Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice

Renal Impairment and Cardiovascular Disease in HIV-positive Individuals; The D:A:D Study

BACKGROUND: While the association between renal impairment and cardiovascular disease (CVD) is well established in the general population, the association remains poorly understood in HIV-positive individuals. METHODS: Individuals with >2 estimated glomerular filtration rate (eGFRs) after 1/2/2004 were followed until CVD, death, last visit plus six months or 1/2/2015. CVD was defined as centrally validated myocardial infarction, stroke, invasive cardiovascular procedures or sudden cardiac death. RESULTS: During 8.0 years median follow-up (Interquartile range 5.4-8.9) 1,357 of 35,357 developed CVD (incidence 5.2/1000 person-years [95%confidence interval, CI [5.0-5.5]). Confirmed baseline eGFR and CVD were closely related with 1.8% [95%CI 1.6-2.0%] estimated to develop CVD at five years at eGFR>90 ml/min/1.73m(2), increasing to 21.1% [95%CI 6.6-35.6%] at eGFR<30 ml/min/1.73m(2) The strong univariate relationship between low current eGFR and CVD was primarily explained by increasing age in adjusted analyses, although all eGFRs<80 ml/min/1.73m(2) remained associated with 30-40% increased CVD rates and particular high rates at eGFR<30 ml/min/1.73m(2) (3.08 [95%CI 2.04-4.65]). CONCLUSIONS: Among HIV-positive individuals in a large contemporary cohort a strong relation between confirmed impaired eGFR and CVD was observed. This finding highlights the need for renal preventive measures and intensified monitoring for emerging CVD, in particular in older individuals with continuously low eGFR

Characterization of extrasolar terrestrial planets from diurnal photometric variability

The detection of massive planets orbiting nearby stars has become almost routine, but current techniques are as yet unable to detect terrestrial planets with masses comparable to the Earth's. Future space-based observatories to detect Earth-like planets are being planned. Terrestrial planets orbiting in the habitable zones of stars-where planetary surface conditions are compatible with the presence of liquid water-are of enormous interest because they might have global environments similar to Earth's and even harbor life. The light scattered by such a planet will vary in intensity and colour as the planet rotates; the resulting light curve will contain information about the planet's properties. Here we report a model that predicts features that should be discernible in light curves obtained by low-precision photometry. For extrasolar planets similar to Earth we expect daily flux variations up to hundreds of percent, depending sensitively on ice and cloud cover. Qualitative changes in surface or climate generate significant changes in the predicted light curves. This work suggests that the meteorological variability and the rotation period of an Earth-like planet could be derived from photometric observations. Other properties such as the composition of the surface (e.g., ocean versus land fraction), climate indicators (for example ice and cloud cover), and perhaps even signatures of Earth-like plant life could be constrained or possibly, with further study, even uniquely determined.Comment: Published in Nature. 9 pages including 3 figure

Temporal Patterns in Perchlorate, Thiocyanate, and Iodide Excretion in Human Milk

BACKGROUND: Perchlorate and thiocyanate interfere with iodide uptake at the sodium–iodide symporter and are potential disruptors of thyroid hormone synthesis. Perchlorate is a common contaminant of water, food, and human milk. Although it is known that iodide undergoes significant diurnal variations in serum and urinary excretion, less is known about diurnal variations of milk iodide levels. OBJECTIVES: Variability in perchlorate and thiocyanate excretion in human milk has not been examined. Our objective was to determine variability of perchlorate, thiocyanate, and iodide in serially collected samples of human milk. METHODS: Ten lactating women were asked to collect six milk samples on each of 3 days. As an alternative, subjects were asked to collect as many milk samples as comfortably possible over 3 days. Samples were analyzed for perchlorate, iodide, and thiocyanate by ion chromatography coupled with mass spectrometry. RESULTS: Individual perchlorate, iodide, and thiocyanate levels varied significantly over time; there was also considerable variation among individuals. The iodide range, mean ± SD, and median for all samples (n = 108) were 3.1–334 μg/L, 87.9 ± 80.9 μg/L, and 55.2 μg/L, respectively. The range, mean ± SD, and median of perchlorate in all samples (n = 147) were 0.5–39.5 μg/L, 5.8 ± 6.2 μg/L, and 4.0 μg/L. The range, mean ± SD, and median of thiocyanate in all samples (n = 117) were 0.4 –228.3 μg/L, 35.6 ± 57.9 μg/L, and 5.6 μg/L. The data are not symmetrically distributed; the mean is higher than the median in all cases. CONCLUSIONS: Iodine intake may be inadequate in a significant fraction of this study population. Perchlorate and thiocyanate appear to be common in human milk. The role of these chemicals in reducing breast milk iodide is in need of further investigation

Evolution of reproductive development in the volvocine algae

The evolution of multicellularity, the separation of germline cells from sterile somatic cells, and the generation of a male–female dichotomy are certainly among the greatest innovations of eukaryotes. Remarkably, phylogenetic analysis suggests that the shift from simple to complex, differentiated multicellularity was not a unique progression in the evolution of life, but in fact a quite frequent event. The spheroidal green alga Volvox and its close relatives, the volvocine algae, span the full range of organizational complexity, from unicellular and colonial genera to multicellular genera with a full germ–soma division of labor and male–female dichotomy; thus, these algae are ideal model organisms for addressing fundamental issues related to the transition to multicellularity and for discovering universal rules that characterize this transition. Of all living species, Volvox carteri represents the simplest version of an immortal germline producing specialized somatic cells. This cellular specialization involved the emergence of mortality and the production of the first dead ancestors in the evolution of this lineage. Volvocine algae therefore exemplify the evolution of cellular cooperation from cellular autonomy. They also serve as a prime example of the evolution of complex traits by a few successive, small steps. Thus, we learn from volvocine algae that the evolutionary transition to complex, multicellular life is probably much easier to achieve than is commonly believed

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

Characterization of soot properties in two-meter JP-8 pool fires.

The thermal hazard posed by large hydrocarbon fires is dominated by the radiative emission from high temperature soot. Since the optical properties of soot, especially in the infrared region of the electromagnetic spectrum, as well as its morphological properties, are not well known, efforts are underway to characterize these properties. Measurements of these soot properties in large fires are important for heat transfer calculations, for interpretation of laser-based diagnostics, and for developing soot property models for fire field models. This research uses extractive measurement diagnostics to characterize soot optical properties, morphology, and composition in 2 m pool fires. For measurement of the extinction coefficient, soot extracted from the flame zone is transported to a transmission cell where measurements are made using both visible and infrared lasers. Soot morphological properties are obtained by analysis via transmission electron microscopy of soot samples obtained thermophoretically within the flame zone, in the overfire region, and in the transmission cell. Soot composition, including carbon-to-hydrogen ratio and polycyclic aromatic hydrocarbon concentration, is obtained by analysis of soot collected on filters. Average dimensionless extinction coefficients of 8.4 {+-} 1.2 at 635 nm and 8.7 {+-} 1.1 at 1310 nm agree well with recent measurements in the overfire region of JP-8 and other fuels in lab-scale burners and fires. Average soot primary particle diameters, radius of gyration, and fractal dimensions agree with these recent studies. Rayleigh-Debye-Gans theory of scattering applied to the measured fractal parameters shows qualitative agreement with the trends in measured dimensionless extinction coefficients. Results of the density and chemistry are detailed in the report

Species by Environment Interactions Affect Pyrrolizidine Alkaloid Expression in Senecio jacobaea, Senecio aquaticus, and Their Hybrids

We examined the effects of water and nutrient availability on the expression of the defense pyrrolizidine alkaloids (PAs) in Senecio jacobaea and S. aquaticus. Senecio jacobaea, and S. aquaticus are adapted to different natural habitats, characterized by differing abiotic conditions and different selection pressures from natural enemies. We tested if PA concentration and diversity are plastic over a range of water and nutrient treatments, and also whether such plasticity is dependent on plant species. We also tested the hypothesis that hybridization may contribute to PA diversity within plants, by comparing PA expression in parental species to that in artificially generated F1 hybrids, and also in later generation natural hybrids between S. jacobaea and S. aquaticus. We showed that total PA concentration in roots and shoots is not dependent on species, but that species determines the pattern of PA diversification. Pyrrolizidine alkaloid diversity and concentration are both dependent on environmental factors. Hybrids produce a putatively novel PA, and this PA is conserved in natural hybrids, that are backcrossed to S. jacobaea. Natural hybrids that are backcrossed several times to S. jacobaea are with regard to PA diversity significantly different from S. jacobaea but not from S. aquaticus, while F1 hybrids are in all cases more similar to S. jacobaea. These results collectively suggest that PA diversity is under the influence of natural selection

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities