Estimating the prevalence of problem drug use from drug-related mortality data.

BACKGROUND AND AIMS: Indirect estimation methods are required for estimating the size of populations where only a proportion of individuals are observed directly, such as problem drug users (PDUs). Capture-recapture and multiplier methods are widely used, but have been criticized as subject to bias. We propose a new approach to estimating prevalence of PDU from numbers of fatal drug-related poisonings (fDRPs) using linked databases, addressing the key limitations of simplistic 'mortality multipliers'. METHODS: Our approach requires linkage of data on a large cohort of known PDUs to mortality registers and summary information concerning additional fDRPs observed outside this cohort. We model fDRP rates among the cohort and assume that rates in unobserved PDUs are equal to rates in the cohort during periods out of treatment. Prevalence is estimated in a Bayesian statistical framework, in which we simultaneously fit regression models to fDRP rates and prevalence, allowing both to vary by demographic factors and the former also by treatment status. RESULTS: We report a case study analysis, estimating the prevalence of opioid dependence in England in 2008/09, by gender, age group and geographical region. Overall prevalence was estimated as 0.82% (95% credible interval = 0.74-0.94%) of 15-64-year-olds, which is similar to a published estimate based on capture-recapture analysis. CONCLUSIONS: Our modelling approach estimates prevalence from drug-related mortality data, while addressing the main limitations of simplistic multipliers. This offers an alternative approach for the common situation where available data sources do not meet the strong assumptions required for valid capture-recapture estimation. In a case study analysis, prevalence estimates based on our approach were surprisingly similar to existing capture-recapture estimates but, we argue, are based on a much more objective and justifiable modelling approach

Elevated Plasma Corticosterone Decreases Yolk Testosterone and Progesterone in Chickens: Linking Maternal Stress and Hormone-Mediated Maternal Effects

Despite considerable research on hormone-mediated maternal effects in birds, the underlying physiology remains poorly understood. This study investigated a potential regulation mechanism for differential accumulation of gonadal hormones in bird eggs. Across vertebrates, glucocorticoids can suppress reproduction by downregulating gonadal hormones. Using the chicken as a model species, we therefore tested whether elevated levels of plasma corticosterone in female birds influence the production of gonadal steroids by the ovarian follicles and thus the amount of reproductive hormones in the egg yolk. Adult laying hens of two different strains (ISA brown and white Leghorn) were implanted subcutaneously with corticosterone pellets that elevated plasma corticosterone concentrations over a period of nine days. Steroid hormones were subsequently quantified in plasma and yolk. Corticosterone-implanted hens of both strains had lower plasma progesterone and testosterone levels and their yolks contained less progesterone and testosterone. The treatment also reduced egg and yolk mass. Plasma estrogen concentrations decreased in white Leghorns only whereas in both strains yolk estrogens were unaffected. Our results demonstrate for the first time that maternal plasma corticosterone levels influence reproductive hormone concentrations in the yolk. Maternal corticosterone could therefore mediate environmentally induced changes in yolk gonadal hormone concentrations. In addition, stressful situations experienced by the bird mother might affect the offspring via reduced amounts of reproductive hormones present in the egg as well as available nutrients for the embryo

The effect of HIV on morbidity and mortality in children with severe malarial anaemia

<p>Abstract</p> <p>Background</p> <p>Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed.</p> <p>Methods</p> <p>Children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children. Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders.</p> <p>Findings</p> <p>Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30–6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91–7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54–9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41–9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 – 6.07, P = 0.02) post-transfusion than HIV-uninfected children.</p> <p>Conclusion</p> <p>HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.</p

Treatment- and Population-Dependent Activity Patterns of Behavioral and Expression QTLs

Genetic control of gene expression and higher-order phenotypes is almost invariably dependent on environment and experimental conditions. We use two families of recombinant inbred strains of mice (LXS and BXD) to study treatment- and genotype-dependent control of hippocampal gene expression and behavioral phenotypes. We analyzed responses to all combinations of two experimental perturbations, ethanol and restraint stress, in both families, allowing for comparisons across 8 combinations of treatment and population. We introduce the concept of QTL activity patterns to characterize how associations between genomic loci and traits vary across treatments. We identified several significant behavioral QTLs and many expression QTLs (eQTLs). The behavioral QTLs are highly dependent on treatment and population. We classified eQTLs into three groups: cis-eQTLs (expression variation that maps to within 5 Mb of the cognate gene), syntenic trans-eQTLs (the gene and the QTL are on the same chromosome but not within 5 Mb), and non-syntenic trans-eQTLs (the gene and the QTL are on different chromosomes). We found that most non-syntenic trans-eQTLs were treatment-specific whereas both classes of syntenic eQTLs were more conserved across treatments. We also found there was a correlation between regions along the genome enriched for eQTLs and SNPs that were conserved across the LXS and BXD families. Genes with eQTLs that co-localized with the behavioral QTLs and displayed similar QTL activity patterns were identified as potential candidate genes associated with the phenotypes, yielding identification of novel genes as well as genes that have been previously associated with responses to ethanol

The Golden Beauty: Brain Response to Classical and Renaissance Sculptures

Is there an objective, biological basis for the experience of beauty in art? Or is aesthetic experience entirely subjective? Using fMRI technique, we addressed this question by presenting viewers, naïve to art criticism, with images of masterpieces of Classical and Renaissance sculpture. Employing proportion as the independent variable, we produced two sets of stimuli: one composed of images of original sculptures; the other of a modified version of the same images. The stimuli were presented in three conditions: observation, aesthetic judgment, and proportion judgment. In the observation condition, the viewers were required to observe the images with the same mind-set as if they were in a museum. In the other two conditions they were required to give an aesthetic or proportion judgment on the same images. Two types of analyses were carried out: one which contrasted brain response to the canonical and the modified sculptures, and one which contrasted beautiful vs. ugly sculptures as judged by each volunteer. The most striking result was that the observation of original sculptures, relative to the modified ones, produced activation of the right insula as well as of some lateral and medial cortical areas (lateral occipital gyrus, precuneus and prefrontal areas). The activation of the insula was particularly strong during the observation condition. Most interestingly, when volunteers were required to give an overt aesthetic judgment, the images judged as beautiful selectively activated the right amygdala, relative to those judged as ugly. We conclude that, in observers naïve to art criticism, the sense of beauty is mediated by two non-mutually exclusive processes: one based on a joint activation of sets of cortical neurons, triggered by parameters intrinsic to the stimuli, and the insula (objective beauty); the other based on the activation of the amygdala, driven by one's own emotional experiences (subjective beauty)

Validation of the conceptual research utilization scale: an application of the standards for educational and psychological testing in healthcare

<p>Abstract</p> <p>Background</p> <p>There is a lack of acceptable, reliable, and valid survey instruments to measure conceptual research utilization (CRU). In this study, we investigated the psychometric properties of a newly developed scale (the CRU Scale).</p> <p>Methods</p> <p>We used the <it>Standards for Educational and Psychological Testing </it>as a validation framework to assess four sources of validity evidence: content, response processes, internal structure, and relations to other variables. A panel of nine international research utilization experts performed a formal content validity assessment. To determine response process validity, we conducted a series of one-on-one scale administration sessions with 10 healthcare aides. Internal structure and relations to other variables validity was examined using CRU Scale response data from a sample of 707 healthcare aides working in 30 urban Canadian nursing homes. Principal components analysis and confirmatory factor analyses were conducted to determine internal structure. Relations to other variables were examined using: (1) bivariate correlations; (2) change in mean values of CRU with increasing levels of other kinds of research utilization; and (3) multivariate linear regression.</p> <p>Results</p> <p>Content validity index scores for the five items ranged from 0.55 to 1.00. The principal components analysis predicted a 5-item 1-factor model. This was inconsistent with the findings from the confirmatory factor analysis, which showed best fit for a 4-item 1-factor model. Bivariate associations between CRU and other kinds of research utilization were statistically significant (p < 0.01) for the latent CRU scale score and all five CRU items. The CRU scale score was also shown to be significant predictor of overall research utilization in multivariate linear regression.</p> <p>Conclusions</p> <p>The CRU scale showed acceptable initial psychometric properties with respect to responses from healthcare aides in nursing homes. Based on our validity, reliability, and acceptability analyses, we recommend using a reduced (four-item) version of the CRU scale to yield sound assessments of CRU by healthcare aides. Refinement to the wording of one item is also needed. Planned future research will include: latent scale scoring, identification of variables that predict and are outcomes to conceptual research use, and longitudinal work to determine CRU Scale sensitivity to change.</p

Biocontrol Potential of Forest Tree Endophytes

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