Early diagnosis and treatment of HIV infection: magnitude of benefit on short-term mortality is greatest in older adults.

BACKGROUND: the number and proportion of adults diagnosed with HIV infection aged 50 years and older has risen. This study compares the effect of CD4 counts and anti-retroviral therapy (ART) on mortality rates among adults diagnosed aged ≥50 with those diagnosed at a younger age. METHODS: retrospective cohort analysis of national surveillance reports of HIV-diagnosed adults (15 years and older) in England, Wales and Northern Ireland. The relative impacts of age, CD4 count at diagnosis and ART on mortality were determined in Cox proportional hazards models. RESULTS: among 63,805 adults diagnosed with HIV between 2000 and 2009, 9% (5,683) were aged ≥50 years; older persons were more likely to be white, heterosexual and present with a CD4 count <200 cells/mm(3) (48 versus 32% P < 0.01) and AIDS at diagnosis (19 versus 9%, P < 0.01). One-year mortality was higher in older adults (10 versus 3%, P < 0.01) and especially in those diagnosed with a CD4 <200 cells/mm(3) left untreated (46 versus 15%, P < 0.01). While the relative mortality risk reduction from ART initiation at CD <200 cells/mm(3) was similar in both age groups, the absolute risk difference was higher among older adults (40 versus 12% fewer deaths) such that the number needed to treat older adults to prevent one death was two compared with eight among younger adults. CONCLUSIONS: the magnitude of benefit from ART is greater in older adults than younger adults. Older persons should be considered as a target for HIV testing. Coupled with prompt treatment, earlier diagnosis is likely to reduce substantially deaths in this group

Harnessing nuclear spin polarization fluctuations in a semiconductor nanowire

Soon after the first measurements of nuclear magnetic resonance (NMR) in a condensed matter system, Bloch predicted the presence of statistical fluctuations proportional to $1/\sqrt{N}$ in the polarization of an ensemble of $N$ spins. First observed by Sleator et al., so-called "spin noise" has recently emerged as a critical ingredient in nanometer-scale magnetic resonance imaging (nanoMRI). This prominence is a direct result of MRI resolution improving to better than 100 nm^3, a size-scale in which statistical spin fluctuations begin to dominate the polarization dynamics. We demonstrate a technique that creates spin order in nanometer-scale ensembles of nuclear spins by harnessing these fluctuations to produce polarizations both larger and narrower than the natural thermal distribution. We focus on ensembles containing ~10^6 phosphorus and hydrogen spins associated with single InP and GaP nanowires (NWs) and their hydrogen-containing adsorbate layers. We monitor, control, and capture fluctuations in the ensemble's spin polarization in real-time and store them for extended periods. This selective capture of large polarization fluctuations may provide a route for enhancing the weak magnetic signals produced by nanometer-scale volumes of nuclear spins. The scheme may also prove useful for initializing the nuclear hyperfine field of electron spin qubits in the solid-state.Comment: 18 pages, 5 figure

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations

Polarization and temperature dependence of photoluminescence from zincblende and wurtzite InP nanowires

We use polarization-resolved and temperature-dependent photoluminescence of single zincblende (ZB) (cubic) and wurtzite (WZ) (hexagonal) InPnanowires to probe differences in selection rules and bandgaps between these two semiconductor nanostructures. The WZ nanowires exhibit a bandgap80meV higher in energy than the ZB nanowires. The temperature dependence of the PL is similar but not identical for the WZ and ZB nanowires. We find that ZB nanowires exhibit strong polarization parallel to the nanowire axis, while the WZ nanowires exhibit polarized emission perpendicular to the nanowire axis. This behavior is interpreted in terms of the different selection rules for WZ and ZB crystal structures.A.M., L.V.T., T.B.H., H.E.J., L.M.S., and J.M.Y.-R. acknowledge support from the Institute for Nanoscale Science and Technology of the University of Cincinnati and the National Science Foundation through Grant Nos. EEC/NUE 0532495 and ECCS 0701703. The Australian authors acknowledge support from the Australian Research Council. Y.K. acknowledges support by the Korean Science and Engineering Foundation KOSEF through Grant No. F01- 2007-000-10087-0

Cirsium species show disparity in patterns of genetic variation at their range-edge, despite similar patterns of reproduction and isolation

Genetic variation was assessed across the UK geographical range of Cirsium acaule and Cirsium heterophyllum. A decline in genetic diversity and increase in population divergence approaching the range edge of these species was predicted based on parallel declines in population density and seed production reported seperately. Patterns were compared with UK populations of the widespread Cirsium arvense.Populations were sampled along a latitudinal transect in the UK and genetic variation assessed using microsatellite markers. Cirsium acaule shows strong isolation by distance, a significant decline in diversity and an increase in divergence among range-edge populations. Geographical structure is also evident in C. arvense, whereas no such patterns are seen in C.heterophyllum. There is a major disparity between patterns of genetic variation in C. acaule and C. heterophyllum despite very similar patterns in seed production and population isolation in these species. This suggests it may be misleading to make assumptions about the geographical structure of genetic variation within species based solely on the present-day reproduction and distribution of populations

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Universality, limits and predictability of gold-medal performances at the Olympic Games

Inspired by the Games held in ancient Greece, modern Olympics represent the world's largest pageant of athletic skill and competitive spirit. Performances of athletes at the Olympic Games mirror, since 1896, human potentialities in sports, and thus provide an optimal source of information for studying the evolution of sport achievements and predicting the limits that athletes can reach. Unfortunately, the models introduced so far for the description of athlete performances at the Olympics are either sophisticated or unrealistic, and more importantly, do not provide a unified theory for sport performances. Here, we address this issue by showing that relative performance improvements of medal winners at the Olympics are normally distributed, implying that the evolution of performance values can be described in good approximation as an exponential approach to an a priori unknown limiting performance value. This law holds for all specialties in athletics-including running, jumping, and throwing-and swimming. We present a self-consistent method, based on normality hypothesis testing, able to predict limiting performance values in all specialties. We further quantify the most likely years in which athletes will breach challenging performance walls in running, jumping, throwing, and swimming events, as well as the probability that new world records will be established at the next edition of the Olympic Games.Comment: 8 pages, 3 figures, 1 table. Supporting information files and data are available at filrad.homelinux.or

A web server for interactive and zoomable Chaos Game Representation images

Chaos Game Representation (CGR) is a generalized scale-independent Markov transition table, which is useful for the visualization and comparative study of genomic signature, or for the study of characteristic sequence motifs. However, in order to fully utilize the scale-independent properties of CGR, it should be accessible through scale-independent user interface instead of static images. Here we describe a web server and Perl library for generating zoomable CGR images utilizing Google Maps API, which is also easily searchable for specific motifs. The web server is freely accessible at , and the Perl library as well as the source code is distributed with the G-language Genome Analysis Environment under GNU General Public License

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations