Undiagnosed dementia in primary care: A record linkage study

BackgroundThe number of people living with dementia is greater than the number with a diagnosis of dementia recorded in primary care. This suggests that a significant number are living with dementia that is undiagnosed. Little is known about this group and there is little quantitative evidence regarding the consequences of diagnosis for people with dementia.ObjectivesThe aims of this study were to (1) describe the population meeting the criteria for dementia but without diagnosis, (2) identify predictors of being diagnosed and (3) estimate the effect of diagnosis on mortality, move to residential care, social participation and well-being.DesignA record linkage study of a subsample of participants (n = 598) from the Cognitive Function and Ageing Study II (CFAS II) (n = 7796), an existing cohort study of the population of England aged ≥ 65 years, with standardised validated assessment of dementia and consent to access medical records.Data sourcesData on dementia diagnoses from each participant’s primary care record and covariate and outcome data from CFAS II.SettingA population-representative cohort of people aged ≥ 65 years from three regions of England between 2008 and 2011.ParticipantsA total of 598 CFAS II participants, which included all those with dementia who consented to medical record linkage (n = 449) and a stratified sample without dementia (n = 149).Main outcome measuresThe main outcome was presence of a diagnosis of dementia in each participant’s primary care record at the time of their CFAS II assessment(s). Other outcomes were date of death, cognitive performance scores, move to residential care, hospital stays and social participation.ResultsAmong people with dementia, the proportion with a diagnosis in primary care was 34% in 2008–11 and 44% in 2011–13. In both periods, a further 21% had a record of a concern or a referral but no diagnosis. The likelihood of having a recorded diagnosis increased with severity of impairment in memory and orientation, but not with other cognitive impairment. In multivariable analysis, those aged ≥ 90 years and those age

Physiological predictors of peak inspiRatory flow using Observed lung function results (POROS) : evaluation at discharge among patients hospitalized for a COPD exacerbation

This study was supported by AstraZeneca. The abstract of this paper was presented at the American Thoracic Society International Conference 2017 as a poster presentation with interim findings.Peer reviewedPublisher PD

Properties of a Gamma-Ray Burst Host Galaxy at z ~ 5

We describe the properties of the host galaxy of the gamma-ray burst GRB 060510B based on a spectrum of the burst afterglow obtained with the Gemini North 8 m telescope. The galaxy lies at a redshift of z = 4.941, making it the fourth highest spectroscopically identified burst host. However, it is the second highest redshift galaxy for which the quality of the spectrum permits a detailed metallicity analysis. The neutral hydrogen column density has a logarithmic value of 21.0-21.2 cm-2, and the weak metal lines of Ni, S, and Fe show that the metallicity is in excess of a tenth of solar, which is far above the metallicities in damped Lya absorbers at high redshift. The tightest constraint is from the Fe lines, which place [Fe/H] in excess of -0.8. We argue that the results suggest that metallicity bias could be a serious obstacle to inferring star formation from the GRB population, and we consider how future higher quality measurements could be used to resolve this issue

A Comprehensive Study of GRB 070125, A Most Energetic Gamma-Ray Burst

We present a comprehensive multiwavelength analysis of the bright, long-duration gamma-ray burst GRB 070125, comprised of observations in gamma-ray, X-ray, optical, millimeter, and centimeter wave bands. Simultaneous fits to the optical and X-ray light curves favor a break on day 3.78, which we interpret as the jet break from a collimated outflow. Independent fits to optical and X-ray bands give similar results in the optical bands but shift the jet break to around day 10 in the X-ray light curve. We show that for the physical parameters derived for GRB 070125, inverse Compton scattering effects are important throughout the afterglow evolution. While inverse Compton scattering does not affect radio and optical bands, it may be a promising candidate to delay the jet break in the X-ray band. Radio light curves show rapid flux variations, which are interpreted as due to interstellar scintillation and used to derive an upper limit of 2.4 × 10 17 cm on the radius of the fireball in the lateral expansion phase of the jet. Radio light curves and spectra suggest a high synchrotron self-absorption frequency indicative of the afterglow shock wave moving in a dense medium. Our broadband modeling favors a constant density profile for the circumburst medium over a windlike profile (R -2). However, keeping in mind the uncertainty of the parameters, it is difficult to unambiguously distinguish between the two density profiles. Our broadband fits suggest that GRB 070125 is a burst with high radiative efficiency (>60%).R. A. C. was supported in part by NASA grant NNG06GJ33G

A preliminary modelling investigation into the safe correction zone for high tibial osteotomy

Purpose: High tibial osteotomy (HTO) re-aligns the weight-bearing axis (WBA) of the lower limb. The surgery reduces medial load (reducing pain and slowing progression of cartilage damage) while avoiding overloading the lateral compartment. The optimal correction has not been established. This study investigated how different WBA re-alignments affected load distribu- tion in the knee, to consider the optimal post-surgery re-alignment. Methods: We collected motion analysis and 7T MRI data from 3 healthy sub- jects, and combined this data to create sets of subject-specific finite element models (total=45 models). Each set of models simulated a range of potential post-HTO knee re-alignments. We shifted the WBA from its native align- ment to between 40% and 80% medial-lateral tibial width (corresponding to 2.8◦-3.1◦ varus and 8.5◦-9.3◦ valgus), in 3% increments. We then compared stress/pressure distributions in the models. Results/Discussion: Correcting the WBA to 50% tibial width (0◦ varus- valgus) approximately halved medial compartment stresses, with minimal changes to lateral stress levels, but provided little margin for error in under- correction. Correcting the WBA to a more commonly-used 62%-65% tibial width (3.4◦-4.6◦ valgus) further reduced medial stresses but introduced the danger of damaging lateral compartment tissues. To balance optimal loading environment with that of the historical risk of under-correction, we propose a new target: WBA correction to 55% tibial width (1.7◦-1.9◦ valgus), which anatomically represented the apex of the lateral tibial spine. Conclusions: Finite element models can successfully simulate a variety of HTO re-alignments. Correcting the WBA to 55% tibial width (1.7◦-1.9◦ valgus) optimally distributes medial and lateral stresses/pressures

Hubble Space Telescope and Spitzer Observations of the Afterglow and Host Galaxy of GRB 050904 at z = 6.295

We present deep Hubble Space Telescope (HST) and Spitzer Space Telescope observations of GRB 050904 at z = 6.295. We detect the afterglow in the H band more than 3 weeks after the burst and confirm the presence of a jet break at t ≈ 2.1 days. This leadsE. B. acknowledges support by NASA through Hubble Fellowship grant HST- 01171.01 awarded by the Space Telescope Science Institute (STScI), which is operated by AURA, Inc., for NASA under contract NAS5-26555. Additional support was provided by NASA through grant HST-GO-10616 from STScI and through a Spitzer award from JPL/Caltech

The Early Optical Afterglow of GRB 030418 and Progenitor Mass Loss

The ROTSE-IIIa telescope and the SSO 40 inch (1.0 m) telescope, both located at Siding Spring Observatory, imaged the early-time afterglow of GRB 030418. In this report, we present observations of the early afterglow, first detected by the ROTSE-IIIa telescope 211 s after the start of the burst and only 76 s after the end of the gamma-ray activity. We detect optical emission that rises for ∼600 s, slowly varies around R = 17.3 mag for ∼1400 s, and then fades as a power law of index α = -1.36. Additionally, the ROTSE-IIIb telescope, located at McDonald Observatory, imaged the early-time afterglow of GRB 030723. The behavior of this light curve was qualitatively similar to that of GRB 030418, but 2 mag dimmer. These two afterglows are dissimilar to other afterglows such as GRB 990123 and GRB 021211. We investigate whether or not the early afterglow can be attributed to a synchrotron break in a cooling synchrotron spectrum as it passes through the optical band, but we find that this model is unable to accurately describe the early light curve. We present a simple model for gamma-ray burst emission emerging from a wind medium surrounding a massive progenitor star. This model provides an effective description of the data and suggests that the rise of the afterglow can be ascribed to extinction in the local circumburst environment. In this interpretation, these events provide further evidence of the connection between gamma-ray bursts and the collapse of massive stars.This work has been supported by NASA grants NAG5- 5281 and F006794, NSF grants AST 01-19685 and 01-05221, the Australian Research Council, the University of New South Wales, and the University of Michigan. Work performed at LANL is supported by NASA SR&T through Department of Energy (DOE) contract W-7405-ENG-36 and through internal LDRD funding

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A Novel Conserved Isoform of the Ubiquitin Ligase UFD2a/UBE4B Is Expressed Exclusively in Mature Striated Muscle Cells

Yeast Ufd2p was the first identified E4 multiubiquitin chain assembly factor. Its vertebrate homologues later referred to as UFD2a, UBE4B or E4B were also shown to have E3 ubiquitin ligase activity. UFD2a function in the brain has been well established in vivo, and in vitro studies have shown that its activity is essential for proper condensation and segregation of chromosomes during mitosis. Here we show that 2 alternative splice forms of UFD2a, UFD2a-7 and -7/7a, are expressed sequentially during myoblast differentiation of C2C12 cell cultures and during cardiotoxin-induced regeneration of skeletal muscle in mice. UFD2a-7 contains an alternate exon 7, and UFD2a-7/7a, the larger of the 2 isoforms, contains an additional novel exon 7a. Analysis of protein or mRNA expression in mice and zebrafish revealed that a similar pattern of isoform switching occurs during developmental myogenesis of cardiac and skeletal muscle. In vertebrates (humans, rodents, zebrafish), UFD2a-7/7a is expressed only in mature striated muscle. This unique tissue specificity is further validated by the conserved presence of 2 muscle-specific splicing regulatory motifs located in the 3′ introns of exons 7 and 7a. UFD2a interacts with VCP/p97, an AAA-type ATPase implicated in processes whose functions appear to be regulated, in part, through their interaction with one or more of 15 previously identified cofactors. UFD2a-7/7a did not interact with VCP/p97 in yeast 2-hybrid experiments, which may allow the ATPase to bind cofactors that facilitate its muscle-specific functions. We conclude that the regulated expression of these UFD2a isoforms most likely imparts divergent functions that are important for myogenisis

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant