The electronic frailty index as an indicator of community healthcare service utilisation in the older population

Background: older people with frailty are particularly high users of healthcare services, however a lack of standardised recording of frailty in different healthcare electronic datasets has limited investigations into healthcare service usage and demand of the older frail population. Objectives: to investigate the community service demand of frail patients using the electronic frailty index (eFI) as a measure of frailty. Study design and setting a retrospective cohort study using anonymised linked healthcare patient data from primary care, community services and acute hospitals in Norfolk. Participants: patients aged 65 and over who had an eFI assessment score established in their primary care electronic patient record in Norwich based General Practices. Results: we include data from 22,859 patients with an eFI score. Frailty severity increased with age and was associated with increased acute hospital admission within a 6-month window. Patients with a frail eFI score were also more likely to have a community service referral within a 6-month window of frailty assessment, with a RR of 1.84 (1.76–1.93) for mild frailty, 1.96 (1.83–2.09) for moderate frailty and 2.95 (2.76–3.14) for severe frailty scores. We also found that frail patients had more community referrals per patient then those classified as fit and required more care plans per community referral. Conclusions: eFI score was an indicator of community service use, with increasing severity of frailty being associated with higher community healthcare requirements. The eFI may help planning of community services for the frail population

Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

Acknowledgments Blood biochemistry analysis and serum analysis were performed by the Easter Bush Pathology Department, University of Edinburgh. Animal husbandry was performed by Centre for Integrative Physiology bio-research restructure technical staff, University of Edinburgh. Assistance with intravenous injections was provided by Ian Coldicott (University of Sheffield) and Hannah Shorrock (University of Edinburgh). Human blood cDNA was a gift to GH from Kathy Evans, University of Edinburgh. Imaging was performed at the IMPACT imaging facility, University of Edinburgh, with technical assistance from Anisha Kubasik-Thayil. The authors would also like to thank Lyndsay Murray for technical discussions relating to qRT-PCR analysis. This work was supported by funding from the SMA Trust and the Anatomical Society (via grants to THG); the Euan MacDonald Centre for Motor Neurone Disease Research (via grants to THG and SHP); the Wellcome Trust (via grants to EJNG and THG); Muscular Dystrophy UK (via grants to THG and CGB); a Elphinstone Scholarship from the University of Aberdeen (to SHP); and The French Muscular Dystrophy Association (via grants to CM and JC).Peer reviewedPublisher PD

Elemental Composition and Chemical Evolution of Geologic Materials in Gale Crater, Mars: APXS Results From Bradbury Landing to the Vera Rubin Ridge

The Alpha Particle X-ray Spectrometer (APXS) on the rover Curiosity has analyzed the composition of geologic materials along a >20-km traverse in Gale crater on Mars. The APXS dataset after 6.5 Earth years (2,301 sols) includes 712 analyses of soil, sand, float, bedrock, and drilled/scooped fines. We present the APXS results over this duration and provide stratigraphic context for each target. We identify the best APXS measurement of each of the 22 drilled and scooped samples that were delivered to the instruments Chemistry and Mineralogy (CheMin; X-ray diffractometer) and Sample Analysis at Mars (SAM; mass spectrometer and gas chromatograph) during this period. The APXS results demonstrate that the basaltic and alkali-rich units in the Bradbury group (sols 0-750) show minimal alteration indicating an arid climate. In contrast, the Murray formation of the Mount Sharp group (sols ∼750-2,301) has compositions indicating pervasive alteration. Diagenetic features are common and show fluid interaction with the sediment after (and possibly during) lithification. A sandstone unit, the Stimson formation, overlies part of the Murray formation. This has a composition similar to the basaltic sand and soil, suggesting a shared source. Cross-cutting, fracture-associated haloes are evidence of late-stage fluid alteration after lithification of the sediment. The APXS dataset, evaluated in concert with the full science payload of Curiosity, indicates that Gale crater was habitable, and that liquid water was stable for extended periods.We are indebted to NASA-JPL, the Canadian Space Agency, and Australian Research Council (DP150104604) for supporting our work and the MSL mission. A portion of this study was conducted at the Jet Propulsion Laboratory, California Institute of Technology under a contract with the National Aeronautics and Space Administration

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo

Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

The fusion crust of the Winchcombe meteorite: a preserved record of atmospheric entry processes

Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred during deceleration in the atmosphere. The fusion crust of the Winchcombe meteorite closely resembles that of other stony meteorites, and in particular CM2 chondrites, since it is dominated by olivine phenocrysts set in a glassy mesostasis with magnetite, and is highly vesicular. Dehydration cracks are unusually abundant in Winchcombe. Failure of this weak layer is an additional ablation mechanism to produce large numbers of particles during deceleration, consistent with the observation of pulses of plasma in videos of the Winchcombe fireball. Calving events might provide an observable phenomenon related to meteorites that are particularly susceptible to dehydration. Oscillatory zoning is observed within olivine phenocrysts in the fusion crust, in contrast to other meteorites, perhaps owing to temperature fluctuations resulting from calving events. Magnetite monolayers are found in the crust, and have also not been previously reported, and form discontinuous strata. These features grade into magnetite rims formed on the external surface of the crust and suggest the trapping of surface magnetite by collapse of melt. Magnetite monolayers may be a feature of meteorites that undergo significant degassing. Silicate warts with dendritic textures were observed and are suggested to be droplets ablated from another stone in the shower. They, therefore, represent the first evidence for intershower transfer of ablation materials and are consistent with the other evidence in the Winchcombe meteorite for unusually intense gas loss and ablation, despite its low entry velocity.Science and Technology Facilities Council (STFC): ST/V000799/