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AbstractObjectivesTo determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes.DesignMulticentre, parallel, cluster randomised controlled trial.SettingLong term care homes in the UK, registered to care for older people or those with dementia.Participants1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care.InterventionsGuide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care.Main outcome measuresPrimary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation.ResultsMean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively.ConclusionsThe GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency.Trial registrationISRCTN34353836.

Acute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance of establishing new experimental models, the present investigation evaluated the modulation of APPs following inflammatory stimulus by the inoculation of Aeromonas hydrophila in tilapias. Fish were sampled 6 and 24 hours post-infection. Tilapias presented increase of positive APPs such as ceruloplasmin, haptoglobin, alpha-2-macroglobulin and complement C3, as well as decrease of negative APPs such as albumin and transferrin. The protein response of tilapias during the course of bacterial infection showed correlation with the kinetics of cellular accumulation in the inflamed focus with significant increase of granulocytes, thrombocytes, lymphocytes and macrophages. However, granulocytes were the predominant cells, associated with increment in the reactive oxygen species (ROS) production. Showing responses similar to those observed in humans, the modulation of APPs and the kinetics of cellular accumulation in the exudate demonstrate the feasibility of this alternative experimental model for advances and studies to understand changes in pathophysiological mechanisms of acute inflammatory reaction due to bacterial infection.

The growth in atmospheric methane (CH4) concentrations over the past 2 decades has shown large variability on a timescale of several years. Prior to 1999 the globally averaged CH4 concentration was increasing at a rate of 6.0 ppb yr−1, but during a stagnation period from 1999 to 2006 this growth rate slowed to 0.6 ppb yr−1. From 2007 to 2009 the growth rate again increased to 4.9 ppb yr−1. These changes in growth rate are usually ascribed to variations in CH4 emissions. We have used a 3-D global chemical transport model, driven by meteorological reanalyses and variations in global mean hydroxyl (OH) concentrations derived from CH3CCl3 observations from two independent networks, to investigate these CH4 growth variations. The model shows that between 1999 and 2006 changes in the CH4 atmospheric loss contributed significantly to the suppression in global CH4 concentrations relative to the pre-1999 trend. The largest factor in this is relatively small variations in global mean OH on a timescale of a few years, with minor contributions of atmospheric transport of CH4 to its sink region and of atmospheric temperature. Although changes in emissions may be important during the stagnation period, these results imply a smaller variation is required to explain the observed CH4 trends. The contribution of OH variations to the renewed CH4 growth after 2007 cannot be determined with data currently available.

The effect of Nb on the properties and microstructure of two novel powder metallurgy (P/M) Ni-based superalloys was evaluated, and the results critically compared with the Rolls-Royce alloy RR1000. The Nb-containing alloy was found to exhibit improved tensile and creep properties as well as superior oxidation resistance compared with both RR1000 and the Nb-free variant tested. The beneficial effect of Nb on the tensile and creep properties was due to the microstructures obtained following the post-solution heat treatments, which led to a higher γ′ volume fraction and a finer tertiary γ′ distribution. In addition, an increase in the anti-phase-boundary energy of the γ′ phase is also expected with the addition of Nb, further contributing to the strength of the material. However, these modifications in the γ′ distribution detrimentally affect the dwell fatigue crack-growth behavior of the material, although this behavior can be improved through modified heat treatments. The oxidation resistance of the Nb-containing alloy was also enhanced as Nb is believed to accelerate the formation of a defect-free Cr2O3 scale. Overall, both developmental alloys, with and without the addition of Nb, were found to exhibit superior properties than RR1000.

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.

To understand the mechanisms responsible for aluminum (Al) toxicity and tolerance in plants, an expressed sequence tag (EST) approach was used to analyze changes in gene expression in roots of rye (Secale cereale L. cv Blanco) under Al stress. Two cDNA libraries were constructed (Al stressed and unstressed), and a total of 1,194 and 774 ESTs were generated, respectively. The putative proteins encoded by these cDNAs were uncovered by Basic Local Alignment Search Tool searches, and those ESTs showing similarity to proteins of known function were classified according to 13 different functional categories. A total of 671 known function genes were used to analyze the gene expression patterns in rye cv Blanco root tips under Al stress. Many of the previously identified Al-responsive genes showed expression differences between the libraries within 6 h of Al stress. Certain genes were selected, and their expression profiles were studied during a 48-h period using northern analysis. A total of 13 novel genes involved in cell elongation and division (tonoplast aquaporin and ubiquitin-like protein SMT3), oxidative stress (glutathione peroxidase, glucose-6-phosphate-dehydrogenase, and ascorbate peroxidase), iron metabolism (iron deficiency-specific proteins IDS3a, IDS3b, and IDS1; S-adenosyl methionine synthase; and methionine synthase), and other cellular mechanisms (pathogenesis-related protein 1.2, heme oxygenase, and epoxide hydrolase) were demonstrated to be regulated by Al stress. These genes provide new insights about the response of Al-tolerant plants to toxic levels of Al.

COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV )/forced vital capacity (FVC) <0.70 and FEV <60% predicted or exacerbation risk requiring further evaluation for COPD. This study tested CAPTURE's ability to identify symptomatic patients with mild-to-moderate COPD (FEV 60%-80% predicted) who may also benefit from diagnosis and treatment. Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) were used to evaluate symptoms and health status. Clinical Trial Registration: NCT01880177, https://ClinicalTrials.gov/ct2/show/NCT01880177?term=NCT01880177&rank=1. Mean age (+SD): 61 (+10.5) years; 41% male. COPD: FEV /FVC=0.60 (+0.1), FEV % predicted=74% (+12.4). SN and SP for differentiating mild-to-moderate and non-COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (≤450 L/min; ≤350 L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%. COPD patients whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52) were more likely to be symptomatic than patients whose results did not (n=21) (mMRC >2: 37% vs 5%, <0.01; CAT>10: 86% vs 57%, <0.01). CAPTURE differentiated COPD from no COPD (n=346): SN: 88.0%, SP: 83.9%. CAPTURE (450/350) may be useful for identifying symptomatic patients with mild-to-moderate airflow obstruction in need of diagnostic evaluation for COPD.

The surname of author Cathy Quantin-Nataf was misspelled ‘Quantin-Nata’ , authors Ehouarn Millour and Roland Young were missing from the ACS Science Team list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.