Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs

Degeneration of skeletal muscle (SkM) with age (sarcopenia) is a major contributor to functional decline, morbidity and mortality. Methodological implications often make it difficult to embark on interventions in already frail and diseased elderly individuals. Using in vitro three-dimensional (3D) bioengineered skeletal muscle constructs that model aged phenotypes and incorporate a representative extracellular matrix (collagen), are under tension, and display morphological and transcript expression of mature skeletal muscle may more accurately characterize the SkM niche. Furthermore, an in vitro model would provide greater experimental manipulation with regard to gene, pharmacological and exercise (mechanical stretch / electrical stimulation) therapies and thus strategies for combating muscle wasting with age. The present study utilized multiple population-doubled (MPD) murine myoblasts compared with parental controls (CON), previously shown to have an aged phenotype in monolayer cultures (Sharples et al., 2011), seeded into 3D type I collagen matrices under uniaxial tension. 3D bioengineered constructs incorporating MPD cells had reduced myotube size and diameter vs. CON constructs. MPD constructs were characterized by reduced peak force development over 24 h after cell seeding, reduced transcript expression of remodelling matrix metalloproteinases, MMP2 and MMP9, with reduced differentiation / hypertrophic potential shown by reduced IGF-I, IGF-IR, IGF-IEa, MGF mRNA. Increased IGFBP2 and myostatin in MPD vs. CON constructs also suggested impaired differentiation / reduced regenerative potential. Overall, 3D bioengineered skeletal muscle constructs represent an in vitro model of the in vivo cell niche with MPD constructs displaying similar characteristics to ageing / atrophied muscle in vivo, thus potentially providing a future test bed for therapeutic interventions to contest muscle degeneration with age

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

Contrasting effects of biochar and hydrothermally treated coal gangue on leachability, bioavailability, speciation and accumulation of heavy metals by rapeseed in copper mine tailings

The purpose of this research was to examine the influence of hydrothermally treated coal gangue (HTCG) with and without biochar (BC) on the leaching, bioavailability, and redistribution of chemical fractions of heavy metals (HMs) in copper mine tailing (Cu-MT). An increase in pH, water holding capacity (WHC) and soil organic carbon (SOC) were observed due to the addition of BC in combination with raw coal gangue (RCG) and HTCG. A high Cu and other HMs concentration in pore water (PW) and amended Cu-MT were reduced by the combination of BC with RCG and/or HTCG, whereas individual application of RCG slightly increased the Cu, Cd, and Zn leaching and bioavailability, compared to the unamended Cu-MT. Sequential extractions results showed a reduction in the exchangeable fraction of Cu, Cd, Pb, and Zn and elevation in the residual fraction following the addition of BC-2% and BC-HTCG. However, individual application of RCG slightly increased the Cu, Cd, and Zn exchangeable fractions assessed by chemical extraction method. Rapeseed was grown for the following 45 days during which physiological parameters, metal uptake transfer rate (TR), bioconcentration factor (BCF), and translocation factor (TF) were measured after harvesting. In the case of plant biomass, no significant difference between applied amendments was observed for the fresh biomass (FBM) and dry biomass (DBM) of shoots and roots of rapeseed. However, BC-2% and BC-HTCG presented the lowest HMs uptake, TR, BCF (BCFroot and BCFshoot), and TF for Cu, Cd, Cr, Ni, Pb, and Zn in rapeseed among the other amendments compared to the unamended Cu -MT. Overall, these findings are indicative that using biochar in combination with RCG and/or HTCG led to a larger reduction in HMs leaching and bioavailability, due to their higher sorption capacity and could be a suitable remediation strategy for heavy metals in a Cu-MT

On the Mental Accounting of Restricted-Use Funds: How Gift Cards Change What People Purchase

Colorado seminar, and members of hocag for their valuable comments and feedback. They also wish to thank the editor, associate editor, and three anonymous reviewers for their constructive feedback. The first author additionally thanks Dan Ariely for his generous support. An attachment to the online-only version of this article includes supplementary materials (additional experiments, analysis, and discussion). Determining order of authorship was more difficult than trying to sneak a sunrise past a gathering of roosters.

Surface energy balance and actual evapotranspiration of the transboundary Indus Basin estimated from satellite measurements and the ETLook model

The surface energy fluxes and related evapotranspiration processes across the Indus Basin were estimated for the hydrological year 2007 using satellite measurements. The new ETLook remote sensing model (version 1) infers information on actual Evaporation (E) and actual Transpiration (T) from combined optical and passive microwave sensors, which can observe the land-surface even under persistent overcast conditions. A two-layer Penman–Monteith equation was applied for quantifying soil and canopy evaporation. The novelty of the paper is the computation of E and T across a vast area (116.2 million ha) by using public domain microwave data that can be applied under all weather conditions, and for which no advanced input data are required. The average net radiation for the basin was estimated as being 112 Wm?2. The basin average sensible, latent and soil heat fluxes were estimated to be 80, 32, and 0 Wm?2, respectively. The average evapotranspiration (ET) and evaporative fraction were 1.2 mm d?1 and 0.28, respectively. The basin wide ET was 496 ± 16.8 km3 yr?1. Monte Carlo analysis have indicated 3.4% error at 95% confidence interval for a dominant land use class. Results compared well with previously conducted soil moisture, lysimeter and Bowen ratio measurements at field scale (R2 = 0.70; RMSE = 0.45 mm d?1; RE = –11.5% for annual ET). ET results were also compared against earlier remote sensing and modeling studies for various regions and provinces in Pakistan (R2 = 0.76; RMSE = 0.29 mmd?1; RE = 6.5% for annual ET). The water balance for all irrigated areas together as one total system in Pakistan and India (26.02 million ha) show a total ET value that is congruent with the ET value from the ETLook surface energy balance computations. An unpublished validation of the same ETLook model for 23 jurisdictional areas covering the entire Australian continent showed satisfactory results given the quality of the watershed data and the diverging physiographic and climatic conditions (R2 = 0.70; RMSE = 0.31 mmd?1; RE = –2.8% for annual ET). Eight day values of latent heat fluxes in Heibei (China) showed a good resemblance (R2 = 0.92; RMSE = 0.04 mm d?1; RE = 9.5% for annual ET). It is concluded that ETLook is a novel model that can be operationalized further—especially after improving the preprocessing of spaceborne soil moisture data. This preprocessing includes (1) downscaling of topsoil moisture from 25 to 1 km pixels, and (2) translation of topsoil moisture into subsoil moisture values.Water ManagementCivil Engineering and Geoscience