Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes.

BACKGROUND A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review. METHODS The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported. RESULTS Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk. CONCLUSIONS DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR

Inference on the Nature and the Mass of Earth's Late Veneer from Noble Metals and Gases

Noble metals and gases are very sensitive to the late accretion to the Earth of asteroids and comets. We present mass balance arguments based on these elements that indicate that 0.7E22-2.7E22 kg of extraterrestrial bodies struck the Earth after core formation and that comets comprised less than 1E-5 by mass of the impacting population. These results imply that the dynamics of asteroids and comets changed drastically with time and that biogenic elements and prebiotic molecules were not delivered to the Earth by comets but rather by carbonaceous asteroids.Comment: 10 pages, 2 figures, 1 table, submitted to JG

Triassic chirotheriid footprints from the Swiss Alps: ichnotaxonomy and depositional environment (Cantons Wallis & Glarus)

Autochthonous Triassic sediments of the Vieux Emosson Formation near Lac d’Emosson, southwestern Switzerland, have yielded assemblages with abundant archosaur footprints that are assigned to chirotheriids based on pentadactyl pes and manus imprints with characteristic digit proportions. Tridactyl footprints formerly considered as those of dinosaurs are identified as incomplete extramorphological variants of chirotheriids. Recently discovered new sites, including a surface with about 1500 imprints, permit re-evaluation of ichnotaxonomy and modes of preservation. Most common are oval to circular impressions arranged in an ‘‘hourglass-like’’ shape, corresponding to pes-manus couples. Sediment displacement rims indicate the presence of true tracks rather than undertracks. A few well-preserved footprints with distinct digit traces allow closer assignments. Several chirotheriid ichnotaxa are present with Chirotherium barthii,?Chirotherium sickleri, Isochirotherium herculis, Chirotheriidae cf. Isochirotherium isp. and indeterminate forms. This corresponds with characteristic assemblages from the Buntsandstein of the Germanic Basin. In the study area, the Vieux Emosson Formation is an up to 10 m thick finingupward sequence with conglomerates, rippled sandstones, siltstones and mudstones and occasionally carbonate nodules. Sedimentological features such as high relief erosion, immature sediments, erosionally truncated metre-scale fining-upward sequences, palaeosols and unidirectional palaeocurrents clearly prove a fluvial depositional environment with sediment transport towards the northwest and the Germanic Basin. This contrasts with former assumptions of a coastal marine environment and a south-facing transport towards the Tethys. The footprints occur in the coarser lower portion of the sequence that is interpreted as a shallow braided river. From Obersand in the eastern Swiss Alps, a surface in dolomitic limestone (Ro¨ti Dolomite) is re-examined. The footprints are identified as Chirotherium barthii and were impressed in a carbonate tidal flat environment. Biostratigraphically, the occurrence of characteristic Buntsandstein assemblages with Chirotherium barthii supports an Anisian age of both locations

A standard protocol for documenting modern and fossil ichnological data

© The Palaeontological Association. The collection and dissemination of vertebrate ichnological data is struggling to keep up with techniques that are becoming commonplace in the wider palaeontological field. A standard protocol is required to ensure that data is recorded, presented and archived in a manner that will be useful both to contemporary researchers, and to future generations. Primarily, our aim is to make the 3D capture of ichnological data standard practice, and to provide guidance on how such 3D data can be communicated effectively (both via the literature and other means) and archived openly and in perpetuity. We recommend capture of 3D data, and the presentation of said data in the form of photographs, false-colour images, and interpretive drawings. Raw data (3D models of traces) should always be provided in a form usable by other researchers (i.e. in an open format). If adopted by the field as a whole, the result will be a more robust and uniform literature, supplemented by unparalleled availability of datasets for future workers

Circulation and oxygen cycling in the Mediterranean Sea: Sensitivity to future climate change

Climate change is expected to increase temperatures and decrease precipitation in the Mediterranean Sea (MS) basin, causing substantial changes in the thermohaline circulation (THC) of both the Western Mediterranean Sea (WMS) and Eastern Mediterranean Sea (EMS). The exact nature of future circulation changes remains highly uncertain, however, with forecasts varying from a weakening to a strengthening of the THC. Here we assess the sensitivity of dissolved oxygen (O2) distributions in the WMS and EMS to THC changes using a mass balance model, which represents the exchanges of O2 between surface, intermediate, and deep water reservoirs, and through the Straits of Sicily and Gibraltar. Perturbations spanning the ranges in O2 solubility, aerobic respiration kinetics, and THC changes projected for the year 2100 are imposed to the O2 model. In all scenarios tested, the entire MS remains fully oxygenated after 100 years; depending on the THC regime, average deep water O2 concentrations fall in the ranges 151–205 and 160–219 µM in the WMS and EMS, respectively. On longer timescales (>1000 years), the scenario with the largest (>74%) decline in deep water formation rate leads to deep water hypoxia in the EMS but, even then, the WMS deep water remains oxygenated. In addition, a weakening of THC may result in a negative feedback on O2 consumption as supply of labile dissolved organic carbon to deep water decreases. Thus, it appears unlikely that climate-driven changes in THC will cause severe O2 depletion of the deep water masses of the MS in the foreseeable future

Basic notions of information structure

This article takes stock of the basic notions of Information Structure (IS). It first provides a general characterization of IS — following Chafe (1976) — within a communicative model of Common Ground(CG), which distinguishes between CG content and CG management. IS is concerned with those features of language that concern the local CG. Second, this paper defines and discusses the notions of Focus (as indicating alternatives) and its various uses, Givenness (as indicating that a denotation is already present in the CG), and Topic (as specifying what a statement is about). It also proposes a new notion, Delimitation, which comprises contrastive topics and frame setters, and indicates that the current conversational move does not entirely satisfy the local communicative needs. It also points out that rhetorical structuring partly belongs to IS.Peer Reviewe

Membrane transporters in the bioproduction of organic acids: state of the art and future perspectives for industrial applications

Organic acids such as monocarboxylic acids, dicarboxylic acids or even more complex molecules such as sugar acids, have displayed great applicability in the industry as these compounds are used as platform chemicals for polymer, food, agricultural and pharmaceutical sectors. Chemical synthesis of these compounds from petroleum derivatives is currently their major source of production. However, increasing environmental concerns have prompted the production of organic acids by microorganisms. The current trend is the exploitation of industrial biowastes to sustain microbial cell growth and valorize biomass conversion into organic acids. One of the major bottlenecks for the efficient and cost-effective bioproduction is the export of organic acids through the microbial plasma membrane. Membrane transporter proteins are crucial elements for the optimization of substrate import and final product export. Several transporters have been expressed in organic acid-producing species, resulting in increased final product titers in the extracellular medium and higher productivity levels. In this review, the state of the art of plasma membrane transport of organic acids is presented, along with the implications for industrial biotechnology.This work was supported by the strategic programme UID/BIA/04050/2019 funded by Portuguese fundsthrough the FCT I.P., and the projects: PTDC/BIAMIC/5184/2014, funded by national funds through the Fundacao para a Ciencia e Tecnologia (FCT) I.P. and by the European Regional Development Fund (ERDF) through the COMPETE 2020-Programa Operacional Competitividade e Internacionalizacao (POCI), and EcoAgriFood: Innovative green products and processes to promote AgriFood BioEconomy (operacao NORTE-01-0145-FEDER-000009), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). DR acknowledges FCT for the SFRH/BD/96166/2013 PhD grant. MSS acknowledges the Norte2020 for the UMINHO/BD/25/2016 PhD grant with the reference NORTE-08-5369-FSE-000060. TR acknowledges Yeastdoc European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 764927