Estimating Nosocomial Infection and its Outcomes in Hospital Patients in England with a Diagnosis of COVID-19 Using Machine Learning

BACKGROUND: COVID-19 nosocomial infections (NIs) may have played a significant role in the dynamics of the pandemic in England, but analysis of their impact at the national scale has been lacking. Our aim was to provide a comprehensive account of NIs, identify their characteristics and outcomes in patients with a diagnosis of COVID-19 and use machine learning modelling to refine these estimates. METHODS: From the Hospital Episodes Statistics database all adult hospital patients in England with a diagnosis of COVID-19 and discharged between March 1st 2020 and March 31st 2021 were identified. A cohort of suspected COVID-19 NIs was identified using four empirical methods linked to hospital coding. A random forest classifier was designed to model the relationship between acquiring NIs and the covariates: patient characteristics, comorbidities, frailty, trust capacity strain and severity of COVID-19 infections. FINDINGS: In total, 374,244 adult patients with COVID-19 were discharged during the study period. The four empirical methods identified 29,896 (8.0%) patients with NIs. The random forest classifier estimated a mean NI rate of 10.5%, with a peak close to 18% during the first wave, but much lower rates thereafter and around 7% in early spring 2021. NIs were highly correlated with longer lengths of stay, high trust capacity strain, greater age and a higher degree of patient frailty. NIs were also found to be associated with higher mortality rates and more severe COVID-19 sequelae, including pneumonia, kidney disease and sepsis. INTERPRETATION: Identification of the characteristics of patients who acquire NIs should help trusts to identify those most at risk. The evolution of the NI rate over time may reflect the impact of changes in hospital management practices and vaccination efforts. Variations in NI rates across trusts may partly reflect different data recording and coding practice

Haploinsufficiency of the schizophrenia and autism risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms

Genetic risk factors can significantly increase chances of developing psychiatric disorders, but the underlying biological processes through which this risk is effected remain largely unknown. Here we show that haploinsufficiency of Cyfip1, a candidate risk gene present in the pathogenic 15q11.2(BP1–BP2) deletion may impact on psychopathology via abnormalities in cell survival and migration of newborn neurons during postnatal hippocampal neurogenesis. We demonstrate that haploinsufficiency of Cyfip1 leads to increased numbers of adult-born hippocampal neurons due to reduced apoptosis, without altering proliferation. We show this is due to a cell autonomous failure of microglia to induce apoptosis through the secretion of the appropriate factors, a previously undescribed mechanism. Furthermore, we show an abnormal migration of adult-born neurons due to altered Arp2/3 mediated actin dynamics. Together, our findings throw new light on how the genetic risk candidate Cyfip1 may influence the hippocampus, a brain region with strong evidence for involvement in psychopathology

N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase

Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation “oligotropic” adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase

Rotation of planet-harbouring stars

The rotation rate of a star has important implications for the detectability, characterisation and stability of any planets that may be orbiting it. This chapter gives a brief overview of stellar rotation before describing the methods used to measure the rotation periods of planet host stars, the factors affecting the evolution of a star's rotation rate, stellar age estimates based on rotation, and an overview of the observed trends in the rotation properties of stars with planets.Comment: 16 pages, 4 figures: Invited review to appear in 'Handbook of Exoplanets', Springer Reference Works, edited by Hans J. Deeg and Juan Antonio Belmont

Untargeted UPLC-MS Profiling Pipeline to Expand Tissue Metabolome Coverage: Application to Cardiovascular Disease.

Metabolic profiling studies aim to achieve broad metabolome coverage in specific biological samples. However, wide metabolome coverage has proven difficult to achieve, mostly because of the diverse physicochemical properties of small molecules, obligating analysts to seek multiplatform and multimethod approaches. Challenges are even greater when it comes to applications to tissue samples, where tissue lysis and metabolite extraction can induce significant systematic variation in composition. We have developed a pipeline for obtaining the aqueous and organic compounds from diseased arterial tissue using two consecutive extractions, followed by a different untargeted UPLC-MS analysis method for each extract. Methods were rationally chosen and optimized to address the different physicochemical properties of each extract: hydrophilic interaction liquid chromatography (HILIC) for the aqueous extract and reversed-phase chromatography for the organic. This pipeline can be generic for tissue analysis as demonstrated by applications to different tissue types. The experimental setup and fast turnaround time of the two methods contributed toward obtaining highly reproducible features with exceptional chromatographic performance (CV % < 0.5%), making this pipeline suitable for metabolic profiling applications. We structurally assigned 226 metabolites from a range of chemical classes (e.g., carnitines, α-amino acids, purines, pyrimidines, phospholipids, sphingolipids, free fatty acids, and glycerolipids) which were mapped to their corresponding pathways, biological functions and known disease mechanisms. The combination of the two untargeted UPLC-MS methods showed high metabolite complementarity. We demonstrate the application of this pipeline to cardiovascular disease, where we show that the analyzed diseased groups (<i>n </i>= 120) of arterial tissue could be distinguished based on their metabolic profiles

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer:A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.</p

Stellar Diameters and Temperatures II. Main Sequence K & M Stars

We present interferometric diameter measurements of 21 K- and M- dwarfs made with the CHARA Array. This sample is enhanced by literature radii measurements to form a data set of 33 K-M dwarfs with diameters measured to better than 5%. For all 33 stars, we compute absolute luminosities, linear radii, and effective temperatures (Teff). We develop empirical relations for \simK0 to M4 main- sequence stars between the stellar Teff, radius, and luminosity to broad-band color indices and metallicity. These relations are valid for metallicities between [Fe/H] = -0.5 and +0.1 dex, and are accurate to ~2%, ~5%, and ~4% for Teff, radius, and luminosity, respectively. Our results show that it is necessary to use metallicity dependent transformations to convert colors into stellar Teffs, radii, and luminosities. We find no sensitivity to metallicity on relations between global stellar properties, e.g., Teff-radius and Teff-luminosity. Robust examinations of single star Teffs and radii compared to evolutionary model predictions on the luminosity-Teff and luminosity-radius planes reveals that models overestimate the Teffs of stars with Teff < 5000 K by ~3%, and underestimate the radii of stars with radii < 0.7 R\odot by ~5%. These conclusions additionally suggest that the models overestimate the effects that the stellar metallicity may have on the astrophysical properties of an object. By comparing the interferometrically measured radii for single stars to those of eclipsing binaries, we find that single and binary star radii are consistent. However, the literature Teffs for binary stars are systematically lower compared to Teffs of single stars by ~ 200 to 300 K. Lastly, we present a empirically determined HR diagram for a total of 74 nearby, main-sequence, A- to M-type stars, and define regions of habitability for the potential existence of sub-stellar mass companions in each system. [abridged]Comment: 73 pages, 12 Tables, 18 Figures. Accepted for publication in The Astrophysical Journa

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Dissociable effects of complement C3 and C3aR on survival and morphology of adult born hippocampal neurons, pattern separation, and cognitive flexibility in male mice

Adult hippocampal neurogenesis (AHN) is a form of ongoing plasticity in the brain that supports specific aspects of cognition. Disruptions in AHN have been observed in neuropsychiatric conditions presenting with inflammatory components and are associated with impairments in cognition and mood. Recent evidence highlights important roles of the complement system in synaptic plasticity and neurogenesis during neurodevelopment and in acute learning and memory processes. In this work we investigated the impact of the complement C3/C3aR pathway on AHN and its functional implications for AHN-related behaviours. In C3−/− mice, we found increased numbers and accelerated migration of adult born granule cells, indicating that absence of C3 leads to abnormal survival and distribution of adult born neurons. Loss of either C3 or C3aR affected the morphology of immature neurons, reducing morphological complexity, though these effects were more pronounced in the absence of C3aR. We assessed functional impacts of the cellular phenotypes in an operant spatial discrimination task that assayed AHN sensitive behaviours. Again, we observed differences in the effects of manipulating C3 or C3aR, in that whilst C3aR−/− mice showed evidence of enhanced pattern separation abilities, C3−/− mice instead demonstrated impaired behavioural flexibility. Our findings show that C3 and C3aR manipulation have distinct effects on AHN that impact at different stages in the development and maturation of newly born neurons, and that the dissociable cellular phenotypes are associated with specific alterations in AHN-related behaviours