The influence of anæsthesia on the restoration of the volume of the blood after hæmorrhage and after transfusion

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The influence of an off the shelf lateral wedge orthotic on knee loading during running

Knee injuries are prevalent in sports and associated with degenerative changes to the joint (Silverwood et al.,2015). High external knee adduction moments (EKAMs), knee adduction angular impulses (KAAIs) and knee flexion moments (KFMs) have been associated with increased cartilage deterioration (Chehab, Favre, Erhart-Hledik, & Andriacchi, 2014). Lateral wedge insoles (LWIs) have demonstrated reductions in biomechanical loading (EKAM, KAAI) associated with osteoarthritis progression during walking in individuals with osteoarthritis (OA; Jones, Chapman, Forsythe, Parkes, & Felson, 2014). Younger individuals who sustain a knee injury during sport are likely to return to physical activity following treatment (Kim, Nagao, Kamata, Maeda, & Nozawa, 2013). With increased risk of developing knee OA, identifying preventative measures to delay the progression of OA during dynamic tasks such as running is required

Potato cyst nematodes Globodera rostochiensis and G. pallida

Innovate UK. Grant Number: 105653 (RESOLVE) Rural and Environment Science and Analytical Services Division. Grant Number: WP2.1 Scottish Funding Council. Grant Number: ODA GCRF XFC105Taxonomy: Phylum Nematoda; class Chromadorea; order Rhabditida; suborder Tylenchina; infraorder Tylenchomorpha; superfamily Tylenchoidea; family Heteroderidae; subfamily Heteroderinae; Genus Globodera. Biology: Potato cyst nematodes (PCN) are biotrophic, sedentary endoparasitic nematodes. Invasive (second) stage juveniles (J2) hatch from eggs in response to the presence of host root exudates and subsequently locate and invade the host. The nematodes induce the formation of a large, multinucleate syncytium in host roots, formed by fusion of up to 300 root cell protoplasts. The nematodes rely on this single syncytium for the nutrients required to develop through a further three moults to the adult male or female stage. This extended period of biotrophy?between 4 and 6 weeks in total?is almost unparalleled in plant?pathogen interactions. Females remain at the root while adult males revert to the vermiform body plan of the J2 and leave the root to locate and fertilize the female nematodes. The female body forms a cyst that contains the next generation of eggs. Host range: The host range of PCN is limited to plants of the Solanaceae family. While the most economically important hosts are potato (Solanum tuberosum), tomato (Solanum lycopersicum), and aubergine (Solanum melongena), over 170 species of Solanaceae are thought to be potential hosts for PCN (Sullivan et al., 2007). Disease symptoms: Symptoms are similar to those associated with nutrient deficiency, such as stunted growth, yellowing of leaves and reduced yields. This absence of specific symptoms reduces awareness of the disease among growers. Disease control: Resistance genes (where available in suitable cultivars), application of nematicides, crop rotation. Great effort is put into reducing the spread of PCN through quarantine measures and use of certified seed stocks. Useful websites: Genomic information for PCN is accessible through WormBase ParaSite.Publisher PDFPeer reviewe

Stable isotope (δ18O and δ13C) sclerochronology of Callovian (Middle Jurassic) bivalves (Gryphaea (Bilobissa) dilobotes) and belemnites (Cylindroteuthis puzosiana) from the Peterborough Member of the Oxford Clay Formation (Cambridgeshire, England): Evidence of palaeoclimate, water depth and belemnite behaviour

Incremental δ18O and δ13C signals were obtained from three well-preserved specimens of Cylindroteuthis puzosiana and from three well-preserved specimens of Gryphaea (Bilobissa) dilobotes from the Peterborough Member of the Oxford Clay Formation (Cambridgeshire, England). Through-ontogeny (sclerochronological) δ18O data from G. (B.) dilobotes appear to faithfully record seasonal temperature variations in benthic Callovian waters of the study area, which range from c. 14 °C to c. 17 °C (arithmetic mean temperature c. 15 °C). Water depth is estimated to have been in the region of c. 50 m, based upon comparisons between these data, previously published non-incremental sea surface δ18O values, and a modern analogue situation. Productivity in Callovian waters was comparable with that in modern seas, based upon δ13C data from G. (B.)dilobotes, with 13C depletion occurring during warmer periods, possibly related to an interaction between plankton blooms and intra-annual variations in mixing across a thermocline. Incremental δ18O data from C.puzosiana provide temperature minima of c.11 °C for all specimens but with maxima varying between c.14 °C and c.16 °C for different individuals (arithmetic mean values c. 13 °C). Temperatures for late ontogeny, when the C. puzosiana individuals must have been living close to the study site and hence the analysed specimens of G. (B.) dilobotes, are closely comparable to those indicated by the latter. However, for significant portions of ontogeny C. puzosiana experienced temperatures between c. 2 °C and c. 3 °C cooler than the winter minimum as recorded by co-occurring G. (B.) dilobotes. Comparisons with modern seas suggest that descent to a depth of c. 1000 m would be necessary to explain such cool minimum temperatures. This can be discounted due to the lack of deep waters locally and due to estimates of the depth tolerance of belemnites. The most likely cause of cool δ18O signals from C. puzosiana is a cosmopolitan lifestyle including migration to more northerly latitudes. Mean δ13C values from C. puzosiana are comparable with those from G.(B.)dilobotes. However, the incrementally acquired data are highly variable and probably influenced by metabolic effects.The probable identification of migratory behaviour in C. puzosiana calls into question the reliability of some belemnite species as place-specific palaeoenvironmental archives and highlights the benefits of adopting a sclerochronological approach

Host-Mediated Post-Translational Prenylation of Novel Dot/Icm-Translocated Effectors of Legionella Pneumophila

The Dot/Icm type IV translocated Ankyrin B (AnkB) effector of Legionella pneumophila is modified by the host prenylation machinery that anchors it into the outer leaflet of the Legionella-containing vacuole (LCV), which is essential for biological function of the effector in vitro and in vivo. Prenylation involves the covalent linkage of an isoprenoid lipid moiety to a C-terminal CaaX motif in eukaryotic proteins enabling their anchoring into membranes. We show here that the LCV harboring an ankB null mutant is decorated with prenylated proteins in a Dot/Icm-dependent manner, indicating that other LCV membrane-anchored proteins are prenylated. In silico analyses of four sequenced L. pneumophila genomes revealed the presence of eleven other genes that encode proteins with a C-terminal eukaryotic CaaX prenylation motif. Of these eleven designated Prenylated effectors of Legionella (Pel), seven are also found in L. pneumophila AA100. We show that six L. pneumophila AA100 Pel proteins exhibit distinct cellular localization when ectopically expressed in mammalian cells and this is dependent on action of the host prenylation machinery and the conserved cysteine residue of the CaaX motif. Although inhibition of the host prenylation machinery completely blocks intra-vacuolar proliferation of L. pneumophila, it only had a modest effect on intracellular trafficking of the LCV. Five of the Pel proteins are injected into human macrophages by the Dot/Icm type IV translocation system of L. pneumophila. Taken together, the Pel proteins are novel Dot/Icm-translocated effectors of L. pneumophila that are post-translationally modified by the host prenylation machinery, which enables their anchoring into cellular membranes, and the prenylated effectors contribute to evasion of lysosomal fusion by the LCV

The inevitable drift to triple therapy in COPD : an analysis of prescribing pathways in the UK

Acknowledgments The analyses reported in this study were funded by Novartis Pharma AG (Basel, Switzerland) and were conducted by Research in Real-Life Ltd (Cambridge, UK), an independent company. The authors also thank David Bergin, Danielle Corbett, and Vivek Khanna (professional medical writers; Novartis) for assistance in the preparation of this paper. Writing support was funded by Novartis Pharma AG.Peer reviewedPublisher PD

Patient and Public Involvement in the Design of Clinical Trials: An Overview of Systematic Reviews

Background Funders encourage lay-volunteer inclusion in research but this is not without controversy or resistance, given concerns of role confusion, exploratory methods and limited evidence about what value this brings to research. This overview explores these elements. Methods Eleven databases and gray literature were searched without date or language restrictions for systematic reviews of public involvement in clinical trials design. This systematic overview of patient and public involvement (PPI) included 27 reviews from which areas of good and bad practice were identified. PPI strengths, weaknesses, opportunities and threats were explored through use of meta-narrative analysis. Results Inclusion criteria was met by 27 reviews. Confidence in the findings was assessed using Cerqual, Nice-H, CASP for qualitative research and CASP systematic reviews. Quality ranged from high (n=7), medium (n=14) to low (n=6) in the reviews. Four reviews report the risk of bias. Public involvement roles were primarily in agenda setting, steering committees, ethical review, protocol development, and piloting. Research summaries, follow-up, and dissemination contained PPI, with lesser involvement in data collection, analysis, or manuscript authoring. Trialists report difficulty in finding, retaining, and reimbursing volunteers. Respectful inclusion, role recognition, mutual flexibility, advance planning and sound methods were reported as facilitating public involvement in research. Public involvement was reported to have increased the quantity and quality of patient relevant priorities and outcomes, enrollment, funding, design, implementation and dissemination. Challenges identified include lack of clarity within common language, roles and research boundaries; while logistical needs include extra time, training and funding, Researchers report struggling to report involvement and avoid tokenism. Conclusions Involving patients and the public in clinical trials design, can be beneficial but requires resources, preparation, training, flexibility and time. Issues to address include reporting deficits in the areas of risk of bias, study quality and conflicts of interests. There is a need for improved dissemination strategies to increase public involvement and health literacy. Improvements in funding, training, and reporting of PPI are needed to facilitate meaningful and effective PPI

Environmental distributions of benzo[a]pyrene in China:current and future emission reduction scenarios explored using a spatially explicit multimedia fate model

SESAMe v3.0, a spatially explicit multimedia fate model with 50 × 50 km(2) resolution, has been developed for China to predict environmental concentrations of benzo[a]pyrene (BaP) using an atmospheric emission inventory for 2007. Model predictions are compared with environmental monitoring data obtained from an extensive review of the literature. The model performs well in predicting multimedia concentrations and distributions. Predicted concentrations are compared with guideline values; highest values with some exceedances occur mainly in the North China Plain, Mid Inner Mongolia, and parts of three northeast provinces, Xi'an, Shanghai, and south of Jiangsu province, East Sichuan Basin, middle of Guizhou and Guangzhou. Two potential future scenarios have been assessed using SESAMe v3.0 for 2030 as BaP emission is reduced by (1) technological improvement for coal consumption in energy production and industry sectors in Scenario 1 (Sc1) and (2) technological improvement and control of indoor biomass burning for cooking and indoor space heating and prohibition of open burning of biomass in 2030 in Scenario 2 (Sc2). Sc2 is more efficient in reducing the areas with exceedance of guideline values. Use of SESAMe v3.0 provides insights on future research needs and can inform decision making on options for source reduction

Can majority support save an endangered language? A case study of language attitudes in Guernsey

Many studies of minority language revitalisation focus on the attitudes and perceptions of minorities, but not on those of majority group members. This paper discusses the implications of these issues, and presents research into majority andf minority attitudes towards the endangered indigenous vernacular of Guernsey, Channel Islands. The research used a multi-method approach (questionnaire and interview) to obtain attitudinal data from a representative sample of the population that included politicians and civil servants (209 participants). The findings suggested a shift in language ideology away from the post-second world war ‘culture of modernisation’ and monolingual ideal, towards recognition of the value of a bi/trilingual linguistic heritage. Public opinion in Guernsey now seems to support the maintenance of the indigenous language variety, which has led to a degree of official support. The paper then discusses to what extent this ‘attitude shift’ is reflected in linguistic behaviour and in concrete language planning measures

Cognitive dysfunction in patients treated with androgen deprivation therapy: a multimodality functional imaging study to evaluate neuroinflammation

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. METHODS: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. RESULTS: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. CONCLUSIONS: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI