Providing Access to Genomic Variant Knowledge in a Healthcare Setting: A Vision for the ClinGen Electronic Health Records Workgroup.

The Clinical Genome Resource (ClinGen) is a National Institutes of Health (NIH)-funded collaborative program that brings together a variety of projects designed to provide high-quality, curated information on clinically relevant genes and variants. ClinGen's EHR (Electronic Health Record) Workgroup aims to ensure that ClinGen is accessible to providers and patients through EHR and related systems. This article describes the current scope of these efforts and progress to date. The ClinGen public portal can be accessed at www.clinicalgenome.org.

Do peer educators make a difference? An evaluation of a youth-led HIV prevention model in Zambian Schools.

Restless Development's youth-led model places trained Volunteer Peer Educators (VPEs), aged 18-25 years, in schools to teach HIV prevention and reproductive health (RH). VPEs also run youth centers, extracurricular and community-based activities. This evaluation assesses (i) program effects on students' HIV/RH knowledge, attitudes and behaviors using a non-randomized quasi-experimental design among 2133 eighth and ninth grade students in 13 intervention versus 13 matched comparison schools and (ii) program costs. Intervention students had significantly higher levels of knowledge related to HIV [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.18-2.19; P < 0.01] and RH (OR 1.71; 95% CI 1.21-2.49; P < 0.01), more positive attitudes toward people living with HIV and greater self-efficacy to refuse unwanted sex and access condoms. No evidence of differences in ever having had sex was found (28% in the intervention; 29% in the comparison schools). However, intervention students were more likely not to have had sex in the previous year (OR 1.26, 95% CI 1.03-1.56; P < 0.05) and to have had only one sex partner ever (OR 1.43, 95% CI 1.00-2.03; P < 0.05). The average annual cost of the program was US$21 per beneficiary. In conclusion, the youth-led model is associated with increased HIV and RH knowledge and self-efficacy and lowered levels of stigma and sexual risk-taking behaviors.

Changes in condom use during a microbicide clinical trial in Pune, India.

Researchers have raised concerns that microbicide use during clinical trials would displace condom use. We sought to understand whether condom use changed for participants in a microbicide clinical trial in Pune, India, to understand whether condom shifts were a legitimate concern. We hypothesize that women participating in a microbicide clinical trial in Pune, India, were more likely, on average, to report condom use at follow-up. We further hypothesize that men, whose female partners participated in a microbicide clinical trial were more likely, on average, to report condom use at follow-up. The outcome measure for reported condom use was a dichotomous variable to indicate whether or not the participant had used a male or female condom with a sexual partner since 2 months before enrollment or since the last survey, depending on the visit. Data are from semi-structured interviews at baseline, 2 months, 4 months, and 6 months with HPTN 059 clinical trial participants (100 women and 57 male partners). We used generalized estimating equations with a logit link function, exchangeable correlation, and a binomial family to model condom use. The odds of condom use for clinical trial women increased from baseline to 6 months by a factor of 3.7 (95% CI: 1.84-7.63) and the change in odds of condom use for clinical trial men from baseline to 6 months increased by a factor of 2.58 (95% CI: 1.37-4.85). We found concerns about microbicide use displacing condom use were not merited in this study population. The percent of participants reporting condom use declined from 4 to 6 months, suggesting that increases in condom use may only be during active study participation. Information about clinical trial factors that enabled these men and women to enact this important HIV prevention behavior is needed to develop interventions.

Constructed wetlands as a component of the agricultural landscape: mitigation of herbicides in simulated runoff from upland drainage areas.

Constructed wetlands are a recommended practice for buffering pollutant source areas and receiving waters. A wetland consisting of a sediment trap and two treatment cells was constructed in a Mississippi Delta lake watershed. A 3-h simulated runoff event was initiated (2003) to evaluate fate and transport of atrazine and fluometuron through the wetland. Water samples were collected during a runoff simulation and then afterward at selected intervals for 21d, and analyzed for the herbicides. Breakthrough patterns for herbicide concentrations in water samples during the first 20h after simulated runoff showed peak concentrations in the first 6h, with gradual tailing as the herbicide pulse was diluted in the second, excavated (deeper) cell. Atrazine and fluometuron concentrations in the first (shallower, non-excavated) cell averaged 12- and 20-fold greater, respectively, than those in the second cell following simulated runoff, indicating entrapment in the first cell. Atrazine and fluometuron concentrations in the shallower cell decreased 32% and 22%, respectively, 9d following simulated runoff, indicating either degradation or sorption to soil or wetland flora. In the excavated cell, concentrations were even lower, and atrazine declined more rapidly than fluometuron. Results indicate constructed wetlands can improve downstream water quality though sequestration or processing of pollutants.

Clinical factors associated with fatigue over time in paediatric oncology patients receiving chemotherapy.

The purpose of this study was to investigate the relationships between clinical factors (including haemoglobin value, chemotherapeutic agents, and corticosteroid use) and changing patterns of fatigue before and for the next 10 days following the start of a new round of chemotherapy in children with cancer. A prospective longitudinal design was used to collect data from 48 paediatric oncology patients who were about to begin a new round of chemotherapy and their parents. Fatigue levels were assessed using multidomain questionnaires with three categories of patient self-report (including 'General Fatigue', 'Sleep/Rest Fatigue', and 'Cognitive Fatigue') and four categories of parent proxy-report (including 'Lack of Energy', 'Unable to Function', 'Altered Sleep', and 'Altered Mood'). The findings suggest that fatigue from both patient self-report and parent proxy-report changed significantly over time. The major findings from this study are that patients have more problems with fatigue in the first few days after the start of a cycle of chemotherapy. Corticosteroid use and haemoglobin value were associated with significant increases in fatigue that were sustained for several days and reached the highest level of fatigue at day 5 for those receiving concurrent steroids. The association of chemotherapeutic agents with fatigue varied between patient self-report and parent report, but the type of chemotherapeutic agents used was not associated with most changes in fatigue.

Laboratory assessment of atrazine and fluometuron degradation in soils from a constructed wetland.

Constructed wetlands offer promise for removal of nonpoint source contaminants such as herbicides from agricultural runoff. Laboratory studies assessed the potential of soils to degrade and sorb atrazine and fluometuron within a recently constructed wetland. The surface 3 cm of soil was sampled from two cells of a Mississippi Delta constructed wetland; one shallow area disturbed only hydrologically, and the second excavated to provide greater water-holding capacity. The excavated area was more acidic on average (pH 4.85 versus 5.21), but otherwise the physical properties and general microbial enzyme activities in the two areas were similar. Soils were treated with 84 and 68 microg kg(-1) soil (14)C-ring labeled atrazine and fluometuron, respectively, and incubated under either saturated (88% moisture, w:w) or flooded (1cm standing water) conditions. Soils were sampled over 32 days and extracted for herbicide and metabolite analysis. Under saturated conditions, fluometuron metabolized to desmethylfluometuron (DMF) with a half-life equal 25-27 days. However, under flooded conditions, the half-life of fluometuron was more than 175 days. Atrazine dissipated rapidly in saturated and flooded soil with a half-life of approximately 23 days, but only 10% of atrazine was mineralized to CO(2). The overall atrazine and fluometuron dissipation rates were similar between the two cells, but each area had a different pattern of metabolite accumulation. The major route of atrazine dissipation was incorporation of atrazine residues into methanol-nonextractable (soil-bound) components, with minimal extractable metabolite accumulation. A mixed-mode extractant (potassium phosphate:acetonitrile) recovered greater amounts of (14)C-residues from atrazine-treated soils, suggesting that hydrolysis of atrazine to hydroxylated metabolites was a major component of the bound residues. These studies indicate the potential for herbicide dissipation in wetland soils and a differential effect of flooding on the fate of these herbicides.

Comparison of cultural and analytical methods for determination of aflatoxin production by Mississippi Delta Aspergillus isolates.

This study compared cultural and analytical methods for detecting aflatoxin production by Aspergillus species. Aspergillus isolates were obtained from various Mississippi Delta crops (corn, peanut, rice, cotton) and soils. Most of the isolates (99%) were A. flavus and the remainder comprised A. parasiticus and A. nomius. The following three cultural methods were evaluated on potato dextrose agar: fluorescence (FL) on beta-cyclodextrin-containing media (CD), yellow pigment (YP) formation in mycelium and medium, and color change after ammonium hydroxide vapor exposure (AV). Aflatoxins in culture extracts were confirmed by thin-layer chromatography (TLC) and quantified by enzyme-linked immunosorbent assay (ELISA). Of the 517 isolates, 314 produced greater than 20 ng/g of total aflatoxin based on ELISA, and 180 produced greater than 10 000 ng/g of aflatoxin in the medium. Almost all the toxigenic isolates (97%) were confirmed by TLC as producers. Of the toxigenic isolates, as determined by ELISA, 93%, 73%, and 70% gave positive FL, YP, and AV responses, respectively. Of the 203 isolates producing less than 20 ng/g of aflatoxin, 20%, 6%, and 0% of respective FL, YP, and AV methods gave false-positive responses. The 9% false-positive results from TLC fall within this range. This study showed good agreement among all tested cultural methods. However, these cultural techniques did not detect aflatoxin in all cultures that were found to produce aflatoxins by ELISA, LC/MS, and TLC. The best results were obtained when the AV color change and CD fluorescence methods were used together, yielding an overall success rate comparable to TLC but without the need for chemical extraction and the time and expense of TLC.

A semiparametric empirical likelihood method for data from an outcome-dependent sampling scheme with a continuous outcome.

Outcome-dependent sampling (ODS) schemes can be a cost effective way to enhance study efficiency. The case-control design has been widely used in epidemiologic studies. However, when the outcome is measured on a continuous scale, dichotomizing the outcome could lead to a loss of efficiency. Recent epidemiologic studies have used ODS sampling schemes where, in addition to an overall random sample, there are also a number of supplemental samples that are collected based on a continuous outcome variable. We consider a semiparametric empirical likelihood inference procedure in which the underlying distribution of covariates is treated as a nuisance parameter and is left unspecified. The proposed estimator has asymptotic normality properties. The likelihood ratio statistic using the semiparametric empirical likelihood function has Wilks-type properties in that, under the null, it follows a chi-square distribution asymptotically and is independent of the nuisance parameters. Our simulation results indicate that, for data obtained using an ODS design, the semiparametric empirical likelihood estimator is more efficient than conditional likelihood and probability weighted pseudolikelihood estimators and that ODS designs (along with the proposed estimator) can produce more efficient estimates than simple random sample designs of the same size. We apply the proposed method to analyze a data set from the Collaborative Perinatal Project (CPP), an ongoing environmental epidemiologic study, to assess the relationship between maternal polychlorinated biphenyl (PCB) level and children's IQ test performance.

Simultaneous assessment of occupational exposures from multiple worker groups.

The methods developed by Rappaport et al. [Ann. Occup. Hyg. 39 (1995) 469] and Lyles et al. [J. Agri. Bio. Environ. Stat. 2 (1997a) 64; Ann. Occup. Hyg. 41 (1997b) 63]) for assessing workplace exposures on a group-by-group basis are extended to allow for the simultaneous assessment of data from multiple worker groups within the same industry. These extended methods allow models to be fit simultaneously to data on all groups in a study, even when some of the groups might not contribute adequate information to be modeled separately. We assume that the exposures are log-normally distributed, and that they can be adequately modeled by a mixed effects regression model with parameters for exposure levels and for between- and within-worker variance components. Simultaneously analyzing data from multiple groups is only advantageous when at least one of these variance components can be assumed to be homogeneous across the groups. Here, we advocate testing an assumption of homogeneous within-worker variance components, sigma(2)(w,h), using a likelihood ratio test to choose between a full model (distinct sigma(2)(w,h) for each group) and a reduced model (common sigma(2)(w) across groups). We then develop a procedure, which is conditional on the results of the likelihood ratio test, for testing whether or not each group of workers is overexposed to the contaminant of interest. This modeling and testing procedure was applied to 39 different data sets, each containing data for multiple groups, from a wide variety of industries. For these data, the testing procedure generally resulted in the same conclusion regarding overexposure under both models, even in those data sets where the within-worker variance components appeared to be quite heterogeneous. We also conducted a small simulation study to estimate the significance level of the proposed testing procedure, and found that the significance levels tended to be adequately close to the specified nominal level when a likelihood ratio test with significance level of at least 0.01 was used as a preliminary test. Additionally, we make specific recommendations for designing studies and suggest a method for determining whether engineering and administrative controls or individual-level interventions would be of most benefit to an overexposed group of workers.

Acute and chronic pain management in palliative care.

Every palliative care patient should have the expectation that acute and chronic pain management will be an integral part of their overall care. However, in all too many instances, the pain of cancer is often grossly under-treated. This issue is of concern because more than 80% of patients with cancer pain can find adequate relief through the use of simple pharmacological methods. It is even more troubling to note that women and minority groups have their cancer pain under-treated more frequently. Physicians with the basic skills of assessment and treatment will be able to control the symptoms in the majority of cancer pain patients. However, there are still some patients who may require other modalities to control their moderate to severe pain. A thorough understanding of all pain management options will help the gynaecological oncologist to maintain an acceptable quality of life for their patients throughout the therapeutic and palliative phases of care.

Psychological testing variables as predictors of return to work by chronic pain patients.

After multidisciplinary pain treatment, pretreatment psychological testing variables were compared for 20 chronic pain patients who were working and 42 who were not working. Symptom Checklist-90-R scores for Depression, Anxiety, Phobic Anxiety, Psychoticism, Global Severity, and Positive Symptom Distress were lower for working subjects as were those on the Beck Depression Inventory. In contrast, workers scored higher on self-efficacy to manage pain, self-efficacy to function, self-efficacy to manage other symptoms, and over all self-efficacy.

A beta-glucuronidase reporter gene construct for monitoring aflatoxin biosynthesis in Aspergillus flavus.

Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and A. parasiticus. Current research is directed at the elimination of these compounds in important food sources. The objective of this research was to develop a method to study the induction and regulation of aflatoxin biosynthesis by examining the expression of one aflatoxin pathway gene, ver1. The promoter region of ver1 was fused to the beta-glucuronidase (GUS) gene (uidA) from Escherichia coli to form the reporter construct, GAP13. A. flavus 656-2 was transformed with this construct. Aflatoxin production, GUS activity, and transcript accumulation were determined in transformants after shifting the cultures from a nonconducive medium to a medium conducive to aflatoxin biosynthesis. Transformants harboring GAP13 displayed GUS expression only when aflatoxin was detected in culture. Further, the transcription of the uidA gene driven by the ver1 promoter followed the same profile as for the ver1 genes. The results show that the GAP13 construct may be useful as a genetic tool to study the induction of aflatoxin in situ and to identify substances that affect the expression of genes involved in aflatoxin biosynthesis. The utility of this construct to detect inducers of aflatoxin biosynthesis in maize kernels was tested in a bioassay. A heat-stable inducer of aflatoxin with a molecular size of less than 10 kDa was detected in extracts from maize kernels colonized by A. flavus.