The relationship between HIV seroconversion illness, HIV test interval and time to AIDS in a seroconverter cohort.

Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated seroconversion. Of 1820 individuals, information on seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on seroconversion illness in studies of HIV disease progression

The admixture maximum likelihood test to test for association between rare variants and disease phenotypes.

BACKGROUND: The development of genotyping arrays containing hundreds of thousands of rare variants across the genome and advances in high-throughput sequencing technologies have made feasible empirical genetic association studies to search for rare disease susceptibility alleles. As single variant testing is underpowered to detect associations, the development of statistical methods to combine analysis across variants - so-called "burden tests" - is an area of active research interest. We previously developed a method, the admixture maximum likelihood test, to test multiple, common variants for association with a trait of interest. We have extended this method, called the rare admixture maximum likelihood test (RAML), for the analysis of rare variants. In this paper we compare the performance of RAML with six other burden tests designed to test for association of rare variants. RESULTS: We used simulation testing over a range of scenarios to test the power of RAML compared to the other rare variant association testing methods. These scenarios modelled differences in effect variability, the average direction of effect and the proportion of associated variants. We evaluated the power for all the different scenarios. RAML tended to have the greatest power for most scenarios where the proportion of associated variants was small, whereas SKAT-O performed a little better for the scenarios with a higher proportion of associated variants. CONCLUSIONS: The RAML method makes no assumptions about the proportion of variants that are associated with the phenotype of interest or the magnitude and direction of their effect. The method is flexible and can be applied to both dichotomous and quantitative traits and allows for the inclusion of covariates in the underlying regression model. The RAML method performed well compared to the other methods over a wide range of scenarios. Generally power was moderate in most of the scenarios, underlying the need for large sample sizes in any form of association testing.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Symptom burden in patients with chronic kidney disease not requiring renal replacement therapy

Background: Although evidence shows that patients with end stage renal disease (ESRD) experience a high symptom burden which impacts on quality of life (QoL), less is known about patients with earlier stages of chronic kidney disease (CKD). This study aimed to explore symptom burden and potential contributing factors in patients with CKD Stage 1-5 not requiring renal replacement therapy (RRT). Methods: Patients with CKD Stage 1-5 and not on RRT were asked to report their symptoms using the Leicester Uraemic Symptom Score (LUSS), a questionnaire which assesses the frequency and intrusiveness of 11 symptoms commonly reported by kidney patients. Results: Symptoms were assessed in 283 CKD Stage 1-5 patients: 54% male, mean age 60.5 standard error± 1.0, mean eGFR 38ml/min/1.73m2. Some 96% (95% confidence interval 93.2-98.0) of participants reported experiencing at least one symptom, the median reported being six. Excessive tiredness (81%;76.0-85.6), sleep disturbance (70%;64.3-75.3) and pain in bones/joints (69%;63.4-74.6) were reported most commonly. Overall, few significant associations were found between biochemical markers of disease severity and symptom burden. Men tended to report fewer symptoms than women and South Asian patients often described experiencing symptoms with a greater severity. Older patients found musculoskeletal symptoms more intrusive whereas younger patients found reduced concentration more intrusive. Conclusions: Our findings suggest that patients with CKD stages 1-5 experience a multitude of symptoms that could potentially impact QoL. Using multidimensional tools like the LUSS, more exploration and focus could provide a greater opportunity for patient focussed symptom control from the earliest stages of CKD.Peer-reviewedPublisher Versio

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

Licensed under a Creative Commons Attribution Non-Commercial Share Alike Licens

Background risk of breast cancer and the association between physical activity and mammographic density

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

National Energy Efficiency and Conservation Policies and Programs in Developed Countries and Middle East

The world's economies should endeavour to ultimately reduce their energy consumption, rather than simply adjusting or optimizing their energy utilisation. The implementation of intelligent strategies, designed to manage human activities which are highly dependent on energy, should be the preferred solution to develop and achieve a sustainable and secure economy. This paper describes policies for energy conservation adopted by developed industrialized countries such as Japan, Germany, France, Britain and the US, as well as developing countries in the Middle East such as Qatar, Kuwait, Syria and the United Arab Emirates. The aim of this document will be to identify and clarify the major factors that drive the creation and implementation of energy policies, as well as the strength and weakness of each of the adopted strategies of energy conservation, including the associated risks and opportunities. The conclusion of this study will offer recommendations for the most suitable framework for determining the best practices to develop sustainable societies in Middle East region, which in turn will equip these countries to respond more efficiently to the implementation of the latest international standards, which are mandatory in order to succeed in the global business field