Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells

Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health. Funding NHMR

Virtual Diagnostic Suite for Electron Beam Prediction and Control at FACET-II

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for the prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile, and non-destructive inference of transverse beam quality (emittance) while using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded into adaptive feedbacks and Machine Learning (ML)-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results that are based on simulation data and discuss progress towards implementation in regular operations

Virtual Diagnostic Suite for Electron Beam Prediction and Control at FACET-II

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for the prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile, and non-destructive inference of transverse beam quality (emittance) while using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded into adaptive feedbacks and Machine Learning (ML)-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results that are based on simulation data and discuss progress towards implementation in regular operations

Artificial Neural Networks to Predict the Apparent Degree of Supersaturation in Supersaturated Lipid-Based Formulations: A Pilot Study

In response to the increasing application of machine learning (ML) across many facets of pharmaceutical development, this pilot study investigated if ML, using artificial neural networks (ANNs), could predict the apparent degree of supersaturation (aDS) from two supersaturated LBFs (sLBFs). Accuracy was compared to partial least squares (PLS) regression models. Equilibrium solubility in Capmul MCM and Maisine CC was obtained for 21 poorly water-soluble drugs at ambient temperature and 60 °C to calculate the aDS ratio. These aDS ratios and drug descriptors were used to train the ML models. When compared, the ANNs outperformed PLS for both sLBFCapmulMC (r2 0.90 vs. 0.56) and sLBFMaisineLC (r2 0.83 vs. 0.62), displaying smaller root mean square errors (RMSEs) and residuals upon training and testing. Across all the models, the descriptors involving reactivity and electron density were most important for prediction. This pilot study showed that ML can be employed to predict the propensity for supersaturation in LBFs, but even larger datasets need to be evaluated to draw final conclusions

RF Design of the UCLA/INFN Hybrid SW/TW Photoinjector

With increasing demand for high brightness, low emittance beams for use with free‐electron lasers, Compton scattering systems and wake‐field accelerator experiments, stringent requirements have been placed on the design and operation of the 1.6 cell photoinjector. The proposed hybrid photoinjector combines the BNL/UCLA/SLAC style 1.5/1.6 cell standing wave gun with a traveling wave accelerator. Our goal is an injector that meets today's requirements and is scalable in design to meet tomorrow's demands: emittances in the region of 1 mm‐mrad for higher brightness as well as higher currents. The hybrid photoinjector also offers higher energy operation, enhanced cost effectiveness and better scalability than current designs such as integrated PWT photoinjectors and split gun/accelerating sections. The use of both SW and TW systems allows for higher gradients (Eo = 70 MV/m) in the SW gun for effective capture at lower emittances, while the lower energy acceleration in the TW sections (Eo = 13.5 MV/m) allows ge..

Cohort profile: the COVID-19 Coping Study, a longitudinal mixed-methods study of middle-aged and older adults’ mental health and well-being during the COVID-19 pandemic in the USA

Purpose The COVID-19 pandemic, beginning in early 2020, has resulted in massive social, economic, political and public health upheaval around the world. We established a national longitudinal cohort study, the COVID-19 Coping Study, to investigate the effects of pandemic-related stressors and changes in life circumstances on mental health and well-being among middle-aged and older adults in the USA.Participants From 2 April to 31 May 2020, 6938 adults aged ≥55 years were recruited from all 50 US states, the District of Columbia and Puerto Rico using online, multi-frame non-probability-based sampling.Findings to date Mean age of the baseline sample was 67.3 years (SD: 7.9 years) and 64% were women. Two in three adults reported leaving home only for essential purposes in the past week (population-weighted proportion: 69%; 95% CI: 68% to 71%). Nearly one in five workers aged 55–64 years was placed on a leave of absence or furloughed since the start of the pandemic (17%; 95% CI: 14% to 20%), compared with one in three workers aged ≥75 years (31%; 95% CI: 21% to 44%). Nearly one-third of adults screened positive for each of depression (32%; 95% CI: 30% to 34%), anxiety (29%; 28% to 31%) and loneliness (29%; 95% CI: 27% to 31%), with decreasing prevalence of each with increasing age.Future plans Monthly and annual follow-ups of the COVID-19 Coping Study cohort will assess longitudinal changes to mental health, cognitive health and well-being in relation to social, behavioural, economic and other COVID-19-related changes to life circumstances. Quantitative and in-depth qualitative interview data will be collected through online questionnaires and telephone interviews. Cohort data will be archived for public use