A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism

We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism

HIV Epidemic Appraisals for Assisting in the Design of Effective Prevention Programmes: Shifting the Paradigm Back to Basics

To design HIV prevention programmes, it is critical to understand the temporal and geographic aspects of the local epidemic and to address the key behaviours that drive HIV transmission. Two methods have been developed to appraise HIV epidemics and guide prevention strategies. The numerical proxy method classifies epidemics based on current HIV prevalence thresholds. The Modes of Transmission (MOT) model estimates the distribution of incidence over one year among risk-groups. Both methods focus on the current state of an epidemic and provide short-term metrics which may not capture the epidemiologic drivers. Through a detailed analysis of country and sub-national data, we explore the limitations of the two traditional methods and propose an alternative approach.We compared outputs of the traditional methods in five countries for which results were published, and applied the numeric and MOT model to India and six districts within India. We discovered three limitations of the current methods for epidemic appraisal: (1) their results failed to identify the key behaviours that drive the epidemic; (2) they were difficult to apply to local epidemics with heterogeneity across district-level administrative units; and (3) the MOT model was highly sensitive to input parameters, many of which required extraction from non-regional sources. We developed an alternative decision-tree framework for HIV epidemic appraisals, based on a qualitative understanding of epidemiologic drivers, and demonstrated its applicability in India. The alternative framework offered a logical algorithm to characterize epidemics; it required minimal but key data.Traditional appraisals that utilize the distribution of prevalent and incident HIV infections in the short-term could misguide prevention priorities and potentially impede efforts to halt the trajectory of the HIV epidemic. An approach that characterizes local transmission dynamics provides a potentially more effective tool with which policy makers can design intervention programmes

Oxidation behaviors of porous Haynes 214 alloy at high temperatures

The oxidation behaviors of porous Haynes 214 alloy at temperatures from 850 to 1000 °C were investigated. The porous alloys before and after the oxidation were examined by optical microscopy, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) analyses, and X-ray photoelectron spectroscopy (XPS). The oxidation kinetics of the porous alloy approximately follows a parabolic rate law and exhibits two stages controlled by different oxidation courses. Complex oxide scales composed of Cr2O3, NiCr2O4 and Al2O3 are formed on the oxidized porous alloys, and the formation of Cr2O3 on its outer layer is promoted with the oxidation proceeding. The rough surface as well as the micropores in the microstructures of the porous alloy caused by the manufacturing process provides fast diffusion paths for oxygen so as to affect the formation of the oxide layers. Both the maximum pore size and the permeability of the porous alloys decrease with the increase of oxidation temperature and exposure time, which may limit its applications