Objectives
Stroke‐associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce.
Materials and methods
This observational study was conducted ...in a cohort of stroke patients admitted consecutively to a tertiary referral center in the east of England, UK (January 2003‐April 2015). Logistic regression models examined inpatient mortality and length of stay (LOS). Cox regression models examined longer‐term mortality at predefined time periods (0‐90 days, 90 days‐1 year, 1‐3 years, and 3‐10 years) for SAP. Effect of SAP on functional outcome at discharge was assessed using logistic regression.
Results
A total of 9238 patients (mean age ±SD 77.61 ± 11.88 years) were included. SAP was diagnosed in 1083 (11.7%) patients. The majority of these cases (n = 658; 60.8%) were aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project (OCSP) classification, prestroke modified Rankin scale, comorbidities, and acute illness markers, mortality estimates remained significant at 3 time periods: inpatient (OR 5.87, 95%CI 4.97‐6.93), 0‐90 days (2.17 1.97‐2.40), and 91‐365 days (HR 1.31 1.03‐1.67). SAP was also associated with higher odds of long LOS (OR 1.93 1.67‐2.22) and worse functional outcome (OR 7.17 5.44‐9.45). In this cohort, SAP did not increase mortality risk beyond 1 year post‐stroke, but it was associated with reduced mortality beyond 3 years.
Conclusions
Stroke‐associated pneumonia is not associated with increased long‐term mortality, but it is linked with increased mortality up to 1 year, prolonged LOS, and poor functional outcome on discharge. Targeted intervention strategies are required to improve outcomes of SAP patients who survive to hospital discharge.
In April 2014 the UK government launched the 'NHS Visitor and Migrant Cost Recovery Programme Implementation Plan' which set out a series of policy changes to recoup costs from 'chargeable' (largely ...non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced.
There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP.
We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13-1.66, p value 0.001).
Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally.
Photosensitive films incorporating molecular photoacid generators compartmentalized within a silica-surfactant mesophase were prepared by an evaporation-induced self-assembly process. Ultraviolet ...exposure promoted localized acid-catalyzed siloxane condensation, which can be used for selective etching of unexposed regions; for "gray-scale" patterning of refractive index, pore size, surface area, and wetting behavior; and for optically defining a mesophase transformation (from hexagonal to tetragonal) within the film. The ability to optically define and continuously control both structure and function on the macro- and mesoscales is of interest for sensor arrays, nanoreactors, photonic and fluidic devices, and low-dielectric-constant films.
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of ...patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL. Using fluorescence in situ hybridisation, we were able to track up to four structural variants in single cells from 47 CRLF2-r B-ALL patients, which in association with our multiplex single-cell analysis of a further four patients, permitted simultaneous tracking of copy number alterations, structural and single nucleotide variants within individual cells. We observed CRLF2-r arising as both early and late events in DS and non-DS-ALL patients. Parallel evolution of discrete clones was observed in the development of CRLF2-r B-ALL, either involving the CRLF2-r or one of the other tracked abnormalities. In-depth single-cell analysis identified both linear and branching evolution with early clones harbouring a multitude of abnormalities, including the CRLF2-r in DS-ALL patients.
Summary Background Depression is common and is associated with poor outcomes among elderly care-home residents. Exercise is a promising low-risk intervention for depression in this population. We ...tested the hypothesis that a moderate intensity exercise programme would reduce the burden of depressive symptoms in residents of care homes. Methods We did a cluster-randomised controlled trial in care homes in two regions in England; northeast London, and Coventry and Warwickshire. Residents aged 65 years or older were eligible for inclusion. A statistician independent of the study randomised each home (1 to 1·5 ratio, stratified by location, minimised by type of home provider local authority, voluntary, private and care home, private and nursing home and size of home <32 or ≥32 residents) into intervention and control groups. The intervention package included depression awareness training for care-home staff, 45 min physiotherapist-led group exercise sessions for residents (delivered twice weekly), and a whole home component designed to encourage more physical activity in daily life. The control consisted of only the depression awareness training. Researchers collecting follow-up data from individual participants and the participants themselves were inevitably aware of home randomisation because of the physiotherapists' activities within the home. A researcher masked to study allocation coded NHS routine data. The primary outcome was number of depressive symptoms on the geriatric depression scale-15 (GDS-15). Follow-up was for 12 months. This trial is registered with ISRCTN Register, number ISRCTN43769277. Findings Care homes were randomised between Dec 15, 2008, and April 9, 2010. At randomisation, 891 individuals in 78 care homes (35 intervention, 43 control) had provided baseline data. We delivered 3191 group exercise sessions attended on average by five study participants and five non-study residents. Of residents with a GDS-15 score, 374 of 765 (49%) were depressed at baseline; 484 of 765 (63%) provided 12 month follow-up scores. Overall the GDS-15 score was 0·13 (95% CI −0·33 to 0·60) points higher (worse) at 12 months for the intervention group compared with the control group. Among residents depressed at baseline, GDS-15 score was 0·22 (95% CI −0·52 to 0·95) points higher at 6 months in the intervention group than in the control group. In an end of study cross-sectional analysis, including 132 additional residents joining after randomisation, the odds of being depressed were 0·76 (95% CI 0·53 to 1·09) for the intervention group compared with the control group. Interpretation This moderately intense exercise programme did not reduce depressive symptoms in residents of care homes. In this frail population, alternative strategies to manage psychological symptoms are required. Funding National Institute for Health Research Health Technology Assessment.
The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown. Here, we report that Drosophila melanogaster Akt/PKB stimulates ...growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex. We show that Akt/PKB directly phosphorylates Drosophila Tsc2 in vitro at the conserved residues, Ser 924 and Thr 1518. Mutation of these sites renders Tsc2 insensitive to Akt/PKB signalling, increasing the stability of the Tsc1-Tsc2 complex within the cell. Stimulating Akt/PKB signalling in vivo markedly increases cell growth/size, disrupts the Tsc1-Tsc2 complex and disturbs the distinct subcellular localization of Tsc1 and Tsc2. Furthermore, all Akt/PKB growth signals are blocked by expression of a Tsc2 mutant lacking Akt phosphorylation sites. Thus, Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway.
The entry of therapeutic compounds into the brain and spinal cord is normally restricted by barrier mechanisms in cerebral blood vessels (blood–brain barrier) and choroid plexuses (blood–CSF ...barrier). In the injured brain, ruptured cerebral blood vessels circumvent these barrier mechanisms by allowing blood contents to escape directly into the brain parenchyma. This process may contribute to the secondary damage that follows the initial primary injury. However, this localized compromise of barrier function in the injured brain may also provide a ‘window of opportunity’ through which drugs that do not normally cross the blood–brain barriers are able to do so. This paper describes a systematic study of barrier permeability in a mouse model of traumatic brain injury using both small and large inert molecules that can be visualized or quantified. The results show that soon after trauma, both large and small molecules are able to enter the brain in and around the injury site. Barrier restriction to large (protein‐sized) molecules is restored by 4–5 h after injury. In contrast, smaller molecules (286–10 000 Da) are still able to enter the brain as long as 4 days postinjury. Thus the period of potential secondary damage from barrier disruption and the period during which therapeutic compounds have direct access to the injured brain may be longer than previously thought.
•Poly(I:C) molecular weight (MW) and endotoxin vary significantly between suppliers.•MW and endotoxin variability predicts rat maternal IL-6 response and litter size.•MW variability predicts rat ...placental weight.•Poly(I:C) supplier predicts a male-specific reduction in fetal brain weight.
The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.
ABSTRACT
We report the discovery of the first transient with MeerKAT, MKT J170456.2–482100, discovered in ThunderKAT images of the low-mass X-ray binary GX339–4. MKT J170456.2–482100 is variable in ...the radio, reaching a maximum flux density of $0.71\pm 0.11\, \mathrm{mJy}$ on 2019 October 12, and is undetected in 15 out of 48 ThunderKAT epochs. MKT J170456.2–482100 is coincident with the chromospherically active K-type sub-giant TYC 8332-2529-1, and $\sim 18\, \mathrm{yr}$ of archival optical photometry of the star shows that it varies with a period of $21.25\pm 0.04\, \mathrm{d}$. The shape and phase of the optical light curve changes over time, and we detect both X-ray and UV emission at the position of MKT J170456.2–482100, which may indicate that TYC 8332-2529-1 has large star spots. Spectroscopic analysis shows that TYC 8332-2529-1 is in a binary, and has a line-of-sight radial velocity amplitude of $43\, \mathrm{km\, s^{-1}}$. We also observe a spectral feature in antiphase with the K-type sub-giant, with a line-of-sight radial velocity amplitude of $\sim 12\pm 10\, \mathrm{km\, s^{-1}}$, whose origins cannot currently be explained. Further observations and investigation are required to determine the nature of the MKT J170456.2–482100 system.
Euclid preparation Gómez-Alvarez, P.; Altieri, B.; Laureijs, R. ...
Astronomy and astrophysics (Berlin),
01/2022, Letnik:
657
Journal Article
Recenzirano
Odprti dostop
Context.
While
Euclid
is an ESA mission specifically designed to investigate the nature of dark energy and dark matter, the planned unprecedented combination of survey area (∼15 000 deg
2
), spatial ...resolution, low sky-background, and depth also make
Euclid
an excellent space observatory for the study of the low surface brightness Universe. Scientific exploitation of the extended low surface brightness structures requires dedicated calibration procedures that are yet to be tested.
Aims.
We investigate the capabilities of
Euclid
to detect extended low surface brightness structure by identifying and quantifying sky-background sources and stray-light contamination. We test the feasibility of generating sky flat-fields to reduce large-scale residual gradients in order to reveal the extended emission of galaxies observed in the
Euclid
survey.
Methods.
We simulated a realistic set of
Euclid
/VIS observations, taking into account both instrumental and astronomical sources of contamination, including cosmic rays, stray-light, zodiacal light, interstellar medium, and the cosmic infrared background, while simulating the effects of background sources in the field of view.
Results.
We demonstrate that a combination of calibration lamps, sky flats, and self-calibration would enable recovery of emission at a limiting surface brightness magnitude of
μ
lim
= 29.5
−0.27
+0.08
mag arcsec
−2
(3
σ
, 10 × 10 arcsec
2
) in the Wide Survey, and it would reach regions deeper by 2 mag in the Deep Surveys.
Conclusions.Euclid
/VIS has the potential to be an excellent low surface brightness observatory. Covering the gap between pixel-to-pixel calibration lamp flats and self-calibration observations for large scales, the application of sky flat-fielding will enhance the sensitivity of the VIS detector at scales larger than 1″, up to the size of the field of view, enabling
Euclid
to detect extended surface brightness structures below
μ
lim
= 31 mag arcsec
−2
and beyond.
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