International Comparisons of Harmonized Laboratory Value Trajectories to Predict Severe COVID-19: Leveraging the 4CE Collaborative Across 342 Hospitals and 6 Countries: A Retrospective Cohort Study.

Objectives: To perform an international comparison of the trajectory of laboratory values among hospitalized patients with COVID-19 who develop severe disease and identify optimal timing of laboratory value collection to predict severity across hospitals and regions.

Design: Retrospective cohort study.

Setting: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), an international multi-site data-sharing collaborative of 342 hospitals in the US and in Europe.

Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092.

Background: Severe acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM.

Materials And Methods: Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing.

Stromal WNTer Keeps the Tumor Cold and Drives Metastasis.

Carcinoma-associated fibroblast (CAF) infiltration confers poor clinical outcomes in colorectal cancer (CRC) through mechanisms that are still unclear. In this issue of Developmental Cell, Kasashima et al. report that loss of PKCζ engenders a SOX2/SFRP2-positive CAF subpopulation that increases CRC aggressiveness by creating an immunosuppressed environment.

Stories from COVID-19 Reveal Hospitalized Patients with Limited English Proficiency Have Always Been Uniquely Prone to Social Isolation.

Through experiences with hospital visitor restrictions during the COVID-19 pandemic, a group of frontline trainees at the University of California San Francisco (UCSF) uncovered patient stories highlighting the unique challenges that patients with limited English proficiency (LEP) face in the hospital, particularly their vulnerability to social isolation. Here, we recount patient stories illustrative of this isolation, generated by insufficient professional interpreter use, ad hoc interpretation, and scarcity of media in preferred languages. When confronted with the social isolation faced by all patients during COVID-19, we more clearly saw the healthcare disparities affecting patients with LEP.

A validated liquid chromatography tandem mass spectrometry assay for the analysis of pretomanid in plasma samples from pulmonary tuberculosis patients.

A method for the extraction and quantification of pretomanid in 40 μL of human plasma, by high performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) detection was developed and validated. Samples were prepared using liquid-liquid extraction and chromatographic separation was achieved on an Agilent Poroshell C18 column using an isocratic elution at a flow rate of 400 μL/min. Electrospray ionization with mass detection at unit resolution in the multiple reaction monitoring (MRM) mode on an AB Sciex API 3200 mass spectrometer was used.

Determining the optimal expression method for dual-color imaging.

Background: Fluorescence imaging is a widely used technique that permits for cell-type-specific recording from hundreds of neurons simultaneously. Often, to obtain cell-type-specific recordings from more than one cell type, researchers add an additional fluorescent protein to mark a second neuronal subpopulation. Currently, however, no consensus exists on the best expression method for multiple fluorescent proteins.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management.

Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis.

Predicting maximal oxygen uptake from the 6 min walk test in patients with heart failure.

Aims: A cardiopulmonary exercise (CPX) test is considered the gold standard in evaluating maximal oxygen uptake. This study aimed to evaluate the predictive validity of equations provided by Burr et al., Ross et al.

Histone H3.3 beyond cancer: Germline mutations in cause a previously unidentified neurodegenerative disorder in 46 patients.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported.

Informing prevention of stillbirth and preterm birth in Malawi: development of a minimum dataset for health facilities participating in the DIPLOMATIC collaboration.

Objective: The global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm births and optimise outcomes for babies born preterm. Minimum datasets for routine data collection in healthcare facilities participating in DIPLOMATIC (initially in Malawi) were designed to assist understanding of baseline maternal and neonatal care processes and outcomes, and facilitate evaluation of improvement interventions and pragmatic clinical trials.

Design: Published and grey literature was reviewed alongside extensive in-country consultation to define relevant clinical best practice guidance, and the existing local data and reporting infrastructure, to identify requirements for the minimum datasets.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data.

Measurement of the Low-Energy Antideuteron Inelastic Cross Section.

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3≤p<4  GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of sqrt[s_{NN}]=5.

Ultrahigh-Q AlGaAs-on-insulator microresonators for integrated nonlinear photonics.

Aluminum gallium arsenide (AlGaAs) and related III-V semiconductors have excellent optoelectronic properties. They also possess strong material nonlinearity as well as high refractive indices. In view of these properties, AlGaAs is a promising candidate for integrated photonics, including both linear and nonlinear devices, passive and active devices, and associated applications.

Implementing Clinical Pharmacists in Primary Care: Care Team Satisfaction Survey Results.

Background: The rising demand on primary care providers encourages innovative use of care extenders, such as primary care pharmacists. Our academic medical center includes 34 multidisciplinary primary care clinics that provide general pediatric and adolescent medicine, internal medicine, and family medicine services. Primary care pharmacy services (PCPS) have grown since 2016 across 13 clinics serving internal and family medicine services.

Contours produced by internal specular interreflections provide visual information for the perception of glass materials.

Two experiments are reported that investigated how the perceptual identification of glass is influenced by banding contours formed by internal specular interreflections within glass materials. Observers made material categorization judgments for images depicting glass, chrome, shiny black and shiny white objects, and for contour drawings that were created by edge filtering images of glass, chrome or textured objects. Observers rated each stimulus by adjusting four sliders to indicate their confidence that the depicted material was glass, metal, shiny black, or something else, and these adjustments were constrained so that the sum of all four settings was always 100%.

Healthy eating and physical activity environments in out-of-school hours care: an observational study protocol.

Introduction: Childcare settings have been widely identified as important venues for promoting healthy lifestyles to children. Out-of-school hours care (OSHC) is a rapidly growing childcare service, yet there has been limited research reported on healthy eating and physical activity (HEPA) environments within the Australian OSHC setting. This research aims to describe the HEPA environments related to foods and beverages served, staff behaviours and child physical activity levels across two local health districts within New South Wales, Australia.

"Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology.".

Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD.

Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.

The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women.

Aging and haptic shape discrimination: the effects of variations in size.

Seventy-two older and younger adults haptically discriminated the solid shape of natural objects (bell peppers, Capsicum annuum). Plastic copies of the original-sized fruits were used as experimental stimuli, as well as copies that were reduced in size to 1/8th and 1/27th of the original object volumes. If haptic object shape is represented in a part-based manner, then haptic shape discrimination performance should be at least partly size invariant, since changes only in scale do not affect an object's constituent parts.

Effect of p-doping on the intensity noise of epitaxial quantum dot lasers on silicon.

This work experimentally investigates the impact of p-doping on the relative intensity noise (RIN) properties and subsequently on the modulation properties of semiconductor quantum dot (QD) lasers epitaxially grown on silicon. Owing to the low threading dislocation density and the p-modulation doped GaAs barrier layer in the active region, the RIN level is found very stable with temperature with a minimum value of -150/. The dynamical features extracted from the RIN spectra show that p-doping between zero and 20 holes/dot strongly modifies the modulation properties and gain nonlinearities through increased internal losses in the active region and thereby hinders the maximum achievable bandwidth.

Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV.

Purpose: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women.

Methods: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled.