[4′-(4-Amino­phen­yl)-2,2′:6′,2′′-terpyridine]­chloridopalladium(II) chloride

The PdII atom in the complex cation of the title compound, [PdCl(C21H16N4)]Cl, is coordinated by three N atoms derived from the terpyridine ligand and a chloride ion, which define a distorted PdClN3 square-planar coordination geometry. In the crystal, the presence of N—H⋯Cl hydrogen bonds involving the amino H atom and chloride anions link two cations and two anions into a four-ion aggregate via centrosymmetric eight-membered [⋯H—N—H⋯Cl]2 synthons. Layers of cations are inter­spersed with the chloride anions with stabilization provided by C—H⋯Cl inter­actions involving both Cl atoms, as well as π–π inter­actions [the closest inter­action of 3.489 (6) Å occurs between a chelate ring and a pyridyl residue]

Stress Corrosion Cracking in an Extruded Cu-Free Al-Zn-Mg Alloy

Stress corrosion cracking (SCC) in Cu-free Al-Zn-Mg (7xxx) aluminium alloys limits its use in many applications. In this work, we study in detail the microstructure of a peak and slightly overaged condition in an AA7003 alloy using transmission- and scanning electron microscopy in order to provide a comprehensive understanding of the microstructural features related to SCC. The SCC properties have been assessed using the double cantilever beam method and slow strain rate tensile tests. Grain boundary particles, precipitate free zones, and matrix precipitates have been studied. A difference in the SCC properties is established between the two ageing conditions. The dominating difference is the size and orientation of the hardening phases. Possible explanations correlating the microstructure and SCC properties are discussed.</jats:p

A Risk Benefit Analysis of Mariculture as a means to Reduce the Impacts of Terrestrial Production of Food and Energy

The Scottish Aquaculture Research Forum (SARF) and WWF-UK commissioned this study to investigate whether the pressure on land and freshwater for future food and energy resources, and impacts on the climate, related to greenhouse gas (GHG) emissions, may be reduced through expansion of global mariculture. The study has undertaken a high level assessment of the &lsquo;environmental footprint&rsquo; of global mariculture and terrestrial-based food and energy production systems through the collation and assessment of available Life Cycle Assessments (LCA) for key food products (beef, pork, chicken, freshwater finfish, marine finfish, shellfish and crustacean species) and biomass (terrestrial and algal) for energy production. The outputs of the footprint comparison were then used to assess the risks and benefits of increasing global mariculture, through the development of projected future scenarios in which mariculture contributes differing proportions of projected future food requirements. The analysis also qualitatively considered the socio-economic and wider environmental risks and benefits (e.g. in relation to ecosystem services) of global mariculture expansion, where expansion may occur geographically and whether future technological developments may help mitigate against identified impacts. The study identifies the key uncertainties and limitations of the risk/benefit analysis and makes prioritised recommendations on how these limitations can be addressed and the analysis developed for more regional or site-specific assessments

Guidelines on the management of abnormal liver blood tests

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.</p

An Interspecific Nicotiana Hybrid as a Useful and Cost-Effective Platform for Production of Animal Vaccines

The use of transgenic plants to produce novel products has great biotechnological potential as the relatively inexpensive inputs of light, water, and nutrients are utilised in return for potentially valuable bioactive metabolites, diagnostic proteins and vaccines. Extensive research is ongoing in this area internationally with the aim of producing plant-made vaccines of importance for both animals and humans. Vaccine purification is generally regarded as being integral to the preparation of safe and effective vaccines for use in humans. However, the use of crude plant extracts for animal immunisation may enable plant-made vaccines to become a cost-effective and efficacious approach to safely immunise large numbers of farm animals against diseases such as avian influenza. Since the technology associated with genetic transformation and large-scale propagation is very well established in Nicotiana, the genus has attributes well-suited for the production of plant-made vaccines. However the presence of potentially toxic alkaloids in Nicotiana extracts impedes their use as crude vaccine preparations. In the current study we describe a Nicotiana tabacum and N. glauca hybrid that expresses the HA glycoprotein of influenza A in its leaves but does not synthesize alkaloids. We demonstrate that injection with crude leaf extracts from these interspecific hybrid plants is a safe and effective approach for immunising mice. Moreover, this antigen-producing alkaloid-free, transgenic interspecific hybrid is vigorous, with a high capacity for vegetative shoot regeneration after harvesting. These plants are easily propagated by vegetative cuttings and have the added benefit of not producing viable pollen, thus reducing potential problems associated with bio-containment. Hence, these Nicotiana hybrids provide an advantageous production platform for partially purified, plant-made vaccines which may be particularly well suited for use in veterinary immunization programs

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

Regional differentiation of felid vertebral column evolution: a study of 3D shape trajectories

Recent advances in geometric morphometrics provide improved techniques for extraction of biological information from shape and have greatly contributed to the study of ecomorphology and morphological evolution. However, the vertebral column remains an under-studied structure due in part to a concentration on skull and limb research, but most importantly because of the difficulties in analysing the shape of a structure composed of multiple articulating discrete units (i.e. vertebrae). Here, we have applied a variety of geometric morphometric analyses to three-dimensional landmarks collected on 19 presacral vertebrae to investigate the influence of potential ecological and functional drivers, such as size, locomotion and prey size specialisation, on regional morphology of the vertebral column in the mammalian family Felidae. In particular, we have here provided a novel application of a method—phenotypic trajectory analysis (PTA)—that allows for shape analysis of a contiguous sequence of vertebrae as functionally linked osteological structures. Our results showed that ecological factors influence the shape of the vertebral column heterogeneously and that distinct vertebral sections may be under different selection pressures. While anterior presacral vertebrae may either have evolved under stronger phylogenetic constraints or are ecologically conservative, posterior presacral vertebrae, specifically in the post-T10 region, show significant differentiation among ecomorphs. Additionally, our PTA results demonstrated that functional vertebral regions differ among felid ecomorphs mainly in the relative covariation of vertebral shape variables (i.e. direction of trajectories, rather than in trajectory size) and, therefore, that ecological divergence among felid species is reflected by morphological changes in vertebral column shape