for soft cataracts using optimized parameters and procedure step toolbar with the CENTURION Vision System and Balanced Tip.

PubMed

Davison, James A

2015-01-01

To present a cause of posterior capsule aspiration and a technique using optimized parameters to prevent it from happening when operating soft cataracts. A prospective list of posterior capsule aspiration cases was kept over 4,062 consecutive cases operated with the Alcon CENTURION machine and Balanced Tip. Video analysis of one case of posterior capsule aspiration was accomplished. A surgical technique was developed using empirically derived machine parameters and customized setting-selection procedure step toolbar to reduce the pace of aspiration of soft nuclear quadrants in order to prevent capsule aspiration. Two cases out of 3,238 experienced posterior capsule aspiration before use of the soft quadrant technique. Video analysis showed an attractive vortex effect with capsule aspiration occurring in 1/5 of a second. A soft quadrant removal setting was empirically derived which had a slower pace and seemed more controlled with no capsule aspiration occurring in the subsequent 824 cases. The setting featured simultaneous linear control from zero to preset maximums for: aspiration flow, 20 mL/min; and vacuum, 400 mmHg, with the addition of torsional tip amplitude up to 20% after the fluidic maximums were achieved. A new setting selection procedure step toolbar was created to increase intraoperative flexibility by providing instantaneous shifting between the soft and normal settings. A technique incorporating a reduced pace for soft quadrant acquisition and aspiration can be accomplished through the use of a dedicated setting of integrated machine parameters. Toolbar placement of the procedure button next to the normal setting procedure button provides the opportunity to instantaneously alternate between the two settings. Simultaneous surgeon control over vacuum, aspiration flow, and torsional tip motion may make removal of soft nuclear quadrants more efficient and safer.

Appendectomy, smoking habits and the risk of developing ulcerative colitis: a case control study in private practice setting.

PubMed

de Saussure, Philippe; Clerson, Pierre; Prost, Pierre-Louis; Truong Tan, Nghiep; Bouhnik, Yoram; Gil-Rch

2007-05-01

The strongest environmental factors identified for ulcerative colitis (UC) are cigarette smoking and appendectomy. However, most studies have been performed using case-controls from hospital-based populations. The purpose of this study was to compare the history of previous appendectomy and smoking habits in a group of patients with UC and a control group, followed by gastroenterologists in private practice. We performed a case control study in which 100 physicians recruited UC-patients and age and sex matched controls. Data were collected during a single visit. Based on a standardized questionnaire, UC patients and controls were divided into never, former or current smokers, and into subjects with or without a previous history of appendectomy. One hundred and ninety eight age- and sex-matched pairs of UC patients and controls were included. The prevalence of appendectomy in the UC-patients and control group was 12% and 46%, respectively. The pairwise-matched OR of ulcerative colitis for previous appendectomy was 0.10 (95% CI, 0.05-0.21) (P<0.0001). The OR for former and never smokers versus current smokers was 2.40 (95% CI 1.31-4.38) (P=0.004). In UC-patients, the OR of family history of UC compared with controls was 2.80 (95% CI, 1.01-7.77) (P=0.048). This case-control study confirmed a strong negative correlation between both appendectomy and tobacco smoking, and ulcerative colitis in patients followed-up by gastroenterological practitioners.

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

PCMO L01-Setting Specifications for Biological Investigational Medicinal Products.

PubMed

Krause, Stephan O

2015-01-01

This paper provides overall guidance and best practices for the setting of specifications for clinical biological drug substances and drug products within the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11], quality risk management (Q9), and quality systems (Q10). A review is provided of the current regulatory expectations for the specification setting process as part of a control strategy during product development, pointing to existing challenges for the investigational new drug/investigational medicinal product dossier (IND/IMPD) sponsor. A case study illustrates how the investigational medicinal product specification revision process can be managed within a flexible quality system, and how specifications can be set and justified for early and late development stages. This paper provides an overview for the setting of product specifications for investigational medicinal products used in clinical trials. A case study illustrates how product specifications of investigational medicinal products can be justified and managed within a modern product quality system. © PDA, Inc. 2015.

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.

A machine learning approach to triaging patients with chronic obstructive pulmonary disease

PubMed Central

Qirko, Klajdi; Smith, Ted; Corcoran, Ethan; Wysham, Nicholas G.; Bazaz, Gaurav; Kappel, George; Gerber, Anthony N.

2017-01-01

COPD patients are burdened with a daily risk of acute exacerbation and loss of control, which could be mitigated by effective, on-demand decision support tools. In this study, we present a machine learning-based strategy for early detection of exacerbations and subsequent triage. Our application uses physician opinion in a statistically and clinically comprehensive set of patient cases to train a supervised prediction algorithm. The accuracy of the model is assessed against a panel of physicians each triaging identical cases in a representative patient validation set. Our results show that algorithm accuracy and safety indicators surpass all individual pulmonologists in both identifying exacerbations and predicting the consensus triage in a 101 case validation set. The algorithm is also the top performer in sensitivity, specificity, and ppv when predicting a patient’s need for emergency care. PMID:29166411

Defining a reference set to support methodological research in drug safety.

PubMed

Ryan, Patrick B; Schuemie, Martijn J; Welebob, Emily; Duke, Jon; Valentine, Sarah; Hartzema, Abraham G

2013-10-01

Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene

PubMed Central

Rafnar, Thorunn; Vermeulen, Sita H.; Sulem, Patrick; Thorleifsson, Gudmar; Aben, Katja K.; Witjes, J. Alfred; Grotenhuis, Anne J.; Verhaegh, Gerald W.; Hulsbergen-van de Kaa, Christina A.; Besenbacher, Soren; Gudbjartsson, Daniel; Stacey, Simon N.; Gudmundsson, Julius; Johannsdottir, Hrefna; Bjarnason, Hjordis; Zanon, Carlo; Helgadottir, Hafdis; Jonasson, Jon Gunnlaugur; Tryggvadottir, Laufey; Jonsson, Eirikur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Bishop, D. Timothy; Chung-Sak, Sei; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H.; Knowles, Margaret A.; de Verdier, Petra J.; Ryk, Charlotta; Lindblom, Annika; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Panadero, Angeles; Sanz-Velez, José I.; Sanchez, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D.; Hengstler, Jan G.; Selinski, Silvia; Gerullis, Holger; Ovsiannikov, Daniel; Khezri, Abdolaziz; Aminsharifi, Alireza; Malekzadeh, Mahyar; van den Berg, Leonard H.; Ophoff, Roel A.; Veldink, Jan H.; Zeegers, Maurice P.; Kellen, Eliane; Fostinelli, Jacopo; Andreoli, Daniele; Arici, Cecilia; Porru, Stefano; Buntinx, Frank; Ghaderi, Abbas; Golka, Klaus; Mayordomo, José I.; Matullo, Giuseppe; Kumar, Rajiv; Steineck, Gunnar; Kiltie, Anne E.; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; Kiemeney, Lambertus A.

2011-01-01

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10−11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the ‘urogenous contact hypothesis’ that urine production and voiding frequency modify the risk of UBC. PMID:21750109

Low control beliefs in relation to school dropout and poor health: findings from the SIODO case-control study.

PubMed

Bosma, Hans; Theunissen, Marie-José; Verdonk, Petra; Feron, Frans

2014-11-28

There is cumulating evidence that health is compromised through adverse socioeconomic conditions negatively affecting how people think, feel, and behave. Low control beliefs might be a key mechanism. The reversed possibility that low control beliefs might set people on a pathway towards adverse socioeconomic and health-related outcomes is much less examined. A case-control design was used, consisting of 330 cases who dropped out of school in the 2010-2011 school year and 330 controls who still attended school at the end of that year. The respondents, aged between 18 and 23, came from Eindhoven and surrounding areas in the south-east of The Netherlands. A questionnaire asked for current health status, recalled socioeconomic and social background, and recalled control beliefs (mastery and general self-efficacy). Logistic regression analyses were used. Recalls of low mastery and low self-efficacy were strongly related to both dropout and less than good health. Low socioeconomic background was also associated to odds of dropout, but did not confound or moderate the associations of low control beliefs with dropout and health. Odds ratios of dropout and less than good health indicated at least twice the odds of a poor outcome with recalls of low control beliefs. Independent of the socioeconomic background, low control beliefs are related to heightened odds of both poor health and school dropout. Individual differences in control beliefs might thus be as fundamental as socioeconomic conditions in generating life-course socioeconomic and health-related pathways. Although the findings should first be cross-validated in prospective studies, public health professionals working with youth might already start considering early interventions in youth with all too fatalistic and powerless mind-sets.

Tailored Case Management for Diabetes and Hypertension (TEACH-DM) in a community population: study design and baseline sample characteristics.

PubMed

Crowley, Matthew J; Bosworth, Hayden B; Coffman, Cynthia J; Lindquist, Jennifer H; Neary, Alice M; Harris, Amy C; Datta, Santanu K; Granger, Bradi B; Pereira, Katherine; Dolor, Rowena J; Edelman, David

2013-09-01

Despite recognition of the benefits associated with well-controlled diabetes and hypertension, control remains suboptimal. Effective interventions for these conditions have been studied within academic settings, but interventions targeting both conditions have rarely been tested in community settings. We describe the design and baseline results of a trial evaluating a behavioral intervention among community patients with poorly-controlled diabetes and comorbid hypertension. Tailored Case Management for Diabetes and Hypertension (TEACH-DM) is a 24-month randomized, controlled trial evaluating a telephone-delivered behavioral intervention for diabetes and hypertension versus attention control. The study recruited from nine community practices. The nurse-administered intervention targets 3 areas: 1) cultivation of healthful behaviors for diabetes and hypertension control; 2) provision of fundamentals to support attainment of healthful behaviors; and 3) identification and correction of patient-specific barriers to adopting healthful behaviors. Hemoglobin A1c and blood pressure measured at 6, 12, and 24 months are co-primary outcomes. Secondary outcomes include self-efficacy, self-reported medication adherence, exercise, and cost-effectiveness. Of 377 randomized patients, 193 were allocated to the intervention and 184 to attention control. The cohort is balanced in terms of gender, race, education level, and income. The cohort's mean baseline hemoglobin A1c and blood pressure are above goal, and mean baseline body mass index falls in the obese range. Baseline self-reported non-adherence is high for diabetes and hypertension medications. Trial results are pending. If effective, the TEACH-DM intervention's telephone-based delivery strategy and nurse administration make it well-suited for rapid implementation and broad dissemination in community settings. © 2013.

Multiple imputation of missing data in nested case-control and case-cohort studies.

PubMed

Keogh, Ruth H; Seaman, Shaun R; Bartlett, Jonathan W; Wood, Angela M

2018-06-05

The nested case-control and case-cohort designs are two main approaches for carrying out a substudy within a prospective cohort. This article adapts multiple imputation (MI) methods for handling missing covariates in full-cohort studies for nested case-control and case-cohort studies. We consider data missing by design and data missing by chance. MI analyses that make use of full-cohort data and MI analyses based on substudy data only are described, alongside an intermediate approach in which the imputation uses full-cohort data but the analysis uses only the substudy. We describe adaptations to two imputation methods: the approximate method (MI-approx) of White and Royston () and the "substantive model compatible" (MI-SMC) method of Bartlett et al. (). We also apply the "MI matched set" approach of Seaman and Keogh () to nested case-control studies, which does not require any full-cohort information. The methods are investigated using simulation studies and all perform well when their assumptions hold. Substantial gains in efficiency can be made by imputing data missing by design using the full-cohort approach or by imputing data missing by chance in analyses using the substudy only. The intermediate approach brings greater gains in efficiency relative to the substudy approach and is more robust to imputation model misspecification than the full-cohort approach. The methods are illustrated using the ARIC Study cohort. Supplementary Materials provide R and Stata code. © 2018, The International Biometric Society.

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.

PubMed

Chaudhury, Sultan; Patel, Tulsi; Barber, Imelda S; Guetta-Baranes, Tamar; Brookes, Keeley J; Chappell, Sally; Turton, James; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Hardy, John; Mann, David; Morgan, Kevin

2018-02-01

Sporadic early-onset Alzheimer's disease (sEOAD) exhibits the symptoms of late-onset Alzheimer's disease but lacks the familial aspect of the early-onset familial form. The genetics of Alzheimer's disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRSs) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases was genotyped on the NeuroX array, and PRSs were generated using PRSice. The target data set consisted of 408 sEOAD cases and 436 controls. The base data set was collated by the International Genomics of Alzheimer's Project consortium, with association data from 17,008 late-onset Alzheimer's disease cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRSs were generated using all common single nucleotide polymorphisms between the base and target data set, PRS were also generated using only single nucleotide polymorphisms within a 500 kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap among the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Empirical performance of the calibrated self-controlled cohort analysis within temporal pattern discovery: lessons for developing a risk identification and analysis system.

PubMed

Norén, G Niklas; Bergvall, Tomas; Ryan, Patrick B; Juhlin, Kristina; Schuemie, Martijn J; Madigan, David

2013-10-01

Observational healthcare data offer the potential to identify adverse drug reactions that may be missed by spontaneous reporting. The self-controlled cohort analysis within the Temporal Pattern Discovery framework compares the observed-to-expected ratio of medical outcomes during post-exposure surveillance periods with those during a set of distinct pre-exposure control periods in the same patients. It utilizes an external control group to account for systematic differences between the different time periods, thus combining within- and between-patient confounder adjustment in a single measure. To evaluate the performance of the calibrated self-controlled cohort analysis within Temporal Pattern Discovery as a tool for risk identification in observational healthcare data. Different implementations of the calibrated self-controlled cohort analysis were applied to 399 drug-outcome pairs (165 positive and 234 negative test cases across 4 health outcomes of interest) in 5 real observational databases (four with administrative claims and one with electronic health records). Performance was evaluated on real data through sensitivity/specificity, the area under receiver operator characteristics curve (AUC), and bias. The calibrated self-controlled cohort analysis achieved good predictive accuracy across the outcomes and databases under study. The optimal design based on this reference set uses a 360 days surveillance period and a single control period 180 days prior to new prescriptions. It achieved an average AUC of 0.75 and AUC >0.70 in all but one scenario. A design with three separate control periods performed better for the electronic health records database and for acute renal failure across all data sets. The estimates for negative test cases were generally unbiased, but a minor negative bias of up to 0.2 on the RR-scale was observed with the configurations using multiple control periods, for acute liver injury and upper gastrointestinal bleeding. The calibrated self-controlled cohort analysis within Temporal Pattern Discovery shows promise as a tool for risk identification; it performs well at discriminating positive from negative test cases. The optimal parameter configuration may vary with the data set and medical outcome of interest.

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.

An artificial neural network prediction model of congenital heart disease based on risk factors: A hospital-based case-control study.

PubMed

Li, Huixia; Luo, Miyang; Zheng, Jianfei; Luo, Jiayou; Zeng, Rong; Feng, Na; Du, Qiyun; Fang, Junqun

2017-02-01

An artificial neural network (ANN) model was developed to predict the risks of congenital heart disease (CHD) in pregnant women.This hospital-based case-control study involved 119 CHD cases and 239 controls all recruited from birth defect surveillance hospitals in Hunan Province between July 2013 and June 2014. All subjects were interviewed face-to-face to fill in a questionnaire that covered 36 CHD-related variables. The 358 subjects were randomly divided into a training set and a testing set at the ratio of 85:15. The training set was used to identify the significant predictors of CHD by univariate logistic regression analyses and develop a standard feed-forward back-propagation neural network (BPNN) model for the prediction of CHD. The testing set was used to test and evaluate the performance of the ANN model. Univariate logistic regression analyses were performed on SPSS 18.0. The ANN models were developed on Matlab 7.1.The univariate logistic regression identified 15 predictors that were significantly associated with CHD, including education level (odds ratio  = 0.55), gravidity (1.95), parity (2.01), history of abnormal reproduction (2.49), family history of CHD (5.23), maternal chronic disease (4.19), maternal upper respiratory tract infection (2.08), environmental pollution around maternal dwelling place (3.63), maternal exposure to occupational hazards (3.53), maternal mental stress (2.48), paternal chronic disease (4.87), paternal exposure to occupational hazards (2.51), intake of vegetable/fruit (0.45), intake of fish/shrimp/meat/egg (0.59), and intake of milk/soymilk (0.55). After many trials, we selected a 3-layer BPNN model with 15, 12, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The prediction model has accuracies of 0.91 and 0.86 on the training and testing sets, respectively. The sensitivity, specificity, and Yuden Index on the testing set (training set) are 0.78 (0.83), 0.90 (0.95), and 0.68 (0.78), respectively. The areas under the receiver operating curve on the testing and training sets are 0.87 and 0.97, respectively.This study suggests that the BPNN model could be used to predict the risk of CHD in individuals. This model should be further improved by large-sample-size research.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci.

PubMed

Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan; Hazelett, Dennis; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bogdanova, Natalia; Brinton, Louise; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Eccles, Diana; Fasching, Peter A; Flanagan, James; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Estrid; Høgdall, Claus K; Huntsman, David G; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Levine, Douglas A; Li, Qiyuan; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Massuger, Leon F A G; McGuire, Valerie; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Permuth, Jennifer B; Phelan, Catherine; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rossing, Mary Anne; Salvesen, Helga B; Schildkraut, Joellen M; Sellers, Thomas A; Sherman, Mark; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa; Terry, Kathryn L; Tworoger, Shelley S; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P; Lawrenson, Kate

2017-02-14

Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). The PAX8-target gene set was ranked 1/615 in the discovery (P GSEA <0.001; FDR=0.21), 7/615 in the replication (P GSEA =0.004; FDR=0.37), and 1/615 in the combined (P GSEA <0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10 -5 (including six with P<5 × 10 -8 ). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (P GSEA =0.025) and IGROV1 (P GSEA =0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC.

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci

PubMed Central

Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan; Hazelett, Dennis; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bogdanova, Natalia; Brinton, Louise; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Dansonka-Mieszkowska, Agnieszka; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Eccles, Diana; Fasching, Peter A; Flanagan, James; Gentry-Maharaj, Aleksandra; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Estrid; Høgdall, Claus K; Huntsman, David G; Jensen, Allan; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Levine, Douglas A; Li, Qiyuan; Lissowska, Jolanta; Lu, Karen H; Lubiński, Jan; Massuger, Leon F A G; McGuire, Valerie; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Permuth, Jennifer B; Phelan, Catherine; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rossing, Mary Anne; Salvesen, Helga B; Schildkraut, Joellen M; Sellers, Thomas A; Sherman, Mark; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa; Terry, Kathryn L; Tworoger, Shelley S; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P; Lawrenson, Kate

2017-01-01

Background: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. Methods: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). Results: The PAX8-target gene set was ranked 1/615 in the discovery (PGSEA<0.001; FDR=0.21), 7/615 in the replication (PGSEA=0.004; FDR=0.37), and 1/615 in the combined (PGSEA<0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P<10−5 (including six with P<5 × 10−8). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (PGSEA=0.025) and IGROV1 (PGSEA=0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Conclusions: Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC. PMID:28103614

An implementation strategy to improve the guideline adherence of insurance physicians: an experiment in a controlled setting

PubMed Central

2011-01-01

Background The aim of this study was to investigate the efficacy of a newly developed implementation strategy for the insurance medicine guidelines for depression in the Netherlands. We hypothesized that an educational intervention would increase the insurance physicians' (IPs) guideline adherence in a controlled setting. Methods Forty IPs were allocated in a randomised controlled trial (RCT) to an intervention group (IG) (n = 21) and a control group (CG) (n = 19). The IG received tailored training in applying the guidelines for depression, while the CG received an alternative programme. Baseline (T0) and follow-up (T1) measurements were conducted before and after the intervention within a period of two weeks. The intervention consisted of a workshop in which the evidence-based theory of the guidelines was translated for use in practice, with the help of various tools. The IPs had to write a case-report on the basis of video cases, two before and two after the training. Specially trained and blinded test IPs judged the case reports independently on the basis of six performance indicators. Primary outcome measure in the controlled setting of the trial was guideline adherence measured by six performance indicators on a scale of one to seven. Secondary outcome measure was knowledge of the guidelines for depression. Analyses were performed using Linear Mixed Models, and ANCOVA. Results We found significantly higher scores in the IG than in the CG at T1 for both outcomes. The interaction effect (standard error; p-value) of group crossed with time was 0.97 (0.19; p < 0.0005) for guideline adherence in the controlled setting. The group effect at T1 for the knowledge test was 0.86 (0.40; p = 0.038). Conclusions The newly developed implementation strategy for the insurance medicine guidelines for depression improved the guideline adherence of the trained IPs in disability assessments of clients with depression when performed in a controlled setting. Furthermore, the trained IPs showed gains in knowledge of the guidelines for depression. Trial registration Netherlands' Trial Register NTR1863. PMID:22188876

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

Alzheimer's Disease Sequencing Project discovery and replication criteria for cases and controls: Data from a community-based prospective cohort study with autopsy follow-up.

PubMed

Crane, Paul K; Foroud, Tatiana; Montine, Thomas J; Larson, Eric B

2017-12-01

The Alzheimer's Disease Sequencing Project (ADSP) used different criteria for assigning case and control status from the discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions and compared the two sets of criteria. We used data from the Adult Changes in Thought (ACT) study including Diagnostic and Statistical Manual-IV criteria for dementia status, McKhann et al. criteria for clinical Alzheimer's disease, and Braak and Consortium to Establish a Registry for AD findings on neurofibrillary tangles and neuritic plaques to categorize the 621 ACT participants of European ancestry who died and came to autopsy. We applied ADSP discovery and replication definitions to identify controls, cases, and people who were neither controls nor cases. There was some agreement between the discovery and replication definitions. Major areas of discrepancy included the finding that only 40% of the discovery sample controls had sufficiently low levels of neurofibrillary tangles and neuritic plaques to be considered controls by the replication criteria and the finding that 16% of the replication phase cases were diagnosed with non-AD dementia during life and thus were excluded as cases for the discovery phase. These findings should inform interpretation of genetic association findings from the ADSP. Differences in genetic association findings between the two phases of the study may reflect these different phenotype definitions from the discovery and replication phase of the ADSP. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The HABP2 G534E Variant Is an Unlikely Cause of Familial Nonmedullary Thyroid Cancer

PubMed Central

Sahasrabudhe, Ruta; Stultz, Jacob; Williamson, John; Lott, Paul; Estrada, Ana; Bohorquez, Mabel; Palles, Claire; Polanco-Echeverry, Guadalupe; Jaeger, Emma; Martin, Lynn; Echeverry, Maria Magdalena; Tomlinson, Ian

2016-01-01

Context: A recent study reported the nonsynonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial nonmedullary thyroid cancer (NMTC). Objective: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multicenter population-based study of NMTC cases from the British Isles. Design and Setting: A case-control analysis of rs7080536 genotypes was performed using 2105 TCUKIN cases and 5172 UK controls. Participants: Cases comprised 2105 NMTC cases. Patient subgroups with papillary (n = 1056), follicular (n = 691), and Hürthle cell (n = 86) thyroid cancer cases were studied separately. Controls comprised 5172 individuals from the 1958 Birth Cohort and the National Blood Donor Service study. The controls had previously been genotyped using genome-wide single nucleotide polymorphism arrays by the Wellcome Trust Case Control Consortium study. Outcome Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. Results: The frequency of the HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (odds ratio [OR] = 0.896; 95% confidence interval, 0.746–1.071; P = .233). We also failed to detect an association between the HABP2 G534E and cases with papillary (1056 cases; G534E frequency = 3.5%; OR = 0.74; P = .017), follicular (691 cases; G534E frequency = 4.7%; OR = 1.00; P = 1.000), or Hürthle cell (86 cases; G534E frequency = 6.3%; OR = 1.40; P = .279) histology. Conclusions: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC, and additional data are required before using this variant in NMTC risk assessment. PMID:26691890

Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

PubMed Central

Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

2009-01-01

Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants. Conclusions We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoring the confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owing to its low effective population size in comparison with autosomal markers and therefore, special care should be taken in the interpretation of seeming signals of positive associations in mtDNA case-control association studies. PMID:20019817

Nitrates in municipal drinking water and non-Hodgkin lymphoma: an ecological cancer case-control study in Taiwan.

PubMed

Chang, Chih-Ching; Tsai, Shang-Shyue; Wu, Trong-Neng; Yang, Chun-Yuh

2010-01-01

The relationship between nitrate levels in drinking water and increased risk of non-Hodgkin lymphoma (NHL) development has been inconclusive. A matched cancer case-control and a nitrate ecology study was used to investigate the association between mortality attributed to NHL and nitrate exposure from Taiwan's drinking water. All deaths due to NHL in Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from the Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios (OR) for NHL death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.02 (0.87-1.2) and 1.05 (0.89-1.24), respectively. The results of the present study show that there was no statistically significant association between nitrates in drinking water at levels in this investigation and increased risk of death attributed to NHL.

Nitrate in drinking water and risk of death from bladder cancer: an ecological case-control study in Taiwan.

PubMed

Chiu, Hui-Fen; Tsai, Shang-Shyue; Yang, Chun-Yuh

2007-06-01

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Population versus hospital controls in the assessment of dietary intake of isoflavone for case-control studies on cancers in China.

PubMed

Li, Lin; Zhang, Min; Holman, C D'Arcy J

2013-01-01

To assess dietary isoflavone intake between population and hospital outpatient controls and examine if cancer risks estimated for isoflavone using hospital outpatient controls would be different from those using population controls. Three parallel case-control studies on leukemia, breast, and colorectal cancers in China in 2009-2010 were conducted, using population and hospital outpatient controls to separately match 560 incident cases at a 1:1 ratio. A validated food frequency questionnaire was administered by face-to-face interview. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The 2 control groups had closely similar distributions of dietary isoflavone intake. Risk estimates for breast cancers were adjusted ORs (95% CI) of 0.39 (0.23-0.66) and 0.31 (0.18-0.55) for daidzein, 0.35 (0.20-0.61) and 0.28 (0.16-0.52) for genistein, 0.66 (0.41-1.08) and 0.53 (0.32-0.88) for glycitein, and 0.53 (0.33-0.85) and 0.43 (0.26-0.71) for total isoflavone using hospital outpatient and population controls respectively. The study found that hospital outpatient controls were comparable to population controls in measured dietary intake of isoflavone in the Chinese hospital setting.

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

PubMed

Pilakkadavath, Zarin; Shaffi, Muhammed

2016-01-01

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

30 CFR 250.1715 - How must I permanently plug a well?

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Zones in open hole, Cement plug(s) set from at least 100 feet below the bottom to 100 feet above the top... cement plug, set by the displacement method, at least 100 feet above and below deepest casing shoe; (ii) A cement retainer with effective back-pressure control set 50 to 100 feet above the casing shoe, and...

30 CFR 250.1715 - How must I permanently plug a well?

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Zones in open hole, Cement plug(s) set from at least 100 feet below the bottom to 100 feet above the top... cement plug, set by the displacement method, at least 100 feet above and below deepest casing shoe; (ii) A cement retainer with effective back-pressure control set 50 to 100 feet above the casing shoe, and...

30 CFR 250.1715 - How must I permanently plug a well?

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Zones in open hole, Cement plug(s) set from at least 100 feet below the bottom to 100 feet above the top... cement plug, set by the displacement method, at least 100 feet above and below deepest casing shoe; (ii) A cement retainer with effective back-pressure control set 50 to 100 feet above the casing shoe, and...

30 CFR 250.1715 - How must I permanently plug a well?

Code of Federal Regulations, 2011 CFR

2011-07-01

... in open hole Cement plug(s) set from at least 100 feet below the bottom to 100 feet above the top of... cement plug, set by the displacement method, at least 100 feet above and below deepest casing shoe;(ii) A cement retainer with effective back-pressure control set 50 to 100 feet above the casing shoe, and a...

A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease

PubMed Central

Mannino, David; Leidy, Nancy Kline; Malley, Karen G.; Bacci, Elizabeth D.; Barr, R. Graham; Bowler, Russ P.; Han, MeiLan K.; Houfek, Julia F.; Make, Barry; Meldrum, Catherine A.; Rennard, Stephen; Thomashow, Byron; Walsh, John; Yawn, Barbara P.

2017-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). Methods: We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). Measurements and Main Results: PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and for all cases versus no-COPD control subjects (89.7% and 93.1%, respectively). Conclusions: CAPTURE with PEF can identify patients with COPD who would benefit from currently available therapy and require further diagnostic evaluation. Clinical trial registered with clinicaltrials.gov (NCT01880177). PMID:27783539

Multisample adjusted U-statistics that account for confounding covariates.

PubMed

Satten, Glen A; Kong, Maiying; Datta, Somnath

2018-06-19

Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.

Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

PubMed Central

Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.

2015-01-01

Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh. PMID:25933377

Effect of active case finding on prevalence and transmission of pulmonary tuberculosis in Dhaka Central Jail, Bangladesh.

PubMed

Banu, Sayera; Rahman, Md Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md Siddiqur Rahman; Rahman, Md Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D

2015-01-01

Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

Risk factors for geriatric patient falls in rehabilitation hospital settings: a systematic review.

PubMed

Vieira, Edgar Ramos; Freund-Heritage, Rosalie; da Costa, Bruno R

2011-09-01

To review the literature to identify and synthesize the evidence on risk factors for patient falls in geriatric rehabilitation hospital settings. Eligible studies were systematically searched on 16 databases from inception to December 2010. The search strategies used a combination of terms for rehabilitation hospital patients, falls, risk factors and older adults. Cross-sectional, cohort, case-control studies and randomized clinical trials (RCTs) published in English that investigated risks for falls among patients ≥65 years of age in rehabilitation hospital settings were included. Studies that investigated fall risk assessment tools, but did not investigate risk factors themselves or did not report a measure of risk (e.g. odds ratio, relative risk) were excluded. A total of 2,824 references were identified; only eight articles concerning six studies met the inclusion criteria. In these, 1,924 geriatric rehabilitation patients were followed. The average age of the patients ranged from 77 to 83 years, the percentage of women ranged from 56% to 81%, and the percentage of fallers ranged from 15% to 54%. Two were case-control studies, two were RCTs and four were prospective cohort studies. Several intrinsic and extrinsic risk factors for falls were identified. Carpet flooring, vertigo, being an amputee, confusion, cognitive impairment, stroke, sleep disturbance, anticonvulsants, tranquilizers and antihypertensive medications, age between 71 and 80, previous falls, and need for transfer assistance are risk factors for geriatric patient falls in rehabilitation hospital settings.

"Alert-Audit-Act": assessment of surveillance and response strategy for malaria elimination in three low-endemic settings of Myanmar in 2016.

PubMed

Kyaw, Aye Mon Mon; Kathirvel, Soundappan; Das, Mrinalini; Thapa, Badri; Linn, Nay Yi Yi; Maung, Thae Maung; Lin, Zaw; Thi, Aung

2018-01-01

Myanmar, a malaria endemic country of Southeast Asia, adopted surveillance and response strategy similar to "1-3-7" Chinese strategy to achieve sub-national elimination in six low-endemic region/states of the country. Among these, Yangon, Bago-East, and Mon region/states have implemented this malaria surveillance and response strategy with modification in 2016. The current study was conducted to assess the case notification, investigation, classification, and response strategy (NICR) in these three states. This was a retrospective cohort study using routine program data of all patients with malaria diagnosed and reported under the National Malaria Control Programme in 2016 from the above three states. As per the program, all malaria cases need to be notified within 1 day and investigated within 3 days of diagnosis and response to control (active case detection and control) should be taken for all indigenous malaria cases within 7 days of diagnosis. A total of 959 malaria cases were diagnosed from the study area in 2016. Of these, the case NICR details were available only for 312 (32.5%) malaria cases. Of 312 cases, the case notification, investigation, and classification were carried out within 3 days of malaria diagnosis in 95.5% cases (298/312). Of 208 indigenous malaria cases (66.7%, 208/312), response to control was taken in 96.6% (201/208) within 7 days of diagnosis. The timeline at each stage of the strategy namely case notification, investigation, classification, and response to control was followed, and response action was taken in nearly all indigenous malaria cases for the available case information. Strengthening of health information and monitoring system is needed to avoid missing information. Future research on feasibility of mobile/tablet-based surveillance system and providing response to all cases including imported malaria can be further studied.

Vitamin A serostatus and heterosexual transmission of HIV: case-control study in Tanzania and review of the evidence.

PubMed

Villamor, Eduardo; Kapiga, Saidi H; Fawzi, Wafaie W

2006-03-01

Results from a randomized clinical trial suggested that vitamin A/beta-carotene supplementation to HIV-1-infected women during pregnancy and lactation may increase the risk of vertical transmission. Limited information is available on the potential role of vitamin A on heterosexual HIV transmission. This is a relevant question in many resource-limited settings where both vitamin A deficiency and HIV infection are highly prevalent. We conducted a case-control study (34 cases and 38 controls) nested within a cohort of HIV-negative women attending family planning clinics in Tanzania, to examine whether low serum concentrations at baseline were associated with the risk of seroconversion. There was not a significant association (OR = 2.14, 95% C I = 0.54, 8.45). In light of these and previous results, we conclude that there is not enough evidence yet to suggest a causal association between vitamin A and heterosexual transmission.

A Multiplexed Serum Biomarker Immunoassay Panel Discriminates Clinical Lung Cancer Patients from High-Risk Individuals Found to be Cancer-Free by CT Screening

PubMed Central

Bigbee, William L.; Gopalakrishnan, Vanathi; Weissfeld, Joel L.; Wilson, David O.; Dacic, Sanja; Lokshin, Anna E.; Siegfried, Jill M.

2012-01-01

Introduction Clinical decision-making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk individuals with indeterminate pulmonary nodules. Methods To identify candidate serum biomarkers, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary non small cell lung cancer and 56 age-, sex- and smoking-matched CT-screened controls. Results We identified a panel of 10 serum biomarkers – prolactin, transthyretin, thrombospondin-1, E-selectin, C-C motif chemokine 5, macrophage migration inhibitory factor, plasminogen activator inhibitor, receptor tyrosine-protein kinase, Cyfra 21.1, and serum amyloid A – that distinguished lung cancer from controls with an estimated balanced accuracy (average of sensitivity and specificity) of 76.0%±3.8% from 20-fold internal cross-validation. We then iteratively evaluated this model in independent test and verification case/control studies confirming the initial classification performance of the panel. The classification performance of the 10-biomarker panel was also analytically validated using ELISAs in a second independent case/control population further validating the robustness of the panel. Conclusions The performance of this 10-biomarker panel based model was 77.1% sensitivity/76.2% specificity in cross-validation in the expanded training set, 73.3% sensitivity/93.3% specificity (balanced accuracy 83.3%) in the blinded verification set with the best discriminative performance in Stage I/II cases: 85% sensitivity (balanced accuracy 89.2%). Importantly, the rate of misclassification of CT-screened controls was not different in most control subgroups with or without airflow obstruction or emphysema or pulmonary nodules. These biomarkers have potential to aid in the early detection of lung cancer and more accurate interpretation of indeterminate pulmonary nodules detected by screening CT. PMID:22425918

Control of endemic nosocomial legionnaires' disease by using sterile potable water for high risk patients.

PubMed Central

Marrie, T. J.; Haldane, D.; MacDonald, S.; Clarke, K.; Fanning, C.; Le Fort-Jost, S.; Bezanson, G.; Joly, J.

1991-01-01

In a setting where potable water is contaminated with Legionella pneumophila serogroup 1, we performed two case control studies. The first case control study consisted of 17 cases of nosocomial Legionnaires' disease (LD) and 33 control (the patients who were admitted to the ward where the case was admitted immediately before and after the case) subjects. Cases had a higher mortality rate 65% vs 12% (P less than 0.004); were more likely to have received assisted ventilation (P less than 0.00001); to have nasogastric tubes (P less than 0.0004) and to be receiving corticosteroids or other immunosuppressive therapy (P less than 0.0001). Based on the results of this study, sterile water was used to flush nasogastric tubes and to dilute nasogastric feeds. Only 3 cases of nosocomial LD occurred during the next year compared with 12 the previous year (P less than 0.0001). Nine cases subsequently occurred and formed the basis for the second case-control study. Eighteen control subjects were those patients admitted to the same unit where the case developed LD, immediately before and after the case. The mortality rate for the cases was 89% vs 6% for controls (P less than 0.00003). The only other significant difference was that cases were more likely to be receiving corticosteroids or other immunosuppressive therapy 89% vs 39% (less than 0.01). We hypothesized that microaspiration of contaminated potable water by immunocompromised patients was a risk factor for nosocomial Legionnaires' disease. From 17 March 1989 onwards such patients were given only sterile potable water. Only two cases of nosocomial LD occurred from June 1989 to September 1990 and both occurred on units where the sterile water policy was not in effect. We conclude that aspiration of contaminated potable water is a possible route for acquisition of nosocomial LD in our hospital and that provision of sterile potable water to high risk patients (those who are receiving corticosteroids or other immunosuppressive drugs; organ transplant recipients or hospitalized in an intensive care unit) should be mandatory. PMID:1752308

Maternal urinary tract infection and related drug treatments during pregnancy and risk of congenital abnormalities in the offspring.

PubMed

Bánhidy, F; Acs, N; Puhó, E H; Czeizel, A E

2006-12-01

The association between urinary tract infection (UTI) of pregnant women and preterm birth/low birthweight is known, but the possible association between UTI and congenital abnormalities (CAs) was evaluated rarely. Only one study showed an association with atrial septal defect, thus we decided to check this possible association. The population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA); most maternal UTIs were based on medically recorded data. SETTING The HCCSCA, 1980-1996, contained 22 843 newborns or fetuses with CAs and 38 151 matched controls, i.e. newborn infants without any HCAs. Hungarian informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. Case-control pair analysis. Twenty-five CA groups. A total of 1542 (6.75%) mothers in the case group had UTI during entire pregnancy compared with 2188 (5.74%) mothers in the control group (adjusted prevalence odds ratios [POR] with 95% CI: 1.15, 1.06-1.24). We did not find a higher prevalence of UTI during the second and/or third months of pregnancy in total case group (adjusted POR with 95% CI: 1.1, 0.9-1.2) and in any group of CAs including atrial septal defect type II. No evidence for the teratogenic effect of maternal UTI and related drug treatments during early pregnancy.

Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.

PubMed

Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta

2018-01-01

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

Exponentially Stabilizing Robot Control Laws

NASA Technical Reports Server (NTRS)

Wen, John T.; Bayard, David S.

1990-01-01

New class of exponentially stabilizing laws for joint-level control of robotic manipulators introduced. In case of set-point control, approach offers simplicity of proportion/derivative control architecture. In case of tracking control, approach provides several important alternatives to completed-torque method, as far as computational requirements and convergence. New control laws modified in simple fashion to obtain asymptotically stable adaptive control, when robot model and/or payload mass properties unknown.

New control concepts for uncertain water resources systems: 1. Theory

NASA Astrophysics Data System (ADS)

Georgakakos, Aris P.; Yao, Huaming

1993-06-01

A major complicating factor in water resources systems management is handling unknown inputs. Stochastic optimization provides a sound mathematical framework but requires that enough data exist to develop statistical input representations. In cases where data records are insufficient (e.g., extreme events) or atypical of future input realizations, stochastic methods are inadequate. This article presents a control approach where input variables are only expected to belong in certain sets. The objective is to determine sets of admissible control actions guaranteeing that the system will remain within desirable bounds. The solution is based on dynamic programming and derived for the case where all sets are convex polyhedra. A companion paper (Yao and Georgakakos, this issue) addresses specific applications and problems in relation to reservoir system management.

Methadone and oedema in the palliative care setting: a case report and review of the literature.

PubMed

Dawson, Camilla; Paterson, Fiona; McFatter, Fiona; Buchanan, Deans

2014-05-01

Methadone is a synthetic opioid which is being used with increased frequency in the palliative care setting for management of complex pain. There have been cases published reporting the development of oedema with methadone maintenance therapy but no cases on the association with methadone and peripheral oedema in the palliative care setting. As yet, the underlying mechanisms are unclear. This case report describes a gentleman with ependymoma and difficult-to-control lower back pain and scrotal pain. This pain had failed to respond to other strong opioids. He was prescribed methadone and then subsequently developed bilateral peripheral oedema. Peripheral oedema resolved following cessation of methadone. This highlights an important potential adverse effect of methadone in a society of increased methadone prescription for pain control. The published literature to date is reviewed and possible underlying mechanisms explored.

Improved minimum cost and maximum power two stage genome-wide association study designs.

PubMed

Stanhope, Stephen A; Skol, Andrew D

2012-01-01

In a two stage genome-wide association study (2S-GWAS), a sample of cases and controls is allocated into two groups, and genetic markers are analyzed sequentially with respect to these groups. For such studies, experimental design considerations have primarily focused on minimizing study cost as a function of the allocation of cases and controls to stages, subject to a constraint on the power to detect an associated marker. However, most treatments of this problem implicitly restrict the set of feasible designs to only those that allocate the same proportions of cases and controls to each stage. In this paper, we demonstrate that removing this restriction can improve the cost advantages demonstrated by previous 2S-GWAS designs by up to 40%. Additionally, we consider designs that maximize study power with respect to a cost constraint, and show that recalculated power maximizing designs can recover a substantial amount of the planned study power that might otherwise be lost if study funding is reduced. We provide open source software for calculating cost minimizing or power maximizing 2S-GWAS designs.

Public transportation and tuberculosis transmission in a high incidence setting.

PubMed

Zamudio, Carlos; Krapp, Fiorella; Choi, Howard W; Shah, Lena; Ciampi, Antonio; Gotuzzo, Eduardo; Heymann, Jody; Seas, Carlos; Brewer, Timothy F

2015-01-01

Tuberculosis (TB) transmission may occur with exposure to an infectious contact often in the setting of household environments, but extra-domiciliary transmission also may happen. We evaluated if using buses and/or minibuses as public transportation was associated with acquiring TB in a high incidence urban district in Lima, Peru. Newly diagnosed TB cases with no history of previous treatment and community controls were recruited from August to December 2008 for a case-control study. Crude and adjusted odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association between bus/minibus use and TB risk. One hundred forty TB cases and 80 controls were included. The overall use of buses/minibuses was 44.9%; 53.3% (72/135) among cases and 30.4% (24/79) among controls [OR: 3.50, (95% CI: 1.60-7.64)]. In the TB group, 25.7% (36/140) of subjects reported having had a recent household TB contact, and 13% (18/139) reported having had a workplace TB contact; corresponding figures for controls were 3.8% (3/80) and 4.1% (3/73), respectively[OR: 8.88 (95% CI: 2.64-29.92), and OR: 3.89 (95% CI: 1.10-13.70)]. In multivariate analyses, age, household income, household contact and using buses/minibuses to commute to work were independently associated with TB [OR for bus/minibus use: 11.8 (95% CI: 1.45-96.07)]. Bus/minibus use to commute to work is associated with TB risk in this high-incidence, urban population in Lima, Peru. Measures should be implemented to prevent TB transmission through this exposure.

DHM simulation in virtual environments: a case-study on control room design.

PubMed

Zamberlan, M; Santos, V; Streit, P; Oliveira, J; Cury, R; Negri, T; Pastura, F; Guimarães, C; Cid, G

2012-01-01

This paper will present the workflow developed for the application of serious games in the design of complex cooperative work settings. The project was based on ergonomic studies and development of a control room among participative design process. Our main concerns were the 3D human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. Using Unity3D platform to design the virtual environment, the virtual human model can be controlled by users on dynamic scenario in order to evaluate the new work settings and simulate work activities. The results obtained showed that this virtual technology can drastically change the design process by improving the level of interaction between final users and, managers and human factors team.

Challenges with controlling varicella in prison settings: Experience of California, 2010–2011

PubMed Central

Leung, Jessica; Lopez, Adriana S.; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H.; Preas, Christopher P.; Cosentino, Giorgio; Bialek, Stephanie R.; Marin, Mona

2015-01-01

We describe the epidemiology of varicella in one state prison in California during 2010–2011, control measures implemented, and associated costs. Eleven varicella cases were reported, 9 associated with 2 outbreaks. One outbreak consisted of 3 cases and the second consisted of 6 cases with 2 generations of spread. Among exposed inmates serologically tested, 98% (643/656) were VZV sero-positive. The outbreaks resulted in >1,000 inmates exposed, 444 staff exposures, and >$160,000 in costs. We documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary for managing cases and outbreaks. PMID:25201912

Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control study.

PubMed

Viney, K; Cavanaugh, J; Kienene, T; Harley, D; Kelly, P M; Sleigh, A; O'Connor, J; Mase, S

2015-05-01

To better inform local management of TB-diabetes collaborative activities, we aimed to determine the prevalence of diabetes among persons with and without TB and to determine the association between TB and diabetes in Kiribati, a Pacific Island nation. We compared consecutively enrolled TB cases to a group of randomly selected community controls without evidence of TB. Diabetes was diagnosed by HbA1c, and clinical and demographic data were collected. A tuberculin skin test was administered to controls. The chi-square test was used to assess significance in differences between cases and controls. We also calculated an odds ratio, with 95% confidence intervals, for the odds of diabetes among cases relative to controls. Unweighted multivariate logistic regression was performed to adjust for the effects of age and sex. A total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic diagnoses were new; this proportion was higher among controls (64.8%) than cases (46.5%). Five patients with TB were screened to detect one patient with diabetes. There is a strong association between TB and diabetes in Kiribati and bidirectional screening should be conducted in this setting. © 2015 John Wiley & Sons Ltd.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

PubMed

Dunlop, Malcolm G; Dobbins, Sara E; Farrington, Susan Mary; Jones, Angela M; Palles, Claire; Whiffin, Nicola; Tenesa, Albert; Spain, Sarah; Broderick, Peter; Ooi, Li-Yin; Domingo, Enric; Smillie, Claire; Henrion, Marc; Frampton, Matthew; Martin, Lynn; Grimes, Graeme; Gorman, Maggie; Semple, Colin; Ma, Yusanne P; Barclay, Ella; Prendergast, James; Cazier, Jean-Baptiste; Olver, Bianca; Penegar, Steven; Lubbe, Steven; Chander, Ian; Carvajal-Carmona, Luis G; Ballereau, Stephane; Lloyd, Amy; Vijayakrishnan, Jayaram; Zgaga, Lina; Rudan, Igor; Theodoratou, Evropi; Starr, John M; Deary, Ian; Kirac, Iva; Kovacević, Dujo; Aaltonen, Lauri A; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Matsuda, Koichi; Nakamura, Yusuke; Okada, Yukinori; Gallinger, Steven; Duggan, David J; Conti, David; Newcomb, Polly; Hopper, John; Jenkins, Mark A; Schumacher, Fredrick; Casey, Graham; Easton, Douglas; Shah, Mitul; Pharoah, Paul; Lindblom, Annika; Liu, Tao; Smith, Christopher G; West, Hannah; Cheadle, Jeremy P; Midgley, Rachel; Kerr, David J; Campbell, Harry; Tomlinson, Ian P; Houlston, Richard S

2012-05-27

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent

PubMed Central

Kistler, Amy L; Gancz, Ady; Clubb, Susan; Skewes-Cox, Peter; Fischer, Kael; Sorber, Katherine; Chiu, Charles Y; Lublin, Avishai; Mechani, Sara; Farnoushi, Yigal; Greninger, Alexander; Wen, Christopher C; Karlene, Scott B; Ganem, Don; DeRisi, Joseph L

2008-01-01

Background Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. Results Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. Conclusion These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD. PMID:18671869

The Impact of Self-Regulatory Skills Training for Reducing in School Suspension Placement: A Case Study

ERIC Educational Resources Information Center

Schilling-Dickey, Gwen

2013-01-01

Researchers have been looking for solutions to disciplinary problems within the school setting. Many studies have been conducted to assess the impact of a variety of intervention strategies with research indicating that strategies involving self-regulatory control of behavioral responses can benefit students. Additionally, positive behavioral…

Two-speed phacoemulsification for soft cataracts using optimized parameters and procedure step toolbar with the CENTURION Vision System and Balanced Tip

PubMed Central

Davison, James A

2015-01-01

Purpose To present a cause of posterior capsule aspiration and a technique using optimized parameters to prevent it from happening when operating soft cataracts. Patients and methods A prospective list of posterior capsule aspiration cases was kept over 4,062 consecutive cases operated with the Alcon CENTURION machine and Balanced Tip. Video analysis of one case of posterior capsule aspiration was accomplished. A surgical technique was developed using empirically derived machine parameters and customized setting-selection procedure step toolbar to reduce the pace of aspiration of soft nuclear quadrants in order to prevent capsule aspiration. Results Two cases out of 3,238 experienced posterior capsule aspiration before use of the soft quadrant technique. Video analysis showed an attractive vortex effect with capsule aspiration occurring in 1/5 of a second. A soft quadrant removal setting was empirically derived which had a slower pace and seemed more controlled with no capsule aspiration occurring in the subsequent 824 cases. The setting featured simultaneous linear control from zero to preset maximums for: aspiration flow, 20 mL/min; and vacuum, 400 mmHg, with the addition of torsional tip amplitude up to 20% after the fluidic maximums were achieved. A new setting selection procedure step toolbar was created to increase intraoperative flexibility by providing instantaneous shifting between the soft and normal settings. Conclusion A technique incorporating a reduced pace for soft quadrant acquisition and aspiration can be accomplished through the use of a dedicated setting of integrated machine parameters. Toolbar placement of the procedure button next to the normal setting procedure button provides the opportunity to instantaneously alternate between the two settings. Simultaneous surgeon control over vacuum, aspiration flow, and torsional tip motion may make removal of soft nuclear quadrants more efficient and safer. PMID:26355695

Negotiating jurisdiction in the workplace: a multiple-case study of nurse prescribing in hospital settings.

PubMed

Kroezen, M; Mistiaen, P; van Dijk, L; Groenewegen, P P; Francke, A L

2014-09-01

This paper reports on a multiple-case study of prescribing by nurse specialists in Dutch hospital settings. Most analyses of interprofessional negotiations over professional boundaries take a macro sociological approach and ignore workplace jurisdictions. Yet boundary blurring takes place and healthcare professionals renegotiate formal policies in the workplace. This paper studies the division of jurisdictional control over prescribing between nurse specialists and medical specialists in the workplace, and examines the relationship between workplace jurisdiction and legal jurisdiction over prescribing. Data collection took place in the Netherlands during the first half of 2013. The study used in-depth interviews with fifteen nurse specialists and fourteen medical specialists, non-participant observation of nurse specialists' prescribing consultations and document analysis. Great variety was found in the extent to which and way in which nurse specialists' legal prescriptive authority had been implemented. These findings suggest that there is considerable discrepancy between the division of jurisdictional control over prescribing at the macro (legal) level and the division at the micro (workplace) level. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global, local and focused geographic clustering for case-control data with residential histories

PubMed Central

Jacquez, Geoffrey M; Kaufmann, Andy; Meliker, Jaymie; Goovaerts, Pierre; AvRuskin, Gillian; Nriagu, Jerome

2005-01-01

Background This paper introduces a new approach for evaluating clustering in case-control data that accounts for residential histories. Although many statistics have been proposed for assessing local, focused and global clustering in health outcomes, few, if any, exist for evaluating clusters when individuals are mobile. Methods Local, global and focused tests for residential histories are developed based on sets of matrices of nearest neighbor relationships that reflect the changing topology of cases and controls. Exposure traces are defined that account for the latency between exposure and disease manifestation, and that use exposure windows whose duration may vary. Several of the methods so derived are applied to evaluate clustering of residential histories in a case-control study of bladder cancer in south eastern Michigan. These data are still being collected and the analysis is conducted for demonstration purposes only. Results Statistically significant clustering of residential histories of cases was found but is likely due to delayed reporting of cases by one of the hospitals participating in the study. Conclusion Data with residential histories are preferable when causative exposures and disease latencies occur on a long enough time span that human mobility matters. To analyze such data, methods are needed that take residential histories into account. PMID:15784151

High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

PubMed

Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje; van der Werf, Tjip S; Wansbrough-Jones, Mark; Bonsu, Frank; Obeng-Baah, Joseph; Phillips, Richard O

2016-06-01

Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting. Copyright © 2016. Published by Elsevier Ltd.

Risk factors for idiopathic intracranial hypertension in men: a case-control study

PubMed Central

Fraser, J. Alexander; Bruce, Beau B.; Rucker, Janet; Fraser, Lisa-Ann; Atkins, Edward J.; Newman, Nancy J.; Biousse, Valérie

2009-01-01

Objective To identify risk factors for idiopathic intracranial hypertension (IIH) in men Design Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis. Setting Outpatient clinics in two US tertiary care centers Participants The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category. Main Outcome Measures Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching. Results Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03). Conclusions Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men. PMID:19945715

Does cataract surgery alleviate poverty? Evidence from a multi-centre intervention study conducted in Kenya, the Philippines and Bangladesh.

PubMed

Kuper, Hannah; Polack, Sarah; Mathenge, Wanjiku; Eusebio, Cristina; Wadud, Zakia; Rashid, Mamunur; Foster, Allen

2010-11-09

Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals.

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit.

PubMed

Silvestre, Julio; Montoya, Maria; Bruera, Eduardo; Elsayem, Ahmed

2015-12-01

We describe an exemplary case of congestive heart failure (CHF) symptoms controlled with milrinone. We also analyze the benefits and risks of milrinone administration in an unmonitored setting. We describe the case of a patient with refractory leukemia and end-stage CHF who developed severe dyspnea after discontinuation of milrinone. At that point, despite starting opioids, she had been severely dyspneic and anxious, requiring admission to the palliative care unit (PCU) for symptom control. After negotiation with hospital administrators, milrinone was administered in an unmonitored setting such as the PCU. A multidisciplinary team approach was also provided. Milrinone produced a dramatic improvement in the patient's symptom scores and performance status. The patient was eventually discharged to home hospice on a milrinone infusion with excellent symptom control. This case suggests that milrinone may be of benefit for short-term inpatient administration for dyspnea management, even in unmonitored settings and consequently during hospice in do-not-resuscitate (DNR) patients. This strategy may reduce costs and readmissions to the hospital related to end-stage CHF.

Many roads may lead to Rome: Selected features of quality control within environmental assessment systems in the US, NL, CA, and UK

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

Günther, Markus, E-mail: markus.guenther@tu-berlin.de; Geißler, Gesa; Köppel, Johann

As there is no one-and-only concept on how to precisely define and establish quality control (QC) or quality assurance (QA) in the making of environmental assessments (EA), this paper presents selected features of international approaches that address quality in EA systems in the USA, the Netherlands, Canada, and the United Kingdom. Based on explanative case studies, we highlight the embedding of specific quality control features within the EA systems, the objectives and processes, and relevant transparency challenges. Such features of QC/QA approaches can be considered in cases where substantial quality control and assurance efforts are still missing. Yet further researchmore » needs to be conducted on the efficacy of these approaches, which remains beyond the scope of this study. - Highlights: • We present four tools for quality control and assurance from different EA systems. • Approaches vary in institutional setting, objectives, procedures, and transparency. • Highlighted features might provide guidance in cases where QC/QA is still lacking.« less

Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.

PubMed

Naj, Adam C; Beecham, Gary W; Martin, Eden R; Gallins, Paul J; Powell, Eric H; Konidari, Ioanna; Whitehead, Patrice L; Cai, Guiqing; Haroutunian, Vahram; Scott, William K; Vance, Jeffery M; Slifer, Michael A; Gwirtsman, Harry E; Gilbert, John R; Haines, Jonathan L; Buxbaum, Joseph D; Pericak-Vance, Margaret A

2010-09-23

Genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) have consistently observed strong evidence of association with polymorphisms in APOE. However, until recently, variants at few other loci with statistically significant associations have replicated across studies. The present study combines data on 483,399 single nucleotide polymorphisms (SNPs) from a previously reported GWAS of 492 LOAD cases and 496 controls and from an independent set of 439 LOAD cases and 608 controls to strengthen power to identify novel genetic association signals. Associations exceeding the experiment-wide significance threshold (alpha=1.03x10(-7)) were replicated in an additional 1,338 cases and 2,003 controls. As expected, these analyses unequivocally confirmed APOE's risk effect (rs2075650, P=1.9x10(-36)). Additionally, the SNP rs11754661 at 151.2 Mb of chromosome 6q25.1 in the gene MTHFD1L (which encodes the methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like protein) was significantly associated with LOAD (P=4.70x10(-8); Bonferroni-corrected P=0.022). Subsequent genotyping of SNPs in high linkage disequilibrium (r2>0.8) with rs11754661 identified statistically significant associations in multiple SNPs (rs803424, P=0.016; rs2073067, P=0.03; rs2072064, P=0.035), reducing the likelihood of association due to genotyping error. In the replication case-control set, we observed an association of rs11754661 in the same direction as the previous association at P=0.002 (P=1.90x10(-10) in combined analysis of discovery and replication sets), with associations of similar statistical significance at several adjacent SNPs (rs17349743, P=0.005; rs803422, P=0.004). In summary, we observed and replicated a novel statistically significant association in MTHFD1L, a gene involved in the tetrahydrofolate synthesis pathway. This finding is noteworthy, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways and as levels of homocysteine are a significant risk factor for LOAD development.

When the Single Matters more than the Group (II): Addressing the Problem of High False Positive Rates in Single Case Voxel Based Morphometry Using Non-parametric Statistics.

PubMed

Scarpazza, Cristina; Nichols, Thomas E; Seramondi, Donato; Maumet, Camille; Sartori, Giuseppe; Mechelli, Andrea

2016-01-01

In recent years, an increasing number of studies have used Voxel Based Morphometry (VBM) to compare a single patient with a psychiatric or neurological condition of interest against a group of healthy controls. However, the validity of this approach critically relies on the assumption that the single patient is drawn from a hypothetical population with a normal distribution and variance equal to that of the control group. In a previous investigation, we demonstrated that family-wise false positive error rate (i.e., the proportion of statistical comparisons yielding at least one false positive) in single case VBM are much higher than expected (Scarpazza et al., 2013). Here, we examine whether the use of non-parametric statistics, which does not rely on the assumptions of normal distribution and equal variance, would enable the investigation of single subjects with good control of false positive risk. We empirically estimated false positive rates (FPRs) in single case non-parametric VBM, by performing 400 statistical comparisons between a single disease-free individual and a group of 100 disease-free controls. The impact of smoothing (4, 8, and 12 mm) and type of pre-processing (Modulated, Unmodulated) was also examined, as these factors have been found to influence FPRs in previous investigations using parametric statistics. The 400 statistical comparisons were repeated using two independent, freely available data sets in order to maximize the generalizability of the results. We found that the family-wise error rate was 5% for increases and 3.6% for decreases in one data set; and 5.6% for increases and 6.3% for decreases in the other data set (5% nominal). Further, these results were not dependent on the level of smoothing and modulation. Therefore, the present study provides empirical evidence that single case VBM studies with non-parametric statistics are not susceptible to high false positive rates. The critical implication of this finding is that VBM can be used to characterize neuroanatomical alterations in individual subjects as long as non-parametric statistics are employed.

Determinants of infant nutritional status in Dabat district, North Gondar, Ethiopia: A case control study.

PubMed

Wubante, Amarech Asratie

2017-01-01

Malnutrition is the top cause of global burden of disease, disability and mortality among infants. Over two-thirds of deaths of children globally occur during the first year of life (infancy). Malnutrition among infants is substantially high in Ethiopia. Therefore, this study is aimed to assess determinants of infant nutritional status. A community based nested case-control study was conducted from February to June 2013 in Dabat district. A total of 80 cases and 320 controls (1:4 ratios) were studied. Relevant data was extracted from the community based survey data set. Anthroplus software was used to identify cases and controls. Determinants of infant nutritional status were identified using multivariate analysis. Among the total of 80 cases and 320 controls, more than half (52.5%) of the cases and the controls (53.8%) were males and females, respectively. Breast Feeding (BF) was started immediately after birth in only 43.8% of the cases. Nearly 94% of the mothers of the cases had no breast feeding information as part of Ante Natal Care (ANC) follow up. Maternal age (AOR: 0.29; 95% CI: 0.11-0.76), having radio (AOR: 0.43; 95% CI: 0.22-0.82), lack of toilet facility (AOR: 2.24; 95% CI: 1.16-4.33), deprivation of colostrum (AOR: 1.76; 95% CI: 1.01-1.06) and method of complementary feeding (AOR: 2.82; 95% CI: 1.33-5.99) were associated with wasting. This study has found that inappropriate infant feeding; nutritional information gap and lack of toilet facility as significant predictors of malnutrition. Hence, joint interventions, including counseling of mothers about benefits of colostrum feeding and use of appropriate feeding method, toilet utilization and mass media such as radio possession, are needed to address the problem in Dabat district.

A Case-control Study to Evaluate the Prevalence of Nonalcoholic Fatty Liver Disease Among Patients with Moderate-to-severe Psoriasis.

PubMed

Awosika, Olabola; Eleryan, Misty G; Rengifo-Pardo, Monica; Doherty, Lindsay; Martin, Lisa W; Ehrlich, Alison

2018-06-01

Objective: International case-control studies have demonstrated that psoriasis is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to establish an association of psoriasis and NAFLD in patients attending a dermatology clinic center in the United States. Design: This was an observational, case-control study. Setting: The study setting was an outpatient dermatology clinic of the George Washington Medical Faculty Associates in Washington DC. Participants: One hundred fifty-one adult patients with psoriasis and 51 control subjects were recruited. Measurements: NAFLD was diagnosed by ultrasonography after excluding secondary causes of liver disease. Regression analysis was used to assess the associations between: 1) NAFLD and psoriasis and 2) metabolic syndrome components and NAFLD among psoriasis patients. Results: NAFLD was more prevalent in patients with psoriasis (21.2% vs. 7.8%, p <0.04). However, psoriasis was not associated with NAFLD when matching for age, sex, and body mass index (BMI) (odds ratio: 2.63, 95% confidence interval [CI]: 0.51-13.6; p =0.25). As compared to patients with psoriasis but without NAFLD, those with NAFLD were more likely to have obesity (BMI: 34.9 vs. 27.2, 95% CI: 32.4-37.5 vs. 25.9-28.5; p <0.01). NAFLD in patients with psoriasis was also associated with select components of metabolic syndrome, including hyperglycemia and hyperlipidemia. Conclusion: Our findings show there is an association of psoriasis with NAFLD. Our findings also suggest an increased presence of metabolic syndrome components in patients with psoriasis and NAFLD. Trial registry: NCT00930384.

A power comparison of generalized additive models and the spatial scan statistic in a case-control setting.

PubMed

Young, Robin L; Weinberg, Janice; Vieira, Verónica; Ozonoff, Al; Webster, Thomas F

2010-07-19

A common, important problem in spatial epidemiology is measuring and identifying variation in disease risk across a study region. In application of statistical methods, the problem has two parts. First, spatial variation in risk must be detected across the study region and, second, areas of increased or decreased risk must be correctly identified. The location of such areas may give clues to environmental sources of exposure and disease etiology. One statistical method applicable in spatial epidemiologic settings is a generalized additive model (GAM) which can be applied with a bivariate LOESS smoother to account for geographic location as a possible predictor of disease status. A natural hypothesis when applying this method is whether residential location of subjects is associated with the outcome, i.e. is the smoothing term necessary? Permutation tests are a reasonable hypothesis testing method and provide adequate power under a simple alternative hypothesis. These tests have yet to be compared to other spatial statistics. This research uses simulated point data generated under three alternative hypotheses to evaluate the properties of the permutation methods and compare them to the popular spatial scan statistic in a case-control setting. Case 1 was a single circular cluster centered in a circular study region. The spatial scan statistic had the highest power though the GAM method estimates did not fall far behind. Case 2 was a single point source located at the center of a circular cluster and Case 3 was a line source at the center of the horizontal axis of a square study region. Each had linearly decreasing logodds with distance from the point. The GAM methods outperformed the scan statistic in Cases 2 and 3. Comparing sensitivity, measured as the proportion of the exposure source correctly identified as high or low risk, the GAM methods outperformed the scan statistic in all three Cases. The GAM permutation testing methods provide a regression-based alternative to the spatial scan statistic. Across all hypotheses examined in this research, the GAM methods had competing or greater power estimates and sensitivities exceeding that of the spatial scan statistic.

A power comparison of generalized additive models and the spatial scan statistic in a case-control setting

PubMed Central

2010-01-01

Background A common, important problem in spatial epidemiology is measuring and identifying variation in disease risk across a study region. In application of statistical methods, the problem has two parts. First, spatial variation in risk must be detected across the study region and, second, areas of increased or decreased risk must be correctly identified. The location of such areas may give clues to environmental sources of exposure and disease etiology. One statistical method applicable in spatial epidemiologic settings is a generalized additive model (GAM) which can be applied with a bivariate LOESS smoother to account for geographic location as a possible predictor of disease status. A natural hypothesis when applying this method is whether residential location of subjects is associated with the outcome, i.e. is the smoothing term necessary? Permutation tests are a reasonable hypothesis testing method and provide adequate power under a simple alternative hypothesis. These tests have yet to be compared to other spatial statistics. Results This research uses simulated point data generated under three alternative hypotheses to evaluate the properties of the permutation methods and compare them to the popular spatial scan statistic in a case-control setting. Case 1 was a single circular cluster centered in a circular study region. The spatial scan statistic had the highest power though the GAM method estimates did not fall far behind. Case 2 was a single point source located at the center of a circular cluster and Case 3 was a line source at the center of the horizontal axis of a square study region. Each had linearly decreasing logodds with distance from the point. The GAM methods outperformed the scan statistic in Cases 2 and 3. Comparing sensitivity, measured as the proportion of the exposure source correctly identified as high or low risk, the GAM methods outperformed the scan statistic in all three Cases. Conclusions The GAM permutation testing methods provide a regression-based alternative to the spatial scan statistic. Across all hypotheses examined in this research, the GAM methods had competing or greater power estimates and sensitivities exceeding that of the spatial scan statistic. PMID:20642827

Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations.

PubMed

Chen, Cheng; Xun, Pengcheng; Nishijo, Muneko; He, Ka

2016-09-01

The association between cadmium exposure and risk of lung cancer is still unclear. We quantitatively reviewed the observational studies that investigated the association between cadmium exposure and lung cancer risk in both general and occupational populations published through April 2015. The final data set is comprised of three cohort studies in the general population totaling 22,551 participants (354 events) with a mean follow-up of 15 years, five occupational cohort studies including 4205 individuals (180 events) with an average follow-up of 31 years, and three occupational case-control studies including 4740 cases and 6268 controls. Comparing the highest to the lowest category of cadmium exposure, the weighted relative risk and 95% confidence interval of lung cancer in the general population was 1.42 (95% CI (0.91, 2.23)); the weighted risk estimates (95% CIs) of lung cancer in three occupational cohort studies and three case-control studies were 0.68 (95% CI (0.33, 1.41)) and 1.61 (95% CI (0.94, 2.75)), respectively. No linear association was found. When comparing participants exposed to cadmium with non-exposed based on available data, the association became statistically significant. According to findings from this meta-analysis, the possibility that cadmium exposure may increase risk of lung cancer cannot be completely ruled out in either general or occupational population.

A two-step hierarchical hypothesis set testing framework, with applications to gene expression data on ordered categories

PubMed Central

2014-01-01

Background In complex large-scale experiments, in addition to simultaneously considering a large number of features, multiple hypotheses are often being tested for each feature. This leads to a problem of multi-dimensional multiple testing. For example, in gene expression studies over ordered categories (such as time-course or dose-response experiments), interest is often in testing differential expression across several categories for each gene. In this paper, we consider a framework for testing multiple sets of hypothesis, which can be applied to a wide range of problems. Results We adopt the concept of the overall false discovery rate (OFDR) for controlling false discoveries on the hypothesis set level. Based on an existing procedure for identifying differentially expressed gene sets, we discuss a general two-step hierarchical hypothesis set testing procedure, which controls the overall false discovery rate under independence across hypothesis sets. In addition, we discuss the concept of the mixed-directional false discovery rate (mdFDR), and extend the general procedure to enable directional decisions for two-sided alternatives. We applied the framework to the case of microarray time-course/dose-response experiments, and proposed three procedures for testing differential expression and making multiple directional decisions for each gene. Simulation studies confirm the control of the OFDR and mdFDR by the proposed procedures under independence and positive correlations across genes. Simulation results also show that two of our new procedures achieve higher power than previous methods. Finally, the proposed methodology is applied to a microarray dose-response study, to identify 17 β-estradiol sensitive genes in breast cancer cells that are induced at low concentrations. Conclusions The framework we discuss provides a platform for multiple testing procedures covering situations involving two (or potentially more) sources of multiplicity. The framework is easy to use and adaptable to various practical settings that frequently occur in large-scale experiments. Procedures generated from the framework are shown to maintain control of the OFDR and mdFDR, quantities that are especially relevant in the case of multiple hypothesis set testing. The procedures work well in both simulations and real datasets, and are shown to have better power than existing methods. PMID:24731138

When repetitive mental sets increase cognitive flexibility in adolescent obsessive-compulsive disorder.

PubMed

Wolff, Nicole; Giller, Franziska; Buse, Judith; Roessner, Veit; Beste, Christian

2018-03-30

A major facet of obsessive-compulsive disorder (OCD) is cognitive inflexibility. However, sometimes, cognitive flexibility can be needed to reuse recently abandoned mental sets. Therefore, cognitive flexibility can in certain cases be useful to reinstate some form of rigid, repetitive behavior characterizing OCD. We test the counterintuitive hypothesis that under such circumstances, cognitive flexibility is better in OCD patients than controls. We examined N = 20 adolescent OCD patients and N = 22 controls in a backward inhibition (BI) paradigm. This was combined with event-related potential (ERP) recordings and source localization. The BI effect describes the cost of overcoming the inhibition of a recently abandoned mental set that is relevant again. Therefore, a strong BI effect is disadvantageous for cognitive flexibility. Compared to controls, OCD patients revealed a smaller backward inhibition effect. The EEG data revealed larger P1 amplitudes in backward inhibition trials in the OCD group, which was due to activation differences in the inferior frontal gyrus (BA47). The severity of clinical symptoms predicted these neurophysiological modulations. The power of the observed effects was about 95%. The study shows that cognitive flexibility can be better in OCD than controls. This may be the case in situations where superior abilities in the reactivation of repeating mental sets and difficulties to process new ones coincide. This may be accomplished by intensified inhibitory control mechanisms. The results challenge the view on OCD, since OCD is not generally associated with cognitive inflexibility. © 2018 Association for Child and Adolescent Mental Health.

Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations

PubMed Central

van Hecke, Oliver; Kamerman, Peter R.; Attal, Nadine; Baron, Ralf; Bjornsdottir, Gyda; Bennett, David L.H.; Bennett, Michael I.; Bouhassira, Didier; Diatchenko, Luda; Freeman, Roy; Freynhagen, Rainer; Haanpää, Maija; Jensen, Troels S.; Raja, Srinivasa N.; Rice, Andrew S.C.; Seltzer, Ze'ev; Thorgeirsson, Thorgeir E.; Yarnitsky, David; Smith, Blair H.

2015-01-01

Abstract For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in part because of differences in phenotypes used for case ascertainment. Because there is no consensus on the nature of these phenotypes, nor on the methods of collecting them, this study aimed to provide guidelines on collecting and reporting phenotypes in cases and controls for genetic studies. Consensus was achieved through a staged approach: (1) systematic literature review to identify all neuropathic pain phenotypes used in previous genetic studies; (2) Delphi survey to identify the most useful neuropathic pain phenotypes and their validity and feasibility; and (3) meeting of experts to reach consensus on the optimal phenotype(s) to be collected from patients with neuropathic pain for genetic studies. A basic “entry level” set of phenotypes was identified for any genetic study of neuropathic pain. This set identifies cases of “possible” neuropathic pain, and controls, and includes: (1) a validated symptom-based questionnaire to determine whether any pain is likely to be neuropathic; (2) body chart or checklist to identify whether the area of pain distribution is neuroanatomically logical; and (3) details of pain history (intensity, duration, any formal diagnosis). This NeuroPPIC “entry level” set of phenotypes can be expanded by more extensive and specific measures, as determined by scientific requirements and resource availability. PMID:26469320

Survival bias and drug interaction can attenuate cross-sectional case-control comparisons of genes with health outcomes. An example of the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism and coronary heart disease.

PubMed

Williams, Paul; Pendyala, Lakshmana; Superko, Robert

2011-03-24

Case-control studies typically exclude fatal endpoints from the case set, which we hypothesize will substantially underestimate risk if survival is genotype-dependent. The loss of fatal cases is particularly nontrivial for studies of coronary heart disease (CHD) because of significantly reduced survival (34% one-year fatality following a coronary attack). A case in point is the KIF6 Trp719Arg polymorphism (rs20455). Whereas six prospective studies have shown that carriers of the KIF6 Trp719Arg risk allele have 20% to 50% greater CHD risk than non-carriers, several cross-sectional case-control studies failed to show that carrier status is related to CHD. Computer simulations were therefore employed to assess the impact of the loss of fatal events on gene associations in cross-sectional case-control studies, using KIF6 Trp719Arg as an example. Ten replicates of 1,000,000 observations each were generated reflecting Canadian demographics. Cardiovascular disease (CVD) risks were assigned by the Framingham equation and events distributed among KIF6 Trp719Arg genotypes according to published prospective studies. Logistic regression analysis was used to estimate odds ratios between KIF6 genotypes. Results were examined for 33%, 41.5%, and 50% fatality rates for incident CVD.In the absence of any difference in percent fatalities between genotypes, the odds ratios (carriers vs. noncarriers) were unaffected by survival bias, otherwise the odds ratios were increasingly attenuated as the disparity between fatality rates increased between genotypes. Additional simulations demonstrated that statin usage, shown in four clinical trials to substantially reduce the excess CHD risk in the KIF6 719Arg variant, should also attenuate the KIF6 719Arg odds ratio in case-control studies. These computer simulations show that exclusions of prior CHD fatalities attenuate odds ratios of case-control studies in proportion to the difference in the percent fatalities between genotypes. Disproportionate CHD survival for KIF6 Trip719Arg carriers is suggested by their 50% greater risk for recurrent myocardial infarction. This, and the attenuation of KIF6 719Arg carrier risk with statin use, may explain the genotype's weak association with CHD in cross-sectional case-control studies. The results may be relevant to the underestimation of risk in cross-sectional case-control studies of other genetic CHD-risk factors affecting survival.

Family-based treatment of a 17-year-old twin presenting with emerging anorexia nervosa: a case study using the "Maudsley method".

PubMed

Loeb, Katharine L; Hirsch, Alicia M; Greif, Rebecca; Hildebrandt, Thomas B

2009-01-01

This article describes the successful application of family-based treatment (FBT) for a 17-year-old identical twin presenting with a 4-month history of clinically significant symptoms of anorexia nervosa (AN). FBT is a manualized treatment that has been studied in randomized controlled trials for adolescents with AN. This case study illustrates the administration of this evidence-based intervention in a clinical setting, highlighting how the best available research was used to make clinical decisions at each stage of treatment delivery.

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

PubMed Central

Ho, Antonia; Aston, Stephen J; Jary, Hannah; Mitchell, Tamara; Alaerts, Maaike; Menyere, Mavis; Mallewa, Jane; Nyirenda, Mulinda; Everett, Dean; Heyderman, Robert S; French, Neil

2018-01-01

Abstract Background The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa. Methods We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]). Results The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02–7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09–11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security). Conclusions HIV is an important risk factor for influenza-associated ILI and severe presentation in this high–HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined. PMID:29045699

Video Capture of Plastic Surgery Procedures Using the GoPro HERO 3+.

PubMed

Graves, Steven Nicholas; Shenaq, Deana Saleh; Langerman, Alexander J; Song, David H

2015-02-01

Significant improvements can be made in recoding surgical procedures, particularly in capturing high-quality video recordings from the surgeons' point of view. This study examined the utility of the GoPro HERO 3+ Black Edition camera for high-definition, point-of-view recordings of plastic and reconstructive surgery. The GoPro HERO 3+ Black Edition camera was head-mounted on the surgeon and oriented to the surgeon's perspective using the GoPro App. The camera was used to record 4 cases: 2 fat graft procedures and 2 breast reconstructions. During cases 1-3, an assistant remotely controlled the GoPro via the GoPro App. For case 4 the GoPro was linked to a WiFi remote, and controlled by the surgeon. Camera settings for case 1 were as follows: 1080p video resolution; 48 fps; Protune mode on; wide field of view; 16:9 aspect ratio. The lighting contrast due to the overhead lights resulted in limited washout of the video image. Camera settings were adjusted for cases 2-4 to a narrow field of view, which enabled the camera's automatic white balance to better compensate for bright lights focused on the surgical field. Cases 2-4 captured video sufficient for teaching or presentation purposes. The GoPro HERO 3+ Black Edition camera enables high-quality, cost-effective video recording of plastic and reconstructive surgery procedures. When set to a narrow field of view and automatic white balance, the camera is able to sufficiently compensate for the contrasting light environment of the operating room and capture high-resolution, detailed video.

Nonlinear model predictive control applied to the separation of praziquantel in simulated moving bed chromatography.

PubMed

Andrade Neto, A S; Secchi, A R; Souza, M B; Barreto, A G

2016-10-28

An adaptive nonlinear model predictive control of a simulated moving bed unit for the enantioseparation of praziquantel is presented. A first principle model was applied at the proposed purity control scheme. The main concern about this kind of model in a control framework is in regard to the computational effort to solve it; however, a fast enough solution was achieved. In order to evaluate the controller's performance, several cases were simulated, including external pumps and switching valve malfunctions. The problem of plant-model mismatch was also investigated, and for that reason a parameter estimation step was introduced in the control strategy. In every studied scenario, the controller was able to maintain the purity levels at their set points, which were set to 99% and 98.6% for extract and raffinate, respectively. Additionally, fast responses and smooth actuation were achieved. Copyright © 2016 Elsevier B.V. All rights reserved.

Breast Cancer and Modifiable Lifestyle Factors in Argentinean Women: Addressing Missing Data in a Case-Control Study

PubMed Central

Coquet, Julia Becaria; Tumas, Natalia; Osella, Alberto Ruben; Tanzi, Matteo; Franco, Isabella; Diaz, Maria Del Pilar

2016-01-01

A number of studies have evidenced the effect of modifiable lifestyle factors such as diet, breastfeeding and nutritional status on breast cancer risk. However, none have addressed the missing data problem in nutritional epidemiologic research in South America. Missing data is a frequent problem in breast cancer studies and epidemiological settings in general. Estimates of effect obtained from these studies may be biased, if no appropriate method for handling missing data is applied. We performed Multiple Imputation for missing values on covariates in a breast cancer case-control study of Córdoba (Argentina) to optimize risk estimates. Data was obtained from a breast cancer case control study from 2008 to 2015 (318 cases, 526 controls). Complete case analysis and multiple imputation using chained equations were the methods applied to estimate the effects of a Traditional dietary pattern and other recognized factors associated with breast cancer. Physical activity and socioeconomic status were imputed. Logistic regression models were performed. When complete case analysis was performed only 31% of women were considered. Although a positive association of Traditional dietary pattern and breast cancer was observed from both approaches (complete case analysis OR=1.3, 95%CI=1.0-1.7; multiple imputation OR=1.4, 95%CI=1.2-1.7), effects of other covariates, like BMI and breastfeeding, were only identified when multiple imputation was considered. A Traditional dietary pattern, BMI and breastfeeding are associated with the occurrence of breast cancer in this Argentinean population when multiple imputation is appropriately performed. Multiple Imputation is suggested in Latin America’s epidemiologic studies to optimize effect estimates in the future. PMID:27892664

Challenges with controlling varicella in prison settings: experience of California, 2010 to 2011.

PubMed

Leung, Jessica; Lopez, Adriana S; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H; Preas, Christopher P; Cosentino, Giorgio; Bialek, Stephanie R; Marin, Mona

2014-10-01

This article describes the epidemiology of varicella in one state prison in California during 2010 and 2011, control measures implemented, and associated costs. Eleven varicella cases were reported, of which nine were associated with two outbreaks. One outbreak consisted of three cases and the second consisted of six cases with two generations of spread. Among exposed inmates serologically tested, 98% (643/656) were varicella-zoster virus seropositive. The outbreaks resulted in > 1,000 inmates exposed, 444 staff exposures, and > $160,000 in costs. The authors documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary to manage cases and outbreaks. © The Author(s) 2014.

Analysis of Control Strategies for Aircraft Flight Upset Recovery

NASA Technical Reports Server (NTRS)

Crespo, Luis G.; Kenny, Sean P.; Cox, David E.; Muri, Daniel G.

2012-01-01

This paper proposes a framework for studying the ability of a control strategy, consisting of a control law and a command law, to recover an aircraft from ight conditions that may extend beyond the normal ight envelope. This study was carried out (i) by evaluating time responses of particular ight upsets, (ii) by evaluating local stability over an equilibrium manifold that included stall, and (iii) by bounding the set in the state space from where the vehicle can be safely own to wings-level ight. These states comprise what will be called the safely recoverable ight envelope (SRFE), which is a set containing the aircraft states from where a control strategy can safely stabilize the aircraft. By safe recovery it is implied that the tran- sient response stays between prescribed limits before converging to a steady horizontal ight. The calculation of the SRFE bounds yields the worst-case initial state corresponding to each control strategy. This information is used to compare alternative recovery strategies, determine their strengths and limitations, and identify the most e ective strategy. In regard to the control law, the authors developed feedback feedforward laws based on the gain scheduling of multivariable controllers. In regard to the command law, which is the mechanism governing the exogenous signals driving the feed- forward component of the controller, we developed laws with a feedback structure that combines local stability and transient response considera- tions. The upset recovery of the Generic Transport Model, a sub-scale twin-engine jet vehicle developed by NASA Langley Research Center, is used as a case study.

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.

A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

PubMed Central

Muhsen, Khitam; Levine, Myron M.

2012-01-01

We performed a systematic literature review and meta-analysis examining the association between diarrhea in young children in nonindustrialized settings and Giardia lamblia infection. Eligible were case/control and longitudinal studies that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly in stools) from diarrhea patients and controls without diarrhea were abstracted. Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric diarrhea studies met the meta-analysis inclusion criteria. Random-effects model meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls) yielded a pooled OR of 0.60 (95% CI, .38–.94; P = .03), indicating that G. lamblia was not associated with acute diarrhea. However, limited data suggest that initial Giardia infections in early infancy may be positively associated with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR of 3.18 (95% CI, 1.50–6.76; P < .001), positively linking Giardia with that syndrome. The well-powered Global Enteric Multicenter Study (GEMS) is prospectively addressing the association between G. lamblia infection and diarrhea in children in developing countries. PMID:23169940

Network-based regularization for matched case-control analysis of high-dimensional DNA methylation data.

PubMed

Sun, Hokeun; Wang, Shuang

2013-05-30

The matched case-control designs are commonly used to control for potential confounding factors in genetic epidemiology studies especially epigenetic studies with DNA methylation. Compared with unmatched case-control studies with high-dimensional genomic or epigenetic data, there have been few variable selection methods for matched sets. In an earlier paper, we proposed the penalized logistic regression model for the analysis of unmatched DNA methylation data using a network-based penalty. However, for popularly applied matched designs in epigenetic studies that compare DNA methylation between tumor and adjacent non-tumor tissues or between pre-treatment and post-treatment conditions, applying ordinary logistic regression ignoring matching is known to bring serious bias in estimation. In this paper, we developed a penalized conditional logistic model using the network-based penalty that encourages a grouping effect of (1) linked Cytosine-phosphate-Guanine (CpG) sites within a gene or (2) linked genes within a genetic pathway for analysis of matched DNA methylation data. In our simulation studies, we demonstrated the superiority of using conditional logistic model over unconditional logistic model in high-dimensional variable selection problems for matched case-control data. We further investigated the benefits of utilizing biological group or graph information for matched case-control data. We applied the proposed method to a genome-wide DNA methylation study on hepatocellular carcinoma (HCC) where we investigated the DNA methylation levels of tumor and adjacent non-tumor tissues from HCC patients by using the Illumina Infinium HumanMethylation27 Beadchip. Several new CpG sites and genes known to be related to HCC were identified but were missed by the standard method in the original paper. Copyright © 2012 John Wiley & Sons, Ltd.

Using public control genotype data to increase power and decrease cost of case-control genetic association studies.

PubMed

Ho, Lindsey A; Lange, Ethan M

2010-12-01

Genome-wide association (GWA) studies are a powerful approach for identifying novel genetic risk factors associated with human disease. A GWA study typically requires the inclusion of thousands of samples to have sufficient statistical power to detect single nucleotide polymorphisms that are associated with only modest increases in risk of disease given the heavy burden of a multiple test correction that is necessary to maintain valid statistical tests. Low statistical power and the high financial cost of performing a GWA study remains prohibitive for many scientific investigators anxious to perform such a study using their own samples. A number of remedies have been suggested to increase statistical power and decrease cost, including the utilization of free publicly available genotype data and multi-stage genotyping designs. Herein, we compare the statistical power and relative costs of alternative association study designs that use cases and screened controls to study designs that are based only on, or additionally include, free public control genotype data. We describe a novel replication-based two-stage study design, which uses free public control genotype data in the first stage and follow-up genotype data on case-matched controls in the second stage that preserves many of the advantages inherent when using only an epidemiologically matched set of controls. Specifically, we show that our proposed two-stage design can substantially increase statistical power and decrease cost of performing a GWA study while controlling the type-I error rate that can be inflated when using public controls due to differences in ancestry and batch genotype effects.

Tune the topology to create or destroy patterns

NASA Astrophysics Data System (ADS)

Asllani, Malbor; Carletti, Timoteo; Fanelli, Duccio

2016-12-01

We consider the dynamics of a reaction-diffusion system on a multigraph. The species share the same set of nodes but can access different links to explore the embedding spatial support. By acting on the topology of the networks we can control the ability of the system to self-organise in macroscopic patterns, emerging as a symmetry breaking instability of an homogeneous fixed point. Two different cases study are considered: on the one side, we produce a global modification of the networks, starting from the limiting setting where species are hosted on the same graph. On the other, we consider the effect of inserting just one additional single link to differentiate the two graphs. In both cases, patterns can be generated or destroyed, as follows the imposed, small, topological perturbation. Approximate analytical formulae allow to grasp the essence of the phenomenon and can potentially inspire innovative control strategies to shape the macroscopic dynamics on multigraph networks.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study

PubMed Central

Baggett, Henry C; Watson, Nora L; Deloria Knoll, Maria; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; Scott, J Anthony G; Thea, Donald M; Antonio, Martin; Awori, Juliet O; Baillie, Vicky L; DeLuca, Andrea N; Driscoll, Amanda J; Duncan, Julie; Ebruke, Bernard E; Goswami, Doli; Higdon, Melissa M; Karron, Ruth A; Moore, David P; Morpeth, Susan C; Mulindwa, Justin M; Park, Daniel E; Paveenkittiporn, Wantana; Piralam, Barameht; Prosperi, Christine; Sow, Samba O; Tapia, Milagritos D; Zaman, Khalequ; Zeger, Scott L; O’Brien, Katherine L; O, K L; L, O S; K, M D; F, D R; D, A N; D, A J; Fancourt, Nicholas; Fu, Wei; H, L L; H, M M; Wangeci Kagucia, E; K, R A; Li, Mengying; P, D E; P, C; Wu, Zhenke; Z, S L; W, N L; Crawley, Jane; M, D R; B, W A; Endtz, Hubert P; Z, K; G, D; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; C H, S R; E, B E; A, M; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M A; Mackenzie, Grant; G S, J A; A, J O; M, S C; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; K, K L; T, M D; S, S O; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; M, S A; M, D P; Adrian, Peter V; B, V L; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J; Mahomed, Nasreen; B, H C; Thamthitiwat, Somsak; Maloney, Susan A; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; T, D M; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P; Mitchell, Joanne

2017-01-01

Abstract Background Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. Methods PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1–59 months hospitalized with World Health Organization–defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. Results Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). Conclusions Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting. PMID:28575365

Lean management in health care: definition, concepts, methodology and effects reported (systematic review protocol).

PubMed

Lawal, Adegboyega K; Rotter, Thomas; Kinsman, Leigh; Sari, Nazmi; Harrison, Liz; Jeffery, Cathy; Kutz, Mareike; Khan, Mohammad F; Flynn, Rachel

2014-09-19

Lean is a set of operating philosophies and methods that help create a maximum value for patients by reducing waste and waits. It emphasizes the consideration of the customer's needs, employee involvement and continuous improvement. Research on the application and implementation of lean principles in health care has been limited. This is a protocol for a systematic review, following the Cochrane Effective Practice and Organisation of Care (EPOC) methodology. The review aims to document, catalogue and synthesize the existing literature on the effects of lean implementation in health care settings especially the potential effects on professional practice and health care outcomes. We have developed a Medline keyword search strategy, and this focused strategy will be translated into other databases. All search strategies will be provided in the review. The method proposed by the Cochrane EPOC group regarding randomized study designs, non-randomised controlled trials controlled before and after studies and interrupted time series will be followed. In addition, we will also include cohort, case-control studies, and relevant non-comparative publications such as case reports. We will categorize and analyse the review findings according to the study design employed, the study quality (low- versus high-quality studies) and the reported types of implementation in the primary studies. We will present the results of studies in a tabular form. Overall, the systematic review aims to identify, assess and synthesize the evidence to underpin the implementation of lean activities in health care settings as defined in this protocol. As a result, the review will provide an evidence base for the effectiveness of lean and implementation methodologies reported in health care. PROSPERO CRD42014008853.

A Pilot Study to Examine Maturation of Body Temperature Control in Preterm Infants

PubMed Central

Knobel, Robin B.; Levy, Janet; Katz, Laurence; Guenther, Bob; Holditch-Davis, Diane

2013-01-01

Objective To test instrumentation and develop analytic models to use in a larger study to examine developmental trajectories of body temperature and peripheral perfusion from birth in extremely low birth weight (EBLW) infants. Design A case study design. Setting The study took place in a level four neonatal intensive care unit (NICU) in North Carolina. Participants Four ELBW infants, less than 29 weeks gestational age at birth. Methods Physiologic data were measured every minute for the first 5 days of life: peripheral perfusion using perfusion index by Masimo and body temperature using thermistors. Body temperature was also measured using infrared thermal imaging. Stimulation and care events were recorded over the first 5 days using video which was coded with Noldus Observer software. Novel analytical models using the state space approach to time series analysis were developed to explore maturation of neural control over central and peripheral body temperature. Results/Conclusion Results from this pilot study confirmed the feasibility of using multiple instruments to measure temperature and perfusion in ELBW infants. This approach added rich data to our case study design and set a clinical context with which to interpret longitudinal physiological data. PMID:24004312

High reprint orders in medical journals and pharmaceutical industry funding: case-control study

PubMed Central

Handel, Adam E; Patel, Sunil V; Pakpoor, Julia; Ebers, George C; Goldacre, Ben

2012-01-01

Objectives To assess the extent to which funding and study design are associated with high reprint orders. Design Case-control study. Setting Top articles by size of reprint orders in seven journals, 2002-09. Participants Lancet, Lancet Neurology, Lancet Oncology (Lancet Group), BMJ, Gut, Heart, and Journal of Neurology, Neurosurgery & Psychiatry (BMJ Group) matched to contemporaneous articles not in the list of high reprint orders. Main outcome measures Funding and design of randomised controlled trials or other study designs. Results Median reprint orders for the seven journals ranged from 3000 to 126 350. Papers with high reprint orders were more likely to be funded by the pharmaceutical industry than were control papers (industry funding versus other or none: odds ratio 8.64, 95% confidence interval 5.09 to 14.68, and mixed funding versus other or none: 3.72, 2.43 to 5.70). Conclusions Funding by the pharmaceutical industry is associated with high numbers of reprint orders. PMID:22745328

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

PubMed Central

Dunlop, Malcolm G; Dobbins, Sara E; Farrington, Susan Mary; Jones, Angela M; Palles, Claire; Whiffin, Nicola; Tenesa, Albert; Spain, Sarah; Broderick, Peter; Ooi, Li-Yin; Domingo, Enric; Smillie, Claire; Henrion, Marc; Frampton, Matthew; Martin, Lynn; Grimes, Graeme; Gorman, Maggie; Semple, Colin; Ma, Yussanne; Barclay, Ella; Prendergast, James; Cazier, Jean-Baptiste; Olver, Bianca; Carvajal-Carmona, Luis G; Ballereau, Stephane; Lloyd, Amy; Vijayakrishnan, Jayaram; Zgaga, Lina; Rudan, Igor; Theodoratou, Evropi; Starr, John M; Deary, Ian; Kirac, Iva; Kovačević, Dujo; Aaltonen, Lauri A; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Matsuda, Koichi; Nakamura, Yusuke; Okada, Yukinori; Gallinger, Steven; Duggan, David J; Conti, David; Newcomb, Polly; Hopper, John; Jenkins, Mark A.; Schumacher, Fredrick; Casey, Graham; Easton, Douglas; Shah, Mitul; Pharoah, Paul; Lindblom, Annika; Liu, Tao; Smith, Christopher G; West, Hannah; Cheadle, Jeremy P.; Midgley, Rachel; Kerr, David J; Campbell, Harry; Tomlinson, Ian P; Houlston, Richard S

2015-01-01

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totalling 21,096 cases and 19,555 controls. We identified three novel CRC risk loci at 6p21 (rs1321311, near CDKN1A; P=1.14×10−10), 11q13.4 (rs3824999, intronic to POLD3; P=3.65×10−10) and Xp22.2 (rs5934683, near SHROOM2; P=7.30×10−10) This brings to 20 the number of independent loci associated with CRC risk, and provides further insight into the genetic architecture of inherited susceptibility to CRC. PMID:22634755

Psychological disorders and oral lichen planus: matched case-control study and literature review.

PubMed

Pippi, R; Romeo, U; Santoro, M; Del Vecchio, A; Scully, C; Petti, S

2016-04-01

Oral lichen planus (OLP) may be linked to psychological disorders. This study investigated psychological factors associated with OLP. A case-control study with incident OLP case patients and age-gender-socio-economic status-matched controls, recruited from among relatives, accompanying persons, and departmental staff, investigated psychological traits using the Psychological General Well-Being Index-Short form. Common factor analysis was used to generate a set of psychological dimensions. The association between these dimensions and OLP adjusted for confounders (education, number of lifetime sexual partners, drinking-smoking) and interactions was assessed through conditional logistic regression and odds ratios (OR) were estimated. A total of 67 case-control pairs were recruited. Psychological dimensions generated were: dimension-1 (anxiety, low vitality), dimension-2 (negative well-being, low vitality), dimension-3 (depressed mood, low self-control). The ORs for OLP were, dimension-1, 1.0 (95% confidence interval -95CI, 0.3-2.6); dimension-2, 0.5 (95CI, 0.2-1.2); dimension-3, 4.8 (95CI, 1.8-12.9). Dimension-3 was highly associated with mild, but not associated with severe, OLP. Literature searching provided 21 studies, with anxiety and depression principally associated with OLP. Depressed mood and low self-control were highly associated with OLP, particularly the reticular-papular forms. These traits could have a causative role in OLP development-progression, but further investigations are necessary. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to household level transmission factors, 2016-2017.

PubMed

Spina, Alexander; Lenglet, Annick; Beversluis, David; de Jong, Marja; Vernier, Larissa; Spencer, Craig; Andayi, Fred; Kamau, Charity; Vollmer, Simone; Hogema, Boris; Irwin, Andrea; Ngueremi Yary, Roger; Mahamat Ali, Açyl; Moussa, Ali; Alfani, Prince; Sang, Sibylle

2017-01-01

In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.

Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor.

PubMed

Kristiansen, Wenche; Karlsson, Robert; Rounge, Trine B; Whitington, Thomas; Andreassen, Bettina K; Magnusson, Patrik K; Fosså, Sophie D; Adami, Hans-Olov; Turnbull, Clare; Haugen, Trine B; Grotmol, Tom; Wiklund, Fredrik

2015-07-15

Genome-wide association (GWA) studies have reported 19 distinct susceptibility loci for testicular germ cell tumor (TGCT). A GWA study for TGCT was performed by genotyping 610 240 single-nucleotide polymorphisms (SNPs) in 1326 cases and 6687 controls from Sweden and Norway. No novel genome-wide significant associations were observed in this discovery stage. We put forward 27 SNPs from 15 novel regions and 12 SNPs previously reported, for replication in 710 case-parent triads and 289 cases and 290 controls. Predefined biological pathways and processes, in addition to a custom-built sex-determination gene set, were subject to enrichment analyses using Meta-Analysis Gene Set Enrichment of Variant Associations (M) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (I). In the combined meta-analysis, we observed genome-wide significant association for rs7501939 on chromosome 17q12 (OR = 0.78, 95% CI = 0.72-0.84, P = 1.1 × 10(-9)) and rs2195987 on chromosome 19p12 (OR = 0.76, 95% CI: 0.69-0.84, P = 3.2 × 10(-8)). The marker rs7501939 on chromosome 17q12 is located in an intron of the HNF1B gene, encoding a member of the homeodomain-containing superfamily of transcription factors. The sex-determination gene set (false discovery rate, FDRM < 0.001, FDRI < 0.001) and pathways related to NF-κB, glycerophospholipid and ether lipid metabolism, as well as cancer and apoptosis, was associated with TGCT (FDR < 0.1). In addition to revealing two new TGCT susceptibility loci, our results continue to support the notion that genes governing normal germ cell development in utero are implicated in the development of TGCT. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

How To Set Up Your Own Small Business. Service Company Case Study. Manufacturing Firm Case Study. Retail Store Case Study.

ERIC Educational Resources Information Center

Fallek, Max

This collection of case studies is intended for use in a course in setting up a small business. The first, a case study of the process of setting up a service company, covers analyzing the pros and cons of starting one's own business, assessing the competition and local market, and selecting a site for and financing the business. The principal…

What puts them at risk? A cross-sectional case-control survey of demographic profile and sexual behavior of patients with sexually transmitted infections at a tertiary care center in North India.

PubMed

Raj, Rama; Gupta, Vishal; Pathak, Mona; Sreenivas, Vishnubhatla; Sood, Seema; Singh, Sarman; Verma, Kaushal K; Khanna, Neena; Das, Bimal K; Gupta, Somesh

2017-01-01

Sexually transmitted infections (STIs) are a major public health problem in developing nations. Identification of risk factors can help in formulating effective strategies against them. The present study was conducted in a tertiary care hospital in North India over 1 year to identify the risk factors associated with STIs. A questionnaire-based cross-sectional case-control survey was conducted where participants answered questions on demographic details, sexual behavior, and awareness of STIs. Cases were patients with STIs whereas controls were randomly selected from healthy individuals accompanying patients with nonvenereal complaints attending our hospital. There were 106 cases and 64 controls. STI patients had sexual debut 2 years before controls. A higher proportion of STI cases had lower education, multiple sexual partners, lived separately from their partner, had nonregular partners, had protected sex in the last month, had sex under influence of alcohol/illicit drugs, sex in unstructured settings, and engaged in transactional sex, in comparison to controls ( P < 0.05). More cases were aware of the symptoms/preventive measures of STIs ( P < 0.001). On multivariate analysis, multiple sexual partners, sex under influence of alcohol/illicit drugs with nonregular partner, protected sex in the last month, and knowledge of preventive measures were found to be statistically associated with STIs ( P < 0.05). Our study identifies risk-behavior patterns in patients with STIs, which should be modified to reduce the burden of these diseases. Increasing the knowledge about STIs in these patients can translate into more common condom usage that lends support for strengthening sexual health programs at grass-root levels. The small size of the study population could have led to decreased power of the study to detect differences between cases and controls. The external validity of our results needs to be tested in different population groups involving larger sample sizes.

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.

An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels

PubMed Central

Nassir, Rami; Kosoy, Roman; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

2009-01-01

Background Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia. Results In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups. Conclusion These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies. PMID:19630973

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus.

PubMed

Roscioni, S S; de Zeeuw, D; Hellemons, M E; Mischak, H; Zürbig, P; Bakker, S J L; Gansevoort, R T; Reinhard, H; Persson, F; Lajer, M; Rossing, P; Lambers Heerspink, H J

2013-02-01

Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise therapeutic intervention. Here we assessed the value of a urinary proteomic-based risk score (classifier) in predicting the development and progression of microalbuminuria. We conducted a prospective case-control study. Cases (n = 44) and controls (n = 44) were selected from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study and from the Steno Diabetes Center (Gentofte, Denmark). Cases were defined by transition from normo- to microalbuminuria or from micro- to macroalbuminuria over a follow-up of 3 years. Controls with no transitions in albuminuria were pair-matched for age, sex and albuminuria status. A model for the progression of albuminuria was built using a proteomic classifier based on 273 urinary peptides. The proteomic classifier was independently associated with transition to micro- or macroalbuminuria (OR 1.35 [95% CI 1.02, 1.79], p = 0.035). The classifier predicted the development and progression of albuminuria on top of albuminuria and estimated GFR (eGFR, area under the receiver operating characteristic [ROC] curve increase of 0.03, p = 0.002; integrated discrimination index [IDI]: 0.105, p = 0.002). Fragments of collagen and α-2-HS-glycoprotein showed significantly different expression between cases and controls. Although limited by the relatively small sample size, these results suggest that analysis of a urinary biomarker set enables early renal risk assessment in patients with diabetes. Further work is required to confirm the role of urinary proteomics in the prevention of renal failure in diabetes.

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.

Malaria Control and Elimination in Sri Lanka: Documenting Progress and Success Factors in a Conflict Setting

PubMed Central

Abeyasinghe, Rabindra R.; Galappaththy, Gawrie N. L.; Smith Gueye, Cara; Kahn, James G.; Feachem, Richard G. A.

2012-01-01

Background Sri Lanka has a long history of malaria control, and over the past decade has had dramatic declines in cases amid a national conflict. A case study of Sri Lanka's malaria programme was conducted to characterize the programme and explain recent progress. Methods The case study employed qualitative and quantitative methods. Data were collected from published and grey literature, district-level and national records, and thirty-three key informant interviews. Expenditures in two districts for two years – 2004 and 2009 – were compiled. Findings Malaria incidence in Sri Lanka has declined by 99.9% since 1999. During this time, there were increases in the proportion of malaria infections due to Plasmodium vivax, and the proportion of infections occurring in adult males. Indoor residual spraying and distribution of long-lasting insecticide-treated nets have likely contributed to the low transmission. Entomological surveillance was maintained. A strong passive case detection system captures infections and active case detection was introduced. When comparing conflict and non-conflict districts, vector control and surveillance measures were maintained in conflict areas, often with higher coverage reported in conflict districts. One of two districts in the study reported a 48% decline in malaria programme expenditure per person at risk from 2004 to 2009. The other district had stable malaria spending. Conclusions/Significance Malaria is now at low levels in Sri Lanka – 124 indigenous cases were found in 2011. The majority of infections occur in adult males and are due to P. vivax. Evidence-driven policy and an ability to adapt to new circumstances contributed to this decline. Malaria interventions were maintained in the conflict districts despite an ongoing war. Sri Lanka has set a goal of eliminating malaria by the end of 2014. Early identification and treatment of infections, especially imported ones, together with effective surveillance and response, will be critical to achieving this goal. PMID:22952642

Time Management in Higher Education Administration: A Case Study.

ERIC Educational Resources Information Center

Lewis, Darrell R.; Dahl, Tor

How do departmental chairpersons and deans in a major university setting manage their time? What are the major administrative activities and functions associated with such responsibilities? What relationships do these have with an ability to delegate, to control one's time for planning and self-initiated activities, or personal sense of…

Dynamic optimization case studies in DYNOPT tool

NASA Astrophysics Data System (ADS)

Ozana, Stepan; Pies, Martin; Docekal, Tomas

2016-06-01

Dynamic programming is typically applied to optimization problems. As the analytical solutions are generally very difficult, chosen software tools are used widely. These software packages are often third-party products bound for standard simulation software tools on the market. As typical examples of such tools, TOMLAB and DYNOPT could be effectively applied for solution of problems of dynamic programming. DYNOPT will be presented in this paper due to its licensing policy (free product under GPL) and simplicity of use. DYNOPT is a set of MATLAB functions for determination of optimal control trajectory by given description of the process, the cost to be minimized, subject to equality and inequality constraints, using orthogonal collocation on finite elements method. The actual optimal control problem is solved by complete parameterization both the control and the state profile vector. It is assumed, that the optimized dynamic model may be described by a set of ordinary differential equations (ODEs) or differential-algebraic equations (DAEs). This collection of functions extends the capability of the MATLAB Optimization Tool-box. The paper will introduce use of DYNOPT in the field of dynamic optimization problems by means of case studies regarding chosen laboratory physical educational models.

Case-control study on the prevention of occupational eye injuries.

PubMed

Ho, Chi-Kung; Yen, Ya-Lin; Chang, Cheng-Hsien; Chiang, Hung-Che; Shen, Ying-Ying; Chang, Po-Ya

2008-01-01

The risk factors for occupational eye injuries have never been published in Taiwan. We conducted a case-control study to analyze the differences among workers on their knowledge, attitude to and practice (KAP) of occupational accident prevention. In the study, a statistical model was also set up for predicting the occupational problem. Subjects, including 31 cases of work-related eye injuries and 62 controls, completed a structured questionnaire on KAP, which revealed that 80.6% and 62.7% of workers in the case and control groups, respectively, did not wear eye protection during work. Furthermore, we found that temporary employment (OR, 10.7; 95% CI, 3.03-36.16) and fewer than 10 years of education (OR, 4.44; 95% CI, 1.73-11.44) were the major risk factors for occupational eye injuries. In addition, we developed a logistic regression model with four predictors (temporary employment, education years less than 10, poor management of industrial health and safety in the workplace, and poor attitude towards accident prevention) for the occurrence of occupational eye injuries. In conclusion, in Taiwan, compulsory regulation of wearing eye protection during work, good education, management of work safety and hygiene and employee (especially temporary worker) commitment to safety and health are strongly recommended prevention strategies.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture

PubMed Central

Hwang, Joo-Yeon; Lee, Seung Hun; Go, Min Jin; Kim, Beom-Jun; Kou, Ikuyo; Ikegawa, Shiro; Guo, Yan; Deng, Hong-Wen; Raychaudhuri, Soumya; Kim, Young Jin; Oh, Ji Hee; Kim, Youngdoe; Moon, Sanghoon; Kim, Dong-Joon; Koo, Heejo; Cha, My-Jung; Lee, Min Hye; Yun, Ji Young; Yoo, Hye-Sook; Kang, Young-Ah; Cho, Eun-Hee; Kim, Sang-Wook; Oh, Ki Won; Kang, Moo II; Son, Ho Young; Kim, Shin-Yoon; Kim, Ghi Su; Han, Bok-Ghee; Cho, Yoon Shin; Cho, Myeong-Chan; Lee, Jong-Young; Koh, Jung-Min

2014-01-01

Background Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions Our findings provide new insights into the genetic architecture underlying OF in East Asians. PMID:23349225

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.

Upper gastrointestinal bleeding in severely burned patients: a case-control study to assess risk factors, causes, and outcome.

PubMed

Kim, Young Jin; Koh, Dong Hee; Park, Se Woo; Park, Sun Man; Choi, Min Ho; Jang, Hyun Joo; Kae, Sea Hyub; Lee, Jin; Byun, Hyun Woo

2014-01-01

To determine the risk factors, causes, and outcome of clinically important upper gastrointestinal bleeding that occurs in severely burned patients. The charts of all patients admitted to the burn intensive care unit were analyzed retrospectively over a 4-year period (from January 2006 to December 2009). Cases consisted of burned patients who developed upper gastrointestinal bleeding more than 24 hours after admission to the burn intensive care unit. Controls were a set of patients, in the burn intensive care unit, without upper gastrointestinal bleeding matched with cases for age and gender. Cases and controls were compared with respect to the risk factors of upper gastrointestinal bleeding and outcomes. During the study period, clinically important upper gastrointestinal bleeding occurred in 20 patients out of all 964 patients. The most common cause of upper gastrointestinal bleeding was duodenal ulcer (11 of 20 cases, 55%). In the multivariate analysis, mechanical ventilation (p = 0.044) and coagulopathy (p = 0.035) were found to be the independent predictors of upper gastrointestinal bleeding in severely burned patients. Upper gastrointestinal hemorrhage tends to occur more frequently after having prolonged mechanical ventilation and coagulopathy.

Ticagrelor and bradycardia: a nested case-control study.

PubMed

Turgeon, Ricky D; Fernandes, Kimberly A; Juurlink, David; Tu, Jack V; Mamdani, Muhammad

2015-12-01

Ticagrelor increases serum adenosine concentrations, slowing conduction and possibly leading to bradycardia. Clinical trial data have shown numerically, though not statistically significantly, higher rates of bradyarrhythmias with ticagrelor versus clopidogrel. Additionally, recent case reports have further raised concerns for this adverse effect. We explored the association between ticagrelor and hospitalization for bradycardia in a real-world setting. We conducted a population-based, nested case-control study of Ontario residents, 66 years of age or older, discharged after a first acute coronary syndrome by linking multiple healthcare databases. Cases included patients hospitalized for bradycardia within 1 year of starting a P2Y12 inhibitor. For each case, we identified 4 controls matched on age, sex, index date, and current use of a P2Y12 inhibitor. The exposure of interest was a prescription for ticagrelor within 90 days, with clopidogrel use as the reference group. From April 2012 to March 2014, we identified 140 cases and 560 controls who met the study criteria. We found no significant association between bradycardia and exposure to ticagrelor relative to clopidogrel in the previous 90 days prior to the index date (adjusted odds ratio 1.06, 95% confidence interval 0.65-2.21). Further adjustment for potential confounders also did not identify a significant association. Among older patients with a first acute coronary syndrome, use of ticagrelor was not associated with a greater risk of admission for bradycardia relative to clopidogrel. Copyright © 2015 John Wiley & Sons, Ltd.

Nitrates in drinking water and risk of death from rectal cancer in Taiwan.

PubMed

Kuo, Hsin-Wei; Wu, Trong-Neng; Yang, Chun-Yuh

2007-10-01

The relationship between nitrate levels in drinking water and rectal cancer development has been inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to rectal cancer and drinking-water nitrate exposure in Taiwan. All deaths due to rectal cancer of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for rectal cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.22 (0.98-1.52) and 1.36 (1.08-1.70), respectively. The findings of this study warrant further investigation of the role of nitrates in drinking water in the etiology of rectal cancer in Taiwan.

Attitudes and Perception Towards Eye Donation in Patients with Corneal Disease: A Case-controlled Population-based Study.

PubMed

Noopur, Gupta; Praveen, Vashist; Radhika, Tandon; Sanjeev K, Gupta; Mani, Kalaivani; Deepak, Kumar

2018-06-01

To assess awareness, barriers, and misconceptions related to eye donation in people with corneal disease as compared to controls in a population setting. A population-based study was conducted in 25 randomly selected clusters of Rural Gurgaon, Haryana, India, as part of the CORE (Cornea Opacity Rural Epidemiological) study. In addition to ophthalmic examination, knowledge and perceptions regarding eye donation were assessed through a validated questionnaire. The questionnaire captured the sociodemographic factors influencing awareness regarding eye donation in participants with corneal disease and twice the number of age- and gender-matched controls recruited from the same study clusters. Descriptive statistics were computed along with multivariable logistic regression analysis to determine associated factors for awareness of eye donation. In the CORE study, 452 participants had corneal opacities on ocular examination. Of these, 442 were assessed for eye donation awareness. Additionally, 884 age- and gender-matched controls were recruited. The mean age of cases and controls was 60.9 ± 15.5 and 59.6 ± 14.3 years, respectively. Awareness of eye donation in cases and controls was 46.4% (n = 205 of 442) and 52.3% (n = 462 of 884), respectively (P = 0.044). Educational status was an important factor determining knowledge about eye donation in both cases and controls (P = < 0.001). Major barriers reported for not pledging eyes were lack of willingness (36.7%) and ignorance (15.3%). Common misconceptions like eyes could be donated before death or even after 24 h of death and that any type of blindness could be treated with corneal transplantation were prevalent. The study demonstrated that although there is substantial awareness about eye donation, there are numerous barriers in this population that need to be resolved to improve donation rates. Additional efforts are needed to translate this awareness into actual eye donation in both cases with corneal disease and controls.

The clinical application of teaching people about pain.

PubMed

Louw, Adriaan; Zimney, Kory; O'Hotto, Christine; Hilton, Sandra

2016-07-01

Teaching people about the neurobiology and neurophysiology of their pain experience has a therapeutic effect and has been referred to as pain neuroscience education (PNE). Various high-quality randomized controlled trials and systematic reviews have shown increasing efficacy of PNE decreasing pain, disability, pain catastrophization, movement restrictions, and healthcare utilization. Research studies, however, by virtue of their design, are very controlled environments and, therefore, in contrast to the ever-increasing evidence for PNE, little is known about the clinical application of this emerging therapy. In contrast, case studies, case series, and expert opinion and perspectives by authorities in the world of pain science provide clinicians with a glimpse into potential "real" clinical application of PNE in the face of the ever-increasing chronic pain epidemic. By taking the material from the randomized controlled trials, systematic reviews, case series, case studies, and expert opinion, this article aims to provide a proposed layout of the clinical application of PNE. The article systematically discusses key elements of PNE including examination, educational content, and delivery methods, merging of PNE with movement, goal setting, and progression. This perspectives article concludes with a call for research into the clinical application of PNE.

Modified directly observed treatment for tuberculosis versus self-administered therapy: an observational study in rural Greece.

PubMed

Charokopos, N; Tsiros, G; Foka, A; Voila, P; Chrysanthopoulos, K; Spiliopoulou, I; Jelastopulu, E

2013-01-01

Directly Observed Treatment (DOT) is the key element of DOTS (directly observed treatment, short course), part of the internationally recommended control strategy for tuberculosis (TB). The evaluation of DOT has not been widely evaluated in rural areas in developed settings. The aim of this pilot study was to evaluate a modified DOT program (MDOT) by a general practitioner (GP) in a rural area of southwest Greece, where there is substantial underreporting of TB cases. Thirteen new TB cases with 30 close contacts were compared with 41 past-treated TB subjects (controls) with 111 close contacts in this observational, case-control study. Home visits by a GP were conducted and comparison of various data (laboratory findings, treatment outcomes, questionnaire-based parameters, on-site recorded conditions) was performed in both newly detected pulmonary TB cases and previously treated TB cases managed without DOT intervention. MDOT by GP implementation revealed that 11 cases (84.6%) were successfully treated, one (7.7%) case died, and one (7.7%) was lost to follow up. None of the close contacts of new TB cases was infected with active TB, while 6.3% of previously-treated TB subjects were infected with active TB and had to receive a complete anti-TB regimen. Chemoprophylaxis was administered to 13.3% of close contacts of new cases; whereas 12.6% of close contacts of previously-treated patients received chemoprophylaxis. This pilot study revealed that a GP is able to implement a program based on DOT resulting in high treatment adherence and prevention of TB compared with the conventional self-administration of treatment.

An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation.

PubMed

Dankbaar, Mary E W; Alsma, Jelmer; Jansen, Els E H; van Merrienboer, Jeroen J G; van Saase, Jan L C M; Schuit, Stephanie C E

2016-08-01

Simulation games are becoming increasingly popular in education, but more insight in their critical design features is needed. This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students' cognitive skills and motivation. We set up a three-group randomized post-test-only design: a control group working on an e-module; a cases group, combining the e-module with low-fidelity text-based patient cases, and a game group, combining the e-module with a high-fidelity simulation game with the same cases. Participants completed questionnaires on cognitive load and motivation. After a 4-week study period, blinded assessors rated students' cognitive emergency care skills in two mannequin-based scenarios. In total 61 students participated and were assessed; 16 control group students, 20 cases students and 25 game students. Learning time was 2 h longer for the cases and game groups than for the control group. Acquired cognitive skills did not differ between groups. The game group experienced higher intrinsic and germane cognitive load than the cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did not profit from working on open cases (in adjunct to an e-module), which nonetheless challenged them to study longer. The e-module appeared to be very effective, while the high-fidelity game, although engaging, probably distracted students and impeded learning. Medical educators designing motivating and effective skills training for novices should align case complexity and fidelity with students' proficiency level. The relation between case-fidelity, motivation and skills development is an important field for further study.

Mixed Model Association with Family-Biased Case-Control Ascertainment.

PubMed

Hayeck, Tristan J; Loh, Po-Ru; Pollack, Samuela; Gusev, Alexander; Patterson, Nick; Zaitlen, Noah A; Price, Alkes L

2017-01-05

Mixed models have become the tool of choice for genetic association studies; however, standard mixed model methods may be poorly calibrated or underpowered under family sampling bias and/or case-control ascertainment. Previously, we introduced a liability threshold-based mixed model association statistic (LTMLM) to address case-control ascertainment in unrelated samples. Here, we consider family-biased case-control ascertainment, where case and control subjects are ascertained non-randomly with respect to family relatedness. Previous work has shown that this type of ascertainment can severely bias heritability estimates; we show here that it also impacts mixed model association statistics. We introduce a family-based association statistic (LT-Fam) that is robust to this problem. Similar to LTMLM, LT-Fam is computed from posterior mean liabilities (PML) under a liability threshold model; however, LT-Fam uses published narrow-sense heritability estimates to avoid the problem of biased heritability estimation, enabling correct calibration. In simulations with family-biased case-control ascertainment, LT-Fam was correctly calibrated (average χ 2 = 1.00-1.02 for null SNPs), whereas the Armitage trend test (ATT), standard mixed model association (MLM), and case-control retrospective association test (CARAT) were mis-calibrated (e.g., average χ 2 = 0.50-1.22 for MLM, 0.89-2.65 for CARAT). LT-Fam also attained higher power than other methods in some settings. In 1,259 type 2 diabetes-affected case subjects and 5,765 control subjects from the CARe cohort, downsampled to induce family-biased ascertainment, LT-Fam was correctly calibrated whereas ATT, MLM, and CARAT were again mis-calibrated. Our results highlight the importance of modeling family sampling bias in case-control datasets with related samples. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Investigating the Feasibility and Utility of Bedside Balance Technology Acutely After Pediatric Concussion: A Pilot Study.

PubMed

Rhine, Tara D; Byczkowski, Terri L; Clark, Ross A; Babcock, Lynn

2016-05-01

To examine postural instability in children acutely after concussion, using the Wii Balance Board (WBB). We hypothesized that children with traumatic brain injury would have significantly worse balance relative to children without brain injury. Prospective case-control pilot study. Emergency department of a tertiary urban pediatric hospital. Cases were a convenience sample 11-16 years old who presented within 6 hours of sustaining concussion. Two controls, matched on gender, height, and age, were enrolled for each case that completed study procedures. Controls were children who presented for a minor complaint that was unlikely to affect balance. Not applicable. The participant's postural sway expressed as the displacement in centimeters of the center of pressure during a timed balance task. Balance testing was performed using 4 stances (single or double limb, eyes open or closed). Three of the 17 (17.6%) cases were too dizzy to complete testing. One stance, double limbs eyes open, was significantly higher in cases versus controls (85.6 vs 64.3 cm, P = 0.04). A simple test on the WBB consisting of a 2-legged standing balance task with eyes open discriminated children with concussion from non-head-injured controls. The low cost and feasibility of this device make it a potentially viable tool for assessing postural stability in children with concussion for both longitudinal research studies and clinical care. These pilot data suggest that the WBB is an inexpensive tool that can be used on the sideline or in the outpatient setting to objectively identify and quantify postural instability.

Case-control studies in cancer patients as a surveillance system of occupational exposure in the European Community. European Community Working Party.

PubMed Central

Rona, R J; Taub, N A; Rasmussen, S

1993-01-01

STUDY OBJECTIVE--The main aim was to detect known relationships between lung and blood cancers and various occupational exposures (using job titles as proxies) using a case-control design. The suitability of this system for routine surveillance could then be assessed. DESIGN--A case-control study was carried out in 1989. SETTING--Hospitals in eight European Community countries. SUBJECTS--Men aged 25 to 75 years with incident and prevalent cancer of the lung (190 cases), haematopoietic system (210 cases), or gastrointestinal tract (245 controls) were studied. MEASUREMENTS AND MAIN RESULTS--The crude estimate of the overall odds ratio exposure (OR) for relevant occupational exposure of lung cancer relative to gastrointestinal cancer was 1.20 (95% confidence interval (CI) 0.82, 1.77). In a logistic regression analysis adjusting for country, age at diagnosis, smoking, and alcohol consumption, the overall OR was not greatly changed. A significant interaction of occupational exposure and age at diagnosis showed that lung cancer patients diagnosed at a younger age had a higher OR than patients diagnosed at an older age. Thus, the overall, insignificant result may have been due to a low reliability of occupational history in older age or to a selective mechanism related to age. The overall OR for occupational exposure of cancer of the blood relative to gastrointestinal cancer was 0.88 (95% CI 0.60, 1.31). The logistic regression analysis did not alter these results. CONCLUSION--A surveillance based on a case-control design using job titles would not be sensitive enough to detect possible occupational risks. PMID:8228771

Outbreak of Tsukamurella species bloodstream infection among patients at an oncology clinic, West Virginia, 2011-2012.

PubMed

See, Isaac; Nguyen, Duc B; Chatterjee, Somu; Shwe, Thein; Scott, Melissa; Ibrahim, Sherif; Moulton-Meissner, Heather; McNulty, Steven; Noble-Wang, Judith; Price, Cindy; Schramm, Kim; Bixler, Danae; Guh, Alice Y

2014-03-01

To determine the source and identify control measures of an outbreak of Tsukamurella species bloodstream infections at an outpatient oncology facility. Epidemiologic investigation of the outbreak with a case-control study. A case was an infection in which Tsukamurella species was isolated from a blood or catheter tip culture during the period January 2011 through June 2012 from a patient of the oncology clinic. Laboratory records of area hospitals and patient charts were reviewed. A case-control study was conducted among clinic patients to identify risk factors for Tsukamurella species bloodstream infection. Clinic staff were interviewed, and infection control practices were assessed. Fifteen cases of Tsukamurella (Tsukamurella pulmonis or Tsukamurella tyrosinosolvens) bloodstream infection were identified, all in patients with underlying malignancy and indwelling central lines. The median age of case patients was 68 years; 47% were male. The only significant risk factor for infection was receipt of saline flush from the clinic during the period September-October 2011 (P = .03), when the clinic had been preparing saline flush from a common-source bag of saline. Other infection control deficiencies that were identified at the clinic included suboptimal procedures for central line access and preparation of chemotherapy. Although multiple infection control lapses were identified, the outbreak was likely caused by improper preparation of saline flush syringes by the clinic. The outbreak demonstrates that bloodstream infections among oncology patients can result from improper infection control practices and highlights the critical need for increased attention to and oversight of infection control in outpatient oncology settings.

Dermatoglyphic patterns in dementia of the Alzheimer type: a case-control study.

PubMed Central

Berr, C; Okra-Podrabinek, N; Feteanu, D; Taurand, S; Hervy, M P; Forette, F; Piette, F; Sebag-Lanoe, R; Alperovitch, A

1992-01-01

STUDY OBJECTIVE--The aim was to compare digital and palmar dermatoglyphics in subjects with dementia of Alzheimer type and in mentally healthy elderly controls. DESIGN--This design was a case-control study. SETTING--The study was carried out in geriatric units and retirement communities in the Paris area. PARTICIPANTS--Cases were women with clinically diagnosed Alzheimer type dementia according to DSM III-R criteria (n = 82), mainly with late onset of the disease. Controls were women aged 85 years or older without cognitive deterioration (n = 76). MEASUREMENTS AND MAIN RESULTS--Finger and palm prints obtained from both hands by the classical ink method were examined. Fingerprints were classified into four types of figures. On palms, palmar flexion creases, palmar axial triradii, true patterns of the hypothenar area, and main line terminations were described. Examinations were performed by two examiners blind to the subjects's diagnostic category. For the different patterns studied, no major differences between dementia patients and elderly controls were found. Nor was there evidence of high frequencies of features commonly observed in Down's syndrome (trisomy 21), which have previously, though sporadically, been reported. CONCLUSIONS--On one of the largest samples of Alzheimer dementia patients studied, and with evaluation blind to diagnosis, no evidence has been found that particular dermatoglyphic patterns occur like those observed in Down's syndrome, a disease which is related to dementia of the Alzheimer type. PMID:1479321

Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): A case-control study

PubMed Central

Aragón, Tomás J; Novotny, Suzanne; Enanoria, Wayne; Vugia, Duc J; Khalakdina, Asheena; Katz, Mitchell H

2003-01-01

Background In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. Methods Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4+ T lymphocyte count, date of CD4+ count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. Results The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37–33.5, and outside the home: OR 3.16; 95% CI 1.23–8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%. Conclusions Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water. PMID:12515584

Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): a case-control study.

PubMed

Aragón, Tomás J; Novotny, Suzanne; Enanoria, Wayne; Vugia, Duc J; Khalakdina, Asheena; Katz, Mitchell H

2003-01-06

In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4+ T lymphocyte count, date of CD4+ count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37-33.5, and outside the home: OR 3.16; 95% CI 1.23-8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%. Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

PubMed

Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

2015-09-22

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Balance of power--do patients use researchers to survive hospital?

PubMed

Haigh, Carol; Neild, Angela; Duncan, Fiona

2005-01-01

This paper focuses on the way research study participants interpret their contact with researchers. Much has been made of the unequal power relationship between researcher and researched, but the case study presented here suggests that patient participants may be 'using' researchers to further their own agenda and to attempt to manipulate or control aspects of their care within the hospital setting.

The Ideological Dilemma in Teaching Literature: Moral Conflicts in a Diversified Society--An Israeli Teacher Case Study

ERIC Educational Resources Information Center

Baratz, Lea; Reingold, Roni

2010-01-01

The current study examines the implications of literary teaching material in a national diversified society in which the governmental educational policy separates between two national educational systems, and controls both of these separate systems. We set out to examine whether, in such realty, teachers are willing to teach texts, not formally…

Video Capture of Plastic Surgery Procedures Using the GoPro HERO 3+

PubMed Central

Graves, Steven Nicholas; Shenaq, Deana Saleh; Langerman, Alexander J.

2015-01-01

Background: Significant improvements can be made in recoding surgical procedures, particularly in capturing high-quality video recordings from the surgeons’ point of view. This study examined the utility of the GoPro HERO 3+ Black Edition camera for high-definition, point-of-view recordings of plastic and reconstructive surgery. Methods: The GoPro HERO 3+ Black Edition camera was head-mounted on the surgeon and oriented to the surgeon’s perspective using the GoPro App. The camera was used to record 4 cases: 2 fat graft procedures and 2 breast reconstructions. During cases 1-3, an assistant remotely controlled the GoPro via the GoPro App. For case 4 the GoPro was linked to a WiFi remote, and controlled by the surgeon. Results: Camera settings for case 1 were as follows: 1080p video resolution; 48 fps; Protune mode on; wide field of view; 16:9 aspect ratio. The lighting contrast due to the overhead lights resulted in limited washout of the video image. Camera settings were adjusted for cases 2-4 to a narrow field of view, which enabled the camera’s automatic white balance to better compensate for bright lights focused on the surgical field. Cases 2-4 captured video sufficient for teaching or presentation purposes. Conclusions: The GoPro HERO 3+ Black Edition camera enables high-quality, cost-effective video recording of plastic and reconstructive surgery procedures. When set to a narrow field of view and automatic white balance, the camera is able to sufficiently compensate for the contrasting light environment of the operating room and capture high-resolution, detailed video. PMID:25750851

Importation, Antibiotics, and Clostridium difficile Infection in Veteran Long-Term Care: A Multilevel Case-Control Study.

PubMed

Brown, Kevin A; Jones, Makoto; Daneman, Nick; Adler, Frederick R; Stevens, Vanessa; Nechodom, Kevin E; Goetz, Matthew B; Samore, Matthew H; Mayer, Jeanmarie

2016-06-21

Although clinical factors affecting a person's susceptibility to Clostridium difficile infection are well-understood, little is known about what drives differences in incidence across long-term care settings. To obtain a comprehensive picture of individual and regional factors that affect C difficile incidence. Multilevel longitudinal nested case-control study. Veterans Health Administration health care regions, from 2006 through 2012. Long-term care residents. Individual-level risk factors included age, number of comorbid conditions, and antibiotic exposure. Regional risk factors included importation of cases of acute care C difficile infection per 10 000 resident-days and antibiotic use per 1000 resident-days. The outcome was defined as a positive result on a long-term care C difficile test without a positive result in the prior 8 weeks. 6012 cases (incidence, 3.7 cases per 10 000 resident-days) were identified in 86 regions. Long-term care C difficile incidence (minimum, 0.6 case per 10 000 resident-days; maximum, 31.0 cases per 10 000 resident-days), antibiotic use (minimum, 61.0 days with therapy per 1000 resident-days; maximum, 370.2 days with therapy per 1000 resident-days), and importation (minimum, 2.9 cases per 10 000 resident-days; maximum, 341.3 cases per 10 000 resident-days) varied substantially across regions. Together, antibiotic use and importation accounted for 75% of the regional variation in C difficile incidence (R2 = 0.75). Multilevel analyses showed that regional factors affected risk together with individual-level exposures (relative risk of regional antibiotic use, 1.36 per doubling [95% CI, 1.15 to 1.60]; relative risk of importation, 1.23 per doubling [CI, 1.14 to 1.33]). Case identification was based on laboratory criteria. Admission of residents with recent C difficile infection from non-Veterans Health Administration acute care sources was not considered. Only 25% of the variation in regional C difficile incidence in long-term care remained unexplained after importation from acute care facilities and antibiotic use were accounted for, which suggests that improved infection control and antimicrobial stewardship may help reduce the incidence of C difficile in long-term care settings. U.S. Department of Veterans Affairs and Centers for Disease Control and Prevention.

Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies.

PubMed

Arnedo, Javier; Svrakic, Dragan M; Del Val, Coral; Romero-Zaliz, Rocío; Hernández-Cuervo, Helena; Fanous, Ayman H; Pato, Michele T; Pato, Carlos N; de Erausquin, Gabriel A; Cloninger, C Robert; Zwir, Igor

2015-02-01

The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes. In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies. The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%). Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.

Effect of case management on glycemic control and behavioral outcomes for chinese people with type 2 diabetes: A 2-year study.

PubMed

Yuan, Xiaodan; Wang, Fengmei; Fish, Anne Folta; Xue, Cunyi; Chen, Tao; Liu, Chao; Lou, Qingqing

2016-08-01

To examine the effect of case management on glycemic control and behavioral outcomes in adults with Type 2 diabetes in China. Participants were randomly assigned to a 1-year case management (CM) group (n=60) or control group (n=60). Monthly case management visits included identifying individuals' diabetes-related problems, setting goals, planning self-care, and evaluating progress. During a 1-year follow-up, all participants attended visits every 3 months without intervention. In the CM vs. the control group, HbA1c was reduced at 6 months compared to baseline (P=0.034), with trends at 12 and 24 months, and empowerment ability improved (P<0.05). Also in the CM vs. controls, total self-care behaviors, the frequency of exercise, blood glucose testing, and foot care were higher (P<0.001) at 12 months, and the percentage of individuals with HbA1c ≤7.0% was higher (P=0.035) at 24 months. The case management intervention in China was effective at 6 months and, based on trends in HbA1c at 12 and 24 months and results for behavioral outcomes, the intervention shows promise and warrants more research. A case management approach can enhance behavior change and glycemic control in Chinese with diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

PubMed Central

Thorleifsson, Gudmar; Walters, G Bragi; Hewitt, Alex W; Masson, Gisli; Helgason, Agnar; DeWan, Andrew; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Gudjonsson, Sigurjon A; Magnusson, Kristinn P; Stefansson, Hreinn; Lam, Dennis S C; Tam, Pancy O S; Gudmundsdottir, Gudrun J; Southgate, Laura; Burdon, Kathryn P; Gottfredsdottir, Maria Soffia; Aldred, Micheala A; Mitchell, Paul; St Clair, David; Collier, David A; Tang, Nelson; Sveinsson, Orn; Macgregor, Stuart; Martin, Nicholas G; Cree, Angela J; Gibson, Jane; MacLeod, Alex; Jacob, Aby; Ennis, Sarah; Young, Terri L; Chan, Juliana C N; Karwatowski, Wojciech S S; Hammond, Christopher J; Thordarson, Kristjan; Zhang, Mingzhi; Wadelius, Claes; Lotery, Andrew J; Trembath, Richard C; Pang, Chi Pui; Hoh, Josephine; Craig, Jamie E; Kong, Augustine; Mackey, David A; Jonasson, Fridbert; Thorsteinsdottir, Unnur; Stefansson, Kari

2011-01-01

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 × 10-10). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG. PMID:20835238

Control of OSA During Automatic Positive Airway Pressure Titration in a Clinical Case Series: Predictors and Accuracy of Device Download Data

PubMed Central

Huang, Hsin-Chia Carol; Hillman, David R.; McArdle, Nigel

2012-01-01

Study Objectives: To investigate the factors associated with physiologic control of obstructive sleep apnea (OSA) during automatic positive airway pressure (APAP) titration in a clinical series. To also assess the usefulness of apnea-hypopnea index (AHI) data downloaded from the APAP device (Dev AHI). Design: Retrospective review of a consecutive series of patients with OSA who underwent APAP titration (Autoset Spirit, ResMed, Bella Vista, New South Wales, Australia ) with simultaneous polysomnographic (PSG) monitoring in the sleep laboratory. Setting: Tertiary sleep clinic. Participants: There were 190 consecutive patients with OSA referred for APAP titration. Measurements and Results: There were 58% of patients who achieved optimal or good control of OSA (titration PSG AHI < 10, or at least 50% reduction in AHI if diagnostic AHI < 15/hr) during APAP titration. The independent predictors of titration PSG AHI were a history of cardiac disease and elevated central apnea and arousal indices during the diagnostic study. Although the median and interquartile range (IQR) AHI from the device (7.0, 3.9-11.6 events/hr) was only slightly less than the PSG AHI (7.8, 3.9-14.4 events/hr, P = 0.04) during titration, case-by-case agreement between the two measures was poor (chi-square < 0.001). Conclusion: In a clinical sample control of OSA during APAP titration is often poor, and close clinical follow-up is particularly needed in patients with a history of cardiac disease or with high arousal or central apnea indices on the diagnostic study. Device AHI does not reliably assess control during APAP titration, and PSG assessment may be required if clinical response to treatment is poor. The findings relate to the ResMed AutoSet device and may not apply to other devices. Citation: Huang HCC; Hillman DR; McArdle N. Control of OSA during automatic positive airway pressure titration in a clinical case series: predictors and accuracy of device download data. SLEEP 2012;35(9):1277–1283. PMID:22942506

[Case-control study on bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle joint].

PubMed

Qi, Yue-Feng; Chen, Fa-Lin; Bao, Shu-Ren; Li, Cheng-Huan; Zhao, Xing-Wei; Liu, Shi-Ming; Chen, Wen-Xue; Li, Ye; Wang, Peng

2012-08-01

To explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism. From 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases were degree II, 11 cases were degree III, and 30 cases were degree IV. There were 52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years] in operative group,and 6 cases were degree II, 18 cases were degree III, and 28 cases were degree IV. Bone setting manipulation and hard splint external fixation were applied to manipulative group. Operative reduction internal fixation was performed in operative group. X-ray was used to evaluate reduction of fracture before and after treatment, 2 months after treatment. Ankle joint function was evaluated according to Olerud-Molander scoring system after 6 months treatment. All patients were followed up with good reduction. Three cases occurred wound complication in operative group, but not in manipulative group. In manipulation group, 19 cases got excellent results, 20 cases good and 4 cases fair; while in operative group, 30 cases got excellent results, 20 cases good and 2 cases poor. There were no significant differences in fracture reduction and ankle joint function recovery between two groups (P > 0.05). Efficacy of operative treatment was better than that of manipulative treatment at degree IV fracture (P < 0.05). Bone setting manipulation is a good method for treating supination-eversion ankle joint fractures, which has advantages of simple and safe operation, reliable efficacy. For ankle join fracture at degree IV, manipulative reduction should be adopted earlier, and operative treatment also necessary

Effectiveness of reactive case detection for malaria elimination in three archetypical transmission settings: a modelling study.

PubMed

Gerardin, Jaline; Bever, Caitlin A; Bridenbecker, Daniel; Hamainza, Busiku; Silumbe, Kafula; Miller, John M; Eisele, Thomas P; Eckhoff, Philip A; Wenger, Edward A

2017-06-12

Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages. Communities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared. Simulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through reactive case detection or mass drug campaigns. Reactive case detection is recommended only for settings where transmission has recently been reduced rather than all low-transmission settings. This is demonstrated in a modelling framework with strong out-of-sample accuracy across a range of transmission settings while including methodologies for understanding the most resource-effective allocations of health workers. This approach generalizes to providing a platform for planning rational scale-up of health systems based on locally-optimized impact according to simplified stratification.

Regional Management of an Aquifer for Mining Under Fuzzy Environmental Objectives

NASA Astrophysics Data System (ADS)

BogáRdi, IstváN.; BáRdossy, AndráS.; Duckstein, Lucien

1983-12-01

A methodology is developed for the dynamic multiobjective management of a multipurpose regional aquifer. In a case study of bauxite mining in Western Hungary, ore deposits are often under the piezometric level of a karstic aquifer, while this same aquifer also provides recharge flows for thermal springs. N + 1 objectives are to be minimized, the first one being total discounted cost of control by dewatering or grouting; the other N objectives consist of the flow of thermal springs at N control points. However, there is no agreement among experts as to a set of numerical values that would constitute a "sound environment"; for this reason a fuzzy set analysis is used, and the N environmental objectives are combined into a single fuzzy membership function. The constraints include ore availability, various capacities, and the state transition function that describes the behavior of both piezometric head and underground flow. The model is linearized and solved as a biobjective dynamic program by using multiobjective compromise programming. A numerical example with N = 2 appears to lead to realistic control policies. Extension of the model to the nonlinear case is discussed.

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.

Cardiovascular health status and metabolic syndrome in Ecuadorian natives/Mestizos aged 40 years or more with and without stroke and ischemic heart disease--an atahualpa project case-control nested study.

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Montalván, Martha; Del Brutto, Victor J; Zambrano, Mauricio; Santamaría, Milton; Tettamanti, Daniel

2014-04-01

Knowledge of regional-specific cardiovascular risk factors is mandatory to reduce the growing burden of stroke and ischemic heart disease in Latin American populations. We conducted a population-based case-control study to assess which risk factors are associated with the occurrence of vascular events in natives/mestizos living in rural coastal Ecuador. We assessed the cardiovascular health (CVH) status and the presence of the metabolic syndrome in all Atahualpa residents aged 40 years or more with stroke and ischemic heart disease and in randomly selected healthy persons to evaluate differences in the prevalence of such risk factors between patients and controls. A total of 120 persons (24 with stroke or ischemic heart disease and 96 matched controls) were included. A poor CVH status (according to the American Heart Association) was found in 87.5% case-patients and 81.3% controls (P = .464). The metabolic syndrome was present in the same proportion (58.3%) of case-patients and controls. Likewise, both sets of risk factors (poor CVH status and the metabolic syndrome) were equally prevalent among both groups (58.3% versus 49%, P = .501). This case-control study suggests that none of the measured risk factors is associated with the occurrence of vascular events. It is possible that some yet unmeasured risk factors or an unknown genetic predisposition may account for a sizable proportion of stroke and ischemic heart disease occurring in the native/mestizo population of rural coastal Ecuador. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

PubMed Central

Hu, Hae-Jin; Jin, Eun-Heui; Yim, Seon-Hee; Yang, So-Young; Jung, Seung-Hyun; Shin, Seung-Hun; Kim, Wan-Uk; Shim, Seung-Cheol; Kim, Tai-Gyu

2011-01-01

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 ± 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA. PMID:21844665

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

PubMed

Toyoda, Hiromi; Miyagawa, Taku; Koike, Asako; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Imai, Makoto; Fujimura, Yota; Tamura, Yoshiyuki; Ikegami, Azusa; Wada, Yamato; Moriya, Shunpei; Furuya, Hirokazu; Takeuchi, Masaki; Kirino, Yohei; Meguro, Akira; Remmers, Elaine F; Kawamura, Yoshiya; Otowa, Takeshi; Miyashita, Akinori; Kashiwase, Koichi; Khor, Seik-Soon; Yamasaki, Maria; Kuwano, Ryozo; Sasaki, Tsukasa; Ishigooka, Jun; Kuroda, Kenji; Kume, Kazuhiko; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Hirata, Koichi; Mizuki, Nobuhisa; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

2015-10-01

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

A serum protein-based algorithm for the detection of Alzheimer disease.

PubMed

O'Bryant, Sid E; Xiao, Guanghua; Barber, Robert; Reisch, Joan; Doody, Rachelle; Fairchild, Thomas; Adams, Perrie; Waring, Steven; Diaz-Arrastia, Ramon

2010-09-01

To develop an algorithm that separates patients with Alzheimer disease (AD) from controls. Longitudinal case-control study. The Texas Alzheimer's Research Consortium project. Patients  We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls. Main Outcome Measure  The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score. The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively. These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.

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.

Occupational exposure to diesel engine emissions and risk of lung cancer: evidence from two case-control studies in Montreal, Canada.

PubMed

Pintos, Javier; Parent, Marie-Elise; Richardson, Lesley; Siemiatycki, Jack

2012-11-01

To examine the risk of lung cancer among men associated with exposure to diesel engine emissions incurred in a wide range of occupations and industries. 2 population-based lung cancer case-control studies were conducted in Montreal. Study I (1979-1986) comprised 857 cases and 533 population controls; study II (1996-2001) comprised 736 cases and 894 population controls. A detailed job history was obtained, from which we inferred lifetime occupational exposure to 294 agents, including diesel engine emissions. ORs were estimated for each study and in the pooled data set, adjusting for socio-demographic factors, smoking history and selected occupational carcinogens. While it proved impossible to retrospectively estimate absolute exposure concentrations, there were estimates and analyses by relative measures of cumulative exposure. Increased risks of lung cancer were found in both studies. The pooled analysis showed an OR of lung cancer associated with substantial exposure to diesel exhaust of 1.80 (95% CI 1.3 to 2.6). The risk associated with substantial exposure was higher for squamous cell carcinomas (OR 2.09; 95% CI 1.3 to 3.2) than other histological types. Joint effects between diesel exhaust exposure and tobacco smoking are compatible with a multiplicative synergistic effect. Our findings provide further evidence supporting a causal link between diesel engine emissions and risk of lung cancer. The risk is stronger for the development of squamous cell carcinomas than for small cell tumours or adenocarcinomas.

Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study.

PubMed

Groome, Michelle J; Page, Nicola; Cortese, Margaret M; Moyes, Jocelyn; Zar, Heather J; Kapongo, Constant N; Mulligan, Christine; Diedericks, Ralph; Cohen, Cheryl; Fleming, Jessica A; Seheri, Mapaseka; Mphahlele, Jeffrey; Walaza, Sibongile; Kahn, Kathleen; Chhagan, Meera; Steele, A Duncan; Parashar, Umesh D; Zell, Elizabeth R; Madhi, Shabir A

2014-11-01

The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH). Copyright © 2014 Elsevier Ltd. All rights reserved.

The rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting: a retrospective cohort study.

PubMed

Marx, Florian M; Dunbar, Rory; Enarson, Donald A; Beyers, Nulda

2012-01-01

High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others. To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases. Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment. A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of re-treatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59-8.41) per 100 person-years compared to 2.09 (95% CI: 1.81-2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00-5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11-2.33) was independently associated with smear-positive tuberculosis re-treatment, regardless of treatment outcome. In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in high-burden settings.

Challenges of Maintaining Good Clinical Laboratory Practices in Low-Resource Settings:  A Health Program Evaluation Framework Case Study From East Africa.

PubMed

Zhang, Helen L; Omondi, Michael W; Musyoka, Augustine M; Afwamba, Isaac A; Swai, Remigi P; Karia, Francis P; Muiruri, Charles; Reddy, Elizabeth A; Crump, John A; Rubach, Matthew P

2016-08-01

Using a clinical research laboratory as a case study, we sought to characterize barriers to maintaining Good Clinical Laboratory Practice (GCLP) services in a developing world setting. Using a US Centers for Disease Control and Prevention framework for program evaluation in public health, we performed an evaluation of the Kilimanjaro Christian Medical Centre-Duke University Health Collaboration clinical research laboratory sections of the Kilimanjaro Clinical Research Institute in Moshi, Tanzania. Laboratory records from November 2012 through October 2014 were reviewed for this analysis. During the 2-year period of study, seven instrument malfunctions suspended testing required for open clinical trials. A median (range) of 9 (1-55) days elapsed between instrument malfunction and biomedical engineer service. Sixteen (76.1%) of 21 suppliers of reagents, controls, and consumables were based outside Tanzania. Test throughput among laboratory sections used a median (range) of 0.6% (0.2%-2.7%) of instrument capacity. Five (55.6%) of nine laboratory technologists left their posts over 2 years. These findings demonstrate that GCLP laboratory service provision in this setting is hampered by delays in biomedical engineer support, delays and extra costs in commodity procurement, low testing throughput, and high personnel turnover. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association between prostate cancer and urinary calculi: a population-based study.

PubMed

Chung, Shiu-Dong; Liu, Shih-Ping; Lin, Herng-Ching

2013-01-01

Understanding the reasons underlying the emerging trend and the changing demographics of Asian prostate cancer (PC) has become an important field of study. This study set out to explore the possibility that urinary calculi (UC) and PC may share an association by conducting a case-control study on a population-based database in Taiwan. The cases of this study included 2,900 subjects ≥ 40 years-old who had received their first-time diagnosis of PC and 14,500 randomly selected controls without PC. Conditional logistic regressions were employed to explore the association between PC and having been previously diagnosed with UC. We found that prior UC was found among 608 (21.0%) cases and 2,037 (14.1%) controls (p<0.001). Conditional logistic regression analysis revealed that compared to controls, the odds ratio (OR) of prior UC for cases was 1.63 (95% CI = 1.47-1.80). Furthermore, we found that cases were more likely to have been previously diagnosed with kidney calculus (OR = 1.71; 95% CI = 1.42-2.05), bladder calculus (OR = 2.06; 95% CI = 1.32-3.23), unspecified calculus (OR = 1.66; 95% CI = 1.37-2.00), and ≥2 locations of UC (OR = 1.73; 1.47-2.02) than controls. However, there was no significant relationship between PC and prior ureter calculus. We also found that of the patients with UC, there was no significant difference between PC and treatment method. This investigation detected an association between PC and prior UC. These results highlight a potential target population for PC screening.

Predictors of immunological failure of antiretroviral therapy among HIV infected patients in Ethiopia: a matched case-control study.

PubMed

Teshome, Wondu; Asefa, Anteneh; Assefa, Anteneh

2014-01-01

In resource constrained settings, immunological assessment through CD4 count is used to assess response to first line Highly Active Antiretroviral Therapy (HAART). In this study, we aim to investigate factors associated with immunological treatment failure. A matched case-control study design was used. Cases were subjects who already experienced immunological treatment failure and controls were those without immunological failure after an exactly or approximately equivalent duration of first line treatment with cases. Data were analyzed using SPSS v16.0. Conditional logistic regression was carried out. A total of 134 cases and 134 controls were included in the study. At baseline, the mean age ± 1 SD of cases was 37.5 ± 9.7 years whereas it was 36.9 ± 9.2 years among controls. The median baseline CD4 counts of cases and controls were 121.0 cells/µl (IQR: 47-183 cells/µl) and 122.0 cells/µl (IQR: 80.0-189.8 cells/µl), respectively. The median rate of CD4 cells increase was comparable for the two groups in the first six months of commencing HAART (P = 0.442). However, the median rate of CD4 increase was significantly different for the two groups in the next 6 months period (M6 to M12). The rate of increment was 8.8 (IQR: 0.5, 14.6) and 1.8 (IQR: 8.8, 11.3) cells/µl/month for controls and cases, respectively (Mann-Whitney U test, P = 0.003). In conditional logistic regressions grouped baseline CD4 count (P = 0.028), old age group and higher educational status (P<0.001) were significant predictors of immunological treatment failure. Subjects with immunological treatment failure have an optimal rate of immunological recovery in the first 6 months of treatment with first line HAART, but relative to the non-failing group the rate declines at a later period, notably between 6 and 12 months. Low baseline CD4 count, old age and higher educational status were associated with immunological treatment failure.

Depression and posttraumatic stress disorder among road traffic accident victims managed in a Tertiary hospital in Southern Nigeria.

PubMed

Asuquo, J E; Edet, B E; Abang, I E; Essien, E A; Osakwe, O G; Aigbomain, E J; Chigbundu, K C

2017-02-01

Psychological responses to traumatic events vary widely across different cultures but studies in the developing countries are scant. The objective of this study is to determine prevalence of depression and posttraumatic stress disorder (PTSD) among patients involved in road traffic accident (RTA) compared with that of the general population using a matched control group. The study design was case control and employed the convenient sampling technique. All consecutive attendees of the trauma clinic of a Tertiary Hospital who had been involved in RTA in the previous year and met inclusion criteria were recruited to participate in the study. Controls were drawn from patient relatives attending other clinics in the same hospital. The final sample comprised of 46 cases and controls, totaling 92 participants. A Sociodemographic questionnaire, the PTSD, and depression modules of the Mini International neuropsychiatric interview were administered to both groups by trained research assistants. The data were analyzed using IBM SPSS version 22. Statistical significance was set at 0.05. The prevalence of PTSD among cases was 41.3% compared with 13% among controls, whereas the prevalence of depression among cases was 63% compared with 30.4% among the controls. Both of these findings were statistically significant (P < 0.002). Sociodemographic variables such as age, sex, marital status, religion, level of education, and occupation did not have statistically significant relationship with neither PTSD nor depression. Mental disorders such as PTSD and depression are common in victims of RTA. They would benefit from comanagement with mental health specialists.

Bias reduction in repeated-measures observational studies by the use of propensity score: the case of enteral sedation for critically ill patients.

PubMed

Umbrello, Michele; Mistraletti, Giovanni; Corbella, Davide; Cigada, Marco; Salini, Silvia; Morabito, Alberto; Iapichino, Gaetano

2012-12-01

Within the evidence-based medicine paradigm, randomized controlled trials represent the "gold standard" to produce reliable evidence. Indeed, planning and implementing randomized controlled trials in critical care medicine presents limitations because of intrinsic and structural problems. As a consequence, observational studies still occur frequently. In these cases, propensity score (PS) (probability of receiving a treatment conditional on observed covariates) is an increasingly used technique to adjust the results. Few studies addressed the specific issue of a PS correction of repeated-measures designs. Three techniques for correcting the analysis of nonrandomized designs (matching, stratification, regression adjustment) are presented in a tutorial form and applied to a real case study: the comparison between intravenous and enteral sedative therapy in the intensive care unit setting. After showing the results before and after the use of PS, we suggest that such a tool allows to partially overcoming the bias associated with the observational nature of the study. It permits to correct the estimates for any observed covariate, while unobserved confounders cannot be controlled for. Propensity score represents a useful additional tool to estimate the effects of treatments in nonrandomized studies. In the case study, an enteral sedation approach was equally effective to an intravenous regime, allowing for a lower level of sedation and spare of resources. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: a case-control study.

PubMed

Gupta, Samir; Sun, Han; Yi, Sang; Storm, Joy; Xiao, Guanghua; Balasubramanian, Bijal A; Zhang, Song; Ashfaq, Raheela; Rockey, Don C

2014-10-01

Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer. We hypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n = 216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, β-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the seven-marker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted. ©2014 American Association for Cancer Research.

Building capacity to address tobacco-related disparities among American Indian and Hispanic/Latino communities: conceptual and systemic considerations.

PubMed

Báezconde-Garbanati, Lourdes; Beebe, Laura A; Pérez-Stable, Eliseo J

2007-10-01

To discuss systemic and conceptual issues that surround capacity building for tobacco control in traditionally underserved communities, by presenting two case studies, one in an American Indian community and another in a Hispanic/Latino community. Key informant interviews, cross-sectional surveys and case study methods were used to create community-specific conceptual frameworks for building capacity for tobacco control. These models of capacity building serve as the backdrop for the development of the two case studies. SETTING, PARTICIPANTS, MEASUREMENTS: Interview and survey participants were identified through convenience and snowball sampling, using a community-based participatory process in an American Indian community in Oklahoma and among the Hispanic/Latino Tobacco Education Partnership (H/LTEP) organizations in California. Using qualitative and quantitative methods, two case studies were created based on the results of interviews with key informants in each of the respective communities, outcomes of efforts to build capacity in tobacco control are presented. The extent to which American Indian and Hispanic/Latino communities have the capacity to address effectively the disproportionate burden of tobacco abuse is contingent upon the presence of leadership, collaboration, programs, distribution of funds and resources, development of policies and an underlying understanding of community strengths, history, values and participation. Common characteristics emerge from the case studies that help bridge differences in definition and measurement across both populations and programs. The conceptual frameworks for capacity building presented provide insight that enhances the ability of priority populations to engage in tobacco control strategies using culturally and language appropriate interventions.

An instructional intervention to encourage effective deep collaborative learning in undergraduate veterinary students.

PubMed

Khosa, Deep K; Volet, Simone E; Bolton, John R

2010-01-01

In recent years, veterinary education has received an increased amount of attention directed at the value and application of collaborative case-based learning. The benefit of instilling deep learning practices in undergraduate veterinary students has also emerged as a powerful tool in encouraging continued professional education. However, research into the design and application of instructional strategies to encourage deep, collaborative case-based learning in veterinary undergraduates has been limited. This study focused on delivering an instructional intervention (via a 20-minute presentation and student handout) to foster productive, collaborative case-based learning in veterinary education. The aim was to instigate and encourage deep learning practices in a collaborative case-based assignment and to assess the impact of the intervention on students' group learning. Two cohorts of veterinary students were involved in the study. One cohort was exposed to an instructional intervention, and the other provided the control for the study. The instructional strategy was grounded in the collaborative learning literature and prior empirical studies with veterinary students. Results showed that the intervention cohort spent proportionally more time on understanding case content material than did the control cohort and rated their face-to-face discussions as more useful in achieving their learning outcomes than did their control counterparts. In addition, the perceived difficulty of the assignment evolved differently for the control and intervention students from start to end of the assignment. This study provides encouraging evidence that veterinary students can change and enhance the way they interact in a group setting to effectively engage in collaborative learning practices.

Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

PubMed Central

Langham, Julia; Bhaskaran, Krishnan; Brauer, Ruth; Smeeth, Liam

2013-01-01

Objective To measure the association between orlistat and acute liver injury. Design Self controlled case series study. Setting Population based primary care setting, United Kingdom. Participants 94 695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011. Main outcome measure Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage. Results Among 94 695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment. Conclusion The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug. PMID:23585064

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.

No association between level of vitamin D and chronic low back pain in Swedish primary care: a cross-sectional case-control study.

PubMed

Thörneby, Andreas; Nordeman, Lena Margareta; Johanson, Else Hellebö

2016-06-01

Assessment of vitamin D levels and deficiency status in individuals with chronic low back pain (CLBP) in a Swedish general population, compared with controls matched for sex and age. Cross-sectional case-control study. Primary care, southern Sweden. Participants (n = 44) with self-reported low back pain for at least 3 months and individually sex- and age-matched controls without a chronic pain condition (n = 44), recruited from the general population by random letter of invitation. Association between vitamin D level and CLBP when adjusting for possible confounders in a multivariate forward conditional logistic regression model. Mean S-25-hydroxyvitamin D levels were 81 and 80 nmol/L in the CLBP and control group, respectively. The prevalence of vitamin D deficiency was low and similar in the CLBP group and the control group. Vitamin D level was not associated with CLBP when potential confounders were taken into account. No difference in vitamin D levels between participants with CLBP and matched controls could be demonstrated in the present sample. Assessment of vitamin D level and deficiency status may be of questionable value in the management of CLBP in primary care settings at similar latitudes, unless there are additional risk factors for deficiency or specific indicators of osteomalacia. Key points Vitamin D deficiency is common and reported in many chronic pain conditions, including chronic low back pain (CLBP), but evidence for an association and causality is insufficient. • The present study found no association between vitamin D levels and CLBP in a case-control sample of 44 + 44 individuals from the Swedish general population. • Prevalence of vitamin D deficiency was low and comparable in individuals with CLBP and controls without chronic pain, matched for sex and age. • Assessment of vitamin D status, for the purpose of finding and treating an underlying cause of pain, may be of limited value in the management of CLBP in primary care settings at similar latitudes.

Identification of facilitators and barriers to residents' use of a clinical reasoning tool.

PubMed

DiNardo, Deborah; Tilstra, Sarah; McNeil, Melissa; Follansbee, William; Zimmer, Shanta; Farris, Coreen; Barnato, Amber E

2018-03-28

While there is some experimental evidence to support the use of cognitive forcing strategies to reduce diagnostic error in residents, the potential usability of such strategies in the clinical setting has not been explored. We sought to test the effect of a clinical reasoning tool on diagnostic accuracy and to obtain feedback on its usability and acceptability. We conducted a randomized behavioral experiment testing the effect of this tool on diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a single internal medical residency program in 2014. Residents completed written clinical cases in a proctored setting with and without prompts to use the tool. The tool encouraged reflection on concordant and discordant aspects of each case. We used random effects regression to assess the effect of the tool on diagnostic accuracy of the independent case sets, controlling for case complexity. We then conducted audiotaped structured focus group debriefing sessions and reviewed the tapes for facilitators and barriers to use of the tool. Of 51 eligible PGY-3 residents, 34 (67%) participated in the study. The average diagnostic accuracy increased from 52% to 60% with the tool, a difference that just met the test for statistical significance in adjusted analyses (p=0.05). Residents reported that the tool was generally acceptable and understandable but did not recognize its utility for use with simple cases, suggesting the presence of overconfidence bias. A clinical reasoning tool improved residents' diagnostic accuracy on written cases. Overconfidence bias is a potential barrier to its use in the clinical setting.

Harnessing case isolation and ring vaccination to control Ebola.

PubMed

Wells, Chad; Yamin, Dan; Ndeffo-Mbah, Martial L; Wenzel, Natasha; Gaffney, Stephen G; Townsend, Jeffrey P; Meyers, Lauren Ancel; Fallah, Mosoka; Nyenswah, Tolbert G; Altice, Frederick L; Atkins, Katherine E; Galvani, Alison P

2015-05-01

As a devastating Ebola outbreak in West Africa continues, non-pharmaceutical control measures including contact tracing, quarantine, and case isolation are being implemented. In addition, public health agencies are scaling up efforts to test and deploy candidate vaccines. Given the experimental nature and limited initial supplies of vaccines, a mass vaccination campaign might not be feasible. However, ring vaccination of likely case contacts could provide an effective alternative in distributing the vaccine. To evaluate ring vaccination as a strategy for eliminating Ebola, we developed a pair approximation model of Ebola transmission, parameterized by confirmed incidence data from June 2014 to January 2015 in Liberia and Sierra Leone. Our results suggest that if a combined intervention of case isolation and ring vaccination had been initiated in the early fall of 2014, up to an additional 126 cases in Liberia and 560 cases in Sierra Leone could have been averted beyond case isolation alone. The marginal benefit of ring vaccination is predicted to be greatest in settings where there are more contacts per individual, greater clustering among individuals, when contact tracing has low efficacy or vaccination confers post-exposure protection. In such settings, ring vaccination can avert up to an additional 8% of Ebola cases. Accordingly, ring vaccination is predicted to offer a moderately beneficial supplement to ongoing non-pharmaceutical Ebola control efforts.

On The Behavior of Subgradient Projections Methods for Convex Feasibility Problems in Euclidean Spaces

PubMed Central

Butnariu, Dan; Censor, Yair; Gurfil, Pini; Hadar, Ethan

2010-01-01

We study some methods of subgradient projections for solving a convex feasibility problem with general (not necessarily hyperplanes or half-spaces) convex sets in the inconsistent case and propose a strategy that controls the relaxation parameters in a specific self-adapting manner. This strategy leaves enough user-flexibility but gives a mathematical guarantee for the algorithm’s behavior in the inconsistent case. We present numerical results of computational experiments that illustrate the computational advantage of the new method. PMID:20182556

On The Behavior of Subgradient Projections Methods for Convex Feasibility Problems in Euclidean Spaces.

PubMed

Butnariu, Dan; Censor, Yair; Gurfil, Pini; Hadar, Ethan

2008-07-03

We study some methods of subgradient projections for solving a convex feasibility problem with general (not necessarily hyperplanes or half-spaces) convex sets in the inconsistent case and propose a strategy that controls the relaxation parameters in a specific self-adapting manner. This strategy leaves enough user-flexibility but gives a mathematical guarantee for the algorithm's behavior in the inconsistent case. We present numerical results of computational experiments that illustrate the computational advantage of the new method.

Temporal analysis of nonresonant two-photon coherent control involving bound and dissociative molecular states

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

Su Jing; Chen Shaohao; Jaron-Becker, Agnieszka

We theoretically study the control of two-photon excitation to bound and dissociative states in a molecule induced by trains of laser pulses, which are equivalent to certain sets of spectral phase modulated pulses. To this end, we solve the time-dependent Schroedinger equation for the interaction of molecular model systems with an external intense laser field. Our numerical results for the temporal evolution of the population in the excited states show that, in the case of an excited dissociative state, control schemes, previously validated for the atomic case, fail due to the coupling of electronic and nuclear motion. In contrast, formore » excitation to bound states the two-photon excitation probability is controlled via the time delay and the carrier-envelope phase difference between two consecutive pulses in the train.« less

Patterns and determinants of malaria risk in urban and peri-urban areas of Blantyre, Malawi.

PubMed

Mathanga, Don P; Tembo, Atupele Kapito; Mzilahowa, Themba; Bauleni, Andy; Mtimaukenena, Kondwani; Taylor, Terrie E; Valim, Clarissa; Walker, Edward D; Wilson, Mark L

2016-12-08

Although malaria disease in urban and peri-urban areas of sub-Saharan Africa is a growing concern, the epidemiologic patterns and drivers of transmission in these settings remain poorly understood. Factors associated with variation in malaria risk in urban and peri-urban areas were evaluated in this study. A health facility-based, age and location-matched, case-control study of children 6-59 months of age was conducted in four urban and two peri-urban health facilities (HF) of Blantyre city, Malawi. Children with fever who sought care from the same HF were tested for malaria parasites by microscopy and PCR. Those testing positive or negative on both were defined as malaria cases or controls, respectively. A total of 187 cases and 286 controls were studied. In univariate analyses, higher level of education, possession of TV, and electricity in the house were negatively associated with malaria illness; these associations were similar in urban and peri-urban zones. Having travelled in the month before testing was strongly associated with clinical malaria, but only for participants living in the urban zones (OR = 5.1; 95% CI = 1.62, 15.8). Use of long-lasting insecticide nets (LLINs) the previous night was not associated with protection from malaria disease in any setting. In multivariate analyses, electricity in the house, travel within the previous month, and a higher level of education were all associated with decreased odds of malaria disease. Only a limited number of Anopheles mosquitoes were found by aspiration inside the households in the peri-urban areas, and none was collected from the urban households. Travel was the main factor influencing the incidence of malaria illness among residents of urban Blantyre compared with peri-urban areas. Identification and understanding of key mobile demographic groups, their behaviours, and the pattern of parasite dispersal is critical to the design of more targeted interventions for the urban setting.

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

No association between FTO or HHEX andendometrial cancer risk

PubMed Central

Gaudet, Mia M.; Yang, Hannah P.; Bosquet, Jesus Gonzalez; Healey, Catherine S.; Ahmed, Shahana; Dunning, Alison M.; Easton, Doug F.; Spurdle, Amanda B.; Ferguson, Kaltin; O’Mara, Tracy; Group, ANECS; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Amant, Frederic; Lacey, James V.; Lissowska, Jola; Peplonska, Beata; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat

2010-01-01

Introduction Obesity and diabetes are known risk factors for endometrial cancer; thus genetic risk factors of these phenotypes may also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tagSNPs and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies. Methods We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP in each of FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs(as an ordinal variable)and endometrial cancer risk using unconditional logistic regression models, controlling for age and site. Results In the primary study, the most significant findings in FTO was rs12927155 (OR=1.56, 95% CI 1.21–2.01, p=5.8×10−4) and HHEX was rs1111875 (OR=0.80, 95% CI 0.66–0.97; p=0.026). In the validation studies, the pooled per allele ORs, adjusted for age and study, were for FTO rs12927155: OR=0.94, 95% CI 0.83–1.06, p=0.29 and for HHEX rs1111875: OR=1.00, 95%CI 0.92–1.10, p=0.96. Conclusion Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans are not associatedwith endometrial cancer risk. Impact Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects. PMID:20647405

Determinants of first trimester attendance at antenatal care clinics in the Amazon region of Peru: A case-control study

PubMed Central

Moore, Nora; Blouin, Brittany; Razuri, Hugo; Casapia, Martin; Gyorkos, Theresa W.

2017-01-01

Objective To identify determinants which influence the timing of the first antenatal care (ANC) visit in pregnant women. Design Retrospective matched nested case-control study. Setting Two health centres, Belén and 6 de Octubre, in the Peruvian Amazon. Population All pregnant women who had attended ANC during the years 2010, 2011, and 2012. Methods All cases (819 women initiating ANC in their first trimester) were selected from ANC registries from 2010 to 2012. A random sample of controls (819 women initiating ANC in their second or third trimester) was matched 1:1 to cases on health centre and date of first ANC visit. Data were obtained from ANC registries. Conditional logistic regression analyses were performed. Main outcome measure Case-control status of each woman determined by the gestational age at first ANC visit. Results Cases had higher odds of: 1) being married or cohabiting (aOR = 1.69; 95% CI: 1.19, 2.41); 2) completing secondary school or attending post-secondary school (aOR = 1.45; 95% CI: 1.02, 2.06); 3) living in an urban environment (aOR = 1.79; 95% CI: 1.04, 3.10) and 4) having had a previous miscarriage (aOR = 1.56; 95% CI: 1.13, 2.15), compared to controls. No statistically significant difference in odds was found for parity (aOR = 1.08; 95% CI: 0.85, 1.36). Conclusions This study provides empirical evidence of determinants of first ANC attendance. These findings are crucial to the planning and timing of local interventions, like deworming, aimed at pregnant women so that they can access and benefit fully from all government-provided ANC services. PMID:28207749

Transmission Dynamics of Carbapenemase-Producing Klebsiella Pneumoniae and Anticipated Impact of Infection Control Strategies in a Surgical Unit

PubMed Central

Sypsa, Vana; Psichogiou, Mina; Bouzala, Georgia-Aikaterina; Hadjihannas, Linos; Hatzakis, Angelos; Daikos, Georgios L.

2012-01-01

Background Carbapenemase-producing Klebsiella pneumoniae (CPKP) has been established as important nosocomial pathogen in many geographic regions. Transmission from patient to patient via the hands of healthcare workers is the main route of spread in the acute-care setting. Methodology/Principal Findings Epidemiological and infection control data were recorded during a prospective observational study conducted in a surgical unit of a tertiary-care hospital in Greece. Surveillance culture for CPKP were obtained from all patients upon admission and weekly thereafter. The Ross-Macdonald model for vector-borne diseases was applied to obtain estimates for the basic reproduction number R0 (average number of secondary cases per primary case in the absence of infection control) and assess the impact of infection control measures on CPKP containment in endemic and hyperendemic settings. Eighteen of 850 patients were colonized with CPKP on admission and 51 acquired CPKP during hospilazation. R0 reached 2 and exceeded unity for long periods of time under the observed hand hygiene compliance (21%). The minimum hand hygiene compliance level necessary to control transmission was 50%. Reduction of 60% to 90% in colonized patients on admission, through active surveillance culture, contact precautions and isolation/cohorting, in combination with 60% compliance in hand hygiene would result in rapid decline in CPKP prevalence within 8–12 weeks. Antibiotics restrictions did not have a substantial benefit when an aggressive control strategy was implemented. Conclusions/Significance Surveillance culture on admission and isolation/cohorting of colonized patients coupled with moderate hand hygiene compliance and contact precautions may lead to rapid control of CPKP in endemic and hyperendemic healthcare settings. PMID:22859965

Red Cell Distribution Width and Serum BNP Level Correlation in Diabetic Patients with Cardiac Failure: A Cross - Sectional Study.

PubMed

A R, Subhashree

2014-06-01

Red cell distribution width (RDW) is a red cell measurement given by fully automated hematology analyzers. It is a measure of heterogeneity in the size of circulating erythrocytes. Studies have shown that it is a prognostic marker in non - anemic diabetic patients with symptomatic cardiovascular disease but its correlation with cardiac failure in diabetics has not been studied so far. Moreover, studies have also shown that a higher RDW may reflect an underlying inflammatory state. Since Diabetes is a pro inflammatory state there is a possibility that it might have an influence on the RDW values even when there is no cardiac failure, but research data on this aspect is lacking. B-type natriuretic peptide (BNP) is a proven marker for cardiac failure whose values are comparable with echo cardio graphic findings in assessing the left ventricular dysfunction. This study aimed to find out the correlation between RDW% and serum BNP levels in Diabetics with heart failure (cases) when compared to those without failure (controls). Further, we compared the RDW % values of the cases with controls. Settings and Design : The study was approved by institutional ethical and research committee. A cross-sectional study was conducted with patients attending the Diabetes clinic of a tertiary care hospital in Chennai, India, during the period of October to December 2013. Hundred known cases of type II Diabetes mellitus attending Diabetes centre of the Hospital, with clinical and Echo cardio graphic features of cardiac failure were included as cases. Hundred age and gender matched diabetics with negative history of cardiovascular disease and with normal Echo cardio graphic features were included as controls. Informed consent was obtained from all the cases and controls. Demographic data and clinical history were gathered from all the cases and controls by using a standardized self - administered questionnaire. Biochemical and hematological parameters which included Fasting and Postprandial blood sugar, Glycosylated hemoglobin, Complete Blood count including RDW and serum BNP were performed for all the cases and controls. RESULTS were tabulated and analysed using SPSS 20.0 version A statistically significant correlation (p<.001) was found between Red cell Distribution Width % and Serum B type Natriuretic Peptide values in the cases. Further, RDW% showed a statistically significant difference between cases and controls. RDW% can be used as a screening parameter to identify cardiac failure in Diabetic patients similar to non-diabetic cardiac failure. RDW% values are significantly higher in cases of Diabetes with failure in comparison to uncomplicated Diabetes.

Risk factors for and perinatal mortality of abruptio placentae in patients hospitalised for early onset severe pre-eclampsia - a case controlled study.

PubMed

Odendaal, H J; Hall, D R; Grové, D

2000-07-01

We set out to determine which patients admitted for expectant management of early onset severe pre-eclampsia develop abruptio placentae and to compare the perinatal mortality rate of patients who developed abruptio placentae with those who did not have this complication. This was a case controlled study, using gestational age at delivery to select a control group for 69 patients who developed abruptio placentae. The only significant difference on admission was the higher uric acid levels in patients who developed abruptio placentae. Mean admission to delivery intervals were 11.9 and 8.8 days for the control and abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in the abruptio placentae group developed late decelerations, as determined by fetal heart rate monitoring compared with 32% in the control group. Lactate dehydrogenase levels before delivery were significantly higher in the abruption group, but it only became elevated shortly before delivery and in the minority of cases. There were two intrauterine and four neonatal deaths in the abruption group and two neonatal deaths in the control group. Late decelerations detected by frequent fetal heart rate monitoring in patients with early onset severe pre-eclampsia is the only early warning of abruptio placentae.

Risk factors for childhood burns: a case-control study of Ghanaian children.

PubMed

Forjuoh, S N; Guyer, B; Strobino, D M; Keyl, P M; Diener-West, M; Smith, G S

1995-04-01

To study risk factors for childhood burns in order to identify possible preventive strategies. Case-control design with pair matching of controls to cases in relation to age, sex, and area of residence. The cases and controls were identified by a community based, multisite survey. The effects of host and socioenvironmental variables reported by mothers were investigated in a multivariate analysis using conditional logistic regression. A developing country setting the Ashanti Region in Ghana. These comprised 610 cases aged 0-5 years who had been burned (as evidenced by a visible scar) and 610 controls with no burn history. The presence of a pre-existing impairment in a child was the strongest risk factor in this population (OR = 6.71; 95% CI 2.78, 16.16). Other significant risk factor included: sibling death from a burn (OR = 4.41; 95% CI 1.16, 16.68); history of burn in a sibling (OR = 1.79; 95% CI 1.24, 2.58); and storage of a flammable substance in the home (OR = 1.51; 95% CI 1.03; 2.21). Maternal education had a protective effect against childhood burns, although this effect was not strong (OR = 0.76; 95% CI 0.55, 1.05). Community programmes to ensure adequate child supervision and general child wellbeing, particularly for those with impairments, as well as parental education about burns are recommended, to reduce childhood burns in this region of Ghana. The public should bed advised against storing flammable substances in the home.

Clinical and treatment-related risk factors for nosocomial colonisation with extensively drug-resistant Pseudomonas aeruginosa in a haematological patient population: a matched case control study.

PubMed

Willmann, Matthias; Klimek, Anna M; Vogel, Wichard; Liese, Jan; Marschal, Matthias; Autenrieth, Ingo B; Peter, Silke; Buhl, Michael

2014-12-10

This study aimed to investigate risk factors for colonisation with extensively drug-resistant P. aeruginosa (XDR-PA) in immunocompromised patients and to build a clinical risk score (CRS) based on these results. We conducted a matched case-control study with 31 cases and 93 controls (1:3). Cases were colonised with XDR-PA during hospitalisation. Independent risk factors were determined using a three step conditional logistic regression procedure. A CRS was built with respect to the corresponding risk fraction of each risk factor, and its discriminatory power was estimated by receiver operating characteristic (ROC) analysis. The presence of a central venous catheter (OR 7.41, P = 0.0008), the presence of a urinary catheter (OR 21.04, P < 0.0001), CRP > 10 mg/dl (OR 7.36, P = 0.0015), and ciprofloxacin administration (OR 5.53, P = 0.025) were independent risk factors. The CRS exhibited a high discriminatory power, defining a high risk population with an approximately fourteen times greater risk for XDR-PA colonisation. Unnecessary use of antibiotics, particularly ciprofloxacin should be avoided, and a high standard of infection control measures must be achieved when using medical devices. A CRS can be used for adaptation of the active screening culture policy to the local setting.

28. A typical main control panel in a 105 reactor ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. A typical main control panel in a 105 reactor building, in this case 105-F in February 1945. A single operator sat at the controls to regulate the pile's rate of reaction and monitor it for safety. The galvanometer screens (the two horizontal bars just below the nine round gauges that showed the positions of the control rods) showed the pile's current power setting. With that information, the operator could set the control rod positions to increase, decrease, or maintain the power. D-8310 - B Reactor, Richland, Benton County, WA

28 CFR 2.68 - Prisoners transferred pursuant to treaty.

Code of Federal Regulations, 2010 CFR

2010-07-01

... date set by the Commission controls. If the release date set by the Commission under 18 U.S.C. 4106A(b... controls. (7) It is the Commission's interpretation of 18 U.S.C. 4106A that U.S. Code provisions for... transferees in mind. Thus, in every transfer treaty case, the release date will be determined through an...

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

PubMed

Baggett, Henry C; Watson, Nora L; Deloria Knoll, Maria; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; Scott, J Anthony G; Thea, Donald M; Antonio, Martin; Awori, Juliet O; Baillie, Vicky L; DeLuca, Andrea N; Driscoll, Amanda J; Duncan, Julie; Ebruke, Bernard E; Goswami, Doli; Higdon, Melissa M; Karron, Ruth A; Moore, David P; Morpeth, Susan C; Mulindwa, Justin M; Park, Daniel E; Paveenkittiporn, Wantana; Piralam, Barameht; Prosperi, Christine; Sow, Samba O; Tapia, Milagritos D; Zaman, Khalequ; Zeger, Scott L; O'Brien, Katherine L

2017-06-15

Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting. 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.

Missed opportunities for HIV testing in health care settings among young African American men who have sex with men: implications for the HIV epidemic.

PubMed

Dorell, Christina G; Sutton, Madeline Y; Oster, Alexandra M; Hardnett, Felicia; Thomas, Peter E; Gaul, Zaneta J; Mena, Leandro A; Heffelfinger, James D

2011-11-01

Limited health care access and missed opportunities for HIV and other sexually transmitted infection (STI) education and testing in health care settings may contribute to risk of HIV infection. In 2008, we conducted a case-control study of African American men who have sex with men (MSM) in a southeastern city (Jackson, Mississippi) with an increase in numbers of newly reported HIV cases. Our aims were to evaluate associations between health care and HIV infection and to identify missed opportunities for HIV/STI testing. We queried 40 potential HIV-infected cases and 936 potential HIV-uninfected controls for participation in this study. Study enrollees included HIV-infected cases (n=30) and HIV-uninfected controls (n=95) who consented to participate and responded to a self-administered computerized survey about sexual risk behaviors and health care utilization. We used bivariate analysis and logistic regression to test for associations between potential risk factors and HIV infection. Cases were more likely than controls to lack health insurance (odds ratio [OR]=2.5; 95% confidence interval [CI]=1.1-5.7), lack a primary care provider (OR=6.3; CI=2.3-16.8), and to not have received advice about HIV or STI testing or prevention (OR=5.4; CI=1.3-21.5) or disclose their sexual identity (OR=7.0; CI=1.6-29.2) to a health care provider. In multivariate analysis, lacking a primary health care provider (adjusted odds ratio [AOR]=4.5; CI=1.4-14.7) and not disclosing sexual identity to a health care provider (AOR=8.6; CI=1.8-40.0) were independent risk factors for HIV infection among African American MSM. HIV prevention interventions for African American MSM should address access to primary health care providers for HIV/STI prevention and testing services and the need for increased discussions about sexual health, sexual identity, and sexual behaviors between providers and patients in an effort to reduce HIV incidence and HIV-related health disparities.

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

Prevalence of and Risk Factors for Multidrug-Resistant Acinetobacter baumannii Colonization Among High-Risk Nursing Home Residents

PubMed Central

Mody, Lona; Gibson, Kristen E.; Horcher, Amanda; Prenovost, Katherine; McNamara, Sara E.; Foxman, Betsy; Kaye, Keith S.; Bradley, Suzanne

2015-01-01

OBJECTIVE To characterize the epidemiology of multidrug-resistant (MDR) Acinetobacter baumannii colonization in high-risk nursing home (NH) residents. DESIGN Nested case-control study within a multicenter prospective intervention trial. SETTING Four NHs in Southeast Michigan. PARTICIPANTS Case patients and control subjects were NH residents with an indwelling device (urinary catheter and/or feeding tube) selected from the control arm of the Targeted Infection Prevention study. Cases were residents colonized with MDR (resistant to ≥3 classes of antibiotics) A. baumannii; controls were never colonized with MDR A. baumannii. METHODS For active surveillance cultures, specimens from the nares, oropharynx, groin, perianal area, wounds, and device insertion site(s) were collected upon study enrollment, day 14, and monthly thereafter. A. baumannii strains and their susceptibilities were identified using standard microbiologic methods. RESULTS Of 168 NH residents, 25 (15%) were colonized with MDR A. baumannii. Compared with the 143 controls, cases were more functionally disabled (Physical Self-Maintenance Score >24; odds ratio, 5.1 [95% CI, 1.8–14.9]; P < .004), colonized with Proteus mirabilis (5.8 [1.9–17.9]; P < .003), and diabetic (3.4 [1.2–9.9]; P < .03). Most cases (22 [88%]) were colonized with multiple antibiotic-resistant organisms and 16 (64%) exhibited co-colonization with at least one other resistant gram-negative bacteria. CONCLUSION Functional disability, P. mirabilis colonization, and diabetes mellitus are important risk factors for colonization with MDR A. baumannii in high-risk NH residents. A. baumannii exhibits widespread antibiotic resistance and a preference to colonize with other antibiotic-resistant organisms, meriting enhanced attention and improved infection control practices in these residents. PMID:26072936

Resurrecting social infrastructure as a determinant of urban tuberculosis control in Delhi, India

PubMed Central

2014-01-01

Background The key to universal coverage in tuberculosis (TB) management lies in community participation and empowerment of the population. Social infrastructure development generates social capital and addresses the crucial social determinants of TB, thereby improving program performance. Recently, there has been renewed interest in the concept of social infrastructure development for TB control in developing countries. This study aims to revive this concept and highlight the fact that documentation on ways to operationalize urban TB control is required from a holistic development perspective. Further, it explains how development of social infrastructure impacts health and development outcomes, especially with respect to TB in urban settings. Methods A wide range of published Government records pertaining to social development parameters and TB program surveillance, between 2001 and 2011 in Delhi, were studied. Social infrastructure development parameters like human development index along with other indicators reflecting patient profile and habitation in urban settings were selected as social determinants of TB. These include adult literacy rates, per capita income, net migration rates, percentage growth in slum population, and percentage of urban population living in one-room dwelling units. The impact of the Revised National Tuberculosis Control Program on TB incidence was assessed as an annual decline in new TB cases notified under the program. Univariate linear regression was employed to examine the interrelationship between social development parameters and TB program outcomes. Results The decade saw a significant growth in most of the social development parameters in the State. TB program performance showed 46% increment in lives saved among all types of TB cases per 100,000 population. The 7% reduction in new TB case notifications from the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases per 100,000 population. Except per capita income, literacy, and net migration rates, other social determinants showed significant correlation with decline in new TB cases per 100,000 population. Conclusions Social infrastructure development leads to social capital generation which engenders positive growth in TB program outcomes. Strategies which promote social infrastructure development should find adequate weightage in the overall policy framework for urban TB control in developing countries. PMID:24438431

Resurrecting social infrastructure as a determinant of urban tuberculosis control in Delhi, India.

PubMed

Chandra, Shivani; Sharma, Nandini; Joshi, Kulanand; Aggarwal, Nishi; Kannan, Anjur Tupil

2014-01-17

The key to universal coverage in tuberculosis (TB) management lies in community participation and empowerment of the population. Social infrastructure development generates social capital and addresses the crucial social determinants of TB, thereby improving program performance. Recently, there has been renewed interest in the concept of social infrastructure development for TB control in developing countries. This study aims to revive this concept and highlight the fact that documentation on ways to operationalize urban TB control is required from a holistic development perspective. Further, it explains how development of social infrastructure impacts health and development outcomes, especially with respect to TB in urban settings. A wide range of published Government records pertaining to social development parameters and TB program surveillance, between 2001 and 2011 in Delhi, were studied. Social infrastructure development parameters like human development index along with other indicators reflecting patient profile and habitation in urban settings were selected as social determinants of TB. These include adult literacy rates, per capita income, net migration rates, percentage growth in slum population, and percentage of urban population living in one-room dwelling units. The impact of the Revised National Tuberculosis Control Program on TB incidence was assessed as an annual decline in new TB cases notified under the program. Univariate linear regression was employed to examine the interrelationship between social development parameters and TB program outcomes. The decade saw a significant growth in most of the social development parameters in the State. TB program performance showed 46% increment in lives saved among all types of TB cases per 100,000 population. The 7% reduction in new TB case notifications from the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases per 100,000 population. Except per capita income, literacy, and net migration rates, other social determinants showed significant correlation with decline in new TB cases per 100,000 population. Social infrastructure development leads to social capital generation which engenders positive growth in TB program outcomes. Strategies which promote social infrastructure development should find adequate weightage in the overall policy framework for urban TB control in developing countries.

A close examination of under-actuated attitude control subsystem design for future satellite missions' life extension

NASA Astrophysics Data System (ADS)

Lam, Quang M.; Barkana, Itzhak

2014-12-01

Satellite mission life, maintained and prolonged beyond its typical norm of their expectancy, are primarily dictated by the state of health of its Reaction Wheel Assembly (RWA), especially for commercial GEO satellites since torquer bars are no longer applicable while thruster assistant is unacceptable due to pointing accuracy impact during jet firing. The RWA is the primary set of actuators (as compared to thrusters for orbit maintenance and maneuvering) mainly responsible for the satellite mission for accurately and precisely pointing its payloads to the right targets to conduct its mission operations. The RWA consisting of either a set of four in pyramid or three in orthogonal is the primary set of actuators to allow the satellite to achieve accurate and precise pointing of the satellite payloads towards the desired targets. Future space missions will be required to achieve much longer lives and are currently perceived by the GEO satellite community as an "expected norm" of 20 years or longer. Driven by customers' demands/goals and competitive market have challenged Attitude Control Subsystems (ACS) engineers to develop better ACS algorithms to address such an emerging need. There are two main directions to design satellite's under-actuated control subsystem: (1) Attitude Feedback with Zero Momentum Principle and (2) Attitude Control by Angular Velocity Tracking via Small Time Local Controllability concept. Successful applications of these control laws have been largely demonstrated via simulation for the rest to rest case. Limited accuracy and oscillatory behaviors are observed in three axes for non-zero wheel momentum while realistic loss of a wheel scenario (i.e., fully actuated to under-actuated) has not been closely examined! This study revisits the under-actuated control design with detailed set ups of multiple scenarios reflecting real life operating conditions which have put current under-actuated control laws mentioned earlier into a re-evaluation mode since rest to rest case is not adequate to truly represent an on orbit failure of a single wheel. The study is intended to facilitate the ACS community to further develop a more practical under-actuated control law and present a path to extend these current thinking to address a more realistic reconfigurable ACS subject to a dynamic transition from a 3 RWs mode to 2 RWs mode.

Impact of Body Mass Index and Genetics on Warfarin Major Bleeding Outcomes in a Community Setting.

PubMed

Hart, Ragan; Veenstra, David L; Boudreau, Denise M; Roth, Joshua A

2017-02-01

Several studies have demonstrated an association between body mass index (BMI) and warfarin therapeutic dose, but none evaluated the association of BMI with the clinically important outcome of major bleeding in a community setting. To address this evidence gap, we conducted a case-control study to evaluate the association between BMI and major bleeding risk among patients receiving warfarin. We used a case-control study design to evaluate the association between obesity (BMI >30.0 kg/m 2 ) and major bleeding risk among 265 cases and 305 controls receiving warfarin at Group Health, an integrated healthcare system in Washington State. Multivariate logistic regression was used to adjust for potential confounders derived from health plan records and a self-report survey. In exploratory analyses we evaluated the interaction between genetic variants potentially associated with warfarin bleeding (CYP2C9, VKORC1, and CYP4F2) and obesity on the risk of major bleeding. Overall, the sample was 55% male, 94% Caucasian, and mean age was 70 years. Cases and controls had an average of 3.4 and 3.7 years of warfarin use, respectively. Obese patients had significantly lower major bleeding risk relative to non-obese patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.92). The OR was 0.56 (95% CI 0.35-0.90) in patients with ≥1 year of warfarin use, and 0.78 (95% CI 0.40-1.54) in patients with <1 year of warfarin use. An exploratory analysis indicated a statistically significant interaction between CYP4F2*3 genetic status and obesity (P = .049), suggesting a protective effect of obesity on the risk of major bleeding among those wild type for CYP4F2*3, but not among variants. Our findings suggest that BMI is an important clinical factor in assessing and managing warfarin therapy. Future studies should confirm the major bleeding associations, including the interaction between obesity and CYP4F2*3 status identified in this study, and evaluate potential mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Neovascular age-related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population-based study.

PubMed

Hu, Chao-Chien; Lin, Herng-Ching; Sheu, Jau-Jiuan; Kao, Li-Ting

2017-11-01

This case-control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age-related macular degeneration (AMD) using a population-based data set in Taiwan. We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age- and sex-matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls. Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04-1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91-1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15-1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05-1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32-1.65) were significantly associated with AMD. This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Examining HIV Viral Load in a Matched Cohort of HIV Positive Individuals With and Without Psoriasis.

PubMed

Wu, Jashin J; Gilbert, Kathleen E; Batech, Michael; Manalo, Iviensan F; Towner, William J; Raposo, Rui André Saraiva; Nixon, Douglas F; Liao, Wilson

2017-04-01

BACKGROUND: HIV-associated psoriasis is well-documented. Genetic, cellular, and cytokine profiles have been used as evidence to suggest psoriasis activates antiviral pathways. There has been a lack of epidemiologic evidence investigating whether psoriasis patients have lower HIV viral counts compared to non-psoriasis patients.

OBJECTIVE: Compare the viral load set point of HIV positive patients with and without psoriasis.

METHODS: A retrospective matched cohort study of HIV positive patients with and without psoriasis using the Kaiser Permanente Southern California Health Plan database.

RESULTS: We identified 101 HIV-positive psoriasis cases; 19 met inclusion criteria and were matched with 3-5 control patients; 94 total patients were analyzed. The mean age was 41.4 (12.07) years and 83% were male. Overall, the median log of the viral load of cases was slightly higher than controls (4.3 vs 4.2; P less than 0.01).

CONCLUSIONS: The serum viral load set point of patients with HIV and psoriasis was slightly higher than the viral load set point of HIV patients without psoriasis.

J Drugs Dermatol. 2017;16(4):372-377.

A time-and-motion approach to micro-costing of high-throughput genomic assays

PubMed Central

Costa, S.; Regier, D.A.; Meissner, B.; Cromwell, I.; Ben-Neriah, S.; Chavez, E.; Hung, S.; Steidl, C.; Scott, D.W.; Marra, M.A.; Peacock, S.J.; Connors, J.M.

2016-01-01

Background Genomic technologies are increasingly used to guide clinical decision-making in cancer control. Economic evidence about the cost-effectiveness of genomic technologies is limited, in part because of a lack of published comprehensive cost estimates. In the present micro-costing study, we used a time-and-motion approach to derive cost estimates for 3 genomic assays and processes—digital gene expression profiling (gep), fluorescence in situ hybridization (fish), and targeted capture sequencing, including bioinformatics analysis—in the context of lymphoma patient management. Methods The setting for the study was the Department of Lymphoid Cancer Research laboratory at the BC Cancer Agency in Vancouver, British Columbia. Mean per-case hands-on time and resource measurements were determined from a series of direct observations of each assay. Per-case cost estimates were calculated using a bottom-up costing approach, with labour, capital and equipment, supplies and reagents, and overhead costs included. Results The most labour-intensive assay was found to be fish at 258.2 minutes per case, followed by targeted capture sequencing (124.1 minutes per case) and digital gep (14.9 minutes per case). Based on a historical case throughput of 180 cases annually, the mean per-case cost (2014 Canadian dollars) was estimated to be $1,029.16 for targeted capture sequencing and bioinformatics analysis, $596.60 for fish, and $898.35 for digital gep with an 807-gene code set. Conclusions With the growing emphasis on personalized approaches to cancer management, the need for economic evaluations of high-throughput genomic assays is increasing. Through economic modelling and budget-impact analyses, the cost estimates presented here can be used to inform priority-setting decisions about the implementation of such assays in clinical practice. PMID:27803594

Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME-ON): study protocol of a cluster controlled trial.

PubMed

Anrys, Pauline; Strauven, Goedele; Boland, Benoit; Dalleur, Olivia; Declercq, Anja; Degryse, Jean-Marie; De Lepeleire, Jan; Henrard, Séverine; Lacour, Valérie; Simoens, Steven; Speybroeck, Niko; Vanhaecht, Kris; Spinewine, Anne; Foulon, Veerle

2016-03-11

Ageing has become a worldwide reality and presents new challenges for the health-care system. Research has shown that potentially inappropriate prescribing, both potentially inappropriate medications and potentially prescribing omissions, is highly prevalent in older people, especially in the nursing home setting. The presence of potentially inappropriate medications/potentially prescribing omissions is associated with adverse drug events, hospitalisations, mortality and health-care costs. The Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME-ON) study aims to evaluate the effect of a complex, multifaceted intervention, including interdisciplinary case conferences, on the appropriateness of prescribing of medicines for older people in Belgian nursing homes. A multicentre cluster-controlled trial is set up in 63 Belgian nursing homes (30 intervention; 33 control). In each of these nursing homes, 35 residents (≥65 years) are selected for participation. The complex, multifaceted intervention comprises (i) health-care professional education and training, (ii) local concertation (discussion on the appropriate use of at least one medication class at the level of the nursing home) and (iii) repeated interdisciplinary case conferences between general practitioner, nurse and pharmacist to perform medication review for each included nursing home resident. The control group works as usual. The study period lasts 15 months. The primary outcome measures relate to the appropriateness of prescribing and are defined as (1) among residents who had at least one potentially inappropriate medication/potentially prescribing omission at baseline, the proportion of them for whom there is a decrease of at least one of these potentially inappropriate medications/potentially prescribing omissions at the end of study, and (2) among all residents, the proportion of them for whom at least one new potentially inappropriate medication/potentially prescribing omission is present at the end of the study, compared to baseline. The secondary outcome measures include individual components of appropriateness of prescribing, medication use, outcomes of the case conferences, clinical outcomes and costs. A process evaluation (focusing on implementation, causal mechanisms and contextual factors) will be conducted alongside the study. The COME-ON study will contribute to a growing body of knowledge concerning the effect of complex interventions on the use of medicines in the nursing home setting, and on factors influencing their effect. The results will inform policymakers on strategies to implement in the near future. Current Controlled Trials ISRCTN66138978.

Nitrate in drinking water and risk of death from pancreatic cancer in Taiwan.

PubMed

Yang, Chun-Yuh; Tsai, Shang-Shyue; Chiu, Hui-Fen

2009-01-01

The relationship between nitrate levels in drinking water and risk of pancreatic cancer development remains inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to pancreatic cancer and nitrate exposure from Taiwan's drinking water. All pancreatic cancer deaths of Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios and confidence limits for pancreatic cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.03 (0.9-1.18) and 1.1 (0.96-1.27), respectively. The results of the present study show that there was no statistically significant association between the levels of nitrate in drinking water and increased risk of death from pancreatic cancer.

A case-control analysis on the association between erectile dysfunction and sudden sensorineural hearing loss in Taiwan.

PubMed

Keller, Joseph J; Chen, Yi-Kuang; Lin, Herng-Ching

2012-05-01

Although the cause of sudden sensorineural hearing loss (SSNHL) is yet to be elucidated, many theories have been proposed regarding potentially contributory etiologies. One increasingly well-supported theory purports an underlying vascular pathomechanism. If this is the case, SSNHL may also associate with conditions comorbid with vascular diseases, such as erectile dysfunction (ED). However, no studies to date have investigated the association between ED and SSNHL. This study set out to estimate a putative association between ED and having been previously diagnosed with SSNHL using a population-based dataset with a case-control design. This study used administrative claim data from the Taiwan National Health Insurance program. We identified 4,504 patients with ED as the study group and randomly selected 22,520 patients as the comparison group. Conditional logistic regression was used to examine the association between ED and having previously received a diagnosis of SSNHL. The prevalence and risk of SSNHL between cases and controls were calculated. Of the sampled patients, 41 (0.15%) had been diagnosed with SSNHL before the index date; 22 (0.49% of the cases) were from the study group and 19 (0.08% of controls) were from the control group. Conditional logistic regression analysis revealed that after adjusting for the patient's monthly income, geographic location, hypertension, diabetes, hyperlipidemia, coronary heart disease, obesity, and alcohol abuse/alcohol dependence syndrome status, patients with ED were more likely than controls to have been diagnosed with SSNHL before the index date (odds ratio = 6.06, 95% confidence interval = 3.25-11.29). There was an association between ED and prior SSNHL. The results of this study add to the evidence supporting an underlying vascular pathomechanism regarding the development of SSNHL and highlight a need for clinicians dealing with SSNHL patients to be alert to the development of ED. © 2012 International Society for Sexual Medicine.

Identification of Occupational Cancer Risks in British Columbia, Canada: A Population-Based Case—Control Study of 1,155 Cases of Colon Cancer

PubMed Central

Fang, Raymond; Le, Nhu; Band, Pierre

2011-01-01

Objective Cancer has been recognized to have environmental origin, but occupational cancer risk studies have not been fully documented. The objective of this paper was to identify occupations and industries with elevated colon cancer risk based on lifetime occupational histories collected from 15,463 incident cancer cases. Method A group matched case-control design was used. All cases were diagnosed with histologically proven colon cancers, with cancer controls being all other cancer sites, excluding rectum, lung and unknown primary, diagnosed at the same period of time from the British Columbia Cancer Registry. Data analyses were done on all 597 Canadian standard occupation titles and 1,104 standard industry titles using conditional logistic regression for matched data sets and the likelihood ratio test. Results Excess colon cancer risks was observed in a number of occupations and industries, particularly those with low physical activity and those involving exposure to asbestos, wood dusts, engine exhaust and diesel engine emissions, and ammonia. Discussion The results of our study are in line with those from the literature and further suggest that exposure to wood dusts and to ammonia may carry an increased occupational risk of colon cancer. PMID:22073015

Impact of traffic oscillations on freeway crash occurrences.

PubMed

Zheng, Zuduo; Ahn, Soyoung; Monsere, Christopher M

2010-03-01

Traffic oscillations are typical features of congested traffic flow that are characterized by recurring decelerations followed by accelerations (stop-and-go driving). The negative environmental impacts of these oscillations are widely accepted, but their impact on traffic safety has been debated. This paper describes the impact of freeway traffic oscillations on traffic safety. This study employs a matched case-control design using high-resolution traffic and crash data from a freeway segment. Traffic conditions prior to each crash were taken as cases, while traffic conditions during the same periods on days without crashes were taken as controls. These were also matched by presence of congestion, geometry and weather. A total of 82 cases and about 80,000 candidate controls were extracted from more than three years of data from 2004 to 2007. Conditional logistic regression models were developed based on the case-control samples. To verify consistency in the results, 20 different sets of controls were randomly extracted from the candidate pool for varying control-case ratios. The results reveal that the standard deviation of speed (thus, oscillations) is a significant variable, with an average odds ratio of about 1.08. This implies that the likelihood of a (rear-end) crash increases by about 8% with an additional unit increase in the standard deviation of speed. The average traffic states prior to crashes were less significant than the speed variations in congestion. Published by Elsevier Ltd.

Effect modification of the association between trihalomethanes and pancreatic cancer by drinking water hardness: evidence from an ecological study.

PubMed

Chiu, Hui-Fen; Tsai, Shang-Shyue; Wu, Trong-Neng; Yang, Chun-Yuh

2010-07-01

The objective of this study was to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of pancreatic cancer and to determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop pancreatic cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to pancreatic cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All pancreatic cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level < 4.9ppb, the adjusted OR (95% CI) for pancreatic cancer was 1.01 (0.85-1.21) for individuals who resided in municipalities served by drinking water with a TTHM exposure > 4.9ppb. There was no evidence of an interaction of drinking water TTHM levels with low Ca intake via drinking water. However, we observed evidence of an interaction between drinking water TTHM concentrations and Mg intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of pancreatic cancer is influenced by Mg in drinking water. Increased knowledge of the interaction between Mg and TTHM in reducing pancreatic cancer risk will aid in public policy making and standard setting. 2010 Elsevier Inc. All rights reserved.

Trihalomethanes in drinking water and the risk of death from esophageal cancer: does hardness in drinking water matter?

PubMed

Tsai, Shang-Shyue; Chiu, Hui-Fen; Yang, Chun-Yuh

2013-01-01

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of esophageal cancer occurrence and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop esophageal cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to esophageal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All esophageal cancer deaths in the 53 municipalities from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level <4.9 ppb, the adjusted odds ratio (OR) with 95% confidence interval (CI) for esophageal cancer was 1.02 (0.84-1.23) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. There was evidence of an interaction between drinking-water TTHM levels and low Ca and Mg intake. Our findings showed that the correlation between TTHM exposure and risk of esophageal cancer development was influenced by Ca and Mg levels in drinking water. This is the first study to report effect modification by Ca and Mg intake from drinking water on the correlation between TTHM exposure and risk of esophageal cancer occurrence. Increased knowledge of the interaction between Ca, Mg, and TTHM in reducing risk of esophageal cancer development will aid in public policymaking and standard setting for drinking water.

Greater retention in care among adolescents on antiretroviral treatment accessing "Teen Club" an adolescent-centred differentiated care model compared with standard of care: a nested case-control study at a tertiary referral hospital in Malawi.

PubMed

MacKenzie, Rachel K; van Lettow, Monique; Gondwe, Chrissie; Nyirongo, James; Singano, Victor; Banda, Victor; Thaulo, Edith; Beyene, Teferi; Agarwal, Mansi; McKenney, Allyson; Hrapcak, Susan; Garone, Daniela; Sodhi, Sumeet K; Chan, Adrienne K

2017-11-01

There are numerous barriers to the care and support of adolescents living with HIV (ALHIV) that makes this population particularly vulnerable to attrition from care, poor adherence and virological failure. In 2010, a Teen Club was established in Zomba Central Hospital (ZCH), Malawi, a tertiary referral HIV clinic. Teen Club provides ALHIV on antiretroviral treatment (ART) with dedicated clinic time, sexual and reproductive health education, peer mentorship, ART refill and support for positive living and treatment adherence. The purpose of this study was to evaluate whether attending Teen Club improves retention in ART care. We conducted a nested case-control study with stratified selection, using programmatic data from 2004 to 2015. Cases (ALHIV not retained in care) and controls (ALHIV retained in care) were matched by ART initiation age group. Patient records were reviewed retrospectively and subjects were followed starting in March 2010, the month in which Teen Club was opened. Follow-up ended at the time patients were no longer considered retained in care or on 31 December 2015. Cases and controls were drawn from a study population of 617 ALHIV. Of those, 302 (48.9%) participated in at least two Teen Club sessions. From the study population, 135 (non-retained) cases and 405 (retained) controls were selected. In multivariable analyses, Teen Club exposure, age at the time of selection and year of ART initiation were independently associated with attrition. ALHIV with no Teen Club exposure were less likely to be retained than those with Teen Club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45) when adjusted for sex, ART initiation age, current age, reason for ART initiation and year of ART initiation. ALHIV in the age group 15 to 19 were more likely to have attrition from care than ALHIV in the age group 10 to 14 years of age (aOR 2.14; 95% CI 1.12, 4.11). This study contributes to the limited evidence evaluating the effectiveness of service delivery interventions to support ALHIV within healthcare settings. Prospective evaluation of the Teen Club package with higher methodological quality is required for programmes and governments in low- and middle-income settings to prioritize interventions for ALHIV and determine their cost-effectiveness. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Insight into Best Variables for COPD Case Identification: A Random Forests Analysis.

PubMed

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

This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV 1 ] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV 1 <60% predicted or history of acute exacerbation) versus all others. From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD.

Computations of Aerodynamic Performance Databases Using Output-Based Refinement

NASA Technical Reports Server (NTRS)

Nemec, Marian; Aftosmis, Michael J.

2009-01-01

Objectives: Handle complex geometry problems; Control discretization errors via solution-adaptive mesh refinement; Focus on aerodynamic databases of parametric and optimization studies: 1. Accuracy: satisfy prescribed error bounds 2. Robustness and speed: may require over 105 mesh generations 3. Automation: avoid user supervision Obtain "expert meshes" independent of user skill; and Run every case adaptively in production settings.

Effects of Weighted Vests on Classroom Behavior for Children with Autism and Cognitive Impairments

ERIC Educational Resources Information Center

Hodgetts, Sandra; Magill-Evans, Joyce; Misiaszek, John

2011-01-01

This randomized controlled single-case study investigated the effects of weighted vests for 10 children with autism in a classroom setting. Blinded observers rated targeted behaviors through video taken during structured table-top activities typically part of the classroom routine. Blinded teachers rated each child's behavior with the Conners'…

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).

Case studies in configuration control for redundant robots

NASA Technical Reports Server (NTRS)

Seraji, H.; Lee, T.; Colbaugh, R.; Glass, K.

1989-01-01

A simple approach to configuration control of redundant robots is presented. The redundancy is utilized to control the robot configuration directly in task space, where the task will be performed. A number of task-related kinematic functions are defined and combined with the end-effector coordinates to form a set of configuration variables. An adaptive control scheme is then utilized to ensure that the configuration variables track the desired reference trajectories as closely as possible. Simulation results are presented to illustrate the control scheme. The scheme has also been implemented for direct online control of a PUMA industrial robot, and experimental results are presented. The simulation and experimental results validate the configuration control scheme for performing various realistic tasks.

A nonlinear controlling function of geological features on magmatic–hydrothermal mineralization

PubMed Central

Zuo, Renguang

2016-01-01

This paper reports a nonlinear controlling function of geological features on magmatic–hydrothermal mineralization, and proposes an alternative method to measure the spatial relationships between geological features and mineral deposits using multifractal singularity theory. It was observed that the greater the proximity to geological controlling features, the greater the number of mineral deposits developed, indicating a nonlinear spatial relationship between these features and mineral deposits. This phenomenon can be quantified using the relationship between the numbers of mineral deposits N(ε) of a D-dimensional set and the scale of ε. The density of mineral deposits can be expressed as ρ(ε) = Cε−(De−a), where ε is the buffer width of geological controlling features, De is Euclidean dimension of space (=2 in this case), a is singularity index, and C is a constant. The expression can be rewritten as ρ = Cεa−2. When a < 2, there is a significant spatial correlation between specific geological features and mineral deposits; lower a values indicate a more significant spatial correlation. This nonlinear relationship and the advantages of this method were illustrated using a case study from Fujian Province in China and a case study from Baguio district in Philippines. PMID:27255794

Thai health education program for improving TB migrant's compliance.

PubMed

Khortwong, Pornsak; Kaewkungwal, Jaranit

2013-03-01

Investigate the effectiveness of health education programs by using the PRECEDE-PROCEED Model to improve non-Thai migrant TB patient's compliance during treatment. This quasi-intervention study was conducted in three targeted hospitals, between August 2009 and December 2010. The study sample consisted of 100 cases, 50 cases who registered in Samutsakorn Province served as the intervention group and 50 cases who registered in Samutprakarn Province served as the control group. At the end of the health education intervention, the intervention group showedsignificantly improved health-behavior scores in nine domains-health promotion, health education, predisposing, reinforcing, enabling factors, behavior and lifestyle, environment, and health status, which were also significantly higher than the control group (p < 0.001). The percentage of patients achieving successful treatment outcomes was 76% in the intervention group and 62% in the control group. The tuberculosis treatment and care program, and the associated health education interventions enabled migrants to complete the treatment regimen and achieve treatment success. It could also help TB staff develop an appropriate program and clear understanding of TB control among migrants. It is recommended that this type of information and health education program be used in other hospitals and healthcare settings providing TB services for migrants throughout the nation.

A nonlinear controlling function of geological features on magmatic-hydrothermal mineralization.

PubMed

Zuo, Renguang

2016-06-03

This paper reports a nonlinear controlling function of geological features on magmatic-hydrothermal mineralization, and proposes an alternative method to measure the spatial relationships between geological features and mineral deposits using multifractal singularity theory. It was observed that the greater the proximity to geological controlling features, the greater the number of mineral deposits developed, indicating a nonlinear spatial relationship between these features and mineral deposits. This phenomenon can be quantified using the relationship between the numbers of mineral deposits N(ε) of a D-dimensional set and the scale of ε. The density of mineral deposits can be expressed as ρ(ε) = Cε(-(De-a)), where ε is the buffer width of geological controlling features, De is Euclidean dimension of space (=2 in this case), a is singularity index, and C is a constant. The expression can be rewritten as ρ = Cε(a-2). When a < 2, there is a significant spatial correlation between specific geological features and mineral deposits; lower a values indicate a more significant spatial correlation. This nonlinear relationship and the advantages of this method were illustrated using a case study from Fujian Province in China and a case study from Baguio district in Philippines.

International travel is a risk factor for extended-spectrum β-lactamase-producing Enterobacteriaceae acquisition in children: A case-case-control study in an urban U.S. hospital.

PubMed

Strysko, Jonathan P; Mony, Vidya; Cleveland, Jeremiah; Siddiqui, Hanna; Homel, Peter; Gagliardo, Christina

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) infections are increasing in both adults and children. The aim of this study was to describe the epidemiology of children with ESBL in an ethnically-diverse population, to determine what proportion of these infections were community-onset, and to identify risk factors predisposing children to ESBL acquisition. A case-case-control study of children aged 0-18 years was conducted from 2012 to 2014. Patients with ESBL (detected via VITEK2) were matched 1:1:5 (based on age, sex, specimen source, and healthcare setting) with non-ESBL and uninfected controls. Data on prior antibiotic and healthcare exposure, international travel, prior urinary tract infection (UTI), comorbid gastrointestinal (GI), genitourinary (GU), neurologic, and immunocompromising conditions were collected and compared. Seventy-six patients were identified with 85 ESBL infections, of which 77 (91%) were E. coli. ESBL was isolated most frequently from urine (n = 72, 85%). Most infections were community-onset (n = 76, 89%) and were managed in the ambulatory setting (n = 47, 62%). On multivariate analysis, international travel (p < 0.001, OR 8.93; CI 2.92-27.78), comorbid GI condition (p = 0.002, OR 2.65, CI 1.36-5.15), Asian race (p = 0.005, OR 2.56, CI 1.34-4.89) and prior UTI (p < 0.001, OR 8.06, CI 3.47-18.87) were significant risk factors for ESBL. Most ESBL infections in this study were community-onset. To our knowledge, this is the first description of international travel as a risk factor for ESBL acquisition in children in the United States. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mathematical models of the simplest fuzzy PI/PD controllers with skewed input and output fuzzy sets.

PubMed

Mohan, B M; Sinha, Arpita

2008-07-01

This paper unveils mathematical models for fuzzy PI/PD controllers which employ two skewed fuzzy sets for each of the two-input variables and three skewed fuzzy sets for the output variable. The basic constituents of these models are Gamma-type and L-type membership functions for each input, trapezoidal/triangular membership functions for output, intersection/algebraic product triangular norm, maximum/drastic sum triangular conorm, Mamdani minimum/Larsen product/drastic product inference method, and center of sums defuzzification method. The existing simplest fuzzy PI/PD controller structures derived via symmetrical fuzzy sets become special cases of the mathematical models revealed in this paper. Finally, a numerical example along with its simulation results are included to demonstrate the effectiveness of the simplest fuzzy PI controllers.

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.

Childhood leukemia and traffic air pollution in Taiwan: petrol station density as an indicator.

PubMed

Weng, Hsu-Huei; Tsai, Shang-Shyue; Chiu, Hui-Fen; Wu, Trong-Neng; Yang, Chun-Yuh

2009-01-01

To investigate the relationship between traffic air pollution exposure and development of childhood leukemia (14 yr of age or younger), a matched case-control study was conducted using childhood deaths that occurred in Taiwan from 1996 through 2006. Data on all eligible childhood leukemia deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of children who died from causes other than neoplasms or diseases that were not associated with respiratory complications. The controls were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in evaporative losses of petrol or to air emissions from motor vehicles. The subjects were divided into tertiles according to PSD in their residential municipality. The results showed that there was a significant exposure-response relationship between PSD and the risk of leukemia development in young children after controlling for possible confounders. The findings of this study warrant further investigation of the role of traffic air pollution exposure in the etiology of childhood leukemia.

Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

PubMed Central

Garrido, Marlucia da Silva; Penna, Maria Lucia; Perez-Porcuna, Tomàs M.; de Souza, Alexandra Brito; Marreiro, Leni da Silva; Albuquerque, Bernardino Claudio; Martínez-Espinosa, Flor Ernestina; Bührer-Sékula, Samira

2012-01-01

Setting Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. Objective This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. Design Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as ‘cases’ and those completing treatment as ‘controls’. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. Results Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. Conclusions Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs. PMID:22720052

Risk factors for invasive pneumococcal disease among children less than 5 years of age in a high HIV prevalence setting, South Africa, 2010 to 2012.

PubMed

von Mollendorf, Claire; Cohen, Cheryl; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Lindani, Sonwabo; Moore, David P; Reubenson, Gary; Moshe, Mamokgethi; Eley, Brian; Hallbauer, Ute M; Finlayson, Heather; Madhi, Shabir A; Conklin, Laura; Zell, Elizabeth R; Klugman, Keith P; Whitney, Cynthia G; von Gottberg, Anne

2015-01-01

Invasive pneumococcal disease (IPD) causes significant disease burden, especially in developing countries, even in the era of pneumococcal conjugate vaccine and maternal-to-child HIV transmission prevention programs. We evaluated factors that might increase IPD risk in young children in a high HIV prevalence setting. We conducted a case-control study using IPD cases identified at 24 Group for Enteric, Respiratory and Meningeal disease Surveillance-South Africa program sites (2010-2012). At least 4 controls were matched by age, HIV status and hospital to each case. Potential risk factors were evaluated using multivariable conditional logistic regression. In total, 486 age-eligible cases were enrolled. Factors associated with IPD in HIV-uninfected children (237 cases, 928 controls) included siblings <5 years [adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI): 1.16-2.46], underlying medical conditions (aOR = 1.99, CI 1.22-3.22), preceding upper respiratory tract infection (aOR = 1.79, CI 1.19-2.69), day-care attendance (aOR = 1.58, CI 1.01-2.47), perinatal HIV exposure (aOR = 1.62, CI 1.10-2.37), household car ownership (aOR = 0.45, CI 0.25-0.83) and ≥2 7-valent pneumococcal conjugate vaccine doses (aOR = 0.67, CI 0.46-0.99). Among HIV-infected children (124 cases, 394 controls), IPD-associated factors included malnutrition (aOR = 2.68, CI 1.40-5.14), upper respiratory tract infection (aOR = 3.49, CI 1.73-7.03), tuberculosis in the last 3 months (aOR = 5.12, CI 1.69-15.50) and current antiretroviral treatment (aOR = 0.13, CI 0.05-0.38). Previously identified factors related to poverty, poor health and intense exposure continue to be risk factors for IPD in children. Ensuring delivery of pneumococcal conjugate vaccine and antiretroviral treatment are important for improving disease prevention.

Recurrence of tuberculosis in a low-incidence setting: a retrospective cross-sectional study augmented by whole genome sequencing.

PubMed

Parvaresh, Laila; Crighton, Taryn; Martinez, Elena; Bustamante, Andrea; Chen, Sharon; Sintchenko, Vitali

2018-06-07

The recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of Mycobacterium tuberculosis due to non-compliance or inadequate therapy or exogenous reinfection with a new strain. Genotyping or whole genome sequencing (WGS) of M. tuberculosis isolates from initial and recurrent cases can differentiate between reinfection and reactivation. This study examined cases of recurrent TB in New South Wales, Australia, using genotyping and WGS. Culture-confirmed TB cases diagnosed at least 12 months apart between January 2011 and December 2016 were included. Isolates of M. tuberculosis from patients were compared using 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-24) typing and WGS. Eighteen cases of recurrent disease were identified but isolates from only 15 (83%) were available for study. MIRU-24 findings classified 13 (13/15; 87%) as reactivation and two (13%), as reinfection. Sequencing 13 cultivable paired isolates demonstrated 11 reactivations and two reinfections. There was genomic similarity in 10 out of 13 pairs while one case (1/13; 8%) had 12 SNPS differences. Two other cases (2/13;15%) had > 200 SNPs differences and were classified as reinfection. No phenotypic or genomic evidence of drug resistance was observed. TB control programs can achieve consistently low rates of recurrent disease in low incidence settings. WGS of implicated isolates augments the differentiation between reactivation and reinfection and indicates that the majority of recurrences are due to reactivation rather than reinfection. Predominance of reactivation over reinfection indicates high-quality public health practices and a low risk of local transmission. This study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (HREC Ref: AU RED LNR/17/WMEAD/190; SSA Ref: LNR SSA/17/WMEAD/191).

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

PubMed

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

2017-03-01

Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Time-Critical Cooperative Path Following of Multiple UAVs: Case Studies

DTIC Science & Technology

2012-10-30

control algorithm for UAVs in 3D space. Section IV derives a strategy for time-critical cooperative path following of multiple UAVs that relies on the...UAVs in 3D space, in which a fleet of UAVs is tasked to converge to and follow a set of desired feasible paths so as to meet spatial and temporal...cooperative trajectory generation is not addressed in this paper. In fact, it is assumed that a set of desired 3D time trajectories pd,i(td) : R → R3

The medline UK filter: development and validation of a geographic search filter to retrieve research about the UK from OVID medline.

PubMed

Ayiku, Lynda; Levay, Paul; Hudson, Tom; Craven, Jenny; Barrett, Elizabeth; Finnegan, Amy; Adams, Rachel

2017-07-13

A validated geographic search filter for the retrieval of research about the United Kingdom (UK) from bibliographic databases had not previously been published. To develop and validate a geographic search filter to retrieve research about the UK from OVID medline with high recall and precision. Three gold standard sets of references were generated using the relative recall method. The sets contained references to studies about the UK which had informed National Institute for Health and Care Excellence (NICE) guidance. The first and second sets were used to develop and refine the medline UK filter. The third set was used to validate the filter. Recall, precision and number-needed-to-read (NNR) were calculated using a case study. The validated medline UK filter demonstrated 87.6% relative recall against the third gold standard set. In the case study, the medline UK filter demonstrated 100% recall, 11.4% precision and a NNR of nine. A validated geographic search filter to retrieve research about the UK with high recall and precision has been developed. The medline UK filter can be applied to systematic literature searches in OVID medline for topics with a UK focus. © 2017 Crown copyright. Health Information and Libraries Journal © 2017 Health Libraries GroupThis article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

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.

The additional benefit of residual spraying and insecticide-treated curtains for dengue control over current best practice in Cuba: Evaluation of disease incidence in a cluster randomized trial in a low burden setting with intensive routine control

PubMed Central

Rosales, Julio Popa; Mirabal, Mayelin; Cabrera, Pedro; Fonseca, Viviana; Gómez Padrón, Tania; Pérez Menzies, Mirtha; Montada, Domingo; Van der Stuyft, Patrick

2017-01-01

Background Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC). Methodology/Principal findings Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function. Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32–0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96–1.40) and 1.25 (95%CI 1.03–1.50) and for dengue incidence RR of 1.43 (95%CI 1.08–1.90) and 0.96 (95%CI 0.72–1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14–7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02–1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00–1.04)). Conclusions Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn’t evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load. PMID:29117180

The additional benefit of residual spraying and insecticide-treated curtains for dengue control over current best practice in Cuba: Evaluation of disease incidence in a cluster randomized trial in a low burden setting with intensive routine control.

PubMed

Toledo, Maria Eugenia; Vanlerberghe, Veerle; Rosales, Julio Popa; Mirabal, Mayelin; Cabrera, Pedro; Fonseca, Viviana; Gómez Padrón, Tania; Pérez Menzies, Mirtha; Montada, Domingo; Van der Stuyft, Patrick

2017-11-01

Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC). Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function. Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32-0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96-1.40) and 1.25 (95%CI 1.03-1.50) and for dengue incidence RR of 1.43 (95%CI 1.08-1.90) and 0.96 (95%CI 0.72-1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14-7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02-1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00-1.04)). Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn't evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load.

Cone Beam Computed Tomography Analysis of Oropharyngeal Airway in Preadolescent Nonsyndromic Bilateral and Unilateral Cleft Lip and Palate Patients.

PubMed

Al-Fahdawi, Mahmood Abd; El-Kassaby, Marwa Abdelwahab; Farid, Mary Medhat; El-Fotouh, Mona Abou

2018-01-01

Objective The objective of this study was to assess the volume, area, and dimensions of the oropharyngeal airway (OPA) in a previously repaired nonsyndromic unilateral cleft lip and palate (UCLP) versus bilateral cleft lip and palate (BCLP) patients when compared with noncleft controls using cone beam computed tomography (CBCT). Design This was a retrospective case-control study. Setting The Cleft Care Center and outpatient clinic that are affiliated to our faculty were the settings for the study. Participants A total of 58 CBCT scans were selected of preadolescent individuals: 14 BCLP, 20 UCLP, and 24 age- and gender-matched noncleft controls. Variables Variables were volume, cross-sectional area (CSA), midsagittal area (MSA), and dimensions of OPA. Statistical analysis One-way analysis of variance and post hoc tests were used to compare variables. Statistical significance was set at P ≤ .05. Results UCLP showed significantly smaller superior oropharyngeal airway volume than both controls and BCLP ( P ≤ .05). BCLP showed significantly larger CSA at soft palate plane and significantly larger MSA than both UCLP and controls ( P < .05). Conclusions UCLP patients at the studied age and stage of previously repaired clefts have significantly less superior oropharyngeal airway volume than both controls and BCLP patients. This confirms that preadolescents with UCLP are at greater risk for superior oropharyngeal airway obstruction when compared with those BCLP and controls. Furthermore, BCLP patients showed significantly larger CSA at soft palate plane and MSA than both controls and UCLP patients. These variations in OPA characteristics of cleft patients can influence function in terms of respiration and vocalization.

Endovascular interventions for traumatic portal venous hemorrhage complicated by portal hypertension

PubMed Central

Sundarakumar, Dinesh Kumar; Smith, Crysela Mirta; Lopera, Jorge Enrique; Kogut, Matthew; Suri, Rajeev

2013-01-01

Life-threatening hemorrhage rarely occurs from the portal vein following blunt hepatic trauma. Traditionally, severe portal bleeding in this setting has been controlled by surgical techniques such as packing, ligation, and venorrhaphy. The presence of portal hypertension could potentially increase the amount of hemorrhage in the setting of blunt portal vein trauma making it more difficult to control. This case series describes the use of indirect carbon dioxide portography to identify portal hemorrhage. Furthermore, these cases illustrate attempted endovascular treatment utilizing a transjugular intrahepatic portosystemic shunt in one scenario and transmesocaval shunt coiling of a jejunal varix in the other. PMID:24179633

Improving the FLORIS wind plant model for compatibility with gradient-based optimization

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

Thomas, Jared J.; Gebraad, Pieter MO; Ning, Andrew

The FLORIS (FLOw Redirection and Induction in Steady-state) model, a parametric wind turbine wake model that predicts steady-state wake characteristics based on wind turbine position and yaw angle, was developed for optimization of control settings and turbine locations. This article provides details on changes made to the FLORIS model to make the model more suitable for gradient-based optimization. Changes to the FLORIS model were made to remove discontinuities and add curvature to regions of non-physical zero gradient. Exact gradients for the FLORIS model were obtained using algorithmic differentiation. A set of three case studies demonstrate that using exact gradients withmore » gradient-based optimization reduces the number of function calls by several orders of magnitude. The case studies also show that adding curvature improves convergence behavior, allowing gradient-based optimization algorithms used with the FLORIS model to more reliably find better solutions to wind farm optimization problems.« less

Optimal control problem for linear fractional-order systems, described by equations with Hadamard-type derivative

NASA Astrophysics Data System (ADS)

Postnov, Sergey

2017-11-01

Two kinds of optimal control problem are investigated for linear time-invariant fractional-order systems with lumped parameters which dynamics described by equations with Hadamard-type derivative: the problem of control with minimal norm and the problem of control with minimal time at given restriction on control norm. The problem setting with nonlocal initial conditions studied. Admissible controls allowed to be the p-integrable functions (p > 1) at half-interval. The optimal control problem studied by moment method. The correctness and solvability conditions for the corresponding moment problem are derived. For several special cases the optimal control problems stated are solved analytically. Some analogies pointed for results obtained with the results which are known for integer-order systems and fractional-order systems describing by equations with Caputo- and Riemann-Liouville-type derivatives.

The Clinical Interview Schedule-Revised (CIS-R)-Malay Version, Clinical Validation.

PubMed

Subramaniam, Kavitha; Krishnaswamy, Saroja; Jemain, Abdul Aziz; Hamid, Abdul; Patel, Vikram

2006-01-01

Use of instruments or questionnaires in different cultural settings without proper validation can result in inaccurate results. Issues like reliability, validity, feasibility and acceptability should be considered in the use of an instrument. The study aims to determine the usefulness of the CIS-R Malay version in detecting common mental health problems specifically to establish the validity. The CIS-R instrument (PROQSY* format) was translated through the back translation process into Malay. Inter rater reliability was established for raters who were medical students. Cases and controls for the study were psychiatric in patients, out patient and relatives or friends accompanying the patients to the clinic or visiting the inpatients. The Malay version of CIS-R was administered to all cases and controls. All cases and controls involved in the study were rated by psychiatrists for psychiatric morbidity using the SCID as a guideline. Specificity and sensitivity of the CIS-R to the assessment by the psychiatrist were determined. The Malay version of CIS-R showed 100% sensitivity and 96.15% specificity at a cut off score of 9. The CIS-R can be a useful instrument for clinical and research use in the Malaysian population for diagnosing common mental disorders like depression and anxiety.

Do Instructional Videos on Sputum Submission Result in Increased Tuberculosis Case Detection? A Randomized Controlled Trial.

PubMed

Mhalu, Grace; Hella, Jerry; Doulla, Basra; Mhimbira, Francis; Mtutu, Hawa; Hiza, Helen; Sasamalo, Mohamed; Rutaihwa, Liliana; Rieder, Hans L; Seimon, Tamsyn; Mutayoba, Beatrice; Weiss, Mitchell G; Fenner, Lukas

2015-01-01

We examined the effect of an instructional video about the production of diagnostic sputum on case detection of tuberculosis (TB), and evaluated the acceptance of the video. Randomized controlled trial. We prepared a culturally adapted instructional video for sputum submission. We analyzed 200 presumptive TB cases coughing for more than two weeks who attended the outpatient department of the governmental Municipal Hospital in Mwananyamala (Dar es Salaam, Tanzania). They were randomly assigned to either receive instructions on sputum submission using the video before submission (intervention group, n = 100) or standard of care (control group, n = 100). Sputum samples were examined for volume, quality and presence of acid-fast bacilli by experienced laboratory technicians blinded to study groups. Median age was 39.1 years (interquartile range 37.0-50.0); 94 (47%) were females, 106 (53%) were males, and 49 (24.5%) were HIV-infected. We found that the instructional video intervention was associated with detection of a higher proportion of microscopically confirmed cases (56%, 95% confidence interval [95% CI] 45.7-65.9%, sputum smear positive patients in the intervention group versus 23%, 95% CI 15.2-32.5%, in the control group, p <0.0001), an increase in volume of specimen defined as a volume ≥3ml (78%, 95% CI 68.6-85.7%, versus 45%, 95% CI 35.0-55.3%, p <0.0001), and specimens less likely to be salivary (14%, 95% CI 7.9-22.4%, versus 39%, 95% CI 29.4-49.3%, p = 0.0001). Older age, but not the HIV status or sex, modified the effectiveness of the intervention by improving it positively. When asked how well the video instructions were understood, the majority of patients in the intervention group reported to have understood the video instructions well (97%). Most of the patients thought the video would be useful in the cultural setting of Tanzania (92%). Sputum submission instructional videos increased the yield of tuberculosis cases through better quality of sputum samples. If confirmed in larger studies, instructional videos may have a substantial effect on the case yield using sputum microscopy and also molecular tests. This low-cost strategy should be considered as part of the efforts to control TB in resource-limited settings. Pan African Clinical Trials Registry PACTR201504001098231.

Computational Test Cases for a Clipped Delta Wing with Pitching and Trailing-Edge Control Surface Oscillations

NASA Technical Reports Server (NTRS)

Bennett, Robert M.; Walker, Charlotte E.

1999-01-01

Computational test cases have been selected from the data set for a clipped delta wing with a six-percent-thick circular-arc airfoil section that was tested in the NASA Langley Transonic Dynamics Tunnel. The test cases include parametric variation of static angle of attack, pitching oscillation frequency, trailing-edge control surface oscillation frequency, and Mach numbers from subsonic to low supersonic values. Tables and plots of the measured pressures are presented for each case. This report provides an early release of test cases that have been proposed for a document that supplements the cases presented in AGARD Report 702.

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

PubMed Central

Chen, Yi-Hsuan; Lu, Ru-Band; Hung, Hung; Kuo, Po-Hsiu

2014-01-01

Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV) is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05). Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions. PMID:27605030

Simpson's Paradox: A Data Set and Discrimination Case Study Exercise

ERIC Educational Resources Information Center

Taylor, Stanley A.; Mickel, Amy E.

2014-01-01

In this article, we present a data set and case study exercise that can be used by educators to teach a range of statistical concepts including Simpson's paradox. The data set and case study are based on a real-life scenario where there was a claim of discrimination based on ethnicity. The exercise highlights the importance of performing…

Infection prevention and control in home nursing: case study of four organisations in Australia.

PubMed

Felemban, Ohood; St John, Winsome; Shaban, Ramon Zenel

2015-09-01

The aim of this case study was to explore the environmental challenges nurses experience with infection control practice, and the strategies they use to overcome those challenges. An exploratory case study was conducted in four home visiting nursing organisations in southeast Queensland, Australia, using data triangulation (document review, individual interviews, and focus groups). Data were analysed using a framework approach to identify themes. Three major infection prevention and control challenges were experienced in the community context. The first challenge is the nature of the work environment, including: poor cleanliness in clients' home environments, pets or vermin, inadequate hand-washing facilities, and a lack of appropriate storage space for clinical materials. The second challenge occurs when nurses lack access to appropriate infection control equipment, including wound-management materials and sharps containers. The third challenge is dealing with clients' poor personal hygiene and health status. Participants addressed these issues by offering assistance, using clean surfaces at clients' homes, applying an alcohol-based hand rub, providing client education, and reducing the cost of purchasing equipment for clients. It is imperative that policy is developed to support nurses' decision making and practices as they address infection control challenges in the community environment. Ensuring staff are well-supported with resources, education, policy, and guidelines to address these challenges is important for the delivery of safe and high-quality care in community settings.

Meta-analysis of the Association Between Variants in SORL1 and Alzheimer Disease

PubMed Central

Reitz, Christiane; Cheng, Rong; Rogaeva, Ekaterina; Lee, Joseph H.; Tokuhiro, Shinya; Zou, Fanggeng; Bettens, Karolien; Sleegers, Kristel; Tan, Eng King; Kimura, Ryo; Shibata, Nobuto; Arai, Heii; Kamboh, M. Ilyas; Prince, Jonathan A.; Maier, Wolfgang; Riemenschneider, Matthias; Owen, Michael; Harold, Denise; Hollingworth, Paul; Cellini, Elena; Sorbi, Sandro; Nacmias, Benedetta; Takeda, Masatoshi; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Younkin, Steven; Williams, Julie; van Broeckhoven, Christine; Farrer, Lindsay A.; St George–Hyslop, Peter H.; Mayeux, Richard

2011-01-01

Objective To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD). Design Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies. Setting Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy. Participants All published white and Asian case-control data sets, which included a total of 12 464 cases and 17 929 controls. Main Outcome Measures Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (now known as the Alzheimer’s Association). Results In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P<.001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P<.001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated with AD risk (P<.001). The disease-associated alleles at SNPs 8, 9, and 10 (120 873 131-120 886 175 base pairs [bp]; C-G-C alleles), at SNP 19 (120 953 300 bp; G allele), and at SNPs 24 through 25 (120 988 611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the human brain. Conclusion This comprehensive meta-analysis provides confirmatory evidence that multiple SORL1 variants in distinct linkage disequilibrium blocks are associated with AD. PMID:21220680

Teaching surgical skills using video internet communication in a resource-limited setting.

PubMed

Autry, Amy M; Knight, Sharon; Lester, Felicia; Dubowitz, Gerald; Byamugisha, Josaphat; Nsubuga, Yosam; Muyingo, Mark; Korn, Abner

2013-07-01

To study the feasibility and acceptability of using video Internet communication to teach and evaluate surgical skills in a low-resource setting. This case-controlled study used video Internet communication for surgical skills teaching and evaluation. We randomized intern physicians rotating in the Obstetrics and Gynecology Department at Mulago Hospital at Makerere University in Kampala, Uganda, to the control arm (usual practice) or intervention arm (three video teaching sessions with University of California, San Francisco faculty). We made preintervention and postintervention videos of all interns tying knots using a small video camera and uploaded the files to a file hosting service that offers cloud storage. A blinded faculty member graded all of the videos. Both groups completed a survey at the end of the study. We randomized 18 interns with complete data for eight in the intervention group and seven in the control group. We found score improvement of 50% or more in six of eight (75%) interns in the intervention group compared with one of seven (14%) in the control group (P=.04). Scores declined in five of the seven (71%) controls but in none in the intervention group. Both intervention and control groups used attendings, colleagues, and the Internet as sources for learning about knot-tying. The control group was less likely to practice knot-tying than the intervention group. The trainees and the instructors felt this method of training was enjoyable and helpful. Remote teaching in low-resource settings, where faculty time is limited and access to visiting faculty is sporadic, is feasible, effective, and well-accepted by both learner and teacher. II.

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: multinational case-control study in Europe

PubMed Central

Dieleman, Jeanne; Romio, Silvana; Johansen, Kari; Weibel, Daniel; Bonhoeffer, Jan

2011-01-01

Objective To assess the association between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. Design Case-control study. Setting Five European countries. Participants 104 patients with Guillain-Barré syndrome and its variant Miller-Fisher syndrome matched to one or more controls. Case status was classified according to the Brighton Collaboration definition. Controls were matched to cases on age, sex, index date, and country. Main outcome measures Relative risk estimate for Guillain-Barré syndrome after pandemic influenza vaccine. Results Case recruitment and vaccine coverage varied considerably between countries; the most common vaccines used were adjuvanted (Pandemrix and Focetria). The unadjusted pooled risk estimate for all countries was 2.8 (95% confidence interval 1.3 to 6.0). After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome (adjusted odds ratio 1.0, 0.3 to 2.7). The 95% confidence interval shows that the absolute effect of vaccination could range from one avoided case of Guillain-Barré syndrome up to three excess cases within six weeks after vaccination in one million people. Conclusions The risk of occurrence of Guillain-Barré syndrome is not increased after pandemic influenza vaccine, although the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people. When assessing the association between pandemic influenza vaccines and Guillain-Barré syndrome it is important to account for the effects of influenza-like illness/upper respiratory tract infection, seasonal influenza vaccination, and calendar time. PMID:21750072

Spatial-temporal epidemiology of human Salmonella Enteritidis infections with major phage types (PTs 1, 4, 5b, 8, 13, and 13a) in Ontario, Canada, 2008-2009.

PubMed

Varga, Csaba; Pearl, David L; McEwen, Scott A; Sargeant, Jan M; Pollari, Frank; Guerin, Michele T

2015-12-17

In Ontario and Canada, the incidence of human Salmonella enterica serotype Enteritidis (S. Enteritidis) infections have increased steadily during the last decade. Our study evaluated the spatial and temporal epidemiology of the major phage types (PTs) of S. Enteritidis infections to aid public health practitioners design effective prevention and control programs. Data on S. Enteritidis infections between January 1, 2008 and December 31, 2009 were obtained from Ontario's disease surveillance system. Salmonella Enteritidis infections with major phage types were classified by their annual health region-level incidence rates (IRs), monthly IRs, clinical symptoms, and exposure settings. A scan statistic was employed to detect retrospective phage type-specific spatial, temporal, and space-time clusters of S. Enteritidis infections. Space-time cluster cases' exposure settings were evaluated to identify common exposures. 1,336 cases were available for analysis. The six most frequently reported S. Enteritidis PTs were 8 (n = 398), 13a (n = 218), 13 (n = 198), 1 (n = 132), 5b (n = 83), and 4 (n = 76). Reported rates of S. Enteritidis infections with major phage types varied by health region and month. International travel and unknown exposure settings were the most frequently reported settings for PT 5b, 4, and 1 cases, whereas unknown exposure setting, private home, food premise, and international travel were the most frequently reported settings for PT 8, 13, and 13a cases. Diarrhea, abdominal pain, and fever were the most commonly reported clinical symptoms. A number of phage type-specific spatial, temporal, and space-time clusters were identified. Space-time clusters of PTs 1, 4, and 5b occurred mainly during the winter and spring months in the North West, North East, Eastern, Central East, and Central West regions. Space-time clusters of PTs 13 and 13a occurred at different times of the year in the Toronto region. Space-time clusters of PT 8 occurred at different times of the year in the North West and South West regions. Phage type-specific differences in exposure settings, and spatial-temporal clustering of S. Enteritidis infections were demonstrated that might guide public health surveillance of disease outbreaks. Our study methodology could be applied to other foodborne disease surveillance data to detect retrospective high disease rate clusters, which could aid public health authorities in developing effective prevention and control programs.

Spatio-Temporal Analysis of Smear-Positive Tuberculosis in the Sidama Zone, Southern Ethiopia

PubMed Central

Dangisso, Mesay Hailu; Datiko, Daniel Gemechu; Lindtjørn, Bernt

2015-01-01

Background Tuberculosis (TB) is a disease of public health concern, with a varying distribution across settings depending on socio-economic status, HIV burden, availability and performance of the health system. Ethiopia is a country with a high burden of TB, with regional variations in TB case notification rates (CNRs). However, TB program reports are often compiled and reported at higher administrative units that do not show the burden at lower units, so there is limited information about the spatial distribution of the disease. We therefore aim to assess the spatial distribution and presence of the spatio-temporal clustering of the disease in different geographic settings over 10 years in the Sidama Zone in southern Ethiopia. Methods A retrospective space–time and spatial analysis were carried out at the kebele level (the lowest administrative unit within a district) to identify spatial and space-time clusters of smear-positive pulmonary TB (PTB). Scan statistics, Global Moran’s I, and Getis and Ordi (Gi*) statistics were all used to help analyze the spatial distribution and clusters of the disease across settings. Results A total of 22,545 smear-positive PTB cases notified over 10 years were used for spatial analysis. In a purely spatial analysis, we identified the most likely cluster of smear-positive PTB in 192 kebeles in eight districts (RR= 2, p<0.001), with 12,155 observed and 8,668 expected cases. The Gi* statistic also identified the clusters in the same areas, and the spatial clusters showed stability in most areas in each year during the study period. The space-time analysis also detected the most likely cluster in 193 kebeles in the same eight districts (RR= 1.92, p<0.001), with 7,584 observed and 4,738 expected cases in 2003-2012. Conclusion The study found variations in CNRs and significant spatio-temporal clusters of smear-positive PTB in the Sidama Zone. The findings can be used to guide TB control programs to devise effective TB control strategies for the geographic areas characterized by the highest CNRs. Further studies are required to understand the factors associated with clustering based on individual level locations and investigation of cases. PMID:26030162

The addition of a regional block team to the orthopedic operating rooms does not improve anesthesia-controlled times and turnover time in the setting of long turnover times.

PubMed

Eappen, Sunil; Flanagan, Hugh; Lithman, Rachel; Bhattacharyya, Neil

2007-03-01

To determine whether a regional block team with a dedicated space for performance of regional anesthetics would decrease turnover time and shorten the working day in a busy orthopedic practice with lengthy turnover times. Prospective, randomized study. Tertiary-care teaching hospital. 927 orthopedic procedures over a three-month period. The randomized placement of a regional block team to the orthopedic operating room (OR) suite. We evaluated the differences in anesthesia-controlled times, first-case start times, turnover times, and OR end times using a computerized OR information system. We also surveyed the surgeons regarding their perceptions of changes in turnover time and anesthesia-controlled times during the study period. Standard descriptive statistics were computed. Of a total of 927 cases, 398 cases were cared for by a regional block team and 529 cases received care in the usual manner, with the OR team providing the regional block. There was no difference between the study and control groups for on-time, first-case starts (57.73% vs 42.27%), induction time (13.2 vs 14.2 min), emergence time (8.1 vs 9.0 min), turnover time (70.3 vs 77.8 min), and OR end times. Most of the surgeons surveyed felt that the regional block team reduced turnover time significantly. A regional block team in this environment does not reduce anesthesia-controlled times and turnover times in an orthopedic OR suite with long turnover times, and it would be virtually impossible to recover the associated extra cost. The surgeons' perspective of turnover time is inaccurate.

Outbreak of Escherichia coli 0157:H7 related to animal contact at a petting zoo

PubMed Central

Warshawsky, Bryna; Gutmanis, Iris; Henry, Bonnie; Dow, Joanne; Reffle, Jim; Pollett, Graham; Ahmed, Rafiq; Aldom, John; Alves, David; Chagla, Abdul; Ciebin, Bruce; Kolbe, Faron; Jamieson, Frances; Rodgers, Frank

2002-01-01

OBJECTIVE: To determine the cause of an outbreak of Escherichia coli 0157:H7 related to animal exposures so that further transmission could be prevented. DESIGN: Description of laboratory investigations and a case control study. SETTING: Agricultural pavilion at an annual fair in Ontario. POPULATION: People with laboratory evidence of E coli 0157:H7 (seven people) and others with diarrhea (155 people) who called the health unit following a media release were interviewed. Animals that were accessed most frequently by the public in the agriculture pavilion were tested for E coli 0157:H7. In the case control study, a case was defined as someone with laboratory confirmed E coli 0157:H7, or someone who developed severe or bloody diarrhea two to eight days after attending the agricultural pavilion at the fair (61 people). A convenience sample of people who attended the agricultural pavilion but did not develop diarrhea was selected as the control group (89 people). INTERVENTIONS: Human and animal E coli 0157:H7 specimens were subtyped. Cases and controls were interviewed using a standardized questionnaire. RESULTS: Subtyping of the seven human isolates of E coli 0157:H7 revealed five that were of an extremely uncommon phage type. Three samples from goats and one from sheep at the petting zoo in the agricultural pavilion were of this same phage type. The case control study also implicated goats (odds ratio [OR] 3.65; 95% CI 1.63 to 8.52) and sheep (OR 2.94; 95% CI 1.33 to 6.57) from the petting zoo. CONCLUSIONS: Results of this investigation suggest strongly that the goats and sheep from the petting zoo were the source of this outbreak of E coli 0157:H7. PMID:18159389

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.

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.

Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder

PubMed Central

Curtin, Paul; Curtin, Austen; Gennings, Chris; Arora, Manish; Siper, Paige; Meyering, Kristin; Kolevzon, Alexander; Mollon, Josephine; Zammit, Stanley; Wright, Robert O.; Reichenberg, Abraham

2018-01-01

Metals are critical to neurodevelopment, and dysregulation in early life has been documented in autism spectrum disorder (ASD). However, underlying mechanisms and biochemical assays to distinguish ASD cases from controls remain elusive. In a nationwide study of twins in Sweden, we tested whether zinc-copper cycles, which regulate metal metabolism, are disrupted in ASD. Using novel tooth-matrix biomarkers that provide direct measures of fetal elemental uptake, we developed a predictive model to distinguish participants who would be diagnosed with ASD in childhood from those who did not develop the disorder. We replicated our findings in three independent studies in the United States and the UK. We show that three quantifiable characteristics of fetal and postnatal zinc-copper rhythmicity are altered in ASD: the average duration of zinc-copper cycles, regularity with which the cycles recur, and the number of complex features within a cycle. In all independent study sets and in the pooled analysis, zinc-copper rhythmicity was disrupted in ASD cases. In contrast to controls, in ASD cases, the cycle duration was shorter (F = 52.25, P < 0.001), regularity was reduced (F = 47.99, P < 0.001), and complexity diminished (F = 57.30, P < 0.001). With two distinct classification models that used metal rhythmicity data, we achieved 90% accuracy in classifying cases and controls, with sensitivity to ASD diagnosis ranging from 85 to 100% and specificity ranging from 90 to 100%. These findings suggest that altered zinc-copper rhythmicity precedes the emergence of ASD, and quantitative biochemical measures of metal rhythmicity distinguish ASD cases from controls. PMID:29854952

Comparison of the population excess fraction of Chlamydia trachomatis infection on pelvic inflammatory disease at 12-months in the presence and absence of chlamydia testing and treatment: Systematic review and retrospective cohort analysis

PubMed Central

Turner, Katy M. E.; Leung, Stella; Yu, B. Nancy; Frølund, Maria; Benfield, Thomas; Blanchard, James; Westh, Henrik; Ward, Helen

2017-01-01

Background The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. Methods We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. Results The systematic review identified a single study, a randomised controlled trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15–10.75); Denmark: 3.84%(3.26–4.45); screened-arm POPI-RCT: 0.99%(0.00–29.06)). In the absence of active chlamydia treatment 26.44%(11.57–46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13–184 cases of PID per 100,000 tested women in the presence of testing and treatment. Conclusion Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women. PMID:28199392

The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility.

PubMed

Castaldi, Peter J; Cho, Michael H; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lomas, David A; Anderson, Wayne; Beaty, Terri H; Hokanson, John E; Crapo, James D; Laird, Nan; Silverman, Edwin K

2011-12-01

Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV(1) and FEV(1)/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate.

Estimating the Marginal Causal Effect of Fish Consumption during Adolescence on Multiple Sclerosis: A Population-Based Incident Case-Control Study.

PubMed

Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Sahraian, Mohammad Ali; Kaufman, Jay S

2018-01-01

Adolescence is considered as a critical time period in multiple sclerosis (MS) etiology. Nonetheless, there are insufficient reports regarding the potential role of fresh and canned fish consumptions during adolescence in MS etiology. The authors investigated the association between fresh and canned fish consumptions and MS. This was a population-based incident case-control study conducted in Tehran. Cases (n = 547) identified from Iranian Multiple Sclerosis Society between August 7, 2013, and November 17, 2015 were included in the study. Population-based controls (n = 1,057) were recruited by random digit telephone dialing without any matching. Inverse-probability-of-treatment weighing (IPTW) using 2 sets of propensity scores and model-based standardization were used to separately estimate the marginal odds ratio between fresh and canned fish consumptions in adolescence and MS. The marginal OR for fresh fish was 0.72 (95% CI 0.58-0.90; p = 0.005) in both IPTW analyses. Similarly, the marginal OR for canned fish consumption was 0.75 (95% CI 0.60-0.95; p = 0.014).The model-based standardized OR was 0.72 (95% CI 0.58-0.91; p = 0.008) for fresh and 0.73 (95% CI 0.59-0.94; p = 0.006) for canned fish consumption in adolescence. Subject to limitation of case-control studies in interpreting associations causally, this study suggests that both fresh and canned fish consumptions in adolescence can decrease the risk of MS. © 2018 S. Karger AG, Basel.

Travel health preparation and travel-related morbidity of splenectomised individuals.

PubMed

Boeddha, Christien; de Graaf, Wilmar; Overbosch, David; van Genderen, Perry J J

2012-07-01

Asplenic or hyposplenic patients are at an increased risk of encapsulated bacterial and intraerythrocytic parasitic infections, which are endemic at many travel destinations. With proper travel health advice and preparation splenectomised individuals could have comparable travel-related morbidity as healthy control subjects. We conducted a prospective case-control study with 21 travel pairs. Each pair consisted of a splenectomised patient (case) and a healthy, non-splenectomised travel companion (control) in order to match for travel destination, duration and potential exposures to travel-related health risks. All participants filled out a questionnaire detailing travel health preparation including vaccination and malaria prophylaxis as well as travel-related morbidity. Cases and controls were comparable for age and gender. Cases received significantly more information about on demand use of antibiotics in case of fever. Immunisation coverage against encapsulated bacteria and adherence to malaria prophylaxis guidelines was suboptimal. There were no significant differences in the occurrence of travel-related ailments nor differences in severity of ailments. The immunisation coverage against encapsulated bacteria and adherence to malaria prophylaxis guidelines was suboptimal in some splenectomised patients and should be improved. Strict adherence to national travel health advice guidelines and specific guidelines for asplenic patients is advisable. However, with regard to travel-related morbidity there are no significant differences in morbidity between splenectomised patients and healthy controls, at least in the setting of short-term travel. Copyright © 2012 Elsevier Ltd. All rights reserved.

Primary health care utilization prior to suicide: a retrospective case-control study among active-duty military personnel.

PubMed

Hochman, Eldar; Shelef, Leah; Mann, J John; Portugese, Shirly; Krivoy, Amir; Shoval, Gal; Weiser, Mark; Fruchter, Eyal

2014-08-01

About 45% of civilians who died by suicide had contact with a doctor within 1 month of death. Thus, educating primary care physicians (PCP) to detect and mitigate depression is an important suicide-prevention strategy. However, the PCP consulting rate before suicide has not been examined in a military population. We investigated the utilization of primary health care and mental health services by active-duty military personnel suicide cases prior to death in comparison to matched military controls. All suicides (N = 170) were extracted from a cohort of all active-duty Israeli military male personnel between 2002 and 2012. Applying a retrospective, nested case-control design, we compared primary care services utilization by suicide cases with demographic and occupationally matched military controls (N = 500). Whereas 38.3% of suicide cases contacted a PCP within the last month before death, only 27.6% of suicide cases contacted a mental health specialist during their entire service time. The PCP contact rate within 1 month before death or index day did not differ between suicide cases and military controls (38.3% vs. 33.8%, χ²₁ = 1.05, P = .3). More suicide cases contacted a mental health specialist within service time than did military controls (27.6% vs. 13.6%, χ²₁ = 10.85, P = .001). Even though PCP contact rate by military personnel who died by suicide is slightly lower than that reported for civilians who died by suicide prior to their death, it is higher than mental health specialist contact rate and higher than that by age-matched civilians who died by suicide. These results imply that PCPs education is a viable approach to suicide prevention in a military setting. © Copyright 2014 Physicians Postgraduate Press, Inc.

Outbreak of legionnaires' disease from a cooling water system in a power station.

PubMed

Morton, S; Bartlett, C L; Bibby, L F; Hutchinson, D N; Dyer, J V; Dennis, P J

1986-09-01

In September and October 1981 six cases of pneumonia occurred among men working in a power station under construction. Three were identified as cases of legionella pneumonia and two others had serology suggestive of legionella infection. In a sample of 92 men from the site 10 had low levels of antibodies to legionella; a similar sample of men working on an adjacent site showed none with positive serology. In a case control study it was found that cases of pneumonia were more likely than controls to have worked on a part of the site where four small capacity cooling towers were located. Legionella pneumophila serogroup 1 was isolated from the water systems of these four towers but was not found in samples from any other cooling towers or hot or cold water outlets on the site. It would appear that there was airborne spread of the organism from these cooling water systems which had not received conventional treatment to inhibit corrosion and organic growth. This is the first outbreak of legionnaires' disease to be recorded in an industrial setting in the United Kingdom. No cases of legionella infection have occurred on the site since the introduction of control measures.

A brief intervention to improve exercising in patients with schizophrenia: a controlled pilot study with mental contrasting and implementation intentions (MCII).

PubMed

Sailer, Pascal; Wieber, Frank; Pröpster, Karl; Stoewer, Steffen; Nischk, Daniel; Volk, Franz; Odenwald, Michael

2015-09-03

Regular exercise can have positive effects on both the physical and mental health of individuals with schizophrenia. However, deficits in cognition, perception, affect, and volition make it especially difficult for people with schizophrenia to plan and follow through with their exercising intentions, as indicated by poor attendance and high drop-out rates in prior studies. Mental Contrasting and Implementation Intentions (MCII) is a well-established strategy to support the enactment of intended actions. This pilot study tests whether MCII helps people with schizophrenia in highly structured or autonomy-focused clinical hospital settings to translate their exercising intentions into action. Thirty-six inpatients (eleven women) with a mean age of 30.89 years (SD = 11.41) diagnosed with schizophrenia spectrum disorders from specialized highly structured or autonomy-focused wards were randomly assigned to two intervention groups. In the equal contact goal intention control condition, patients read an informative text about physical activity; they then set and wrote down the goal to attend jogging sessions. In the MCII experimental condition, patients read the same informative text and then worked through the MCII strategy. We hypothesized that MCII would increase attendance and persistence relative to the control condition over the course of four weeks and this will be especially be the case when applied in an autonomy-focused setting compared to when applied in a highly structured setting. When applied in autonomy-focused settings, MCII increased attendance and persistence in jogging group sessions relative to the control condition. In the highly structured setting, no differences between conditions were found, most likely due to a ceiling effect. These results remained even when adjusting for group differences in the pre-intervention scores for the control variables depression (BDI), physical activity (IPAQ), weight (BMI), age, and education. Whereas commitment and physical activity apart from the jogging sessions remained stable over the course of the treatment, depression and negative symptoms were reduced. There were no differences in pre-post treatment changes between intervention groups. The intervention in the present study provides initial support for the hypothesis that MCII helps patients to translate their exercising intentions into real-life behavior even in autonomously-focused settings without social control. ClinicalTrials.gov ID; URL: NCT01547026 Registered 3 March 2012.

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.

Risk Factors Associated with MDR-TB at the Onset of Therapy among New Cases Registered with the RNTCP in Mumbai, India

PubMed Central

Atre, Sachin R.; D’Souza, Desiree T. B.; Vira, Tina S.; Chatterjee, Anirvan; Mistry, Nerges F.

2014-01-01

Background Multidrug-resistant TB (MDR-TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high-burden countries, including India. In hyper-endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR-TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. Objective To assess risk factors associated with MDR-TB among Category I, new sputum smear-positive cases, at the onset of therapy. Materials and Methods The study applied an unmatched case-control design for 514 patients (106 cases with MDR-TB strains and 408 controls with non-MDR-TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004-January 2007. Data were collected through semi-structured interviews and drug susceptibility test results. Results Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12-8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02-2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. Conclusion The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited. PMID:21727675

[Community outbreak of hepatitis A in a marginal population. Vaccination for its control and acceptance of the measure].

PubMed

Arce Arnáez, Araceli; Cabello Ballesteros, Luisa; Iñigo Martínez, Jesús

2007-03-01

To study a community outbreak of hepatitis A in a marginal population and the public health response in order to bring it under control. Descriptive study of the outbreak that occurred in February-June, 2004. An epidemiological survey was conducted to detect prior cases and active vigilance was set up. Case and susceptibility definitions were established. A gypsy population in Madrid, Spain. They had basic provision of sewerage, water supply and waste disposal. A population of 550 in census; estimated population, 800. 70% were under 40 and 55% were illiterate. Control measures were: a) health education activities to strengthen habits of hygiene, and b) immunisation of susceptible individuals. A total of 646 people were vaccinated, with the active help of staff from the Institute of Rehousing and Integration into Society. The outbreak affected 26 people, with an average age of 8 (95% CI, 6.2-9.8), similar distribution by sex and 3.3% attack rate. Fourteen cases were students at state schools, not all in the same classes. There were 7 pairs of siblings among the cases. The diagnosis was conformed by serology in 17 cases. Five needed hospital admission. The epidemic curve suggested person-person transmission. All those affected were under 20 years old. Vaccination was seen to be effective in controlling the outbreak. Interventions were assisted by intermediaries in order to respect the gypsies' cultural context and were well accepted.

MCP1 SNPs and Pulmonary Tuberculosis in Cohorts from West Africa, the USA and Argentina: Lack of Association or Epistasis with IL12B Polymorphisms

PubMed Central

Velez Edwards, Digna R.; Tacconelli, Alessandra; Wejse, Christian; Hill, Philip C.; Morris, Gerard A. J.; Edwards, Todd L.; Gilbert, John R.; Myers, Jamie L.; Park, Yo Son; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Rabna, Paulo; Novelli, Giuseppe; Hamilton, Carol D.; Adegbola, Richard; Østergaard, Lars; Williams, Scott M.; Scott, William K.; Sirugo, Giorgio

2012-01-01

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (−2581A/G), rs2857656 (−362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility. PMID:22384203

An In-Law Comes To Stay: Examination of Interdisciplinary Conflict in a School-Based Health Center.

ERIC Educational Resources Information Center

Fast, Jonathan D.

2003-01-01

Social workers often work in settings where other professions exert a higher level of control. The organizational literature on causes of conflict and conflict resolution is briefly reviewed. A case study of a newly opened school-based health center provides an opportunity to analyze conflicts between the school and health center personnel and…

Mobile Learning: Two Case Studies of Supporting Inquiry Learning in Informal and Semiformal Settings

ERIC Educational Resources Information Center

Jones, Ann C.; Scanlon, Eileen; Clough, Gill

2013-01-01

Mobile technologies can support learning across different contexts as their portability enables them to be used by the learner in whichever context she or he is in. They can be particularly beneficial in informal and semiformal contexts where learners have more control over their learning goals and where motivation is often high. Inquiries in…

Multiple Loci With Different Cancer Specificities Within the 8q24 Gene Desert

PubMed Central

Song, Honglin; Koessler, Thibaud; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Driver, Kristy E.; Pooley, Karen A.; Ramus, Susan J.; Kjaer, Susanne Krüger; Hogdall, Estrid; DiCioccio, Richard A.; Whittemore, Alice S.; Gayther, Simon A.; Giles, Graham G.; Guy, Michelle; Edwards, Stephen M.; Morrison, Jonathan; Donovan, Jenny L.; Hamdy, Freddie C.; Dearnaley, David P.; Ardern-Jones, Audrey T.; Hall, Amanda L.; O'Brien, Lynne T.; Gehr-Swain, Beatrice N.; Wilkinson, Rosemary A.; Brown, Paul M.; Hopper, John L.; Neal, David E.; Pharoah, Paul D. P.; Ponder, Bruce A. J.; Eeles, Rosalind A.; Easton, Douglas F.; Dunning, Alison M.

2008-01-01

Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case–control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region. PMID:18577746

Risk factors associated with sporadic salmonellosis in adults: a case-control study.

PubMed

Ziehm, D; Dreesman, J; Campe, A; Kreienbrock, L; Pulz, M

2013-02-01

In order to identify and assess recent risk factors for sporadic human infections with Salmonella enterica, we conducted a case-control study in Lower Saxony, Germany. The data collection was based on standardized telephone interviews with 1017 cases and 346 controls aged >14 years. Odds ratios were calculated in single-factor and multi-factor analyses for Salmonella cases and two different control groups, i.e. population controls and controls with rotavirus infection. Multi-factor analysis revealed associations between sporadic Salmonella infections for two exposures by both sets of controls: consumption of raw ground pork [adjusted odds ratio (aOR) 2·38, 95% confidence interval (CI) 1·27-4·44] and foreign travel (aOR 2·12, 95% CI 1·00-4·52). Other exposures included consumption of food items containing eggs (aOR 1·43, 95% CI 0·80-2·54), consumption of chicken meat (aOR 1·77, 95% CI 1·26-2·50), outdoor meals/barbecues (aOR 3·96, 95% CI 1·41-11·12) and taking gastric acidity inhibitors (aOR 2·42, 95% CI 1·19-4·92), all were significantly associated with respect to one of the two control groups. The impact of consuming food items containing eggs or chicken meat was lower than expected from the literature. This might be a consequence of Salmonella control programmes as well as increased public awareness of eggs and chicken products being a risk factor for salmonellosis. Efforts to reduce Salmonella infections due to raw pork products should be intensified.

The burden of acute respiratory infections in crisis-affected populations: a systematic review

PubMed Central

2010-01-01

Crises due to armed conflict, forced displacement and natural disasters result in excess morbidity and mortality due to infectious diseases. Historically, acute respiratory infections (ARIs) have received relatively little attention in the humanitarian sector. We performed a systematic review to generate evidence on the burden of ARI in crises, and inform prioritisation of relief interventions. We identified 36 studies published since 1980 reporting data on the burden (incidence, prevalence, proportional morbidity or mortality, case-fatality, attributable mortality rate) of ARI, as defined by the International Classification of Diseases, version 10 and as diagnosed by a clinician, in populations who at the time of the study were affected by natural disasters, armed conflict, forced displacement, and nutritional emergencies. We described studies and stratified data by age group, but did not do pooled analyses due to heterogeneity in case definitions. The published evidence, mainly from refugee camps and surveillance or patient record review studies, suggests very high excess morbidity and mortality (20-35% proportional mortality) and case-fatality (up to 30-35%) due to ARI. However, ARI disease burden comparisons with non-crisis settings are difficult because of non-comparability of data. Better epidemiological studies with clearer case definitions are needed to provide the evidence base for priority setting and programme impact assessments. Humanitarian agencies should include ARI prevention and control among infants, children and adults as priority activities in crises. Improved data collection, case management and vaccine strategies will help to reduce disease burden. PMID:20181220

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

PubMed

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

2016-02-01

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

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study.

PubMed

Schmidt, Axel J; Rockstroh, Jürgen K; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

2011-03-08

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.

The postural stability of children with foetal alcohol spectrum disorders during one-leg stance: A feasibility study

PubMed Central

2018-01-01

Background Postural control may be impaired in children with foetal alcohol spectrum disorders (FASD). The study assessed the protocol feasibility in terms of (1) recruiting children with FASD in a rural, small town; (2) using the measurement instruments in a real-life setting; (3) the one-leg standing (OLS) task and (4) presenting preliminary results on postural stability of children with and without FASD. Methods Nine-year-old children diagnosed with and without FASD were invited to participate. Twenty-eight children performed OLS. Feasibility outcomes included recruitment, measurement instrument use and task instruction. Postural stability outcomes included standing duration, centre of pressure (COP) and body segment acceleration. Results Participants recruitment was feasible in terms of the (1) ability to sample a reasonable participant number in a rural town setting and the capacity to increase the sample size if more schools are included in the sampling frame and (2) use of assent and consent forms that were appropriate for this population. The measurement instruments were user-friendly, cost-effective and time-efficient. Instructions for the task require amendment to address foot placement of the non-weight–bearing leg. There was a significant difference between cases and controls on mean COP velocity (p = 0.001) and the pelvis segment acceleration in the mediolateral direction (p = 0.01) and the anteroposterior direction (p = 0.027). The control children took longer to achieve postural control. The girls demonstrated a significant difference for the COP anteroposterior displacement (p = 0.008) and velocity (p = 0.049). Conclusions The recruitment of children with and without FASD in a rural, small town and the administration of measurement instruments in a real-life, school-based setting was feasible. However, the verbal instructions for the task require revision. The male control group took longer to achieve postural control because the task was performed differently between the two groups. However, the case girls were slower to achieve postural control than control girls though performing the task similarly. PMID:29707515

Optimising UAV topographic surveys processed with structure-from-motion: Ground control quality, quantity and bundle adjustment

NASA Astrophysics Data System (ADS)

James, M. R.; Robson, S.; d'Oleire-Oltmanns, S.; Niethammer, U.

2017-03-01

Structure-from-motion (SfM) algorithms greatly facilitate the production of detailed topographic models from photographs collected using unmanned aerial vehicles (UAVs). However, the survey quality achieved in published geomorphological studies is highly variable, and sufficient processing details are never provided to understand fully the causes of variability. To address this, we show how survey quality and consistency can be improved through a deeper consideration of the underlying photogrammetric methods. We demonstrate the sensitivity of digital elevation models (DEMs) to processing settings that have not been discussed in the geomorphological literature, yet are a critical part of survey georeferencing, and are responsible for balancing the contributions of tie and control points. We provide a Monte Carlo approach to enable geomorphologists to (1) carefully consider sources of survey error and hence increase the accuracy of SfM-based DEMs and (2) minimise the associated field effort by robust determination of suitable lower-density deployments of ground control. By identifying appropriate processing settings and highlighting photogrammetric issues such as over-parameterisation during camera self-calibration, processing artefacts are reduced and the spatial variability of error minimised. We demonstrate such DEM improvements with a commonly-used SfM-based software (PhotoScan), which we augment with semi-automated and automated identification of ground control points (GCPs) in images, and apply to two contrasting case studies - an erosion gully survey (Taroudant, Morocco) and an active landslide survey (Super-Sauze, France). In the gully survey, refined processing settings eliminated step-like artefacts of up to 50 mm in amplitude, and overall DEM variability with GCP selection improved from 37 to 16 mm. In the much more challenging landslide case study, our processing halved planimetric error to 0.1 m, effectively doubling the frequency at which changes in landslide velocity could be detected. In both case studies, the Monte Carlo approach provided a robust demonstration that field effort could by substantially reduced by only deploying approximately half the number of GCPs, with minimal effect on the survey quality. To reduce processing artefacts and promote confidence in SfM-based geomorphological surveys, published results should include processing details which include the image residuals for both tie points and GCPs, and ensure that these are considered appropriately within the workflow.

Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes

PubMed Central

Malki, K; Pain, O; Tosto, M G; Du Rietz, E; Carboni, L; Schalkwyk, L C

2015-01-01

Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case–control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix's HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis. PMID:25734512

Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma

PubMed Central

Chang, Ellen T.; Ambinder, Richard F.; Lennette, Evelyne T.; Rubertone, Mark V.; Mann, Risa B.; Borowitz, Michael; Weir, Edward G.; Abbondanzo, Susan L.; Mueller, Nancy E.

2012-01-01

An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma. PMID:22972983

Fuzzy-Set Case Studies

ERIC Educational Resources Information Center

Mikkelsen, Kim Sass

2017-01-01

Contemporary case studies rely on verbal arguments and set theory to build or evaluate theoretical claims. While existing procedures excel in the use of qualitative information (information about kind), they ignore quantitative information (information about degree) at central points of the analysis. Effectively, contemporary case studies rely on…

Timing control system

NASA Technical Reports Server (NTRS)

Wiker, Gordon A. (Inventor); Wells, Jr., George H. (Inventor)

1989-01-01

A timing control system is disclosed which is particularly useful in connection with simulated mortar shells. Special circuitry is provided to assure that the shell does not overshoot, but rather detonates early in case of an improper condition; this ensures that ground personnel will not be harmed by a delayed detonation. The system responds to an externally applied frequency control code which is configured to avoid any confusion between different control modes. A premature detonation routine is entered in case an improper time-setting signal is entered, or if the shell is launched before completion of the time-setting sequence. Special provisions are also made for very early launch situations and improper detonator connections. An alternate abort mode is provided to discharge the internal power supply without a detonation in a manner that can be externally monitored, thereby providing a mechanism for non-destructive testing. The abort mode also accelerates the timing function for rapid testing.

Timing Control System

NASA Technical Reports Server (NTRS)

Wiker, Gordon A. (Inventor); Wells, George H., Jr. (Inventor)

1987-01-01

A timing control system is disclosed which is particularly useful in connection with simulated mortar shells. Special circuitry is provided to assure that the shell does not over shoot, but rather detonates early in case of an improper condition; this ensures that ground personnel will not be harmed by a delayed detonation. The system responds to an externally applied frequency control code which is configured to avoid any confusion between different control modes. A premature detonation routine is entered in case an improper time-setting signal is entered, or if the shell is launched before completion of the time-setting sequence. Special provisions are also made for very early launch situations and improper detonator connections. An alternate abort mode is provided to discharge the internal power supply without a detonation in a manner that can be externally monitored, thereby providing a mechanism for non-destructive testing. The abort mode also accelerates the timing function for rapid testing.

Risk Prediction for Epithelial Ovarian Cancer in 11 United States–Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci

PubMed Central

Clyde, Merlise A.; Palmieri Weber, Rachel; Iversen, Edwin S.; Poole, Elizabeth M.; Doherty, Jennifer A.; Goodman, Marc T.; Ness, Roberta B.; Risch, Harvey A.; Rossing, Mary Anne; Terry, Kathryn L.; Wentzensen, Nicolas; Whittemore, Alice S.; Anton-Culver, Hoda; Bandera, Elisa V.; Berchuck, Andrew; Carney, Michael E.; Cramer, Daniel W.; Cunningham, Julie M.; Cushing-Haugen, Kara L.; Edwards, Robert P.; Fridley, Brooke L.; Goode, Ellen L.; Lurie, Galina; McGuire, Valerie; Modugno, Francesmary; Moysich, Kirsten B.; Olson, Sara H.; Pearce, Celeste Leigh; Pike, Malcolm C.; Rothstein, Joseph H.; Sellers, Thomas A.; Sieh, Weiva; Stram, Daniel; Thompson, Pamela J.; Vierkant, Robert A.; Wicklund, Kristine G.; Wu, Anna H.; Ziogas, Argyrios; Tworoger, Shelley S.; Schildkraut, Joellen M.

2016-01-01

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted. PMID:27698005

Sexual and gender-based violence in areas of armed conflict: a systematic review of mental health and psychosocial support interventions

PubMed Central

2013-01-01

Background Sexual and other forms of gender-based violence are common in conflict settings and are known risk factors for mental health and psychosocial wellbeing. We present findings from a systematic review of the academic and grey literature focused on the effectiveness of mental health and psychosocial support interventions for populations exposed to sexual and other forms of gender-based violence in the context of armed conflicts. Methods We searched the Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PubMed/ Medline, psycINFO, and PILOTS, as well as grey literature to search for evaluations of interventions, without date limitations. Results Out of 5,684 returned records 189 full text papers were assessed for eligibility. Seven studies met inclusion criteria: 1 non-randomized controlled study; 3 non-controlled pre- post-test designs; 1 retrospective cohort with a matched comparison group; and 2 case studies. Studies were conducted in West and Central Africa; Albania; UK and USA, included female participants, and focused on individual and group counseling; combined psychological, medical, social and economic interventions; and cognitive behavioral therapy (two single case studies). Conclusions The seven studies, while very limited, tentatively suggest beneficial effects of mental health and psychosocial interventions for this population, and show feasibility of evaluation and implementation of such interventions in real-life settings through partnerships with humanitarian organizations. Robust conclusions on the effectiveness of particular approaches are not possible on the basis of current evidence. More rigorous research is urgently needed. PMID:23915821

Vitamin D deficiency in first episode psychosis: a case-control study.

PubMed

Crews, Matthieu; Lally, John; Gardner-Sood, Poonam; Howes, Oliver; Bonaccorso, Stefania; Smith, Shubulade; Murray, Robin M; Di Forti, Marta; Gaughran, Fiona

2013-11-01

Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP). We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis. Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827). We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies. © 2013 Elsevier B.V. All rights reserved.

Investigation of Metabolomic Blood Biomarkers for Detection of Adenocarcinoma Lung Cancer

PubMed Central

Fahrmann, Johannes F.; Kim, Kyoungmi; DeFelice, Brian C.; Taylor, Sandra L.; Gandara, David R.; Yoneda, Ken Y.; Cooke, David T.; Fiehn, Oliver; Kelly, Karen; Miyamoto, Suzanne

2015-01-01

Background Untargeted metabolomics was utilized in case control studies of adenocarcinoma (ADC) lung cancer in order to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer. Methods Serum and plasma were collected and used in two independent case-control studies (ADC1 and ADC2). Controls were frequency matched for gender, age and smoking history. There were 52 ADC cases and 31 controls in ADC1 and 43 ADC cases and 43 controls in ADC2. Metabolomics was conducted using gas chromatography time-of-flight mass spectrometry. Differential analysis was performed on ADC1 and the top candidates (FDR < 0.05) for serum and plasma used to develop individual and multiplex-classifiers that were then tested on an independent set of serum and plasma samples (ADC2). Results Aspartate provided the best accuracy (81.4%) for an individual metabolite classifier in serum whereas pyrophosphate had the best accuracy (77.9%) in plasma when independently tested. Multiplex classifiers of either 2 or 4 serum metabolites had an accuracy of 72.7% when independently tested. For plasma, a multi-metabolite classifier consisting of 8 metabolites gave an accuracy of 77.3% when independently tested. Comparison of overall diagnostic performance between the two blood matrices yielded similar performances. However, serum is most ideal given higher sensitivity for low abundant metabolites. Conclusion This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted. Impact These biomarkers could improve early detection and diagnosis of lung cancer. PMID:26282632

Risk factors for syphilis infection among pregnant women: results of a case‐control study in Shenzhen, China

PubMed Central

Zhou, Hua; Chen, Xiang‐Sheng; Hong, Fu‐Chang; Pan, Peng; Yang, Fan; Cai, Yu‐Mao; Yin, Yue‐Ping; Peeling, Rosanna W; Mabey, David

2007-01-01

Background China has been experiencing a rapidly growing syphilis epidemic since the early 1990s, with the reported incidence of congenital syphilis increasing from 0.01 cases per 100 000 live births in 1991 to 19.7 cases per 100 000 live births in 2005. Detailed studies of risk factors for syphilis in pregnant women are needed to inform new preventive interventions. Objective To investigate factors associated with recent syphilis infection among pregnant women and recommend strategies for improved preventive interventions in the community. Methods A case–control study was conducted among women attending antenatal clinics in Shenzhen City, South China. Cases were antenatal clinic women testing positive for early syphilis, based on laboratory results, with those testing negative being controls. All participants completed the same anonymous questionnaire covering demographics, lifestyle, sexual behaviour, and sexual partnerships. Results 129 cases and 345 controls were recruited. Syphilis was significantly associated with unmarried status, less education, multiple sex partners, travel of sex partner in the past 12 months, a history of induced abortion, and previous sexually transmitted infections. Overall, there were no differences between syphilis‐positive and negative women in household registration status (hukou), living district and duration in Shenzhen, monthly income, and age at first sex. Conclusions Many demographic and behavioural risk factors are associated with syphilis among pregnant women. In the government congenital syphilis control programme, comprehensive preventive interventions should be provided in all clinical settings in addition to the current procedures for syphilis screening among antenatal women. PMID:17675391

Emulating RRTMG Radiation with Deep Neural Networks for the Accelerated Model for Climate and Energy

NASA Astrophysics Data System (ADS)

Pal, A.; Norman, M. R.

2017-12-01

The RRTMG radiation scheme in the Accelerated Model for Climate and Energy Multi-scale Model Framework (ACME-MMF), is a bottleneck and consumes approximately 50% of the computational time. To simulate a case using RRTMG radiation scheme in ACME-MMF with high throughput and high resolution will therefore require a speed-up of this calculation while retaining physical fidelity. In this study, RRTMG radiation is emulated with Deep Neural Networks (DNNs). The first step towards this goal is to run a case with ACME-MMF and generate input data sets for the DNNs. A principal component analysis of these input data sets are carried out. Artificial data sets are created using the previous data sets to cover a wider space. These artificial data sets are used in a standalone RRTMG radiation scheme to generate outputs in a cost effective manner. These input-output pairs are used to train multiple architectures DNNs(1). Another DNN(2) is trained using the inputs to predict the error. A reverse emulation is trained to map the output to input. An error controlled code is developed with the two DNNs (1 and 2) and will determine when/if the original parameterization needs to be used.

Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT)

PubMed Central

Kern, Elizabeth O; Erhard, Penny; Sun, Wanjie; Genuth, Saul; Weiss, Miriam F

2010-01-01

Background Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in type 1 diabetes. Study Design Nested case:control of participants in the Diabetes Control and Complications Trial (DCCT) Setting & Participants Eighty-seven cases of microalbuminuria were matched to 174 controls in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio, resulting in 91 cases and 178 controls for microalbuminuria. Fifty-five cases of macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free of micro/macroalbuminuria when their matching case first developed micro/macroalbuminuria. Predictors Urinary N-acetyl-β-D-glucosaminidase, pentosidine, AGE fluorescence, albumin excretion rate (AER) Outcomes Incident microalbuminuria (two consecutive annual AER > 40 but <= 300 mg/day), or macroalbuminuria (AER > 300 mg/day) Measurements Stored urine samples from DCCT entry, and 1–9 years later when macroalbuminuria or microalbuminuria occurred, were measured for the lysosomal enzyme, N-acetyl-β-D-glucosaminidase, and the advanced glycosylation end-products (AGEs) pentosidine and AGE-fluorescence. AER and adjustor variables were obtained from the DCCT. Results Sub-microalbuminuric levels of AER at baseline independently predicted microalbuminuria (adjusted OR 1.83; p<.001) and macroalbuminuria (adjusted OR 1.82; p<.001). Baseline N-acetyl-β-D-glucosaminidase independently predicted macroalbuminuria (adjusted OR 2.26; p<.001), and microalbuminuria (adjusted OR 1.86; p<.001). Baseline pentosidine predicted macroalbuminuria (adjusted OR 6.89; p=.002). Baseline AGE fluorescence predicted microalbuminuria (adjusted OR 1.68; p=.02). However, adjusted for N-acetyl-β-D-glucosaminidase, pentosidine and AGE-fluorescence lost predictive association with macroalbuminuria and microalbuminuria, respectively. Limitations Use of angiotensin converting-enzyme inhibitors was not directly ascertained, although their use was proscribed during the DCCT. Conclusions Early in type 1 diabetes, repeated measurements of AER and urinary NAG may identify individuals susceptible to future diabetic nephropathy. Combining the two markers may yield a better predictive model than either one alone. Renal tubule stress may be more severe, reflecting abnormal renal tubule processing of AGE-modified proteins, among individuals susceptible to diabetic nephropathy. PMID:20138413

Risk factors for acute asthma in tropical America: a case-control study in the City of Esmeraldas, Ecuador.

PubMed

Ardura-Garcia, Cristina; Vaca, Maritza; Oviedo, Gisela; Sandoval, Carlos; Workman, Lisa; Schuyler, Alexander J; Perzanowski, Matthew S; Platts-Mills, Thomas A E; Cooper, Philip J

2015-08-01

Despite the high asthma rates described in Latin America, asthma risk factors in poor urban settings are not well established. We investigated risk factors for acute asthma among Ecuadorian children. A matched case-control study was carried out in a public hospital serving a coastal city. Children with acute asthma were age- and sex-matched to non-asthmatics. A questionnaire was administered, and blood, as well as stool, and nasopharyngeal swabs were collected. Sixty cases and 119 controls aged 5-15 were evaluated. High proportions of cases were atopic with population-attributable fractions for atopy of 68.5% for sIgE and 57.2% for SPT. Acute asthma risk increased with greater titers of mite IgE (3.51-50 kU/l vs. <0.70kU/l - OR 4.56, 95% CI 1.48-14.06, p = 0.008; >50kU/l vs. <0.70kU/l - OR 41.98, 95% CI: 8.97-196.39, p < 0.001). Asthma risk was significantly independently associated with bronchiolitis (adj. OR: 38.9, 95% CI 3.26-465), parental educational level (adj. OR 1.26, 95% CI: 1.08-1.46), and presence of sIgE (adj. OR: 36.7, 95% CI: 4.00-337), while a reduced risk was associated with current contact with pets (adj. OR: 0.07, 95% CI: 0.01-0.56). Rhinovirus infection was more frequent in cases (cases 35.6% vs. controls 7.8%, p = 0.002). None of the cases were on maintenance therapy with inhaled corticosteroids and most relied on emergency department for control. A high proportion of children presenting to a public hospital with acute asthma were allergic to mite, particularly at high IgE titer. Poor asthma control resulted in overuse of emergency care. © 2015 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.

Reengagement in PTSD psychotherapy: A case-control study.

PubMed

Buchholz, Katherine R; Bohnert, Kipling M; Pfeiffer, Paul N; Valenstein, Marcia; Ganoczy, Dara; Anderson, RaeAnn E; Sripada, Rebecca K

2017-09-01

This study sought to identify patient characteristics and care processes related to reengagement in VA psychotherapy. Using national VA data, a retrospective cohort was constructed (N=24,492) of veterans who received a new PTSD diagnosis in FY08/FY09 and attended only one to five PTSD psychotherapy sessions. A nested case-control study was conducted comparing veterans who reengaged in psychotherapy (n=9649) in a 1:5 ratio with those who did not reengage by the end of FY12. Conditional logistic regression models were run to examine differences in sociodemographic, mental health, and service utilization factors between cases and controls. Among veterans in the study cohort, 39.4% reengaged in psychotherapy. In adjusted analyses, all measured types of health system encounters (primary care [OR=1.61], primary care mental health [OR=1.61], non-PTSD psychotherapy [OR=1.76], other non-PTSD mental health care [OR=1.43], other non-psychotherapy PTSD care [OR=3.31], emergency room [OR=1.14], and psychiatric hospitalization [OR=1.56]) were related to greater odds of reengagement in PTSD psychotherapy. Veterans' receipt of a broad range of care services may play an important role in reengagement in PCT psychotherapy, suggesting providers across care settings should be knowledgeable in how to support a Veteran's return to psychotherapy for PTSD. Published by Elsevier Inc.

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

PubMed Central

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

2014-01-01

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

Understanding enrolment in community health insurance in sub-Saharan Africa: a population-based case-control study in rural Burkina Faso.

PubMed Central

De Allegri, Manuela; Kouyaté, Bocar; Becher, Heiko; Gbangou, Adjima; Pokhrel, Subhash; Sanon, Mamadou; Sauerborn, Rainer

2006-01-01

OBJECTIVE: To identify factors associated with decision to enrol in a community health insurance (CHI) scheme. METHODS: We conducted a population-based case-control study among 15 communities offered insurance in 2004 in rural Burkina Faso. For inclusion in the study, we selected all 154 enrolled (cases) and a random sample of 393 non-enrolled (controls) households. We used unconditional logistic regression (applying Huber-White correction to account for clustering at the community level) to explore the association between enrolment status and a set of household head, household and community characteristics. FINDINGS: Multivariate analysis revealed that enrolment in CHI was associated with Bwaba ethnicity, higher education, higher socioeconomic status, a negative perception of the adequacy of traditional care, a higher proportion of children living within the household, greater distance from the health facility, and a lower level of socioeconomic inequality within the community, but not with household health status or previous household health service utilization. CONCLUSION: Our study provides evidence that the decision to enrol in CHI is shaped by a combination of household head, household, and community factors. Policies aimed at enhancing enrolment ought to act at all three levels. On the basis of our findings, we discuss specific policy recommendations and highlight areas for further research. PMID:17143458

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

NASA Astrophysics Data System (ADS)

Alexander, Janice; Lee, Christopher A.

2010-09-01

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks.

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

PubMed Central

Alexander, Janice

2010-01-01

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks. PMID:20559634

Preventing Community-wide Transmission of Cryptosporidium: A Proactive Public Health Response to a Swimming Pool–Associated Outbreak — Auglaize County, Ohio, USA

PubMed Central

Cope, J.R.; Prosser, A.; Nowicki, S.; Roberts, M.W.; Scheer, D.; Anderson, C.; Longsworth, A.; Parsons, C.; Goldschmidt, D.; Johnston, S.; Bishop, H.; Xiao, L.; Hill, V.; Beach, M.; Hlavsa, M.C.

2015-01-01

Summary The incidence of recreational water–associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues, (e.g., pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g., child care facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to Pool A. Within 5 days of the first case being reported, Pool A was hyperchlorinated to achieve 99.9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in Pool A (matched odds ratio 121.7, 95% confidence interval 27.4–∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak. PMID:25907106

Child Behavior Check List 1 1/2-5 as a Tool to Identify Toddlers with Autism Spectrum Disorders: A Case-Control Study

ERIC Educational Resources Information Center

Narzisi, Antonio; Calderoni, Sara; Maestro, Sandra; Calugi, Simona; Mottes, Emanuela; Muratori, Filippo

2013-01-01

Tools to identify toddlers with autism in clinical settings have been recently developed. This study evaluated the sensitivity and specificity of the Child Behavior Check List 1 1/2-5 (CBCL 1 1/2-5) in the detection of toddlers subsequently diagnosed with an Autism Spectrum Disorder (ASD), ages 18-36 months. The CBCL of 47 children with ASD were…

Actuator placement for active sound and vibration control of cylinders

NASA Technical Reports Server (NTRS)

Kincaid, Rex K.

1995-01-01

Active structural acoustic control is a method in which the control inputs (used to reduce interior noise) are applied directly to a vibrating structural acoustic system. The control concept modeled in this work is the application of in-plane force inputs to piezoceramic patches bonded to the wall of a vibrating cylinder. The cylinder is excited by an exterior noise source -- an acoustic monopole -- located near the outside of the cylinder wall. The goal is to determine the force inputs and sites for the piezoelectric actuators so that (1) the interior noise is effectively damped; (2) the level of vibration of the cylinder shell is not increased; and (3) the power requirements needed to drive the actuators are not excessive. We studied external monopole excitations at two frequencies. A cylinder resonance of 100 Hz, where the interior acoustic field is driven in multiple, off-resonance cylinder cavity modes, and a cylinder resonance of 200 Hz are characterized by both near and off-resonance cylinder vibration modes which couple effectively with a single, dominant, low-order acoustic cavity mode at resonance. Previous work has focused almost exclusively on meeting objective (1) and solving a complex least-squares problem to arrive at an optimal force vector for a given set of actuator sites. In addition, it has been noted that when the cavity mode couples with cylinder vibration modes (our 200 Hz case) control spillover may occur in higher order cylinder shell vibrational modes. How to determine the best set of actuator sites to meet objectives (1)-(3) is the main contribution of our research effort. The selection of the best set of actuator sites from a set of potential sites is done via two metaheuristics -- simulated annealing and tabu search. Each of these metaheuristics partitions the set of potential actuator sites into two disjoint sets: those that are selected to control the noise (on) and those that are not (off). Next, each metaheuristic attempts to improve this initial solution by calculating the change in the objective value when one selected actuator site is turned off and one actuator site that previously was not selected is turned on. All such pairwise exchanges are performed and the exchange that improves the objective the most is made. Eventually the search is unable to improve the objective value and a local optimum (with respect to pairwise exchanges) is reached. Both simulated annealing and tabu search provide mechanisms to escape local optima and allow the search to continue until (hopefully) a global optimum is found. Our experiments with the 100 Hz and 200 Hz cases confirm that both metaheuristics are able to uncover better solutions than those selected based upon engineering judgement alone. In addition, the high quality solutions generated by these metaheuristics, when minimizing interior noise, do not further excite the cylinder shell. Thus, we are able to meet objective (2) without imposing an additional constraint or forming a multiobjective performance measure. An additional observation is that in many cases the amplitude and phase values for several chosen actuator sites were nearly identical. This natural grouping means that fewer control channels are needed and the resulting control system is simpler. Currently no power requirements have been set, so objective (3) cannot be addressed. A set of experiments is planned with a laboratory test article (a cylinder). For these experiments the transfer matrices will be generated experimentally. It is hoped that the predicted performance of the best actuator sites found by our metaheuristics will correlate well with the measured performance.

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.

Factors associated with negative histamine control for penicillin allergy skin testing in the inpatient setting.

PubMed

Geng, Bob; Thakor, Ami; Clayton, Elisabeth; Finkas, Lindsay; Riedl, Marc A

2015-07-01

Identification of factors adversely affecting the utility of allergy skin testing is important in optimizing patient care. Inpatient penicillin skin test data from 1997 through 2007 demonstrate that up to 20% of attempted penicillin skin tests are indeterminate owing to a negative histamine test response, despite exclusion of H1 antagonists. Critical illness, vasopressors, steroid use, and psychotropic medications have been postulated to influence outcomes, but large studies are lacking. To identify factors associated with a negative histamine test response for the inpatient setting. Fifty-two cases were identified with a negative histamine response after penicillin skin testing in the absence of antihistamine therapy for 72 hours before testing. One hundred twenty-five controls with a normal histamine response were randomly selected from same population. Independent variables assessed included stay in the intensive care unit (ICU), skin color, diabetes, age, use of vasopressors, H2 blocker, steroids, other immunosuppressive drugs, thyroid replacement, proton pump inhibitors, diuretics, 5 categories of psychotropic medications, and amiodarone. Mean age was 68 years for cases vs 60 years for controls (P = .002). Bivariate analysis showed ICU stay was more frequent in cases than in controls (73.1% vs 33.6%, P < .001). Regression analysis yielded odds ratios (ORs) of 8.18 (95% confidence interval 3.22-20.76) for ICU status, 3.76 (1.30-10.92) for systemic corticosteroids, and 4.90 (1.17-20.62) for H2 blockers as associated with lack of histamine response. For every additional year in age, there was increase in the OR of 1.04 (1.01-1.07). Regression analysis supports ICU stay during skin testing as associated with a high OR for a negative histamine response independent of age. Systemic corticosteroids, H2 blockers, and older age are associated with a significant OR for a negative histamine response. This is one of largest studies on factors associated with a negative histamine response for the inpatient setting and has significant implications for clinical practice. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Missing heritability in the tails of quantitative traits? A simulation study on the impact of slightly altered true genetic models.

PubMed

Pütter, Carolin; Pechlivanis, Sonali; Nöthen, Markus M; Jöckel, Karl-Heinz; Wichmann, Heinz-Erich; Scherag, André

2011-01-01

Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in a bimodal mixture situation on the power to detect associations. We performed simulations of quantitative phenotypes analysed by standard linear regression and dichotomized case-control data sets from the extremes of the quantitative trait analysed by standard logistic regression. Using linear regression, markers with an effect in the extremes of the traits were almost undetectable, whereas analysing extremes by case-control design had superior power even for much smaller sample sizes. Two real data examples are provided to support our theoretical findings and to explore our mixture and parameter assumption. Our findings support the idea to re-analyse the available meta-analysis data sets to detect new loci in the extremes. Moreover, our investigation offers an explanation for discrepant findings when analysing quantitative traits in the general population and in the extremes. Copyright © 2011 S. Karger AG, Basel.

Inhaled methoxyflurane for pain and anxiety relief during burn wound care procedures: an Australian case series.

PubMed

Wasiak, Jason; Mahar, Patrick D; Paul, Eldho; Menezes, Hana; Spinks, Anneliese B; Cleland, Heather

2014-02-01

Pain is a common and significant feature of burn injury. The use of intravenous opioids forms the mainstay of procedural burn pain management, but in an outpatient setting, the demand for novel agents that do not require parenteral access, are easy to administer and have a rapid onset are urgently needed. One such agent is the inhaled anaesthetic agent, methoxyflurane (MF). The aim of this study was to conduct a pilot investigation into the clinical effectiveness of MF inhaler on pain and anxiety scores in patients undergoing burn wound care procedures in an outpatient setting. A prospective case series involved recruiting patients undergoing a burn wound care procedure in an ambulatory burn care setting. Pain and anxiety were assessed using numerical rating scales. Overall, median numerical pain rating score was significantly higher post-dressing [pre-dressing: 2; interquartile range (IQR): 1-3 versus post-dressing: 3; IQR 1·5-4; P = 0·01], whereas median numerical anxiety score significantly reduced following the dressing (pre-dressing: 5; IQR 4-7 versus post-dressing: 2; IQR 1-2; P < 0·001). Our study suggests that there is a role for MF in the pain management armamentarium in those undergoing burn care procedures in the ambulatory care setting. However, there is an urgent need for larger case series and randomised controlled trials to determine its overall clinical effectiveness. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Adaptive use of research aircraft data sets for hurricane forecasts

NASA Astrophysics Data System (ADS)

Biswas, M. K.; Krishnamurti, T. N.

2008-02-01

This study uses an adaptive observational strategy for hurricane forecasting. It shows the impacts of Lidar Atmospheric Sensing Experiment (LASE) and dropsonde data sets from Convection and Moisture Experiment (CAMEX) field campaigns on hurricane track and intensity forecasts. The following cases are used in this study: Bonnie, Danielle and Georges of 1998 and Erin, Gabrielle and Humberto of 2001. A single model run for each storm is carried out using the Florida State University Global Spectral Model (FSUGSM) with the European Center for Medium Range Weather Forecasts (ECMWF) analysis as initial conditions, in addition to 50 other model runs where the analysis is randomly perturbed for each storm. The centers of maximum variance of the DLM heights are located from the forecast error variance fields at the 84-hr forecast. Back correlations are then performed using the centers of these maximum variances and the fields at the 36-hr forecast. The regions having the highest correlations in the vicinity of the hurricanes are indicative of regions from where the error growth emanates and suggests the need for additional observations. Data sets are next assimilated in those areas that contain high correlations. Forecasts are computed using the new initial conditions for the storm cases, and track and intensity skills are then examined with respect to the control forecast. The adaptive strategy is capable of identifying sensitive areas where additional observations can help in reducing the hurricane track forecast errors. A reduction of position error by approximately 52% for day 3 of forecast (averaged over 7 storm cases) over the control runs is observed. The intensity forecast shows only a slight positive impact due to the model’s coarse resolution.

The ethics of placebo-controlled trials: methodological justifications.

PubMed

Millum, Joseph; Grady, Christine

2013-11-01

The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling. © 2013.

Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14).

PubMed

Wainiqolo, Iris; Kafoa, Berlin; Kool, Bridget; Robinson, Elizabeth; Herman, Josephine; McCaig, Eddie; Ameratunga, Shanthi

2016-01-01

To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available. Data for this population-based case-control study were collected from drivers of 'case' vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and 'control' vehicles representative of 'driving time' in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk. Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90-11.63). The related population attributable risk was 18.37% (95% CI: 13.77-22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use. In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common.

Livelihood opportunities amongst adults with and without disabilities in Cameroon and India: A case control study

PubMed Central

Banks, Lena Morgon; Kuper, Hannah; Murthy, G. V. S.; Sagar, Jayanthi; Oye, Joseph; Polack, Sarah

2018-01-01

Proven links between disability and poverty suggest that development programmes and policies that are not disability-inclusive will leave persons with disabilities behind. Despite this, there is limited quantitative evidence on livelihood opportunities amongst adults with disabilities in Low and Middle Income Countries. This study adds to the limited evidence base, contributing data from one African and one Asian Setting. We undertook a population-based case–control study of adults (18+) with and without disabilities in North-West Cameroon and in Telangana State, India. We found that adults with disabilities were five times less likely to be working compared to age-sex matched controls in both settings. Amongst adults with disabilities, current age, marital status and disability type were key predictors of working. Inclusive programmes are therefore needed to provide adequate opportunities to participate in livelihood prospects for adults with disabilities in Cameroon and India, on an equal basis as others. These findings are of crucial importance at this stage of the Sustainable Development Agenda, to ensure that the mandate of inclusive development is achieved. PMID:29630606

Dextromethorphan Abuse in Adolescence

PubMed Central

Bryner, Jodi K.; Wang, Uerica K.; Hui, Jenny W.; Bedodo, Merilin; MacDougall, Conan; Anderson, Ilene B.

2008-01-01

Objectives To analyze the trend of dextromethorphan abuse in California and to compare these findings with national trends. Design A 6-year retrospective review. Setting California Poison Control System (CPCS), American Association of Poison Control Centers (AAPCC), and Drug Abuse Warning Network (DAWN) databases from January 1, 1999, to December 31, 2004. Participants All dextromethorphan abuse cases reported to the CPCS, AAPCC, and DAWN. The main exposures of dextromethorphan abuse cases included date of exposure, age, acute vs long-term use, coingestants, product formulation, and clinical outcome. Main Outcome Measure The annual proportion of dextromethorphan abuse cases among all exposures reported to the CPCS, AAPCC, and DAWN databases. Results A total of 1382 CPCS cases were included in the study. A 10-fold increase in CPCS dextromethorphan abuse cases from 1999 (0.23 cases per 1000 calls) to 2004 (2.15 cases per 1000 calls) (odds ratio, 1.48; 95% confidence interval, 1.43–1.54) was identified. Of all CPCS dextromethorphan abuse cases, 74.5% were aged 9 to 17 years; the frequency of cases among this age group increased more than 15-fold during the study (from 0.11 to 1.68 cases per 1000 calls). Similar trends were seen in the AAPCC and DAWN databases. The highest frequency of dextromethorphan abuse occurred among adolescents aged 15 and 16 years. The most commonly abused product was Coricidin HBP Cough & Cold Tablets. Conclusions Our study revealed an increasing trend of dextromethorphan abuse cases reported to the CPCS that is paralleled nationally as reported to the AAPCC and DAWN. This increase was most evident in the adolescent population. PMID:17146018

Personal hygiene and methicillin-resistant Staphylococcus aureus infection.

PubMed

Turabelidze, George; Lin, Mei; Wolkoff, Barbara; Dodson, Douglas; Gladbach, Stephen; Zhu, Bao-Ping

2006-03-01

Methicillin-resistant Staphylococcus aureus (MRSA) infections outside the healthcare setting are an increasing concern. We conducted a case-control study to investigate an MRSA outbreak during 2002-2003 in a Missouri prison and focused on hygiene factors. Information on sociodemographic characteristics, medical history, and hygiene practices of study participants was collected by interview and medical record review. Logistic regression was used to evaluate MRSA infection in relation to hygiene factors individually and as a composite hygiene score; potential confounding factors were controlled. Selected MRSA isolates were analyzed by pulsed-field gel electrophoresis (PFGE). MRSA infection was significantly associated with a low composite hygiene score. Transmission among prison inmates appeared to be responsible for this outbreak. PFGE analysis showed that isolates were indistinguishable and associated with community-onset MRSA infections in other US prisons. Improving hygiene practices and environmental conditions may help prevent and interrupt future MRSA outbreaks in prison settings.

Recurrence of tuberculosis among patients following treatment completion in eight provinces of Vietnam: a nested case-control study.

PubMed

Bestrashniy, Jessica Rutledge Bruce Musselman; Nguyen, Viet Nhung; Nguyen, Thi Loi; Pham, Thi Lieu; Nguyen, Thu Anh; Pham, Duc Cuong; Nghiem, Le Phuong Hoa; Le, Thi Ngoc Anh; Nguyen, Binh Hoa; Nguyen, Kim Cuong; Nguyen, Huy Dung; Buu, Tran Ngoc; Le, Thi Nhung; Nguyen, Viet Hung; Dinh, Ngoc Sy; Britton, Warwick John; Marks, Guy Barrington; Fox, Greg James

2018-06-23

Patients completing treatment for tuberculosis (TB) in high-prevalence settings face a risk of developing recurrent disease. This has important consequences for public health, given its association with drug resistance and a poor prognosis. Previous research has implicated individual factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug resistant disease as risk factors for recurrence. However, little is known about how these factors co-act to produce recurrent disease. Furthermore, perhaps factors related to the index disease means higher burden/low resource settings may be more prone to recurrent disease that could be preventable. We conducted a case-control study nested within a cohort of consecutively enrolled adults who were being treated for smear positive pulmonary TB in 70 randomly selected district clinics in Vietnam. Cases were patients with recurrent TB, identified by follow-up from the parent cohort study. Controls were selected from the cohort by random sampling. Information on demographic, clinical and disease-related characteristics was obtained by interview. information was extracted from clinic registries. Logistic regression, with stepwise selection, was used to develop a fully adjusted model for the odds of recurrence of TB. We recruited 10,964 patients between October 2010 and July 2013. Median follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with recurrence were identified as cases and 630 other patients were randomly selected as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB (adjusted odds ratio 79.6; 95% CI: 25.1-252.0), self-reported prior TB therapy (aOR=2.5; 95% CI: 1.7-3.5), and incomplete adherence (aOR=1.9; 95% CI 1.1-3.1). Index disease treatment history is a leading determinant of relapse among patients with TB in Vietnam. Further research is required to identify interventions that will reduce the risk of recurrent disease and enhance its early detection within high-risk populations. Copyright © 2018. Published by Elsevier Ltd.

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

Factors related to the development of health-promoting community activities in Spanish primary healthcare: two case–control studies

PubMed Central

March, Sebastià; Ripoll, Joana; Jordan Martin, Matilde; Zabaleta-del-Olmo, Edurne; Benedé Azagra, Carmen Belén; Elizalde Soto, Lázaro; Vidal, Mª Clara; Bauzà Amengual, María de Lluc; Planas Juan, Trinidad; Pérez Mariano, Damiana Maria; Llull Sarralde, Micaela; Ruiz-Giménez, Juan Luís; Bajo Viñas, Rosa; Solano Villarubia, Carmen; Rodriguez Bajo, Maria; Cordoba Victoria, Manuela; Badia Capdevila, Marta; Serrano Ferrandez, Elena; Bosom Diumenjo, Maria; Montaner-Gomis, Isabel; Bolibar-Ribas, Buenaventura; Antoñanzas Lombarte, Angel; Bregel Cotaina, Samantha; Calvo Tocado, Ana; Olivan Blázquez, Barbara; Magallon Botaya, Rosa; Marín Palacios, Pilar; Echauri Ozcoidi, Margarita; Perez - arauta, María Jose; Llobera, Joan; Ramos, Maria

2017-01-01

Objective Spanish primary healthcare teams have the responsibility of performing health-promoting community activities (CAs), although such activities are not widespread. Our aim was to identify the factors related to participation in those activities. Design Two case–control studies. Setting Performed in primary care of five Spanish regions. Subjects In the first study, cases were teams that performed health-promoting CAs and controls were those that did not. In the second study (on case teams from the first study), cases were professionals who developed these activities and controls were those who did not. Main outcome measures Team, professional and community characteristics collected through questionnaires (team managers/professionals) and from secondary sources. Results The first study examined 203 teams (103 cases, 100 controls). Adjusted factors associated with performing CAs were percentage of nurses (OR 1.07, 95% CI 1.01 to 1.14), community socioeconomic status (higher vs lower OR 2.16, 95% CI 1.18 to 3.95) and performing undergraduate training (OR 0.44, 95% CI 0.21 to 0.93). In the second study, 597 professionals responded (254 cases, 343 controls). Adjusted factors were professional classification (physicians do fewer activities than nurses and social workers do more), training in CAs (OR 1.9, 95% CI 1.2 to 3.1), team support (OR 2.9, 95% CI 1.5 to 5.7), seniority (OR 1.06, 95% CI 1.03 to 1.09), nursing tutor (OR 2.0, 95% CI 1.1 to 3.5), motivation (OR 3.7, 95% CI 1.8 to 7.5), collaboration with non-governmental organisations (OR 1.9, 95% CI 1.2 to 3.1) and participation in neighbourhood activities (OR 3.1, 95% CI 1.9 to 5.1). Conclusions Professional personal characteristics, such as social sensitivity, profession, to feel team support or motivation, have influence in performing health-promoting CAs. In contrast to the opinion expressed by many professionals, workload is not related to performance of health-promoting CAs. PMID:28993380

Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region

PubMed Central

Jun, Gyungah; Vardarajan, Badri N.; Buros, Jacqueline; Yu, Chang-En; Hawk, Michele V.; Dombroski, Beth A.; Crane, Paul K.; Larson, Eric B.; Mayeux, Richard; Haines, Jonathan L.; Lunetta, Kathryn L.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Farrer, Lindsay A.

2013-01-01

Objective To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523). Design Conditional logistic regression models and survival analysis. Setting Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium. Participants Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls. Main Outcome Measures Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls. Results In models adjusting for APOE ε4, no SNPs in the entire region were significantly associated with AAO at P<.001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of ε3/ε3 subjects. Conclusions APOE alleles ε2, ε3, and ε4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci. PMID:22869155

Advance Care Planning in an Accountable Care Organization Is Associated with Increased Advanced Directive Documentation and Decreased Costs

PubMed Central

Kim, Minchul; Franciskovich, Chris M.; Weinberg, Jason E.; Svendsen, Jessica D.; Fehr, Linda S.; Funk, Amy; Sawicki, Robert; Asche, Carl V.

2018-01-01

Abstract Background: Advance care planning (ACP) documents patient wishes and increases awareness of palliative care options. Objective: To study the association of outpatient ACP with advanced directive documentation, utilization, and costs of care. Design: This was a case–control study of cases with ACP who died matched 1:1 with controls. We used 12 months of data pre-ACP/prematch and predeath. We compared rates of documentation with logit model regression and conducted a difference-in-difference analysis using generalized linear models for utilization and costs. Setting/subjects: Medicare beneficiaries attributed to a large rural-suburban-small metro multisite accountable care organization from January 2013 to April 2016, with cross reference to ACP facilitator logs to find cases. Measurements: The presence of advance directive forms was verified by chart review. Cost analysis included all utilization and costs billed to Medicare. Results: We matched 325 cases and 325 controls (51.1% female and 48.9% male, mean age 81). 320/325 (98.5%) ACP versus 243/325 (74.8%) of controls had a Healthcare Power of Attorney (odds ratio [OR] 21.6, 95% CI 8.6–54.1) and 172/325(52.9%) ACP versus 145/325 (44.6%) controls had Practitioner Orders for Life Sustaining Treatment (OR 1.40, 95% CI 1.02–1.90) post-ACP/postmatch. Adjusted results showed ACP cases had fewer inpatient admissions (−0.37 admissions, 95% CI −0.66 to −0.08), and inpatient days (−3.66 days, 95% CI −6.23 to −1.09), with no differences in hospice, hospice days, skilled nursing facility use, home health use, 30-day readmissions, or emergency department visits. Adjusted costs were $9,500 lower in the ACP group (95% CI −$16,207 to −$2,793). Conclusions: ACP increases documentation and was associated with a reduction in overall costs driven primarily by a reduction in inpatient utilization. Our data set was limited by small numbers of minorities and cancer patients. PMID:29206564

Trihalomethanes in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter?

PubMed

Kuo, Hsin-Wei; Chen, Pei-Shih; Ho, Shu-Chen; Wang, Li-Yu; Yang, Chun-Yuh

2010-01-01

The objectives of this study were (1) to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of rectal cancer development and (2) to determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of TTHM on risk of developing rectal cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to rectal cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All rectal cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from the Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for rectal cancer occurrence was 1.04 (0.88-1.22) for individuals who resided in municipalities served by drinking water with a TTHM exposure >or=4.9 ppb. There was no evidence of an interaction of drinking-water TTHM levels with low Ca intake via drinking water. However, evidence of an interaction was noted between drinking-water TTHM concentrations and Mg intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of rectal cancer is influenced by Mg in drinking water. Increased knowledge of the interaction between Mg and TTHM in reducing rectal cancer risk will aid in public policymaking and standard setting.

Development and External Validation of a Melanoma Risk Prediction Model Based on Self-assessed Risk Factors.

PubMed

Vuong, Kylie; Armstrong, Bruce K; Weiderpass, Elisabete; Lund, Eiliv; Adami, Hans-Olov; Veierod, Marit B; Barrett, Jennifer H; Davies, John R; Bishop, D Timothy; Whiteman, David C; Olsen, Catherine M; Hopper, John L; Mann, Graham J; Cust, Anne E; McGeechan, Kevin

2016-08-01

Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates. A risk prediction model was developed using the Australian Melanoma Family Study (629 cases and 535 controls) and externally validated using 4 independent population-based studies: the Western Australia Melanoma Study (511 case-control pairs), Leeds Melanoma Case-Control Study (960 cases and 513 controls), Epigene-QSkin Study (44 544, of which 766 with melanoma), and Swedish Women's Lifestyle and Health Cohort Study (49 259 women, of which 273 had melanoma). We validated model performance internally and externally by assessing discrimination using the area under the receiver operating curve (AUC). Additionally, using the Swedish Women's Lifestyle and Health Cohort Study, we assessed model calibration and clinical usefulness. The risk prediction model included hair color, nevus density, first-degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use. On internal validation, the AUC was 0.70 (95% CI, 0.67-0.73). On external validation, the AUC was 0.66 (95% CI, 0.63-0.69) in the Western Australia Melanoma Study, 0.67 (95% CI, 0.65-0.70) in the Leeds Melanoma Case-Control Study, 0.64 (95% CI, 0.62-0.66) in the Epigene-QSkin Study, and 0.63 (95% CI, 0.60-0.67) in the Swedish Women's Lifestyle and Health Cohort Study. Model calibration showed close agreement between predicted and observed numbers of incident melanomas across all deciles of predicted risk. In the external validation setting, there was higher net benefit when using the risk prediction model to classify individuals as high risk compared with classifying all individuals as high risk. The melanoma risk prediction model performs well and may be useful in prevention interventions reliant on a risk assessment using self-assessed risk factors.

The global economic burden of dengue: a systematic analysis.

PubMed

Shepard, Donald S; Undurraga, Eduardo A; Halasa, Yara A; Stanaway, Jeffrey D

2016-08-01

Dengue is a serious global burden. Unreported and unrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue and current estimates of the incidence and costs of dengue have substantial uncertainty. Objective, systematic, comparable measures of dengue burden are needed to track health progress, assess the application and financing of emerging preventive and control strategies, and inform health policy. We estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries). We used the latest dengue incidence estimates from the Institute for Health Metrics and Evaluation's Global Burden of Disease Study 2013 and several other data sources to assess the economic burden of symptomatic dengue cases in the 141 countries and territories with active dengue transmission. From the scientific literature and regressions, we estimated cases and costs by setting, including the non-medical setting, for all countries and territories. Our global estimates suggest that in 2013 there were a total of 58·40 million symptomatic dengue virus infections (95% uncertainty interval [95% UI] 24 million-122 million), including 13 586 fatal cases (95% UI 4200-34 700), and that the total annual global cost of dengue illness was US$8·9 billion (95% UI 3·7 billion-19·7 billion). The global distribution of dengue cases is 18% admitted to hospital, 48% ambulatory, and 34% non-medical. The global cost of dengue is substantial and, if control strategies could reduce dengue appreciably, billions of dollars could be saved globally. In estimating dengue costs by country and setting, this study contributes to the needs of policy makers, donors, developers, and researchers for economic assessments of dengue interventions, particularly with the licensure of the first dengue vaccine and promising developments in other technologies. Sanofi Pasteur. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Effect of handoff skills training for students during the medicine clerkship: a quasi-randomized study.

PubMed

Reyes, Juan A; Greenberg, Larrie; Amdur, Richard; Gehring, James; Lesky, Linda G

2016-03-01

Continuity is critical for safe patient care and its absence is associated with adverse outcomes. Continuity requires handoffs between physicians, but most published studies of educational interventions to improve handoffs have focused primarily on residents, despite interns expected to being proficient. The AAMC core entrustable activities for graduating medical students includes handoffs as a milestone, but no controlled studies with students have assessed the impact of training in handoff skills. The purpose of this study was to assess the impact of an educational intervention to improve third-year medical student handoff skills, the durability of learned skills into the fourth year, and the transfer of skills from the simulated setting to the clinical environment. Trained evaluators used standardized patient cases and an observation tool to assess verbal handoff skills immediately post intervention and during the student's fourth-year acting internship. Students were also observed doing real time sign-outs during their acting internship. Evaluators assessed untrained control students using a standardized case and performing a real-time sign-out. Intervention students mean score demonstrated improvement in handoff skills immediately after the workshop (2.6-3.8; p < 0.0001) that persisted into their fourth year acting internship when compared to baseline performance (3.9-3.5; p = 0.06) and to untrained control students (3.5 vs. 2.5; p < 0.001, d = 1.2). Intervention students evaluated in the clinical setting also scored higher than control students when assessed doing real-time handoffs (3.8 vs. 3.3; p = 0.032, d = 0.71). These findings should be useful to others considering introducing handoff teaching in the undergraduate medical curriculum in preparation for post-graduate medical training. Trial Registration Number NCT02217241.

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.

Prototype ultra wideband-based wireless body area network--consideration of CAP and CFP slot allocation during human walking motion.

PubMed

Takei, Yuichiro; Katsuta, Hiroki; Takizawa, Kenichi; Ikegami, Tetsushi; Hamaguchi, Kiyoshi

2012-01-01

This paper presents an experimental evaluation of communication during human walking motion, using the medium access control (MAC) evaluation system for a prototype ultra-wideband (UWB) based wireless body area network for suitable MAC parameter settings for data transmission. Its physical layer and MAC specifications are based on the draft standard in IEEE802.15.6. This paper studies the effects of the number of retransmissions and the number of commands of GTS (guaranteed time slot) request packets in the CAP (contention access period) during human walking motion by varying the number of sensor nodes or the number of CFP (contention free period) slots in the superframe. The experiments were performed in an anechoic chamber. The number of packets received is decreased by packet loss caused by human walking motion in the case where 2 slots are set for CFP, regardless of the number of nodes, and this materially decreases the total number of packets received. The number of retransmissions and the GTS request commands increase according to increases in the number of nodes, largely reflecting the effects of the number of CFP slots in the case where 4 nodes are attached. In the cases where 2 or 3 nodes are attached and 4 slots are set for CFP, the packet transmission rate is more than 95%. In the case where 4 nodes are attached and 6 slots are set for CFP, the packet transmission rate is reduced to 88% at best.

New class of control laws for robotic manipulators. I - Nonadaptive case. II - Adaptive case

NASA Technical Reports Server (NTRS)

Wen, John T.; Bayard, David S.

1988-01-01

A new class of exponentially stabilizing control laws for joint level control of robot arms is discussed. Closed-loop exponential stability has been demonstrated for both the set point and tracking control problems by a slight modification of the energy Lyapunov function and the use of a lemma which handles third-order terms in the Lyapunov function derivatives. In the second part, these control laws are adapted in a simple fashion to achieve asymptotically stable adaptive control. The analysis addresses the nonlinear dynamics directly without approximation, linearization, or ad hoc assumptions, and uses a parameterization based on physical (time-invariant) quantities.

Breast Reference Set Application: Chris Li-FHCRC (2014) — EDRN Public Portal

Cancer.gov

This application proposes to use Reference Set #1. We request access to serum samples collected at the time of breast biopsy from subjects with IC (n=30) or benign disease without atypia (n=30). Statistical power: With 30 BC cases and 30 normal controls, a 25% difference in mean metabolite levels can be detected between groups with 80% power and α=0.05, assuming coefficients of variation of 30%, consistent with our past studies. These sample sizes appear sufficient to enable detection of changes similar in magnitude to those previously reported in pre-clinical (BC recurrence) specimens (20).

Vehicle year and the risk of car crash injury

PubMed Central

Blows, S; Ivers, R; Woodward, M; Connor, J; Ameratunga, S; Norton, R

2003-01-01

Objective: To quantify the association between vehicle age and risk of car crash injury. Design and setting: Data from a population based case-control study conducted in the Auckland region in 1998/99 was used to examine the adjusted risk of car crash injury or death due to vehicle age, after controlling for a range of known confounders. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region, and controls were randomly selected cars on Auckland roads. The drivers of the 571 case vehicles and 588 control vehicles completed a structured interview. Main outcome measure: Hospitalisation or death of a vehicle occupant due to car crash injury. Results: Vehicles constructed before 1984 had significantly greater chance of being involved in an injury crash than those constructed after 1994 (odds ratio 2.88, 95% confidence interval (CI) 1.20 to 6.91), after adjustment for potential confounders. There was also a trend for increasing crash risk with each one year increase in vehicle age after adjustment for potential confounders (odds ratio 1.05, 95% CI 0.99 to 1.11; p = 0.09). Conclusion: This study quantifies the increased risk of car crash injury associated with older vehicle year and confirms this as an important public health issue. PMID:14693899

Application of multi-dimensional discrimination diagrams and probability calculations to Paleoproterozoic acid rocks from Brazilian cratons and provinces to infer tectonic settings

NASA Astrophysics Data System (ADS)

Verma, Sanjeet K.; Oliveira, Elson P.

2013-08-01

In present work, we applied two sets of new multi-dimensional geochemical diagrams (Verma et al., 2013) obtained from linear discriminant analysis (LDA) of natural logarithm-transformed ratios of major elements and immobile major and trace elements in acid magmas to decipher plate tectonic settings and corresponding probability estimates for Paleoproterozoic rocks from Amazonian craton, São Francisco craton, São Luís craton, and Borborema province of Brazil. The robustness of LDA minimizes the effects of petrogenetic processes and maximizes the separation among the different tectonic groups. The probability based boundaries further provide a better objective statistical method in comparison to the commonly used subjective method of determining the boundaries by eye judgment. The use of readjusted major element data to 100% on an anhydrous basis from SINCLAS computer program, also helps to minimize the effects of post-emplacement compositional changes and analytical errors on these tectonic discrimination diagrams. Fifteen case studies of acid suites highlighted the application of these diagrams and probability calculations. The first case study on Jamon and Musa granites, Carajás area (Central Amazonian Province, Amazonian craton) shows a collision setting (previously thought anorogenic). A collision setting was clearly inferred for Bom Jardim granite, Xingú area (Central Amazonian Province, Amazonian craton) The third case study on Older São Jorge, Younger São Jorge and Maloquinha granites Tapajós area (Ventuari-Tapajós Province, Amazonian craton) indicated a within-plate setting (previously transitional between volcanic arc and within-plate). We also recognized a within-plate setting for the next three case studies on Aripuanã and Teles Pires granites (SW Amazonian craton), and Pitinga area granites (Mapuera Suite, NW Amazonian craton), which were all previously suggested to have been emplaced in post-collision to within-plate settings. The seventh case studies on Cassiterita-Tabuões, Ritápolis, São Tiago-Rezende Costa (south of São Francisco craton, Minas Gerais) showed a collision setting, which agrees fairly reasonably with a syn-collision tectonic setting indicated in the literature. A within-plate setting is suggested for the Serrinha magmatic suite, Mineiro belt (south of São Francisco craton, Minas Gerais), contrasting markedly with the arc setting suggested in the literature. The ninth case study on Rio Itapicuru granites and Rio Capim dacites (north of São Francisco craton, Serrinha block, Bahia) showed a continental arc setting. The tenth case study indicated within-plate setting for Rio dos Remédios volcanic rocks (São Francisco craton, Bahia), which is compatible with these rocks being the initial, rift-related igneous activity associated with the Chapada Diamantina cratonic cover. The eleventh, twelfth and thirteenth case studies on Bom Jesus-Areal granites, Rio Diamante-Rosilha dacite-rhyolite and Timbozal-Cantão granites (São Luís craton) showed continental arc, within-plate and collision settings, respectively. Finally, the last two case studies, fourteenth and fifteenth showed a collision setting for Caicó Complex and continental arc setting for Algodões (Borborema province).

Combinations of SNP genotypes from the Wellcome Trust Case Control Study of bipolar patients.

PubMed

Mellerup, Erling; Jørgensen, Martin Balslev; Dam, Henrik; Møller, Gert Lykke

2018-04-01

Combinations of genetic variants are the basis for polygenic disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs in The Wellcome Trust Case Control Study of bipolar patients. Parallel computing by graphics processing units, cloud computing, and data mining tools were used to scan The Wellcome Trust data set for combinations. Two clusters of combinations were significantly associated with bipolar disorder. One cluster contained 68 combinations, each of which included five SNP genotypes. Of the 1998 patients, 305 had combinations from this cluster in their genome, but none of the 1500 controls had any of these combinations in their genome. The other cluster contained six combinations, each of which included five SNP genotypes. Of the 1998 patients, 515 had combinations from the cluster in their genome, but none of the 1500 controls had any of these combinations in their genome. Clusters of combinations of genetic variants can be considered general risk factors for polygenic disorders, whereas accumulation of combinations from the clusters in the genome of a patient can be considered a personal risk factor.

Smart Buildings and Demand Response

NASA Astrophysics Data System (ADS)

Kiliccote, Sila; Piette, Mary Ann; Ghatikar, Girish

2011-11-01

Advances in communications and control technology, the strengthening of the Internet, and the growing appreciation of the urgency to reduce demand side energy use are motivating the development of improvements in both energy efficiency and demand response (DR) systems in buildings. This paper provides a framework linking continuous energy management and continuous communications for automated demand response (Auto-DR) in various times scales. We provide a set of concepts for monitoring and controls linked to standards and procedures such as Open Automation Demand Response Communication Standards (OpenADR). Basic building energy science and control issues in this approach begin with key building components, systems, end-uses and whole building energy performance metrics. The paper presents a framework about when energy is used, levels of services by energy using systems, granularity of control, and speed of telemetry. DR, when defined as a discrete event, requires a different set of building service levels than daily operations. We provide examples of lessons from DR case studies and links to energy efficiency.

Traffic air pollution and risk of death from bladder cancer in Taiwan using petrol station density as a pollutant indicator.

PubMed

Ho, Chi-Kung; Peng, Chiung-Yu; Yang, Chun-Yuh

2010-01-01

To investigate the relationship between air pollution and risk of death from bladder cancer, a matched cancer case-control study was conducted using deaths that occurred in Taiwan from 1997 through 2006. Data for all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of individuals who died from causes other than cancer or diseases associated with genitourinary problems. The controls were pair matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data for the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in ambient evaporative losses of petrol or to air emissions from motor vehicles. The subjects were divided into tertiles according to PSD in their residential municipality. The present study showed that individuals who resided in municipalities with high PSD levels were at an increased risk of death from bladder cancer compared to subjects living in municipalities with a low PSD level; however, the differences are not statistically significant. The findings of this study warrant further investigation of the role of vehicular air pollutant emissions in the etiology of bladder cancer development.

Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA

PubMed Central

Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Rosen, Jennifer B; Motala, Tasneem; Mascola, Laurene; Eason, Jeffery; Scherzinger, Karen; Holtzman, Corinne; Reingold, Arthur L; Barnes, Meghan; Petit, Susan; Farley, Monica M; Harrison, Lee H; Zansky, Shelley; Thomas, Ann; Schaffner, William; McGee, Lesley; Whitney, Cynthia G; Moore, Matthew R

2017-01-01

Objectives External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case–control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. Design Matched case–control study. Setting Thirteen active surveillance sites for invasive pneumococcal disease in the USA. Participants Cases were identified from active surveillance and controls were age and zip code matched. Outcome measures Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. Results We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. Conclusions We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted. PMID:28851801

Epidemiological study of the characteristics of veterinarians who pursue a research career: part I.

PubMed

Murray, J K; French, N P; Fitzpatrick, J L; Pinchbeck, G L

2005-09-24

This retrospective, matched case-control study compared the characteristics of veterinary surgeons employed in veterinary research with those who had never held a research post. The cases were randomly selected from graduates of veterinary schools in Great Britain or Ireland who were employed at universities or institutes that conduct research and who played a major role in veterinary research projects during 2001 to 2003. The controls were veterinary surgeons who had not held any post that was primarily a research post since they graduated. The cases and controls were matched by year of graduation and data were obtained for 173 matched sets. Graduates who were significantly (P<0.05) more likely to have a career involving research included male graduates, graduates who had completed a summer studentship, graduates who had completed an internship, residency or houseman's programme, graduates who held a veterinary diploma, and graduates who had intended to pursue a career in research or academia when they graduated from veterinary school. A career involving research was significantly (P<0.05) more likely to be associated with full-time employment and a lower salary than a career that did not involve research.

Risk factors and outcome of Shigella encephalopathy in Bangladeshi children.

PubMed

Afroze, Farzana; Ahmed, Tahmeed; Sarmin, Monira; Smsb Shahid, Abu; Shahunja, K M; Shahrin, Lubaba; Chisti, Mohammod Jobayer

2017-04-01

Although, Shigella encephalopathy, a serious extra-intestinal complication of shigellosis, significantly increases the risks of death, data are very limited on predicting factors particularly related to electrolyte profiles in children below five years of age with Shigella encephalopathy. Our objective was to determine the clinical as well as laboratory predicting factors and outcome of children with Shigella encephalopathy. In this unmatched case-control design, children aged 2-59 months having a positive stool culture for Shigella and who had their serum electrolytes been done from July 2012 to June 2015 were studied. Children with Shigella encephalopathy, defined as having abnormal mentation, constituted the cases, and those without encephalopathy constituted the controls. During the study period, we identified a total of 541 children less than five years of age, who had Shigella in their stool culture. Only 139 children fulfilled the study criteria and among them 69 were cases and 70 were controls. The cases more often had fatal outcome compared to the controls (7% vs. 0%, P = 0.02). In logistic regression analysis, the cases were independently associated with shorter duration (1.2 ± 0.4 days) of diarrhea prior to admission, dehydrating diarrhea, sepsis and hyponatremia (p<0.05 for all). Among 139 Shigella isolates, S. flexneri (88/139, 63%) and S. sonnei(34/139, 24%) were the dominant species. S. dysenteriae was not isolated throughout the study period. S.sonnei was more frequently isolated from the cases (24/69, 35%) than the controls (10/70, 14%), whereas the isolation of S. flexneri was comparable between the groups (40/69, 58% vs 48/70, 69%). A total of 94 (67.6%) isolates were resistant to trimethoprim-sulphamethoxazole, 84 (60.4%) to ciprofloxacin, 66/138 (48%) to ampicillin, 5 (3.5%) to ceftriaxone, 17 (12.2%) to mecillinum and 35 (25%) to azithromycin. The case-fatality-rate was significantly higher among the children with Shigella encephalopathy compared to those without encephalopathy. Early identification and aggressive management of simple risk factors for Shigella encephalopathy may help to reduce morbidity and deaths in such children especially in resource-limited settings.

Risk factors and outcome of Shigella encephalopathy in Bangladeshi children

PubMed Central

Afroze, Farzana; Ahmed, Tahmeed; Sarmin, Monira; SMSB Shahid, Abu; Shahunja, K. M.; Shahrin, Lubaba

2017-01-01

Background Although, Shigella encephalopathy, a serious extra-intestinal complication of shigellosis, significantly increases the risks of death, data are very limited on predicting factors particularly related to electrolyte profiles in children below five years of age with Shigella encephalopathy. Our objective was to determine the clinical as well as laboratory predicting factors and outcome of children with Shigella encephalopathy. Methodology/Principal findings In this unmatched case-control design, children aged 2–59 months having a positive stool culture for Shigella and who had their serum electrolytes been done from July 2012 to June 2015 were studied. Children with Shigella encephalopathy, defined as having abnormal mentation, constituted the cases, and those without encephalopathy constituted the controls. During the study period, we identified a total of 541 children less than five years of age, who had Shigella in their stool culture. Only 139 children fulfilled the study criteria and among them 69 were cases and 70 were controls. The cases more often had fatal outcome compared to the controls (7% vs. 0%, P = 0.02). In logistic regression analysis, the cases were independently associated with shorter duration (1.2 ± 0.4 days) of diarrhea prior to admission, dehydrating diarrhea, sepsis and hyponatremia (p<0.05 for all). Among 139 Shigella isolates, S. flexneri (88/139, 63%) and S. sonnei(34/139, 24%) were the dominant species. S. dysenteriae was not isolated throughout the study period. S.sonnei was more frequently isolated from the cases (24/69, 35%) than the controls (10/70, 14%), whereas the isolation of S. flexneri was comparable between the groups (40/69, 58% vs 48/70, 69%). A total of 94 (67.6%) isolates were resistant to trimethoprim-sulphamethoxazole, 84 (60.4%) to ciprofloxacin, 66/138 (48%) to ampicillin, 5 (3.5%) to ceftriaxone, 17 (12.2%) to mecillinum and 35 (25%) to azithromycin. Conclusions/Significance The case-fatality-rate was significantly higher among the children with Shigella encephalopathy compared to those without encephalopathy. Early identification and aggressive management of simple risk factors for Shigella encephalopathy may help to reduce morbidity and deaths in such children especially in resource-limited settings. PMID:28453565

The association of contact lens solution use and Acanthamoeba keratitis

PubMed Central

Joslin, Charlotte E.; Tu, Elmer Y.; Shoff, Megan E.; Booton, Gregory C.; Fuerst, Paul A.; McMahon, Timothy T.; Anderson, Robert J.; Dworkin, Mark S.; Sugar, Joel; Davis, Faith G.; Stayner, Leslie T.

2009-01-01

Purpose Diagnosis of Acanthamoeba keratitis, a rare but serious corneal infection, has recently increased significantly at the University of Illinois at Chicago (UIC) Cornea Service. The purpose is to investigate Acanthamoeba keratitis risk factors. Design Retrospective case-control study. Methods Setting University, tertiary care hospital. Patients Fifty-five Acanthamoeba keratitis cases with contact lens use were diagnosed between May 1, 2003 and September 15, 2006. Clinic-matched controls with contact lens use were recruited. Subjects completed surveys targeting lens hygiene, contact lens solution use, and water exposure. Main Outcome Measure Acanthamoeba keratitis. Results Thirty-nine (73.6%) cases and 113 (65.3%) controls participated; 38 cases had complete contact lens data. Thirty-five of 38 cases (92.1%) and 47 of 100 controls (47.0%) used soft lenses. Analysis was performed on 30 cases and 39 controls with matched pairs with soft lens use. Exclusive use of AMO Complete MoisturePlus Multi-Purpose Solution was independently associated with Acanthamoeba keratitis in multivariable analysis (55.2% vs. 10.5%; OR, 16.67; 95% CI, 2.11–162.63; p = 0.008). However, 38.8% of cases reported no use of AMO Complete MoisturePlus Multi-Purpose Solution or used it in combination with other solutions. Although not statistically significant, additional hygiene-related variables (solution ‘reuse’, lack of ‘rubbing’, and showering with lenses) suggest a pattern of risk,. Conclusions AMO Complete MoisturePlus Multi-Purpose Solution use is independently associated with Acanthamoeba keratitis among soft contact lens users. However, it does not explain all cases, suggesting additional factors. Further research into environmental risk factors and hygiene practices is warranted, especially considering this is the second outbreak of an atypical, contact lens-related infection. PMID:17588524

The association of contact lens solution use and Acanthamoeba keratitis.

PubMed

Joslin, Charlotte E; Tu, Elmer Y; Shoff, Megan E; Booton, Gregory C; Fuerst, Paul A; McMahon, Timothy T; Anderson, Robert J; Dworkin, Mark S; Sugar, Joel; Davis, Faith G; Stayner, Leslie T

2007-08-01

To investigate Acanthamoeba keratitis (AK) risk factors. Diagnosis of AK, a rare but serious corneal infection, has recently increased significantly at the University of Illinois at Chicago (UIC) Cornea Service. Retrospective case-control study. settings: University, tertiary care hospital. patients: Fifty-five AK cases with contact lens use were diagnosed between May 1, 2003 and September 15, 2006. Clinic-matched controls with contact lens use were recruited. Subjects completed surveys targeting lens hygiene, contact lens solution use, and water exposure. main outcome measure: Acanthamoeba keratitis. Thirty-nine (73.6%) cases and 113 (65.3%) controls participated; 38 cases had complete contact lens data. Thirty-five of 38 cases (92.1%) and 47 of 100 controls (47.0%) used soft lenses. Analysis was performed on 30 cases and 39 controls with matched pairs with soft lens use. Exclusive use of Advance Medical Optics (AMO) Complete MoisturePlus Multi-Purpose Solution was independently associated with AK in multivariable analysis (55.2% vs 10.5%; odds ratio [OR], 16.67; 95% confidence interval [CI] 2.11 to 162.63; P = .008). However, 38.8% of cases reported no use of AMO Complete MoisturePlus Multi-Purpose Solution either alone or in combination with other solutions. Although not statistically significant, additional hygiene-related variables (solution "reuse," lack of "rubbing," and showering with lenses) suggest a pattern of risk. AMO Complete MoisturePlus Multi-Purpose Solution use is independently associated with AK among soft contact lens users. However, it does not explain all cases, suggesting additional factors. Further research into environmental risk factors and hygiene practices is warranted, especially considering this is the second outbreak of an atypical, contact lens-related infection.

Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study.

PubMed

Platts-Mills, James A; Taniuchi, Mami; Uddin, Md Jashim; Sobuz, Shihab Uddin; Mahfuz, Mustafa; Gaffar, Sm Abdul; Mondal, Dinesh; Hossain, Md Iqbal; Islam, M Munirul; Ahmed, Am Shamsir; Petri, William A; Haque, Rashidul; Houpt, Eric R; Ahmed, Tahmeed

2017-05-01

Background: Early exposure to enteropathogens has been associated with malnutrition in children in low-resource settings. However, the contribution of individual enteropathogens remains poorly defined. Molecular diagnostics offer an increase in sensitivity for detecting enteropathogens but have not been comprehensively applied to studies of malnutrition. Objective: We sought to identify enteropathogens associated with malnutrition in Bangladesh. Design: Malnourished children [weight-for-age z score (WAZ) <-2] aged 6-23 mo in Dhaka, Bangladesh, and identified by active community surveillance were enrolled as cases, and normal-weight children (WAZ >-1) of the same age and from the same community were enrolled as controls. Stools were collected at enrollment and, for cases, after a 5-mo nutritional intervention. Enrollment and follow-up stools were tested by quantitative polymerase chain reaction for 32 enteropathogens with the use of a custom-developed TaqMan Array Card. Results: Enteropathogen testing was performed on 486 cases and 442 controls upon enrollment and 365 cases at follow-up. At enrollment, the detection of enteroaggregative Escherichia coli (OR: 1.39; 95% CI: 1.05, 1.83), Campylobacter spp. (OR: 1.46; 95% CI: 1.11, 1.91), heat-labile enterotoxin-producing E. coli (OR: 1.55; 95% CI: 1.04, 2.33), Shigella /enteroinvasive E. coli (OR: 1.65; 95% CI: 1.10, 2.46), norovirus genogroup I (OR: 1.66; 95% CI: 1.23, 2.25), and Giardia (OR: 1.73; 95% CI: 1.20, 2.49) were associated with malnourished cases, and the total burden of these pathogens remained associated with malnutrition after adjusting for sociodemographic factors. The number of these pathogens at follow-up was negatively associated with the change in WAZ during the intervention (-0.10 change in WAZ per pathogen detected; 95% CI: -0.14, -0.06), whereas the number at enrollment was positively associated with the change in WAZ (0.05 change in WAZ per pathogen detected; 95% CI: 0.00, 0.10). Conclusions: A subset of enteropathogens was associated with malnutrition in this setting. Broad interventions designed to reduce the burden of infection with these pathogens are needed. This trial was registered at clinicaltrials.gov as NCT02441426.

Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis.

PubMed

Smith, Jeffrey D; MacDougall, Colin C; Johnstone, Jennie; Copes, Ray A; Schwartz, Brian; Garber, Gary E

2016-05-17

Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections. We searched various electronic databases and the grey literature for relevant studies published from January 1990 to December 2014. Randomized controlled trials (RCTs), cohort studies and case-control studies that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections were included in the meta-analysis. Surrogate exposure studies comparing N95 respirators and surgical masks using manikins or adult volunteers under simulated conditions were summarized separately. Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage and total inward leakage. We identified 6 clinical studies (3 RCTs, 1 cohort study and 2 case-control studies) and 23 surrogate exposure studies. In the meta-analysis of the clinical studies, we found no significant difference between N95 respirators and surgical masks in associated risk of (a) laboratory-confirmed respiratory infection (RCTs: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.64-1.24; cohort study: OR 0.43, 95% CI 0.03-6.41; case-control studies: OR 0.91, 95% CI 0.25-3.36); (b) influenza-like illness (RCTs: OR 0.51, 95% CI 0.19-1.41); or (c) reported workplace absenteeism (RCT: OR 0.92, 95% CI 0.57-1.50). In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage and less total inward leakage under laboratory experimental conditions, compared with surgical masks. Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings. © 2016 Canadian Medical Association or its licensors.

Investigating Fourth Amendment Judicial Outcomes across Contrasting Minority School Settings: Subjectivity in Disciplinary Decision Making in Diverse Settings?

ERIC Educational Resources Information Center

Torres, Mario S., Jr.; Callahan, Jamie L.

2008-01-01

This study explores the court system's treatment of students' Fourth Amendment rights in cases emerging from contrasting minority school settings and whether discrepancies exist in case outcomes between these extremes. From virtually every search and seizure case that occurred between the 1985 U.S. Supreme Court case in "New Jersey v.…

Local problems, local solutions: improving tuberculosis control at the district level in Malawi.

PubMed Central

Kelly, P. M.

2001-01-01

OBJECTIVE: To examine the causes of a low cure rate at the district level of a tuberculosis (TB) control programme and to formulate, implement, and evaluate an intervention to improve the situation. METHODS: The study setting was Mzuzu (population 60,000), where the annual smear-positive pulmonary TB incidence was 160 per 100,000 and the human immunodeficiency virus (HIV) seroprevalence was 67% among TB patients. There is one TB treatment unit, but several other organizations are involved with TB control. An examination of case-holding activities was carried out, potential areas for improvement were identified, and interventions performed. FINDINGS: In 1990-91, the cure rate was 24% among smear-positive cases (29% among survivors to end of treatment). Problems identified included a fragmented TB control programme; inadequate training and supervision; suboptimal recording of patients' addresses; and nonadherence to national TB control programme protocols. These problems were addressed, and in 1992-93 the cure rate rose to 68% (relative risk (RR) = 2.85 (95% confidence interval (CI) = 1.63, 4.96)) and to 92% among survivors to the end of treatment (RR = 3.12 (95% CI = 1.84, 5.29)). High cure rates are therefore achievable despite high HIV prevalence. CONCLUSIONS: Simple, inexpensive, local programmatic interventions can dramatically improve TB case holding. This study demonstrates the need for evaluation, training, and supervision at all levels of the programme. PMID:11242817

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru

PubMed Central

Ticona, Eduardo; Huaroto, Luz; Kirwan, Daniela E.; Chumpitaz, Milagros; Munayco, César V.; Maguiña, Mónica; Tovar, Marco A.; Evans, Carlton A.; Escombe, Roderick; Gilman, Robert H.

2016-01-01

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000—56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug–susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB–coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective. PMID:27621303

Seismic, structural, and individual factors associated with earthquake related injury

PubMed Central

Peek-Asa, C; Ramirez, M; Seligson, H; Shoaf, K

2003-01-01

Background: Earthquakes cause thousands of deaths worldwide every year, and systematic study of the causes of these deaths can lead to their prevention. Few studies have examined how multiple types of risk factors are related to physical injury during an earthquake. Methods: A population based case-control study was conducted to examine how individual characteristics, building characteristics, and seismic features of the 1994 Northridge, California, earthquake contributed to physical injury. Cases included fatal and hospital-admitted injuries caused by the earthquake. Controls were drawn from a population based phone survey of county residents. Cases were individually matched to two sets of controls: one matched by age and gender and one matched by location at the time of the earthquake. Results: Individuals over age 65 had 2.9 times the risk of injury as younger people (95% confidence interval (CI) 1.2 to 7.4) and women had a 2.4 times greater risk than men (95% CI 1.2 to 5.1). Location in multiple unit residential and commercial structures each led to increased injury risk compared with single unit residential structures, but the exact estimate varied depending on the control group used. With every increase in ground motion of 10%g, injury risk increased 2.2 times (95% CI 1.6 to 3.3). Conclusions: Controlling for other factors, it was found that individual, building, and seismic characteristics were independently predictive of increased injury risk. Prevention and preparedness efforts should focus on each of these as potential points of intervention. PMID:12642562

Toxoplasma gondii exposure and Parkinson's disease: a case–control study

PubMed Central

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-01-01

Objectives To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Design Case–control study. Setting Cases and controls were enrolled in Durango City, Mexico. Participants 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Primary and secondary outcome measures Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Results Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. Conclusions The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. PMID:28193849

Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness

PubMed Central

MacIntyre, Chandini Raina; Zhang, Yi; Chughtai, Abrar Ahmad; Seale, Holly; Zhang, Daitao; Chu, Yanhui; Zhang, Haiyan; Rahman, Bayzidur; Wang, Quanyi

2016-01-01

Rationale Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. Objective Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. Setting 6 major hospitals in 2 districts of Beijing, China. Design Cluster randomised controlled trial. Participants 245 index cases with ILI. Intervention Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). Main outcome measure Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. Results In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. Conclusions The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. Trial registration number ACTRN12613000852752; Results. PMID:28039289

Prevalence of dental attrition in in vitro fertilization children of West Bengal

PubMed Central

Kar, Sudipta; Sarkar, Subrata; Mukherjee, Ananya

2014-01-01

CONTEXT: Dental attrition is one of the problems affecting the tooth structure. It may affect both in vitro fertilization (IVF) and spontaneously conceived children. AIMS: This study was aimed to evaluate and to compare the prevalence of dental attrition in deciduous dentition of IVF and spontaneously conceived children. SETTINGS AND DESIGN: In a cross-sectional case control study dental attrition status of 3-5 years old children were assessed. The case group consisted of term, singleton babies who were the outcome of IVF in the studied area in 2009. SUBJECTS AND METHODS: The control group consisted of term, first child, singleton and spontaneously conceived 3-5 years old children who were also resident of the studied area. A sample of 153 IVF and 153 spontaneously conceived children was examined according to Hansson and Nilner classification. STATISTICAL ANALYSIS USED: Statistical analysis was carried out using Chi-square tests (χ2 ) or Z test. RESULTS: No statistically significant difference found in studied (IVF children) and control group (spontaneously conceived children). CONCLUSIONS: IVF children are considered same as spontaneously conceived children when studied in relation to dental attrition status. PMID:24829529

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.

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

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.

Priority setting and implementation in a centralized health system: a case study of Kerman province in Iran.

PubMed

Khayatzadeh-Mahani, Akram; Fotaki, Marianna; Harvey, Gillian

2013-08-01

The question of how priority setting processes work remains topical, contentious and political in every health system across the globe. It is particularly acute in the context of developing countries because of the mismatch between needs and resources, which is often compounded by an underdeveloped capacity for decision making and weak institutional infrastructures. Yet there is limited research into how the process of setting and implementing health priorities works in developing countries. This study aims to address this gap by examining how a national priority setting programme works in the centralized health system of Iran and what factors influence its implementation at the meso and micro levels. We used a qualitative case study approach, incorporating mixed methods: in-depth interviews at three levels and a textual analysis of policy documents. The data analysis showed that the process of priority setting is non-systematic, there is little transparency as to how specific priorities are decided, and the decisions made are separated from their implementation. This is due to the highly centralized system, whereby health priorities are set at the macro level without involving meso or micro local levels or any representative of the public. Furthermore, the two main benefit packages are decided by different bodies (Ministry of Health and Medical Education and Ministry of Welfare and Social Security) and there is no co-ordination between them. The process is also heavily influenced by political pressure exerted by various groups, mostly medical professionals who attempt to control priority setting in accordance with their interests. Finally, there are many weaknesses in the implementation of priorities, resulting in a growing gap between rural and urban areas in terms of access to health services.

An updated investigation of cancer incidence and mortality at a Scottish semiconductor manufacturing facility with case-control and case-only studies of selected cancers.

PubMed

Darnton, Andrew; Miller, Brian G; Maccalman, Laura; Galea, Karen S; Wilkinson, Sam; Cherrie, John W; Shafrir, Amy; McElvenny, Damien; Osman, John

2012-10-01

An earlier investigation raised concern that some cancer cases might be linked to work at a semiconductor manufacturing plant. The aim of this study was to describe an update of the cancer incidence and mortality of these workers and assess whether workplace exposures contributed to any increased risk of selected cancers. Standardised mortality ratios and standardised incidence ratios were calculated for cancer site groups of a priori interest in a cohort previously flagged against the National Health Service Central Register, with follow-up extended to the 2007 for deaths and 2006 for cancer registrations. Cases of female breast cancer, lung and stomach cancer, and male brain cancer, and a random sample of control subjects individually age-matched to the breast cancer cases, were identified from within the cohort dataset and invited to participate via general practitioners. Exposures were estimated using a job exposure matrix developed from a historical hygiene assessment and assigned to job histories obtained from personal interview of subjects (or proxies). Though the findings were uncertain, there were no excesses of mortality or cancer incidence, either overall or for specific cancer sites, suggestive of a workplace effect. Logistic regression analyses comparing 20 cases of breast cancer with 83 matched controls showed no consistent evidence of any relationship with occupational exposures. Assessment of commonalities of workplace exposures among case sets for other cancer types was limited by the small numbers. These results do not support earlier concerns about occupational cancer risks among this cohort.

Occupational UV-Exposure is a Major Risk Factor for Basal Cell Carcinoma: Results of the Population-Based Case-Control Study FB-181.

PubMed

Schmitt, Jochen; Haufe, Eva; Trautmann, Freya; Schulze, Hans-Joachim; Elsner, Peter; Drexler, Hans; Bauer, Andrea; Letzel, Stephan; John, Swen Malte; Fartasch, Manigé; Brüning, Thomas; Seidler, Andreas; Dugas-Breit, Susanne; Gina, Michal; Weistenhöfer, Wobbeke; Bachmann, Klaus; Bruhn, Ilka; Lang, Berenice Mareen; Bonness, Sonja; Allam, Jean Pierre; Grobe, William; Stange, Thoralf; Westerhausen, Stephan; Knuschke, Peter; Wittlich, Marc; Diepgen, Thomas Ludwig

2018-01-01

The aim of this study was to investigate the role of occupational and nonoccupational ultraviolet (UV)-exposure concerning the development of basal cell carcinoma (BCC). We undertook a population-based multicenter case-control study. Patients with first incident BCC (n = 836) were propensity score matched by age and sex to controls without skin cancer (n = 836). Sociodemographic characteristics, clinical characteristics, and lifetime UV-exposure were assessed by trained investigators. The differential estimation of occupational and nonoccupational UV-exposure dosages was based on validated instruments and established reference values. Associations were assessed using multivariable-adjusted conditional logistic regression models. Individuals with high levels of occupational UV-exposure were at significantly increased BCC-risk compared with individuals with low [odds ratio (OR) 1.84; 95% confidence interval (95% CI) 1.19 to 2.83 and moderate (OR 1.97; 95% CI 1.20 to 3.22) occupational UV-exposure. Nonoccupational UV-exposure was not independently associated with BCC. Skin cancer prevention strategies should be expanded to the occupational setting.

Methylphenidate as a treatment for stuttering: a case report.

PubMed

Devroey, D; Beerens, G; Van De Vijver, E

2012-10-01

A randomized placebo controlled trial with methylphenidate (MPH) was set up to identify the effects of MPH on cognition in healthy young adults (ea. without attention deficit hyperactivity disorder, ADHD). Subjects repeatedly performed tests of the immediate and delayed memory and vigilance tasks after administration of placebo or 20 mg MPH. We report the case of an 18 year old man who participated in the study. He suffered from stuttering since childhood. During the study phase he reported a remarkable relief of the stuttering after the intake of 20 mg MPH. For D-amphetamine the beneficial effect on stuttering has been demonstrated but it was never implemented in clinical practice because of important adverse events. MPH, an amphetamine analogue, doesn't present these side effects. For this reason, MPH seems to merit further investigation in a randomized-controlled trial as a possible agent in the treatment of stuttering.Methylphenidate, Stuttering.

A comparison of estimators from self-controlled case series, case-crossover design, and sequence symmetry analysis for pharmacoepidemiological studies.

PubMed

Takeuchi, Yoshinori; Shinozaki, Tomohiro; Matsuyama, Yutaka

2018-01-08

Despite the frequent use of self-controlled methods in pharmacoepidemiological studies, the factors that may bias the estimates from these methods have not been adequately compared in real-world settings. Here, we comparatively examined the impact of a time-varying confounder and its interactions with time-invariant confounders, time trends in exposures and events, restrictions, and misspecification of risk period durations on the estimators from three self-controlled methods. This study analyzed self-controlled case series (SCCS), case-crossover (CCO) design, and sequence symmetry analysis (SSA) using simulated and actual electronic medical records datasets. We evaluated the performance of the three self-controlled methods in simulated cohorts for the following scenarios: 1) time-invariant confounding with interactions between the confounders, 2) time-invariant and time-varying confounding without interactions, 3) time-invariant and time-varying confounding with interactions among the confounders, 4) time trends in exposures and events, 5) restricted follow-up time based on event occurrence, and 6) patient restriction based on event history. The sensitivity of the estimators to misspecified risk period durations was also evaluated. As a case study, we applied these methods to evaluate the risk of macrolides on liver injury using electronic medical records. In the simulation analysis, time-varying confounding produced bias in the SCCS and CCO design estimates, which aggravated in the presence of interactions between the time-invariant and time-varying confounders. The SCCS estimates were biased by time trends in both exposures and events. Erroneously short risk periods introduced bias to the CCO design estimate, whereas erroneously long risk periods introduced bias to the estimates of all three methods. Restricting the follow-up time led to severe bias in the SSA estimates. The SCCS estimates were sensitive to patient restriction. The case study showed that although macrolide use was significantly associated with increased liver injury occurrence in all methods, the value of the estimates varied. The estimations of the three self-controlled methods depended on various underlying assumptions, and the violation of these assumptions may cause non-negligible bias in the resulting estimates. Pharmacoepidemiologists should select the appropriate self-controlled method based on how well the relevant key assumptions are satisfied with respect to the available data.

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.

Nanosensors: towards morphological control of gas sensing activity. SnO2, In2O3, ZnO and WO3 case studies.

PubMed

Gurlo, Aleksander

2011-01-01

Anisotropy is a basic property of single crystals. Dissimilar facets/surfaces have different geometric and electronic structure that results in dissimilar functional properties. Several case studies unambiguously demonstrated that the gas sensing activity of metal oxides is determined by the nature of surfaces exposed to ambient gas. Accordingly, a control over crystal morphology, i.e. over the angular relationships, size and shape of faces in a crystal, is required for the development of better sensors with increased selectivity and sensitivity in the chemical determination of gases. The first step toward this nanomorphological control of the gas sensing properties is the design and synthesis of well-defined nanocrystals which are uniform in size, shape and surface structure. These materials possess the planes of the symmetrical set {hkl} and must therefore behave identically in chemical reactions and adsorption processes. Because of these characteristics, the form-controlled nanocrystals are ideal candidates for fundamental studies of mechanisms of gas sensing which should involve (i) gas sensing measurements on specific surfaces, (ii) their atomistic/quantum chemical modelling and (ii) spectroscopic information obtained on same surfaces under operation conditions of sensors.

Nosocomial transmission of respiratory syncytial virus in an outpatient cancer center.

PubMed

Chu, Helen Y; Englund, Janet A; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P; Boeckh, Michael; Pergam, Steven A; Casper, Corey

2014-06-01

Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. We performed a retrospective cohort study of 2 nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance. Subjects included patients seen at the Seattle Cancer Care Alliance with RSV detected in 2 outbreaks in 2007-2008 and 2012 and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested PCR targeting the RSV attachment glycoprotein coding region. Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 of 15 patients (67%) with RSV sequenced from 2007 to 2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; 9 of 10 patients (90%) had the same viral strain, and 1 (10%) had another viral strain. We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.

Nosocomial Transmission of Respiratory Syncytial Virus in an Outpatient Cancer Center

PubMed Central

Chu, Helen Y.; Englund, Janet A.; Podczervinski, Sara; Kuypers, Jane; Campbell, Angela P.; Boeckh, Michael; Pergam, Steven A.; Casper, Crey

2014-01-01

Background Respiratory syncytial virus (RSV) outbreaks in inpatient settings are associated with poor outcomes in cancer patients. The use of molecular epidemiology to document RSV transmission in the outpatient setting has not been well described. Methods We performed a retrospective cohort study of two nosocomial outbreaks of RSV at the Seattle Cancer Care Alliance (SCCA). Subjects included patients seen at the SCCA with RSV detected in two outbreaks in 2007-2008 and 2012, and all employees with respiratory viruses detected in the 2007-2008 outbreak. A subset of samples was sequenced using semi-nested polymerase chain reaction targeting the RSV attachment glycoprotein coding region. Results Fifty-one cases of RSV were identified in 2007-2008. Clustering of identical viral strains was detected in 10 (67%) of 15 patients with RSV sequenced from 2007-2008. As part of a multimodal infection control strategy implemented as a response to the outbreak, symptomatic employees had nasal washes collected. Of 254 employee samples, 91 (34%) tested positive for a respiratory virus, including 14 with RSV. In another RSV outbreak in 2012, 24 cases of RSV were identified; nine (90%) of 10 patients had the same viral strain, and 1 (10%) had another viral strain. Conclusions We document spread of clonal strains within an outpatient cancer care setting. Infection control interventions should be implemented in outpatient, as well as inpatient, settings to reduce person-to-person transmission and limit progression of RSV outbreaks. PMID:24607551

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

PubMed

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

2014-03-01

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

Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study

PubMed Central

Nakakeeto, Margaret; Willey, Barbara A; Sewegaba, Margaret; Webb, Emily L; Oke, Ibby; Mutuuza, Emmanuel Derek; Peebles, Donald; Musoke, Margaret; Harris, Kathryn A; Sebire, Neil J; Kurinczuk, Jennifer J; Elliott, Alison M

2018-01-01

Objective Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda. Design Unmatched case–control study. Setting Mulago National Referral Hospital, Kampala, Uganda. Methods 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE. Results Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74). Conclusions Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted. PMID:28780500

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

PubMed

Beyer, Alexander; Rees, Ryan; Palmer, Christopher; Wessman, Brian T; Fuller, Brian M

2017-12-01

Blood product transfusion occurs in a significant percentage of intensive care unit (ICU) patients. Pulmonary complications, such as acute respiratory distress syndrome (ARDS), occurring in the setting of transfusion, are associated with increased morbidity and mortality. Contrary to the ICU setting, there is little evidence describing the epidemiology of transfusion in the emergency department (ED) or its potential impact on outcome. The objectives of this study were to: (1) characterize transfusion practices in the ED with respect to patient characteristics and pre-transfusion laboratory values; and (2) investigate the effect of ED blood product transfusion on the incidence of pulmonary complications after admission. We hypothesized that blood product transfusion would increase the event rate for pulmonary complications, and have a negative impact on other clinically significant outcomes. This was a retrospective case-control study with one-one matching of 204 transfused ED patients to 204 non-transfused controls. The primary outcome was a composite pulmonary outcome that included: acute respiratory failure, new need for ICU admission, and ARDS. Multivariable logistic regression was used to evaluate the primary outcome as a function of transfusion. One-hundred twenty four (60.8%) patients were transfused packed red blood cells (PRBC) in the ED. The mean pre-transfusion hemoglobin level was 8.5 g/dl. There were 73 patients with a hemoglobin value ≥10 g/dl; 19 (26.0%) received a PRBC transfusion. A total of 54 (26.5%) patients were transfused platelets. The main indications were thrombocytopenia (27.8%) and neurologic injury (24.1%). Ten patients had a platelet level <10,000 (guideline recommended threshold for transfusion to prevent spontaneous hemorrhage). The mean platelet count for neurologic injury patients was 197,000 prior to transfusion. The primary outcome occurred in 26 control patients (12.7%), as compared with 28 cases (13.7%). In multivariable logistic regression analysis, ED transfusion was not associated with an increased odds of primary outcome [adjusted OR 0.91 (0.48-1.72), P = 0.77]. The mortality rate was 10.8% in the cases and 8.8% in the controls, P = 0.51. A significant percentage of ED blood product transfusions are discordant with guideline recommendations. However, there was no association with ED transfusion and worse clinical outcome.

Risk factors for clinical coronary heart disease in systemic lupus erythematosus: the lupus and atherosclerosis evaluation of risk (LASER) study.

PubMed

Haque, Sahena; Gordon, Caroline; Isenberg, David; Rahman, Anisur; Lanyon, Peter; Bell, Aubrey; Emery, Paul; McHugh, Neil; Teh, Lee Suan; Scott, David G I; Akil, Mohamed; Naz, Sophia; Andrews, Jacqueline; Griffiths, Bridget; Harris, Helen; Youssef, Hazem; McLaren, John; Toescu, Veronica; Devakumar, Vinodh; Teir, Jamal; Bruce, Ian N

2010-02-01

Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same "dummy-date" in controls. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

Predictors of early postpartum mental distress in mothers with midwifery home care--results from a nested case-control study.

PubMed

Staehelin, Katharina; Kurth, Elisabeth; Schindler, Christian; Schmid, Monika; Zemp Stutz, Elisabeth

2013-08-27

The prevalence of early postpartum mental health conditions is high. Midwives and other health professionals visiting women at home may identify mothers at risk. This seems crucial given decreasing trends of length of hospital stay after childbirth. This study aimed to identify predictors of maternal mental distress in a midwifery home care setting. Using the statistical database of independent midwives' services in Switzerland in 2007, we conducted a matched nested case-control study. Out of a source population of 34,295 mothers with midwifery home care in the first ten days after childbirth, 935 mothers with maternal distress and 3,645 controls, matched by midwife, were included. We analysed whether socio-demographic, maternal and neonatal factors predict maternal mental distress by multivariable conditional logistic regression analysis. Infant crying problems and not living with a partner were the strongest predictors for maternal distress, whereas higher parity was the most protective factor. Significantly elevated risks were also found for older age, lower educational levels, breast/breastfeeding problems, infant weight gain concerns, neonatal pathologies and use of midwifery care during pregnancy. A lower likelihood for maternal distress was seen for non-Swiss nationality, full-time employment before birth, intention to return to work after birth and midwife-led birth. The study informs on predictors of maternal mental distress identified in a home care setting in the early postpartum period. Midwives and other health care professionals should pay particular attention to mothers of excessively crying infants, single mothers and primipara, and assess the need for support of these mothers.

Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa

PubMed Central

Tudor, Carrie; Van der Walt, Martie L.; Margot, Bruce; Dorman, Susan E.; Pan, William K.; Yenokyan, Gayane; Farley, Jason E.

2016-01-01

Background. Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. Methods. We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. Results. Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54–11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40–3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. Conclusions. HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients. PMID:27118855

[Giardia duodenalis and chronic malnutrition in children under five from a rural area of Guinea-Bissau].

PubMed

Centeno-Lima, Sónia; Rosado-Marques, Vítor; Ferreira, Filipa; Rodrigues, Ruben; Indeque, Benjamim; Camará, Idrissa; De Sousa, Bruno; Aguiar, Pedro; Nunes, Baltazar; Ferrinho, Paulo

2013-01-01

Malnutrition and infections by intestinal parasites such as Giardia duodenalis coexist in the same geographical regions, reaching the highest prevalence in developing countries. The cycle of malnutrition and infection implies that both conditions can aggravate each other and compromise the growth and development of children with special relevance for under-five. The aim of this study was to investigate the association between chronic malnutrition and infection by G. duodenalis in children under five in a rural community in Guinea-Bissau. A case-control study that included 109 children aged 0 to 59 months of a rural community in Guinea-Bissau was conducted. The anthropometric assessment of children in the study identified 31 cases of chronic malnutrition (z-score height for age < -2) and 78 controls (z-score height for age = -2). Microscopic examination of stools was performed for detection and identification of G. duodenalis and other parasites. The microscopic analysis of stool samples revealed G. duodenalis infection in 29.0% (9/31) of cases and 35.9% (28/78) of controls. No association between the infection with G. duodenalis and chronic malnutrition in children under study could be established. The results reinforce the interest in designing further studies exploring this association in different regions and epidemiological settings, while direct to the importance of the criteria for malnutrition definition which influences the subsequent analysis.

Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.

PubMed

de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Verheijen, Mark H G; Posthuma, Danielle

2015-11-01

Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.

Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

PubMed Central

de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Scharf, J M; Pauls, D L; Yu, D; Illmann, C; Osiecki, L; Neale, B M; Mathews, C A; Reus, V I; Lowe, T L; Freimer, N B; Cox, N J; Davis, L K; Rouleau, G A; Chouinard, S; Dion, Y; Girard, S; Cath, D C; Posthuma, D; Smit, J H; Heutink, P; King, R A; Fernandez, T; Leckman, J F; Sandor, P; Barr, C L; McMahon, W; Lyon, G; Leppert, M; Morgan, J; Weiss, R; Grados, M A; Singer, H; Jankovic, J; Tischfield, J A; Heiman, G A; Verheijen, Mark H G; Posthuma, Danielle

2015-01-01

Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis. PMID:25735483

Controllability in nonlinear systems

NASA Technical Reports Server (NTRS)

Hirschorn, R. M.

1975-01-01

An explicit expression for the reachable set is obtained for a class of nonlinear systems. This class is described by a chain condition on the Lie algebra of vector fields associated with each nonlinear system. These ideas are used to obtain a generalization of a controllability result for linear systems in the case where multiplicative controls are present.

Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells

PubMed Central

Kariminia, Amina; Holtan, Shernan G.; Ivison, Sabine; Rozmus, Jacob; Hebert, Marie-Josée; Martin, Paul J.; Lee, Stephanie J.; Wolff, Daniel; Subrt, Peter; Abdossamadi, Sayeh; Sung, Susanna; Storek, Jan; Levings, Megan; Aljurf, Mahmoud; Arora, Mukta; Cutler, Corey; Gallagher, Geneviève; Kuruvilla, John; Lipton, Jeff; Nevill, Thomas J.; Newell, Laura F.; Panzarella, Tony; Pidala, Joseph; Popradi, Gizelle; Szwajcer, David; Tay, Jason; Toze, Cynthia L.; Walker, Irwin; Couban, Stephen; Storer, Barry E.

2016-01-01

Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3+CD56bright natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates. PMID:27020088

A novel approach to simulate gene-environment interactions in complex diseases.

PubMed

Amato, Roberto; Pinelli, Michele; D'Andrea, Daniel; Miele, Gennaro; Nicodemi, Mario; Raiconi, Giancarlo; Cocozza, Sergio

2010-01-05

Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study.

Using Small-Scale Randomized Controlled Trials to Evaluate the Efficacy of New Curricular Materials

PubMed Central

Bass, Kristin M.; Stark, Louisa A.

2014-01-01

How can researchers in K–12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The researchers asked whether the curricular materials improved students’ understanding of the content more than an alternative set of activities. The field test was conducted in a diverse public high school setting with 145 students who were randomly assigned to a treatment or comparison condition. Findings indicate that students in the treatment condition scored significantly higher on the posttest than did students in the comparison group (effect size: Cohen's d = 0.40). The paper discusses the strengths and limitations of the RCT, the contextual factors that influenced its enactment, and recommendations for others wishing to conduct small-scale rigorous evaluations in educational settings. Our intention is for this paper to serve as a case study for university science faculty members who wish to employ scientifically rigorous evaluations in K–12 settings while limiting the scope and budget of their work. PMID:25452482

A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

PubMed

Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

2016-05-05

One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Evaluation of paradoxical TB–associated IRIS with the use of standardized case definitions for resource limited settings

PubMed Central

Eshun-Wilson, Ingrid; Havers, Fiona; Nachega, Jean B; Prozesky, Hans W; Taljaard, Jantjie J; Zeier, Michele D; Cotton, Mark; Simon, Gary; Soentjens, Patrick

2011-01-01

Objective Standardized case definitions have recently been proposed by the International Network for the Study of HIV-associated IRIS (INSHI) for use in resource-limited settings. We evaluated paradoxical TB-associated IRIS in a large cohort from a TB endemic setting with the use of these case definitions. Design A retrospective cohort analysis. Methods We reviewed records from 1250 South African patients who initiated anti-retroviral therapy (ART) over a five-year period. Results 333 (27%) of the patients in the cohort had prevalent TB at the initiation of ART. Of 54 possible paradoxical TB-associated IRIS cases, 35 fulfilled the INSHI case definitions (11% of TB cases). Conclusions INSHI standardised case definitions were used successfully in identifying paradoxical TB-associated IRIS in this cohort and resulted in a similar proportion of TB IRIS cases (11%) as that reported in previous studies from resource-limited settings (8-13%). This case definition should be evaluated prospectively. PMID:20160249

Risk factors for cartilage damage and osteoarthritis of the elbow joint: case-control study and systematic literature review.

PubMed

Spahn, Gunter; Lipfert, Jens Uwe; Maurer, Constance; Hartmann, Bernd; Schiele, Rainer; Klemm, Holm-Torsten; Grifka, Joachim; Hofmann, Gunther O

2017-04-01

This case-control study compares patients with healthy elbows to a group of symptomatic patients with cartilage damage/osteoarthritis. The control group (n = 126) was recruited during routine medical examinations of patients (general medical offices). Included in the case group were a total of 92 patients who were undergoing arthroscopy as a result of chronic elbow discomfort. All patients were questioned with regard to occupational stress and athletic stress. A significantly increased risk of cartilage damage/osteoarthritis was found with subjectively perceived increased stress in occupational settings: OR = 3.8 (95% CI 2.1-6.7); p < 0.001; for the individual stresses of the elbow joint in occupational settings, the following severities in effects were found: Exposure to heavy work OR = 3.9 (95% CI 2.2-6.8); Force OR = 3.7 (95% CI 2.1-6.5); Vibration OR = 4.6 (95% CI 2.5-8.5); Repetition OR = 9.2 (95% CI 3.6-23.3); p < 0.001. Elbow-stressing sport types represent a potential risk factor for the development of cartilage damage/osteoarthritis of the elbow joint: OR = 2.5 (95% CI 1.3-4.7); p = 0.003. Cartilage damage/radiographic osteoarthritis of the elbow joint are rare with respect to the overall prevalence of osteoarthritis. In the large number of patients with cartilage damage/radiographic osteoarthritis of the elbow joint, occupational or athletic stress factors and injuries sustained, in addition to other causes (rheumatism, gout), can prove as possible causes of these as secondary to symptomatic forms of osteoarthritis.

More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS--a case-control study in primary care.

PubMed

Grodzinsky, Ewa; Walter, Susanna; Viktorsson, Lisa; Carlsson, Ann-Kristin; Jones, Michael P; Faresjö, Åshild

2015-01-28

Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder, that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care. A case-control study in primary care setting among IBS patients meeting the ROME III criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any present or previous gastrointestinal complaints. The data were collected through self-reported questionnaires of psychosocial factors. IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report 'good' health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation in negative self-esteem among IBS patients remained statistically significant (p = 0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04). The more frequently reported negative self-esteem and inferior coping strategies among IBS patients found in this study suggest the possibility that psychological therapies might be helpful for these patients. However these data do not indicate the causal direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

Serratia marcescens Bacteremia: Nosocomial Cluster Following Narcotic Diversion.

PubMed

Schuppener, Leah M; Pop-Vicas, Aurora E; Brooks, Erin G; Duster, Megan N; Crnich, Christopher J; Sterkel, Alana K; Webb, Aaron P; Safdar, Nasia

2017-09-01

OBJECTIVE To describe the investigation and control of a cluster of Serratia marcescens bacteremia in a 505-bed tertiary-care center. METHODS Cluster cases were defined as all patients with S. marcescens bacteremia between March 2 and April 7, 2014, who were found to have identical or related blood isolates determined by molecular typing with pulsed-field gel electrophoresis. Cases were compared using bivariate analysis with controls admitted at the same time and to the same service as the cases, in a 4:1 ratio. RESULTS In total, 6 patients developed S. marcescens bacteremia within 48 hours after admission within the above period. Of these, 5 patients had identical Serratia isolates determined by molecular typing, and were included in a case-control study. Exposure to the post-anesthesia care unit was a risk factor identified in bivariate analysis. Evidence of tampered opioid-containing syringes on several hospital units was discovered soon after the initial cluster case presented, and a full narcotic diversion investigation was conducted. A nurse working in the post-anesthesia care unit was identified as the employee responsible for the drug diversion and was epidemiologically linked to all 5 patients in the cluster. No further cases were identified once the implicated employee's job was terminated. CONCLUSION Illicit drug use by healthcare workers remains an important mechanism for the development of bloodstream infections in hospitalized patients. Active mechanisms and systems should remain in place to prevent, detect, and control narcotic drug diversions and associated patient harm in the healthcare setting. Infect Control Hosp Epidemiol 2017;38:1027-1031.

Hyperendemic pulmonary tuberculosis in peri-urban areas of Karachi, Pakistan

PubMed Central

Akhtar, Saeed; White, Franklin; Hasan, Rumina; Rozi, Shafquat; Younus, Mohammad; Ahmed, Faiza; Husain, Sara; Khan, Bilquis Sana

2007-01-01

Background Currently there are very limited empirical data available on the prevalence of pulmonary tuberculosis among residents of marginalized settings in Pakistan. This study assessed the prevalence of pulmonary tuberculosis through active case detection and evaluated predictors of pulmonary tuberculosis among residents of two peri-urban neighbourhoods of Karachi, Pakistan. Methods A cross-sectional study was conducted in two peri-urban neighbourhoods from May 2002 to November 2002. Systematic sampling design was used to select households for inclusion in the study. Consenting subjects aged 15 years or more from selected households were interviewed and, whenever possible, sputum samples were obtained. Sputum samples were subjected to direct microscopy by Ziehl-Neelson method, bacterial culture and antibiotic sensitivity tests. Results The prevalence (per 100,000) of pulmonary tuberculosis among the subjects aged 15 years or more, who participated in the study was 329 (95% confidence interval (CI): 195 – 519). The prevalence (per 100,000) of pulmonary tuberculosis adjusted for non-sampling was 438 (95% CI: 282 – 651). Other than cough, none of the other clinical variables was significantly associated with pulmonary tuberculosis status. Analysis of drug sensitivity pattern of 15 strains of Mycobacterium tuberculosis revealed that one strain was resistant to isoniazid alone, one to streptomycin alone and one was resistant to isoniazid and streptomycin. The remaining 12 strains were susceptible to all five drugs including streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. Conclusion This study of previously undetected tuberculosis cases in an impoverished peri-urban setting reveals the poor operational performance of Pakistan's current approach to tuberculosis control; it also demonstrates a higher prevalence of pulmonary tuberculosis than current national estimates. Public health authorities may wish to augment health education efforts aimed at prompting health-seeking behaviour to facilitate more complete and earlier case detection. Such efforts to improve passive case-finding, if combined with more accessible DOTS infra-structure for treatment of detected cases, may help to diminish the high tuberculosis-related morbidity and mortality in marginalized populations. The economics of implementing a more active approach to case finding in resource-constrained setting also deserve further study. PMID:17477870

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

PubMed Central

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

2015-01-01

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

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.

Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence.

PubMed

Liu, Gang; Mukherjee, Bhramar; Lee, Seunggeun; Lee, Alice W; Wu, Anna H; Bandera, Elisa V; Jensen, Allan; Rossing, Mary Anne; Moysich, Kirsten B; Chang-Claude, Jenny; Doherty, Jennifer A; Gentry-Maharaj, Aleksandra; Kiemeney, Lambertus; Gayther, Simon A; Modugno, Francesmary; Massuger, Leon; Goode, Ellen L; Fridley, Brooke L; Terry, Kathryn L; Cramer, Daniel W; Ramus, Susan J; Anton-Culver, Hoda; Ziogas, Argyrios; Tyrer, Jonathan P; Schildkraut, Joellen M; Kjaer, Susanne K; Webb, Penelope M; Ness, Roberta B; Menon, Usha; Berchuck, Andrew; Pharoah, Paul D; Risch, Harvey; Pearce, Celeste Leigh

2018-02-01

There have been recent proposals advocating the use of additive gene-environment interaction instead of the widely used multiplicative scale, as a more relevant public health measure. Using gene-environment independence enhances statistical power for testing multiplicative interaction in case-control studies. However, under departure from this assumption, substantial bias in the estimates and inflated type I error in the corresponding tests can occur. In this paper, we extend the empirical Bayes (EB) approach previously developed for multiplicative interaction, which trades off between bias and efficiency in a data-adaptive way, to the additive scale. An EB estimator of the relative excess risk due to interaction is derived, and the corresponding Wald test is proposed with a general regression setting under a retrospective likelihood framework. We study the impact of gene-environment association on the resultant test with case-control data. Our simulation studies suggest that the EB approach uses the gene-environment independence assumption in a data-adaptive way and provides a gain in power compared with the standard logistic regression analysis and better control of type I error when compared with the analysis assuming gene-environment independence. We illustrate the methods with data from the Ovarian Cancer Association Consortium. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Control systems for platform landings cushioned by air bags

NASA Astrophysics Data System (ADS)

Ross, Edward W.

1987-07-01

This report presents an exploratory mathematical study of control systems for airdrop platform landings cushioned by airbags. The basic theory of airbags is reviewed and solutions to special cases are noted. A computer program is presented, which calculates the time-dependence of the principal variables during a landing under the action of various control systems. Two existing control systems of open-loop type are compared with a conceptual feedback (closed-loop) system for a fairly typical set of landing conditions. The feedback controller is shown to have performance much superior to the other systems. The feedback system undergoes an interesting oscillation not present in the other systems, the source of which is investigated. Recommendations for future work are included.

Quality of Interhospital Transfer Communication Practices and Association With Adverse Events on an Internal Medicine Hospitalist Service.

PubMed

Borofsky, Jennifer S; Bartsch, Jason C; Howard, Alan B; Repp, Allen B

Communication practices around interhospital transfer have not been rigorously assessed in adult medicine patients. Furthermore, the clinical implications of such practices have not been reported. This case-control study was designed to assess the quality of communication between clinicians during interhospital transfer and to determine if posttransfer adverse events (PTAEs) are associated with suboptimal communication. Cases included patients transferred to a Medicine Hospitalist Service from an outside hospital who subsequently experienced a PTAE, defined as unplanned transfer to an intensive care unit or death within 24 hours of transfer. Control patients also underwent interhospital transfer but did not experience a PTAE. A blinded investigator retrospectively reviewed the recorded pretransfer phone conversations between sending and receiving clinicians for adherence to a set of 13 empiric best practice communication elements. The primary outcome was the mean communication score, on a scale of 0-13. Mean scores between PTAE (8.3; 95% confidence interval [CI], 7.6-8.9) and control groups (7.9; 95% CI, 7.1-8.8) did not differ significantly (p = .50), although suboptimal communication on a subset of these elements was associated with increased PTAEs. Communication around interhospital transfer appears suboptimal compared with an empiric set of standard communication elements. Posttransfer adverse events were not associated with aggregate adherence to these standards.

SIMPLE MEASURES ARE AS EFFECTIVE AS INVASIVE TECHNIQUES IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS IN MALAWI

PubMed Central

Bell, David J; Dacombe, Russell; Graham, Stephen M; Hicks, Alexander; Cohen, Danielle; Chikaonda, Tarsizio; French, Neil; Molyneux, Malcolm E; Zijlstra, Ed E; Squire, S Bertel; Gordon, Stephen B

2010-01-01

Setting Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis control. Methods to augment sputum collection are available but their additional benefit is uncertain in resource-limited settings. Objective To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. Design Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients, provided physiotherapy-assisted sputum and induced sputum followed, the next morning, by gastric washing and bronchoalveolar-lavage samples. Results 150 patients, diagnosed with smear-negative PTB by the hospital service, were screened. 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled; 89% were HIV positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. 44 (95.6%) of the 46 smear-positive cases could be detected from self-expectorated and physiotherapy-assisted samples Conclusions For countries like Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using bronchoalveolar-lavage after induced sputum is limited. PMID:19105886

Yard flooding by irrigation canals increased the risk of West Nile disease in El Paso, Texas

PubMed Central

Cardenas, Victor M.; Jaime, Javier; Ford, Paula B.; Gonzalez, Fernando J.; Carrillo, Irma; Gallegos, Jorge E.; Watts, Douglas M.

2011-01-01

Purpose To investigate the effects of use of water from irrigation canals to flood residential yards on the risk of West Nile disease in El Paso, Texas. Methods West Nile disease confirmed cases in 2009–2010 were compared with a random sample of 50 residents of the county according to access to and use of water from irrigation canals by subjects or their neighbors, as well as geo-referenced closest distance between their home address and the nearest irrigation canal. A windshield survey of 600 meters around the study subjects’ home address recorded the presence of irrigation canals. The distance from the residence of 182 confirmed cases of West Nile disease reported in 2003–2010 to canals was compared to that of the centroids of 182 blocks selected at random. Results Cases were more likely than controls to report their neighbors flooded their yards with water from canals. Irrigation canals were more often observed in neighborhoods of cases than of controls. Using the set of addresses of 182 confirmed cases and 182 hypothetic controls the authors found a statistically significant inverse relation with risk of West Nile disease. Conclusions Flooding of yards with water from canals increased the risk of West Nile disease. PMID:21943648

Yard flooding by irrigation canals increased the risk of West Nile disease in El Paso, Texas.

PubMed

Cardenas, Victor M; Jaime, Javier; Ford, Paula B; Gonzalez, Fernando J; Carrillo, Irma; Gallegos, Jorge E; Watts, Douglas M

2011-12-01

To investigate the effects of use of water from irrigation canals to flood residential yards on the risk of West Nile disease in El Paso, Texas. West Nile disease confirmed cases in 2009 through 2010 were compared with a random sample of 50 residents of the county according to access to and use of water from irrigation canals by subjects or their neighbors, as well as geo-referenced closest distance between their home address and the nearest irrigation canal. A windshield survey of 600 m around the study subjects' home address recorded the presence of irrigation canals. The distance from the residence of 182 confirmed cases of West Nile disease reported in 2003 through 2010 to canals was compared with that of the centroids of 182 blocks selected at random. Cases were more likely than controls to report their neighbors flooded their yards with water from canals. Irrigation canals were more often observed in neighborhoods of cases than of controls. Using the set of addresses of 182 confirmed cases and 182 hypothetical controls the authors found a significant, inverse relation with risk of West Nile disease. Flooding of yards with water from canals increased the risk of West Nile disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of Humidity Control Options in Hot-Humid Climate Homes (Fact Sheet)

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

Not Available

2011-12-01

This technical highlight describes NREL research to analyze the indoor relative humidity in three home types in the hot-humid climate zone, and examine the impacts of various dehumidification equipment and controls. As the Building America program researches construction of homes that achieve greater source energy savings over typical mid-1990s construction, proper modeling of whole-house latent loads and operation of humidity control equipment has become a high priority. Long-term high relative humidity can cause health and durability problems in homes, particularly in a hot-humid climate. In this study, researchers at the National Renewable Energy Laboratory (NREL) used the latest EnergyPlus toolmore » equipped with the moisture capacitance model to analyze the indoor relative humidity in three home types: a Building America high-performance home; a mid-1990s reference home; and a 2006 International Energy Conservation Code (IECC)-compliant home in hot-humid climate zones. They examined the impacts of various dehumidification equipment and controls on the high-performance home where the dehumidification equipment energy use can become a much larger portion of whole-house energy consumption. The research included a number of simulated cases: thermostat reset, A/C with energy recovery ventilator, heat exchanger assisted A/C, A/C with condenser reheat, A/C with desiccant wheel dehumidifier, A/C with DX dehumidifier, A/C with energy recovery ventilator, and DX dehumidifier. Space relative humidity, thermal comfort, and whole-house source energy consumption were compared for indoor relative humidity set points of 50%, 55%, and 60%. The study revealed why similar trends of high humidity were observed in all three homes regardless of energy efficiency, and why humidity problems are not necessarily unique in the high-performance home. Thermal comfort analysis indicated that occupants are unlikely to notice indoor humidity problems. The study confirmed that supplemental dehumidification is needed to maintain space relative humidity (RH) below 60% in a hot-humid climate home. Researchers also concluded that while all the active dehumidification options included in the study successfully controlled space relative humidity excursions, the increase in whole-house energy consumption was much more sensitive to the humidity set point than the chosen technology option. In the high-performance home, supplemental dehumidification equipment results in a significant source energy consumption penalty at 50% RH set point (12.6%-22.4%) compared to the consumption at 60% RH set point (1.5%-2.7%). At 50% and 55% RH set points, A/C with desiccant wheel dehumidifier and A/C with ERV and high-efficiency DX dehumidifier stand out as the two cases resulting in the smallest increase of source energy consumption. At an RH set point of 60%, all explicit dehumidification technologies result in similar insignificant increases in source energy consumption and thus are equally competitive.« 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.

Case Studies Nested in Fuzzy-Set QCA on Sufficiency: Formalizing Case Selection and Causal Inference

ERIC Educational Resources Information Center

Schneider, Carsten Q.; Rohlfing, Ingo

2016-01-01

Qualitative Comparative Analysis (QCA) is a method for cross-case analyses that works best when complemented with follow-up case studies focusing on the causal quality of the solution and its constitutive terms, the underlying causal mechanisms, and potentially omitted conditions. The anchorage of QCA in set theory demands criteria for follow-up…

Assimilation of Quality Controlled AIRS Temperature Profiles using the NCEP GFS

NASA Technical Reports Server (NTRS)

Susskind, Joel; Reale, Oreste; Iredell, Lena; Rosenberg, Robert

2013-01-01

We have previously conducted a number of data assimilation experiments using AIRS Version-5 quality controlled temperature profiles as a step toward finding an optimum balance of spatial coverage and sounding accuracy with regard to improving forecast skill. The data assimilation and forecast system we used was the Goddard Earth Observing System Model , Version-5 (GEOS-5) Data Assimilation System (DAS), which represents a combination of the NASA GEOS-5 forecast model with the National Centers for Environmental Prediction (NCEP) operational Grid Point Statistical Interpolation (GSI) global analysis scheme. All analyses and forecasts were run at a 0.5deg x 0.625deg spatial resolution. Data assimilation experiments were conducted in four different seasons, each in a different year. Three different sets of data assimilation experiments were run during each time period: Control; AIRS T(p); and AIRS Radiance. In the "Control" analysis, all the data used operationally by NCEP was assimilated, but no AIRS data was assimilated. Radiances from the Aqua AMSU-A instrument were also assimilated operationally by NCEP and are included in the "Control". The AIRS Radiance assimilation adds AIRS observed radiance observations for a select set of channels to the data set being assimilated, as done operationally by NCEP. In the AIRS T(p) assimilation, all information used in the Control was assimilated as well as Quality Controlled AIRS Version-5 temperature profiles, i.e., AIRS T(p) information was substituted for AIRS radiance information. The AIRS Version-5 temperature profiles were presented to the GSI analysis as rawinsonde profiles, assimilated down to a case-by-case appropriate pressure level p(sub best) determined using the Quality Control procedure. Version-5 also determines case-by-case, level-by-level error estimates of the temperature profiles, which were used as the uncertainty of each temperature measurement. These experiments using GEOS-5 have shown that forecasts resulting from analyses using the AIRS T(p) assimilation system were superior to those from the Radiance assimilation system, both with regard to global 7 day forecast skill and also the ability to predict storm tracks and intensity.

Quantitative analysis of multiple biokinetic models using a dynamic water phantom: A feasibility study

PubMed Central

Chiang, Fu-Tsai; Li, Pei-Jung; Chung, Shih-Ping; Pan, Lung-Fa; Pan, Lung-Kwang

2016-01-01

ABSTRACT This study analyzed multiple biokinetic models using a dynamic water phantom. The phantom was custom-made with acrylic materials to model metabolic mechanisms in the human body. It had 4 spherical chambers of different sizes, connected by 8 ditches to form a complex and adjustable water loop. One infusion and drain pole connected the chambers to an auxiliary silicon-based hose, respectively. The radio-active compound solution (TC-99m-MDP labeled) formed a sealed and static water loop inside the phantom. As clean feed water was infused to replace the original solution, the system mimicked metabolic mechanisms for data acquisition. Five cases with different water loop settings were tested and analyzed, with case settings changed by controlling valve poles located in the ditches. The phantom could also be changed from model A to model B by transferring its vertical configuration. The phantom was surveyed with a clinical gamma camera to determine the time-dependent intensity of every chamber. The recorded counts per pixel in each chamber were analyzed and normalized to compare with theoretical estimations from the MATLAB program. Every preset case was represented by uniquely defined, time-dependent, simultaneous differential equations, and a corresponding MATLAB program optimized the solutions by comparing theoretical calculations and practical measurements. A dimensionless agreement (AT) index was recommended to evaluate the comparison in each case. ATs varied from 5.6 to 48.7 over the 5 cases, indicating that this work presented an acceptable feasibility study. PMID:27286096

T-cell acute lymphoblastic leukemia associated with complex karyotype and SET-NUP214 rearrangement: a case study and review of the literature.

PubMed

Lee, Sang-Guk; Park, Tae Sung; Cho, Sun Young; Lim, Gayoung; Park, Gwang Jin; Oh, Seung Hwan; Cho, Eun Hae; Chong, So Young; Huh, Ji Young

2011-01-01

SET-NUP214 rearrangements have been rarely reported in T-cell acute lymphoblastic leukemia (T-ALL), acute undifferentiated leukemia, and acute myeloid leukemia, and most documented cases have been associated with normal karyotypes in conventional cytogenetic analyses. Here, we describe a novel case of T-ALL associated with a mediastinal mass and a SET-NUP214 rearrangement, which was masked by a complex karyotype at the time of initial diagnosis. Using multiplex reverse transcriptase-polymerase chain reaction analysis, we detected a cryptic SET-NUP214 rearrangement in our patient. As only 11 cases (including the present study) of T-ALL with SET-NUP214 rearrangement have been reported, the clinical features and treatment outcomes have not been fully determined. Further studies are necessary to evaluate the incidence of SET-NUP214 rearrangement in T-ALL patients and the treatment responses as well as prognosis of these patients.

Hybrid time-variant reliability estimation for active control structures under aleatory and epistemic uncertainties

NASA Astrophysics Data System (ADS)

Wang, Lei; Xiong, Chuang; Wang, Xiaojun; Li, Yunlong; Xu, Menghui

2018-04-01

Considering that multi-source uncertainties from inherent nature as well as the external environment are unavoidable and severely affect the controller performance, the dynamic safety assessment with high confidence is of great significance for scientists and engineers. In view of this, the uncertainty quantification analysis and time-variant reliability estimation corresponding to the closed-loop control problems are conducted in this study under a mixture of random, interval, and convex uncertainties. By combining the state-space transformation and the natural set expansion, the boundary laws of controlled response histories are first confirmed with specific implementation of random items. For nonlinear cases, the collocation set methodology and fourth Rounge-Kutta algorithm are introduced as well. Enlightened by the first-passage model in random process theory as well as by the static probabilistic reliability ideas, a new definition of the hybrid time-variant reliability measurement is provided for the vibration control systems and the related solution details are further expounded. Two engineering examples are eventually presented to demonstrate the validity and applicability of the methodology developed.

The relationship between prior antimicrobial prescription and meningitis: a case–control study

PubMed Central

Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

2016-01-01

Background Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. Aim The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome. Design and setting A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression. Results A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received ≥4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls. Conclusion There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients. PMID:26965030

Design and rationale for Home Blood Pressure Telemonitoring and Case Management to Control Hypertension (HyperLink): a cluster randomized trial.

PubMed

Margolis, Karen L; Kerby, Tessa J; Asche, Stephen E; Bergdall, Anna R; Maciosek, Michael V; O'Connor, Patrick J; Sperl-Hillen, JoAnn M

2012-07-01

Patients with high blood pressure (BP) visit a physician an average of 4 times or more per year in the U.S., yet BP is controlled in fewer than half. Practical, robust and sustainable models are needed to improve BP in patients with uncontrolled hypertension. The Home Blood Pressure Telemonitoring and Case Management to Control Hypertension study (HyperLink) is a cluster-randomized trial designed to determine whether an intervention that combines home BP telemonitoring with pharmacist case management improves BP control compared to usual care at 6 and 12 months in patients with uncontrolled hypertension. Secondary outcomes are maintenance of BP control at 18 months, patient satisfaction with their health care, and costs of care. HyperLink enrolled 450 hypertensive patients with uncontrolled BP from 16 primary care clinics. Eight clinics were randomized to provide usual care (UC) to their patients (n=222) and 8 were randomized to provide the telemonitoring intervention (TI) (n=228). TI patients received home BP telemonitors that internally store and electronically transmit BP data to a secure database. Pharmacist case managers adjust antihypertensive therapy based on the home BP data under a collaborative practice agreement with the clinics' primary care teams. The length of the intervention is 12 months, with follow-up to 18 months to determine the durability of the intervention. We will test in a real primary care setting whether combining BP telemonitoring and pharmacist case management can achieve and maintain high rates of BP control compared to usual care. Copyright © 2012 Elsevier Inc. All rights reserved.

A Comprehensive Analysis of Nuclear-Encoded Mitochondrial Genes in Schizophrenia.

PubMed

Gonçalves, Vanessa F; Cappi, Carolina; Hagen, Christian M; Sequeira, Adolfo; Vawter, Marquis P; Derkach, Andriy; Zai, Clement C; Hedley, Paula L; Bybjerg-Grauholm, Jonas; Pouget, Jennie G; Cuperfain, Ari B; Sullivan, Patrick F; Christiansen, Michael; Kennedy, James L; Sun, Lei

2018-05-01

The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial dysfunction may play a role in SCZ, but comprehensive association studies are lacking. We hypothesized that variants in nuclear-encoded mitochondrial genes influence susceptibility to SCZ. We conducted gene-based and gene-set analyses using summary association results from the Psychiatric Genomics Consortium Schizophrenia Phase 2 (PGC-SCZ2) genome-wide association study comprising 35,476 cases and 46,839 control subjects. We applied the MAGMA method to three sets of nuclear-encoded mitochondrial genes: oxidative phosphorylation genes, other nuclear-encoded mitochondrial genes, and genes involved in nucleus-mitochondria crosstalk. Furthermore, we conducted a replication study using the iPSYCH SCZ sample of 2290 cases and 21,621 control subjects. In the PGC-SCZ2 sample, 1186 mitochondrial genes were analyzed, among which 159 had p values < .05 and 19 remained significant after multiple testing correction. A meta-analysis of 818 genes combining the PGC-SCZ2 and iPSYCH samples resulted in 104 nominally significant and nine significant genes, suggesting a polygenic model for the nuclear-encoded mitochondrial genes. Gene-set analysis, however, did not show significant results. In an in silico protein-protein interaction network analysis, 14 mitochondrial genes interacted directly with 158 SCZ risk genes identified in PGC-SCZ2 (permutation p = .02), and aldosterone signaling in epithelial cells and mitochondrial dysfunction pathways appeared to be overrepresented in this network of mitochondrial and SCZ risk genes. This study provides evidence that specific aspects of mitochondrial function may play a role in SCZ, but we did not observe its broad involvement even using a large sample. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Temporal patterns of change in vital signs and Cardiac Arrest Risk Triage scores over the 48 hours preceding fatal in-hospital cardiac arrest.

PubMed

Oh, HyunSoo; Lee, KangIm; Seo, WhaSook

2016-05-01

To determine temporal patterns of vital sign and Cardiac Arrest Risk Triage score changes over the 48-hour period preceding cardiac arrest in an ICU setting. Vital sign instability usually occurs prior to cardiac arrest. However, few studies have been conducted on the temporal patterns of individual vital signs preceding cardiac arrest. A retrospective case-control study. The study subjects were 140 ICU patients (1 June 2011-31 December 2012): 46 died of cardiac arrest (case group), 45 died of other illnesses (control I group) and 49 were discharged after recovering (control II group). Initial detectable changes in blood pressure appeared 18-20 hours and became dramatic at 5-10 hours before cardiac arrest. Noticeable changes in heart rates began at 4 hours and became more prominent at 2 hours pre-arrest. No apparent patterns in respiratory rate changes were observed. Body temperatures usually indicated a hypothermic state pre-arrest. Cardiac Arrest Risk Triage scores were 16-18 at 48 hours pre-arrest and then continuously increased to 20. Only mean values of systolic blood pressures were significantly different between the three study groups. Mean diastolic blood pressures, heart rates, respiratory rates and Cardiac Arrest Risk Triage scores differed between the case and control II groups and between the control I and II groups. The study demonstrates vital sign instability preceded cardiac arrest and that the temporal patterns of changes in individual vital signs and Cardiac Arrest Risk Triage scores differed between groups. The findings of this study may aid the development of management strategies for cardiac arrest. © 2016 John Wiley & Sons Ltd.

CYP1A1, GCLC, AGT, AGTR1 gene-gene interactions in community-acquired pneumonia pulmonary complications.

PubMed

Salnikova, Lyubov E; Smelaya, Tamara V; Golubev, Arkadiy M; Rubanovich, Alexander V; Moroz, Viktor V

2013-11-01

This study was conducted to establish the possible contribution of functional gene polymorphisms in detoxification/oxidative stress and vascular remodeling pathways to community-acquired pneumonia (CAP) susceptibility in the case-control study (350 CAP patients, 432 control subjects) and to predisposition to the development of CAP complications in the prospective study. All subjects were genotyped for 16 polymorphic variants in the 14 genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFα. Risk of pulmonary complications (PC) in the single locus analysis was associated with CYP1A1, GCLC and AGTR1 genes. Extra PC (toxic shock syndrome and myocarditis) were not associated with these genes. We evaluated gene-gene interactions using multi-factor dimensionality reduction, and cumulative gene risk score approaches. The final model which included >5 risk alleles in the CYP1A1 (rs2606345, rs4646903, rs1048943), GCLC, AGT, and AGTR1 genes was associated with pleuritis, empyema, acute respiratory distress syndrome, all PC and acute respiratory failure (ARF). We considered CYP1A1, GCLC, AGT, AGTR1 gene set using Set Distiller mode implemented in GeneDecks for discovering gene-set relations via the degree of sharing descriptors within a given gene set. N-acetylcysteine and oxygen were defined by Set Distiller as the best descriptors for the gene set associated in the present study with PC and ARF. Results of the study are in line with literature data and suggest that genetically determined oxidative stress exacerbation may contribute to the progression of lung inflammation.

Cognitive switching processes in young people with attention-deficit/hyperactivity disorder.

PubMed

Oades, Robert D; Christiansen, Hanna

2008-01-01

Patients with attention-deficit/hyperactivity disorder (ADHD) can be slow at switching between stimuli, or between sets of stimuli to control behaviour appropriate to changing situations. We examined clinical and experimental parameters that may influence the speed of such processes measured in the trail-making (TMT) and switch-tasks in cases with ADHD combined type, their non-affected siblings and unrelated healthy controls. The latency for completion of the trail-making task controlling for psychomotor processing (TMT-B-A) was longer for ADHD cases, and correlated with Conners' ratings of symptom severity across all subjects. The effect decreased with age. Switch-task responses to questions of "Which number?" and "How many?" between sets of 1/111 or 3/333 elicited differential increases in latency with condition that affected all groups. But there was evidence for increased symptom-related intra-individual variability among the ADHD cases, and across all subjects. Young siblings showed familiality for some measures of TMT and switch-task performance but these were modest. The potential influences of moderator variables on the efficiency of processing stimulus change rather than the speed of processing are discussed.

How State-Funded Home Care Programs Respond to Changes in Medicare Home Health Care: Resource Allocation Decisions on the Front Line

PubMed Central

Corazzini, Kirsten

2003-01-01

Objective To examine how case managers in a state-funded home care program allocate home care services in response to information about a client's Medicare home health care status, with particular attention to the influence of work environment. Data Sources/Study Setting Primary data collected on 355 case managers and 26 agency directors employed in June 1999 by 26 of the 27 regional agencies administering the Massachusetts Home Care Program for low-income elders. Study Design Data were collected in a cross-sectional survey study design. A case manager survey included measures of work environment, demographics, and factorial survey vignette clients (N=2,054), for which case managers assessed service eligibility levels. An agency director survey included measures of management practices. Data Collection/Extraction Methods Hierarchical linear models estimated the effects of work environment on the relationship between client receipt of Medicare home health care and care plan levels while controlling for case-mix differences in agencies' clients. Principal Findings Case managers did not supplement extant Medicare home health services, but did allocate more generous service plans to clients who have had Medicare home health care services recently terminated. This finding persisted when controlling for case mix and did not vary by work environment. Work environment affected overall care plan levels. Conclusions Study findings indicate systematic patterns of frontline resource allocation shaping the relationships among community-based long-term care payment sources. Further, results illustrate how nonuniform implementation of upper-level initiatives may be partially attributed to work environment characteristics. PMID:14596390

The Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplant

PubMed Central

Stewart, Darren E.; Bista, Bipin R.; Salkowski, Nicholas; Snyder, Jon J.; Israni, Ajay K.; Crary, Gretchen S.; Rosendale, John D.; Matas, Arthur J.; Delmonico, Francis L.

2014-01-01

Background and objectives There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. Design, setting, participants, & measurements In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). Results The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R2) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. Conclusions Routine use of biopsies could lead to unnecessary kidney discards. PMID:24558053

Ada (Trademark) Case Studies II.

DTIC Science & Technology

1984-01-01

number ( CSN ) in that character set’s "transmission identifier". The array is named START CSN , but a better name would be STARTOFCSN. The word of...protocols), CSN (Channel Sequence Number), EON (End of Message), LMF (Line Media Format), MCB (Message Control Block), RI (Routing Indicator), and TI...component names should end with -PART, - FIELD , or COMPONENT.El - Package names should end with PACKAGE. - Enumeration literals should have suffixes

Cochlear implantation in patients with autoimmune inner ear disease including cogan syndrome: a comparison with age- and sex-matched controls.

PubMed

Wang, Jenny R; Yuen, Heng W; Shipp, David B; Stewart, Suzanne; Lin, Vincent Y W; Chen, Joseph M; Nedzelski, Julian M

2010-12-01

Evaluate the characteristics and outcomes of patients with autoimmune inner ear disease (AIED) who have undergone cochlear implantation (CI) and compare post-CI performance in AIED to matched controls. Retrospective case control study. Study cohort was comprised of 25 adult implantees (AIED [n = 18], Cogan syndrome [n = 7]). The AIED group was defined by rapidly progressive bilateral sensorineural hearing loss leading to unusable hearing within weeks to months. Patients with Cogan syndrome, the archetypal inner ear autoimmune disease, were also examined and used for within-cohort comparison. Clinical and operative records were reviewed. Post-CI performance was assessed using open-set sentence tests. Age- and sex-matched individuals deafened by other postlingual causes were used as controls. Of 25 patients, 24 had uneventful, full electrode insertions. One AIED patient had partial insertion due to cochlear ossification and did not achieve open-set speech perception post-CI. Mean open-set sentence scores for study patients with uneventful insertions were 92.8%, 97.3%, and 96.4% at 6 months, 1 year, and ≥ 2 years, respectively. Compared to matched controls, patients deafened by autoimmune causes had significantly higher post-CI performance at all postoperative test intervals (P < .05). There was no significant difference in postimplantation performance between Cogan syndrome and AIED patients. To our knowledge this was the largest study of cochlear implantation in AIED and Cogan syndrome patients. In our experience, both groups generally attained high levels of post-CI speech perception and performed above average. Cochlear ossification affecting implantation in Cogan syndrome patients was not observed in our series, contrary to some reports.

Is gamma-glutamyl transpeptidase a biomarker for oxidative stress in periodontitis?

PubMed Central

Sreeram, Meenakshi; Suryakar, Adinath Narayan; Dani, Nitin Hemchandra

2015-01-01

Context: Periodontal disease and oxidative stress (OS) are part of a vicious cycle with each causing a deleterious effect on the other causing changes in the levels of antioxidants, and enzymes of antioxidant defense. Biomarkers and methods used for measuring OS are very expensive. Aims: To see how gamma-glutamyltransferase (GGT) fares, as a biomarker for OS in periodontits along with other routinely used biomarkers. Design: A cross-sectional study involving 300 people of which 150 were cases and 150 were controls. Setting: Candidates enrolled were patients visiting the OPD of MGV's Dental College and Hospital, Nasik, India between January 2011 and December 2012. Materials and Methods: Serum samples of patients with periodontitis, and controls were analyzed for malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, and GGT. Statistical Analysis Used: Analysis was performed using Student's t test. P <0.05 were considered to be significant. Results: Malondialdehyde values were found to be significantly higher cases, while SOD, GPx and uric acid levels were found to be lower than controls. GGT levels were significantly higher in cases as compared to controls. Conclusions: GGT may be used as a cheap, quick, easy and precise marker for measuring OS. PMID:26015663

Assessing the Sensitivity of Treatment Effect Estimates to Differential Follow-Up Rates: Implications for Translational Research

PubMed Central

McCaffrey, Daniel; Ramchand, Rajeev; Hunter, Sarah B.; Suttorp, Marika

2012-01-01

We develop a new tool for assessing the sensitivity of findings on treatment effectiveness to differential follow-up rates in the two treatment conditions being compared. The method censors the group with the higher response rate to create a synthetic respondent group that is then compared with the observed cases in the other condition to estimate a treatment effect. Censoring is done under various assumptions about the strength of the relationship between follow-up and outcomes to determine how informative differential dropout can alter inferences relative to estimates from models that assume the data are missing at random. The method provides an intuitive measure for understanding the strength of the association between outcomes and dropout that would be required to alter inferences about treatment effects. Our approach is motivated by translational research in which treatments found to be effective under experimental conditions are tested in standard treatment conditions. In such applications, follow-up rates in the experimental setting are likely to be substantially higher than in the standard setting, especially when observational data are used in the evaluation. We test the method on a case study evaluation of the effectiveness of an evidence-supported adolescent substance abuse treatment program (Motivational Enhancement Therapy/Cognitive Behavioral Therapy-5 [MET/CBT-5]) delivered by community-based treatment providers relative to its performance in a controlled research trial. In this case study, follow-up rates in the community based settings were extremely low (54%) compared to the experimental setting (95%) giving raise to concerns about non-ignorable drop-out. PMID:22956890

Translating childhood tuberculosis case management research into operational policies.

PubMed

Safdar, N; Hinderaker, S G; Baloch, N A; Enarson, D A; Khan, M A; Morkve, O

2011-08-01

The control of childhood tuberculosis (TB) has been of low priority in TB programmes in high-burden settings. The objective of this paper was to describe the development and testing of tools for the management of childhood TB. The Pakistan National TB Control Programme embarked on a number of activities, including the establishment of policy guidelines for the management of childhood TB and later a guidance document, 'Case Management Desk Guide and Structured Monitoring', to demonstrate the implementation of childhood TB interventions in a programme context. Initial results showed improved case finding and treatment outcome in implementation sites compared with control districts. However, further programme attention is required to improve quality.

Association between protozoa in sputum and asthma: a case-control study.

PubMed

van Woerden, Hugo C; Ratier-Cruz, Adriana; Aleshinloye, Olabode B; Martinez-Giron, Rafael; Gregory, Clive; Matthews, Ian P

2011-06-01

Atypical infectious agents have been proposed as potential contributors to asthma. A novel set of morphological and staining criteria permit the identification of flagellated protozoa in sputum. This case-control study was designed to use this novel method and to assess: (1) are protozoa more common in asthmatics than in non-asthmatics; (2) is the presence of protozoa associated with the use of steroid inhalers; and (3) is the presence of protozoa associated with living in damp housing? Induced sputum samples were collected from asthma patients and local non-atopic, non-smoking controls. Questionnaires assessed asthma severity and housing conditions. Sputum was examined for flagellated protozoa using a previously described staining technique. 96 participants were recruited for this study; 54 asthma patients and 42 controls, age range 21-62 years, 70% female participants. Limiting results to those who were clearly positive or negative for flagellated protozoa, 66.7% (20/30) of asthmatics and 30.8% (4/13) of controls had protozoa (p = 0.046). Among the asthma patients, prevalence of protozoa was not significantly different between those who had (10/18), and those who had not (10/12), used steroid inhaler in the preceding two weeks (p = 0.11). Similarly, the prevalence of protozoa was not significantly different between those who did (6/11) and those who did not (18/32), live in damp homes (p = 0.92). This case-control study demonstrates an association between flagellated protozoa in sputum and asthma. It is now necessary to confirm and characterise the protozoa using genetic techniques based on 18S ribosomal RNA. Once tis is established it would be worthwhile to determine if asthma symptoms improve when treated by anti-protozoal agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

On Making a Distinguished Vertex Minimum Degree by Vertex Deletion

NASA Astrophysics Data System (ADS)

Betzler, Nadja; Bredereck, Robert; Niedermeier, Rolf; Uhlmann, Johannes

For directed and undirected graphs, we study the problem to make a distinguished vertex the unique minimum-(in)degree vertex through deletion of a minimum number of vertices. The corresponding NP-hard optimization problems are motivated by applications concerning control in elections and social network analysis. Continuing previous work for the directed case, we show that the problem is W[2]-hard when parameterized by the graph's feedback arc set number, whereas it becomes fixed-parameter tractable when combining the parameters "feedback vertex set number" and "number of vertices to delete". For the so far unstudied undirected case, we show that the problem is NP-hard and W[1]-hard when parameterized by the "number of vertices to delete". On the positive side, we show fixed-parameter tractability for several parameterizations measuring tree-likeness, including a vertex-linear problem kernel with respect to the parameter "feedback edge set number". On the contrary, we show a non-existence result concerning polynomial-size problem kernels for the combined parameter "vertex cover number and number of vertices to delete", implying corresponding nonexistence results when replacing vertex cover number by treewidth or feedback vertex set number.

Estimation of the marginal effect of regular drug use on multiple sclerosis in the Iranian population.

PubMed

Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Schuster, Tibor

2018-01-01

There are only few reports regarding the role of lifetime drug or substance use in multiple sclerosis (MS) etiology. In this study, we investigated the potential effect of drug or substance exposure on the onset of MS diagnosis. We conducted a population-based incident case control study in Tehran. Cases (n = 547) were 15-50 years old persons with MS identified from the Iranian Multiple Sclerosis Society (IMSS) register during August 7, 2013, and November 17, 2015. Population-based controls (n = 1057) were 15-50 years old and were recruited by random digit telephone dialing. Inverse-probability-of-treatment weighing (IPTW) using two sets of propensity scores (PSs) was used to estimate marginal incidence odds ratios (ORs) for MS contrasting pre-specified substance use. The estimated marginal OR was 6.03 (95% confidence interval: 3.54;10.3, using trimmed weights at the 95th percentile of the stabilized weight distribution) in both IPTW analyses comparing lifetime substance use (opioids, cannabis, inhalants, hallucinogens and stimulants) for at least one time monthly during a six-months or longer period vs. no such history of drug use. Subject to limitation of causal claims based on case-control studies, this study suggests that monthly drug or substance use for a period of at least six consecutive months, may increase the risk of MS by factor 3.5 or higher.

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

PubMed Central

Hernandez, Rohini K

2011-01-01

Objective To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel. Design Nested case-control and cohort study. Setting The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans. Participants The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time. Main outcome measures Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives. Results 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100 000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100 000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8). Conclusions The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account. PMID:21511805

Costs of newly diagnosed neovascular age-related macular degeneration among medicare beneficiaries, 2004-2008.

PubMed

Qualls, Laura G; Hammill, Bradley G; Wang, Fang; Lad, Eleonora M; Schulman, Kevin A; Cousins, Scott W; Curtis, Lesley H

2013-04-01

To examine associations between newly diagnosed neovascular age-related macular degeneration and direct medical costs. This retrospective observational study matched 23,133 Medicare beneficiaries diagnosed with neovascular age-related macular degeneration between 2004 and 2008 with a control group of 92,532 beneficiaries on the basis of age, sex, and race. The index date for each case-control set corresponded to the first diagnosis for the case. Main outcome measures were total costs per patient and age-related macular degeneration-related costs per case 1 year before and after the index date. Mean cost per case in the year after diagnosis was $12,422, $4,884 higher than the year before diagnosis. Postindex costs were 41% higher for cases than controls after adjustment for preindex costs and comorbid conditions. Age-related macular degeneration-related costs represented 27% of total costs among cases in the postindex period and were 50% higher for patients diagnosed in 2008 than in 2004. This increase was attributable primarily to the introduction of intravitreous injections of vascular endothelial growth factor antagonists. Intravitreous injections averaged $203 for patients diagnosed in 2004 and $2,749 for patients diagnosed in 2008. Newly diagnosed neovascular age-related macular degeneration was associated with a substantial increase in total medical costs. Costs increased over time, reflecting growing use of anti-vascular endothelial growth factor therapies.

[Incidence study of listeriosis in Spain].

PubMed

Valero, Fernando Parrilla; Rafart, Josep Vaqué

2014-01-01

We performed a descriptive retrospective study of cases of listeriosis occurring in Spain from 2001 to 2007 to determine the burden and trend of this disease in our setting. Several sources of information were used. Epidemiological information was collected from 1.242 cases of listeriosis, representing a mean incidence rate of 0,56 cases per 100.000 inhabitants per year, which was extrapolated as an overall estimate for Spain. The annual incidence showed a statistically significant increasing trend (p <0,001) over the study period. This figure was higher than that reported in Spain (0,16) by the Microbiological Information System, which is voluntary, showing that underreporting exists. The inclusion of listeriosis in the Mandatory Notification System would allow determination of the distribution and characteristics of this infection in humans, as well as promotion of effective prevention and control. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study.

PubMed

Irving, W L; James, D K; Stephenson, T; Laing, P; Jameson, C; Oxford, J S; Chakraverty, P; Brown, D W; Boon, A C; Zambon, M C

2000-10-01

To determine whether maternal influenza virus infection in the second and third trimesters of pregnancy results in transplacental transmission of infection, maternal auto-antibody production or an increase in complications of pregnancy. Case-control cohort study. Study and control cohorts were derived from 3,975 women who were consecutively delivered at two Nottingham teaching hospitals between May 1993 and July 1994. A complete set of three sera was available for 1,659 women. Paired maternal ante- and postnatal sera were screened for a rise in anti-influenza virus antibody titre by single radial haemolysis and haemagglutination inhibition. Routine obstetric data collected during and after pregnancy were retrieved from the Nottingham obstetric database. Cord samples were tested for the presence of IgM anti-influenza antibodies, and postnatal infant sera were tested for the persistence of influenza-virus specific IgG. Paired antenatal and postnatal sera were tested against a standard range of auto-antigens by immunofluorescence. Classification of women as having definite serological evidence of an influenza virus infection in pregnancy (cases) or as controls. Intercurrent influenza virus infections were identified in 182/1,659 (11.0%) pregnancies. None of 138 cord sera from maternal influenza cases was positive for influenza A virus specific IgM. IgG anti-influenza antibodies did not persist in any of 12 infant sera taken at age 6-12 months. Six of 172 postnatal maternal sera from cases of influenza were positive for auto-antibodies. In all cases the corresponding antenatal serum was also positive for the same auto-antibody. There were no significant differences in pregnancy outcome measures between cases and controls. Overall, there were significantly more complications of pregnancy in the cases versus the controls, but no single type of complication achieved statistical significance. Influenza infection in the second and third trimesters of pregnancy is a relatively common event. We found no evidence for transplacental transmission of influenza virus or auto-antibody production in pregnancies complicated by influenza infections. There was an increase in the complications of pregnancy in our influenza cohort.

Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study

PubMed Central

Xu, Wang Hong; Zheng, Wei; Xiang, Yong Bing; Ruan, Zhi Xian; Cheng, Jia Rong; Dai, Qi; Gao, Yu Tang; Shu, Xiao Ou

2004-01-01

Objective To evaluate the association of intake of soya food, a rich source of phytoestrogens, with the risk of endometrial cancer. Design Population based case-control study, with detailed information on usual soya food intake over the past five years collected by face to face interview using a food frequency questionnaire. Setting Urban Shanghai, China. Participants 832 incident cases of endometrial cancer in women aged of 30 to 69 years diagnosed during 1997-2001 and identified from the Shanghai Cancer Registry; 846 control women frequency matched to cases on age and randomly selected from the Shanghai Residential Registry. Main outcome measures Odds ratios for risk of endometrial cancer in women with different intakes of soya foods. Results Regular consumption of soya foods, measured as amount of either soya protein or soya isoflavones, was inversely associated with the risk of endometrial cancer. Compared with women with the lowest quarter of intake, the adjusted odds ratio of endometrial cancer was reduced from 0.93 to 0.85 and 0.67 with increasing quarter of soya protein intake (P for trend 0.01). A similar inverse association was observed for soya isoflavones and soya fibre intake. The inverse association seemed to be more pronounced among women with high body mass index and waist:hip ratio. Conclusion Regular intake of soya foods is associated with a reduced risk of endometrial cancer. PMID:15136343

[Study protocol of a prevention of recurrent suicidal behaviour program based on case management (PSyMAC)].

PubMed

Sáiz, Pilar A; Rodríguez-Revuelta, Julia; González-Blanco, Leticia; Burón, Patricia; Al-Halabí, Susana; Garrido, Marlen; García-Alvarez, Leticia; García-Portilla, Paz; Bobes, Julio

2014-01-01

Prevention of suicidal behaviour is a public health priority in the European Union. A previous suicide attempt is the best risk predictor for future attempts, as well as completed suicides. The primary aim of this article is to describe a controlled study protocol designed for prevention of recurrent suicidal behaviour that proposes case management, and includes a psychoeducation program, as compared with the standard intervention (PSyMAC). Patients admitted from January 2011 to June 2013 to the emergency room of the Hospital Universitario Central de Asturias were evaluated using a protocol including sociodemographic, psychiatric, and psychosocial assessment. Patients were randomly assigned to either a group receiving continuous case management including participation in a psychoeducation program (experimental group), or a control group receiving standard care. The primary objective is to examine whether or not the period of time until recurrent suicidal behaviour in the experimental group is significantly different from that of the control group. PSyMAC proposes low cost and easily adaptable interventions to the usual clinical setting that can help to compensate the shortcoming of specific action protocols and suicidal behaviour prevention programs in our country. The evaluation of PSyMAC results will determine their real effectivity as a case-magament program to reduce suicidal risk. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

Performance factors of mobile rich media job aids for community health workers

PubMed Central

Florez-Arango, Jose F; Dunn, Kim; Zhang, Jiajie

2011-01-01

Objective To study and analyze the possible benefits on performance of community health workers using point-of-care clinical guidelines implemented as interactive rich media job aids on small-format mobile platforms. Design A crossover study with one intervention (rich media job aids) and one control (traditional job aids), two periods, with 50 community health workers, each subject solving a total 15 standardized cases per period per period (30 cases in total per subject). Measurements Error rate per case and task, protocol compliance. Results A total of 1394 cases were evaluated. Intervention reduces errors by an average of 33.15% (p=0.001) and increases protocol compliance 30.18% (p<0.001). Limitations Medical cases were presented on human patient simulators in a laboratory setting, not on real patients. Conclusion These results indicate encouraging prospects for mHealth technologies in general, and the use of rich media clinical guidelines on cell phones in particular, for the improvement of community health worker performance in developing countries. PMID:21292702

Performance factors of mobile rich media job aids for community health workers.

PubMed

Florez-Arango, Jose F; Iyengar, M Sriram; Dunn, Kim; Zhang, Jiajie

2011-01-01

To study and analyze the possible benefits on performance of community health workers using point-of-care clinical guidelines implemented as interactive rich media job aids on small-format mobile platforms. A crossover study with one intervention (rich media job aids) and one control (traditional job aids), two periods, with 50 community health workers, each subject solving a total 15 standardized cases per period per period (30 cases in total per subject). Error rate per case and task, protocol compliance. A total of 1394 cases were evaluated. Intervention reduces errors by an average of 33.15% (p = 0.001) and increases protocol compliance 30.18% (p < 0.001). Limitations Medical cases were presented on human patient simulators in a laboratory setting, not on real patients. These results indicate encouraging prospects for mHealth technologies in general, and the use of rich media clinical guidelines on cell phones in particular, for the improvement of community health worker performance in developing countries.

Control landscapes are almost always trap free: a geometric assessment

NASA Astrophysics Data System (ADS)

Russell, Benjamin; Rabitz, Herschel; Wu, Re-Bing

2017-05-01

A proof is presented that almost all closed, finite dimensional quantum systems have trap free (i.e. free from local optima) landscapes for a large and physically general class of circumstances, which includes qubit evolutions in quantum computing. This result offers an explanation for why gradient-based methods succeed so frequently in quantum control. The role of singular controls is analyzed using geometric tools in the case of the control of the propagator, and thus in the case of observables as well. Singular controls have been implicated as a source of landscape traps. The conditions under which singular controls can introduce traps, and thus interrupt the progress of a control optimization, are discussed and a geometrical characterization of the issue is presented. It is shown that a control being singular is not sufficient to cause control optimization progress to halt, and sufficient conditions for a trap free landscape are presented. It is further shown that the local surjectivity (full rank) assumption of landscape analysis can be refined to the condition that the end-point map is transverse to each of the level sets of the fidelity function. This mild condition is shown to be sufficient for a quantum system’s landscape to be trap free. The control landscape is shown to be trap free for all but a null set of Hamiltonians using a geometric technique based on the parametric transversality theorem. Numerical evidence confirming this analysis is also presented. This new result is the analogue of the work of Altifini, wherein it was shown that controllability holds for all but a null set of quantum systems in the dipole approximation. These collective results indicate that the availability of adequate control resources remains the most physically relevant issue for achieving high fidelity control performance while also avoiding landscape traps.

Screening for Chlamydia trachomatis in Egyptian women with unexplained infertility, comparing real-time PCR techniques to standard serology tests: case control study.

PubMed

Abdella, Rana M A; Abdelmoaty, Hatem I; Elsherif, Rasha H; Sayed, Ahmed Mahmoud; Sherif, Nadine Alaa; Gouda, Hisham M; El Lithy, Ahmed; Almohamady, Maged; Abdelbar, Mostafa; Hosni, Ahmed Naguib; Magdy, Ahmed; Ma, Youssef

2015-06-02

To study the prevalence of Chlamydia infection in women with primary and secondary unexplained infertility using ELISA technique for antibody detection and real time, fully automated PCR for antigen detection and to explore its association with circulating antisperm antibodies (ASA). A total of 50 women with unexplained infertility enrolled in this case control study and a control group of 44 infertile women with a known cause of infertility. Endocervical specimens were collected for Chlamydia antigen detection using PCR and serum samples for antibodies detection. Circulating anti-sperm antibodies were detected using sperm antibody Latex Agglutination tests. The overall prevalence of Chlamydial infection in unexplained infertility cases as detected by both ELISA and PCR was 40 % (20/50). The prevalence of current Chlamydial genital infection as detected by real-time PCR was only 6.0 % (3/50); two of which were also IgM positive. Prevalence of ASA was 6.0 % (3/50); all were sero-negative for anti-C.trachomatis IgM and were PCR negative. The incidence of Chlamydial infection in Egyptian patients with unexplained infertility is relatively high. In the setting of fertility investigations; screening for anti. C.trachomatis antibodies using ELISA, and treatment of positive cases should be considered. The presence of circulating ASA does not correlate with the presence of old or current Chlamydia infection in women with unexplained infertility.

Repeated mass distributions and continuous distribution of long-lasting insecticidal nets: modelling sustainability of health benefits from mosquito nets, depending on case management.

PubMed

Briët, Olivier Jt; Penny, Melissa A

2013-11-07

Stagnating funds for malaria control have spurred interest in the question of how to sustain the gains of recent successes with long-lasting insecticidal nets (LLINs) and improved case management (CM). This simulation study examined the malaria transmission and disease dynamics in scenarios with sustained LLINs and CM interventions and tried to determine optimal LLIN distribution rates. The effects of abruptly halting LLIN distribution were also examined. Dynamic simulations of malaria in humans and mosquitoes were run on the OpenMalaria platform, using stochastic individual-based simulation models. LLINs were distributed in a range of transmission settings, with varying CM coverage levels. In the short-term, LLINs were beneficial over the entire transmission spectrum, reducing both transmission and disease burden. In the long-term, repeated distributions sustainably reduced transmission in all settings. However, because of the resulting reduction in acquired immunity in the population, the malaria disease burden, after initially being reduced, gradually increased and eventually stabilized at a new level. This new level was higher than the pre-intervention level in previously high transmission settings, if there is a maximum disease burden in the relationship between transmission and disease burden at intermediate transmission levels. This result could lead one to conclude that sustained LLIN distribution might not be cost-effective in high transmission settings in the long term. However, improved CM rendered LLINs more cost-effective in higher transmission settings than in those without improved CM and the majority of the African population lives in areas where CM and LLINs are sustainably combined. The effects of changes in LLIN distribution rate on cost-effectiveness were relatively small compared to the effects of changes in transmission setting and CM. Abruptly halting LLIN distribution led to temporary morbidity peaks, which were particularly large in low to intermediate transmission settings. This study reaffirms the importance of context specific intervention planning. Intervention planning must include combinations of malaria vector control and CM, and must consider both the pre-intervention transmission level and the intervention history to account for the loss of immunity and the potential for rebounds in disease burden.