Burden for family carers at the end of life : a mixed-method study of the perspectives of family carers and GPs

Background: Since many patients spend most of the time at home at the end of life, this may affect the burden for family carers and constitute a risk factor for the patients' hospitalisation. This study aimed to explore family carers' burden in the final three months of the patient's life, from the perspective of both carers and general practitioners (GPs), and to assess whether family burden, as defined by the GP, is associated with hospitalisation. Methods: A cross-sectional nationwide survey among GPs and family carers was performed. Participants were 194 GPs and 74 family carers of patients who died non-suddenly. Additionally, in-depth interviews were conducted with 18 family carers. For the quantitative analyses descriptive statistics, weighted Kappa and multivariate logistic regression analysis was performed. For the qualitative part thematic analysis was conducted. Results: The proportion of family carers experiencing a fairly heavy or severe burden increased significantly from 32% (second and third months before death) to 66% (one week before death). Most carers (95%) felt an emotional burden and 29% felt a physical burden in the final week. Three-quarters of carers did not perceive their burden as a problem because caring often felt rewarding. No significant association was found between the characteristics of family caregivers or professional care and the degree of family caregiver burden. Also, there was no significant evidence that patients of family carers for whom the GP assessed a fairly heavy to severe burden, were more likely to be hospitalised. Conclusions: The different overall assessment of family carers' burden between GPs and family carers and the increasing emotional and physical burden of family carers towards the end constitute relevant information for GPs that will help them understand and anticipate carers' personal needs

Comparative Study of rK39 Leishmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis

Visceral Leishmaniasis (VL) is a neglected tropical disease for which serodiagnostic tests are available, but not yet widely implemented in rural areas. The rK39 recombinant protein is derived from a kinesin-like protein of parasites belonging to the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of VL. We present here a systematic review and meta-analysis of studies evaluating serologic assays (rK39 strip-test, rK39 ELISA, Direct Agglutination Test [DAT], Indirect Immunofluorescence test [IFAT] and ELISA with a promastigote antigen preparation [p-ELISA]) to diagnose VL to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. Fourteen papers fulfilled the inclusion and exclusion selection criteria. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity (94%) and specificity (89%). However, the rK39 strip test was more specific than the IFAT and p-ELISA. In conclusion, we found the rK39 protein used either in a strip test or in an ELISA is a good choice for the serodiagnosis of VL

Prevalence and factors associated with alcohol and drug-related disorders in prison: a French national study

BACKGROUND: Most studies measuring substance-use disorders in prisons focus on incoming or on remand prisoners and are generally restricted to drugs. However, there is evidence that substance use initiation or continuation occurs in prison, and that alcohol use is common. The aim of this study is 1) to assess prevalence of both drug and alcohol abuse and dependence (DAD/AAD) in a national randomised cohort of French prisoners, short or long-term sentence 2) to assess the risk factors associated with DAD/AAD in prison. a stratified random strategy was used to select 1) 23 prisons among the different types of prison 2) 998 prisoners. Diagnoses were assessed according to a standardized procedure, each prisoner being assessed by two psychiatrists, one junior, using a structured interview (MINI 5 plus), and one senior, completing the procedure with an open clinical interview. At the end of the interview the clinicians met and agreed on a list of diagnoses. Cloninger's Temperament and Character Inventory (TCI) was also used. RESULTS: More than a third of prisoners presented either AAD or DAD in the last 12 months. Cannabis was the most frequent drug and just under a fifth of prisoners had AAD. AAD and DAD were clearly different for the following: socio-demographic variables, childhood history, imprisonment characteristics, psychiatric comorbidity and Cloninger's TCI. Profiles of AAD in prison are similar to type II alcoholism. CONCLUSION: Regular screening of AAD/DAD in prison, and specific treatment programmes taking into account differences between prisoners with an AAD and prisoners with a DAD should be a public health priority in priso

Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders:A Role for Serotonergic and Catecholamine Pathways

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal ‘programming’ of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11β-HSD2, an enzyme that inactivates glucocorticoids, increases anxiety‐ and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways

A new tool called DISSECT for analyzing large genomic datasets using a Big Data approach

Large-scale genetic and genomic data are increasingly available and the major bottleneck in their analysis is a lack of sufficiently scalable computational tools. To address this problem in the context of complex traits analysis, we present DISSECT. DISSECT is a new and freely available software that is able to exploit the distributed-memory parallel computational architectures of compute clusters, to perform a wide range of genomic and epidemiologic analyses, which currently can only be carried out on reduced sample sizes or under restricted conditions. We demonstrate the usefulness of our new tool by addressing the challenge of predicting phenotypes from genotype data in human populations using mixed-linear model analysis. We analyse simulated traits from 470,000 individuals genotyped for 590,004 SNPs in ∼4 h using the combined computational power of 8,400 processor cores. We find that prediction accuracies in excess of 80% of the theoretical maximum could be achieved with large sample sizes

Mycoplasma genitalium: An Emerging Cause of Sexually Transmitted Disease in Women

Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women including cervicitis, pelvic inflammatory disease (PID), and infertility. This comprehensive review critically examines epidemiologic studies of M. genitalium infections in women with the goal of assessing the associations with reproductive tract disease and enhancing awareness of this emerging pathogen. Over 27,000 women from 48 published reports have been screened for M. genitalium urogenital infection in high- or low-risk populations worldwide with an overall prevalence of 7.3% and 2.0%, respectively. M. genitalium was present in the general population at rates between those of Chlamydia trachomatis and Neisseria gonorrhoeae. Considering more than 20 studies of lower tract inflammation, M. genitalium has been positively associated with urethritis, vaginal discharge, and microscopic signs of cervicitis and/or mucopurulent cervical discharge in seven of 14 studies. A consistent case definition of cervicitis is lacking and will be required for comprehensive understanding of these associations. Importantly, evidence for M. genitalium PID and infertility are quite convincing and indicate that a significant proportion of upper tract inflammation may be attributed to this elusive pathogen. Collectively, M. genitalium is highly prevalent in high- and low-risk populations, and should be considered an etiologic agent of select reproductive tract disease syndromes in women

Genomics-assisted breeding in four major pulse crops of developing countries: present status and prospects

The global population is continuously increasing and is expected to reach nine billion by 2050. This huge population pressure will lead to severe shortage of food, natural resources and arable land. Such an alarming situation is most likely to arise in developing countries due to increase in the proportion of people suffering from protein and micronutrient malnutrition. Pulses being a primary and affordable source of proteins and minerals play a key role in alleviating the protein calorie malnutrition, micronutrient deficiencies and other undernourishment-related issues. Additionally, pulses are a vital source of livelihood generation for millions of resource-poor farmers practising agriculture in the semi-arid and sub-tropical regions. Limited success achieved through conventional breeding so far in most of the pulse crops will not be enough to feed the ever increasing population. In this context, genomics-assisted breeding (GAB) holds promise in enhancing the genetic gains. Though pulses have long been considered as orphan crops, recent advances in the area of pulse genomics are noteworthy, e.g. discovery of genome-wide genetic markers, high-throughput genotyping and sequencing platforms, high-density genetic linkage/QTL maps and, more importantly, the availability of whole-genome sequence. With genome sequence in hand, there is a great scope to apply genome-wide methods for trait mapping using association studies and to choose desirable genotypes via genomic selection. It is anticipated that GAB will speed up the progress of genetic improvement of pulses, leading to the rapid development of cultivars with higher yield, enhanced stress tolerance and wider adaptability

First Observation of the Decay B0→D∗+D∗−B^{0}\to D^{*+}D^{*-}

We have observed four fully reconstructed B0 -> D*+D*- candidates in 5.8 million Upsilon(4S) -> BBbar decays recorded with the CLEO detector. The background is estimated to be 0.31 +- 0.10 events. The probability that the background could produce four or more signal candidates with the observed distribution among D*+ and D*- decay modes is 1.1 X 10^{-4}. The measured decay rate, Br(B0 -> D*+D*-) = [6.2 +4.0-2.9 (stat) +- 1.0(syst)] X 10^{-4}, is large enough for this decay mode to be of interest for the measurement of a time-dependent CP asymmetry.Comment: 10 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

A predictive assessment of genetic correlations between traits in chickens using markers

International audienceAbstractBackgroundGenomic selection has been successfully implemented in plant and animal breeding programs to shorten generation intervals and accelerate genetic progress per unit of time. In practice, genomic selection can be used to improve several correlated traits simultaneously via multiple-trait prediction, which exploits correlations between traits. However, few studies have explored multiple-trait genomic selection. Our aim was to infer genetic correlations between three traits measured in broiler chickens by exploring kinship matrices based on a linear combination of measures of pedigree and marker-based relatedness. A predictive assessment was used to gauge genetic correlations.MethodsA multivariate genomic best linear unbiased prediction model was designed to combine information from pedigree and genome-wide markers in order to assess genetic correlations between three complex traits in chickens, i.e. body weight at 35 days of age (BW), ultrasound area of breast meat (BM) and hen-house egg production (HHP). A dataset with 1351 birds that were genotyped with the 600 K Affymetrix platform was used. A kinship kernel (K) was constructed as K = λG + (1 − λ)A, where A is the numerator relationship matrix, measuring pedigree-based relatedness, and G is a genomic relationship matrix. The weight (λ) assigned to each source of information varied over the grid λ = (0, 0.2, 0.4, 0.6, 0.8, 1). Maximum likelihood estimates of heritability and genetic correlations were obtained at each λ, and the “optimum” λ was determined using cross-validation.ResultsEstimates of genetic correlations were affected by the weight placed on the source of information used to build K. For example, the genetic correlation between BW–HHP and BM–HHP changed markedly when λ varied from 0 (only A used for measuring relatedness) to 1 (only genomic information used). As λ increased, predictive correlations (correlation between observed phenotypes and predicted breeding values) increased and mean-squared predictive error decreased. However, the improvement in predictive ability was not monotonic, with an optimum found at some 0 < λ < 1, i.e., when both sources of information were used together.ConclusionsOur findings indicate that multiple-trait prediction may benefit from combining pedigree and marker information. Also, it appeared that expected correlated responses to selection computed from standard theory may differ from realized responses. The predictive assessment provided a metric for performance evaluation as well as a means for expressing uncertainty of outcomes of multiple-trait selection