A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Integration of formal fault analysis in ASSERT: Case studies and lessons learnt

International audienceThe ASSERT European Integrated Project (Automated proof-based System and Software Engineering for Real-Time systems; EC FP6, IST-004033) has investigated, elaborated and experimented advanced methods based on the AltaRica language and support tool OCAS for architecture and fault approach propagation description analysis, and integrated in the complete ASSERT process. The paper describes lessons learnt from three case studies: safety critical spacecraft, autonomous deep exploration spacecraft, and civil aircraft

Physical and rehabilitation medicine (PRM) care pathways: Adults with severe traumatic brain injury

AbstractThis document is part of a series of guidelines documents designed by the French Physical and Rehabilitation Medicine Society (SOFMER) and the French Federation of PRM (FEDMER). These reference documents focus on a particular pathology (here patients with severe TBI). They describe for each given pathology patients’ clinical and social needs, PRM care objectives and necessary human and material resources of the pathology-dedicated pathway. ‘Care pathways in PRM’ is therefore a short document designed to enable readers (physician, decision-maker, administrator, lawyer, finance manager) to have a global understanding of available therapeutic care structures, organization and economic needs for patients’ optimal care and follow-up. After a severe traumatic brain injury, patients might be divided into three categories according to impairment's severity, to early outcomes in the intensive care unit and to functional prognosis. Each category is considered in line with six identical parameters used in the International Classification of Functioning, Disability and Health (World Health Organization), focusing thereafter on personal and environmental factors liable to affect the patients’ needs

Killing them softly:managing pathogen polymorphism and virulence in spatially variable environments

Understanding why pathogen populations are genetically variable is vital because genetic variation fuels evolution, which often hampers disease control efforts. Here I argue that classical models of evolution in spatially variable environments – specifically, models of hard and soft selection – provide a useful framework to understand the maintenance of pathogen polymorphism and the evolution of virulence. First, the similarities between models of hard and soft selection and pathogen life cycles are described, highlighting how the type and timing of pathogen control measures impose density regulation that may affect both the level of pathogen polymorphism and virulence. The article concludes with an outline of potential lines of future theoretical and experimental work

Unresolved orthology and peculiar coding sequence properties of lamprey genes: the KCNA gene family as test case

Background:In understanding the evolutionary process of vertebrates, cyclostomes (hagfishes and lamprey) occupy crucial positions. Resolving molecular phylogenetic relationships of cyclostome genes with gnathostomes (jawed vertebrates) genes is indispensable in deciphering both the species tree and gene trees. However, molecular phylogenetic analyses, especially those including lamprey genes, have produced highly discordant results between gene families. To efficiently scrutinize this problem using partial genome assemblies of early vertebrates, we focused on the potassium voltage-gated channel, shaker-related (KCNA) family, whose members are mostly single-exon.Results:Seven sea lamprey KCNA genes as well as six elephant shark genes were identified, and their orthologies to bony vertebrate subgroups were assessed. In contrast to robustly supported orthology of the elephant shark genes to gnathostome subgroups, clear orthology of any sea lamprey gene could not be established. Notably, sea lamprey KCNA sequences displayed unique codon usage pattern and amino acid composition, probably associated with exceptionally high GC-content in their coding regions. This lamprey-specific property of coding sequences was also observed generally for genes outside this gene family.Conclusions:Our results suggest that secondary modifications of sequence properties unique to the lamprey lineage may be one of the factors preventing robust orthology assessments of lamprey genes, which deserves further genome-wide validation. The lamprey lineage-specific alteration of protein-coding sequence properties needs to be taken into consideration in tackling the key questions about early vertebrate evolution

Pyrolysis Gas Composition for a Phenolic Impregnated Carbon Ablator Heatshield

Published physical properties of phenolic impregnated carbon ablator (PICA) are compiled, and the composition of the pyrolysis gases that form at high temperatures internal to a heatshield is investigated. A link between the composition of the solid resin, and the composition of the pyrolysis gases created is provided. This link, combined with a detailed investigation into a reacting pyrolysis gas mixture, allows a consistent, and thorough description of many of the physical phenomena occurring in a PICA heatshield, and their implications, to be presented

Characterization of proton irradiated 3D-DDTC pixel sensor prototypes fabricated at FBK

In this paper we discuss results relevant to 3D Double-Side Double Type Column (3D-DDTC) pixel sensors fabricated at FBK (Trento, Italy) and oriented to the ATLAS upgrade. Some assemblies of these sensors featuring different columnar electrode configurations (2, 3, or 4 columns per pixel) and coupled to the ATLAS FEI3 read-out chip were irradiated up to large proton fluences and tested in laboratory with radioactive sources. In spite of the non optimized columnar electrode overlap, sensors exhibit reasonably good charge collection properties up to an irradiation fluence of 2 x 10**15 neq/cm2, while requiring bias voltages in the order of 100 V. Sensor operation is further investigated by means of TCAD simulations which can effectively explain the basic mechanisms responsible for charge loss after irradiation.Comment: Preprint submitted to Nuclear Instruments and Methods A, 11 pages, 13 fig