Gathering requirements for the development of an online RAT tool

This work documents the requirements gathering process for the design of a Readiness Assurance Test (RAT) tool to be used in online Team Based Learning (TBL) classrooms. Gathering requirements is the first step in the User-Centered Design (UCD) process. After gathering requirements for the tool, a preliminary design would be created, implemented, and evaluated. The process would then start again with requirements gathering for the next design iteration. Team Based Learning has been shown to provide positive learning outcomes in face to face classrooms. Because of these positive outcomes, there has been interest in using the technique in online environments. This study determines student and faculty attitudes toward TBL and RATs (in current face-to-face classrooms and potential online classrooms), challenges associated with the RATs (both in face to face and potential online environments), and features needed by both faculty and students in an online RAT tool. This investigation was composed of three parts: student surveys, faculty surveys, and faculty interviews

A 100 kHz time-resolved multiple-probe femtosecond to second infrared absorption spectrometer

We present a dual-amplifier laser system for time-resolved multiple-probe infrared (IR) spectroscopy based on the ytterbium potassium gadolinium tungstate (Yb:KGW) laser medium. Comparisons are made between the ytterbium-based technology and titanium sapphire laser systems for time-resolved IR spectroscopy measurements. The 100 kHz probing system provides new capability in time-resolved multiple-probe experiments, as more information is obtained from samples in a single experiment through multiple-probing. This method uses the high repetition-rate probe pulses to repeatedly measure spectra at 10 μs intervals following excitation allowing extended timescales to be measured routinely along with ultrafast data. Results are presented showing the measurement of molecular dynamics over >10 orders of magnitude in timescale, out to 20 ms, with an experimental time response o

New Polymyxin B Dosing Strategies To Fortify Old Allies in the War against KPC-2-Producing Klebsiella pneumoniae

ABSTRACT Pharmacodynamics of a polymyxin B, meropenem, and rifampin triple combination were examined against Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) ST258. In time-kill experiments against three KPC-Kp isolates, triple combination generated 8.14, 8.19, and 8.29 log 10 CFU/ml reductions within 24 h. In the hollow-fiber infection model, the triple combination caused maximal killing of 5.16 log 10 CFU/ml at 78 h and the time required for regrowth was more than doubled versus the 2-drug combinations. Remarkably, combinations with a high single-dose polymyxin B burst plus rifampin preserved KPC-Kp polymyxin susceptibility (MIC 240 h = 0.5 mg/liter) versus the same combination with traditionally dosed polymyxin B, where resistance was amplified (MIC 240 h = 32 mg/liter)

Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients

Polymyxin B (PMB) has reemerged as a last-line therapy for infections caused by multidrug-resistant gram-negative pathogens, but dosing is challenging because of its narrow therapeutic window and pharmacokinetic (PK) variability. Population PK (POPPK) models based on suitably powered clinical studies with appropriate sampling strategies that take variability into consideration can inform PMB dosing to maximize efficacy and minimize toxicity and resistance. Here we reviewed published PMB POPPK models and evaluated them using an external validation data set (EVD) of patients who are critically ill and enrolled in an ongoing clinical study to assess their utility. Seven published POPPK models were employed using the reported model equations, parameter values, covariate relationships, interpatient variability, parameter covariance, and unexplained residual variability in NONMEM (Version 7.4.3). The predictive ability of the models was assessed using prediction-based and simulation-based diagnostics. Patient characteristics and treatment information were comparable across studies and with the EVD (n = 40), but the sampling strategy was a main source of PK variability across studies. All models visually and statistically underpredicted EVD plasma concentrations, but the two-compartment models more accurately described the external data set. As current POPPK models were inadequately predictive of the EVD, creation of a new POPPK model based on an appropriately powered clinical study with an informed PK sampling strategy would be expected to improve characterization of PMB PK and identify covariates to explain interpatient variability. Such a model would support model-informed precision dosing frameworks, which are urgently needed to improve PMB treatment efficacy, limit resistance, and reduce toxicity in patients who are critically ill

SAGUARO: Time-domain Infrastructure for the Fourth Gravitational-wave Observing Run and Beyond

We present upgraded infrastructure for Searches after Gravitational Waves Using ARizona Observatories (SAGUARO) during LIGO, Virgo, and KAGRA's fourth gravitational-wave (GW) observing run (O4). These upgrades implement many of the lessons we learned after a comprehensive analysis of potential electromagnetic counterparts to the GWs discovered during the previous observing run. We have developed a new web-based target and observation manager (TOM) that allows us to coordinate sky surveys, vet potential counterparts, and trigger follow-up observations from one centralized portal. The TOM includes software that aggregates all publicly available information on the light curves and possible host galaxies of targets, allowing us to rule out potential contaminants like active galactic nuclei, variable stars, solar-system objects, and preexisting supernovae, as well as to assess the viability of any plausible counterparts. We have also upgraded our image-subtraction pipeline by assembling deeper reference images and training a new neural network-based real-bogus classifier. These infrastructure upgrades will aid coordination by enabling the prompt reporting of observations, discoveries, and analysis to the GW follow-up community, and put SAGUARO in an advantageous position to discover kilonovae in the remainder of O4 and beyond. Many elements of our open-source software stack have broad utility beyond multimessenger astronomy, and will be particularly relevant in the "big data" era of transient discoveries by the Vera C. Rubin Observatory.Comment: submitted to AAS Journal

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: Methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD)

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria > 30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated GFR (eGFR). RESULTS: 2996 participants were enrolled. Median (interquartile range) age was 66 (54 to 74) years, 58.5% were male, eGFR 33.8 (24.0 to 46.6) ml/min/1.73m2 and UACR 209 (33 to 926) mg/g. 1883 participants (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and investigate underlying mechanisms to inform new treatment development

A programme to spread eGFR graph surveillance for the early identification, support and treatment of people with progressive chronic kidney disease (ASSIST-CKD): protocol for the stepped wedge implementation and evaluation of an intervention to reduce late presentation for renal replacement therapy

Background Patients who start renal replacement therapy (RRT) for End-Stage Kidney Disease (ESKD) without having had timely access to specialist renal services have poor outcomes. At one NHS Trust in England, a community-wide CKD management system has led to a decline in the incident rate of RRT and the lowest percentage of patients presenting within 90 days of starting RRT in the UK. We describe the protocol for a quality improvement project to scale up and evaluate this innovation. Methods The intervention is based upon an off-line database that integrates laboratory results from blood samples taken in all settings stored under different identifying labels relating to the same patient. Graphs of estimated glomerular filtration rate (eGFR) over time are generated for patients 65 years with an incoming eGFR <40 ml/min/1.73 m2. Graphs where kidney function is deteriorating are flagged by a laboratory scientist and details sent to the primary care doctor (GP) with a prompt that further action may be needed. We will evaluate the impact of implementing this intervention across a large population served by a number of UK renal centres using a mixed methods approach. We are following a stepped-wedge design. The order of implementation among participating centres will be randomly allocated. Implementation will proceed with unidirectional steps from control group to intervention group until all centres are generating graphs of eGFR over time. The primary outcome for the quantitative evaluation is the proportion of patients referred to specialist renal services within 90 days of commencing RRT, using data collected routinely by the UK Renal Registry. The qualitative evaluation will investigate facilitators and barriers to adoption and spread of the intervention. It will include: semi-structured interviews with laboratory staff, renal centre staff and service commissioners; an online survey of GPs receiving the intervention; and focus groups of primary care staff. Discussion Late presentation to nephrology for patients with ESKD is a source of potentially avoidable harm. This protocol describes a robust quantitative and qualitative evaluation of a quality improvement intervention to reduce late presentation and improve the outcomes for patients with ESKD

Child maltreatment and health service use: findings of the Australian Child Maltreatment Study

Objectives To examine associations between child maltreatment and health service use, both overall, by type and by the number of types of maltreatment reported. Design, setting Cross-sectional, retrospective survey using the Juvenile Victimization Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study); computer-assisted mobile telephone interviews using random digit dialling, Australia, 9 April – 11 October 2021. Participants Australians aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16–24 years and 1000 respondents each from the five age groups (25–34, 35–44, 45–54, 55–64, 65 years or more). Main outcome measures Self-reported health service use during the past twelve months: hospital admissions, length of stay, and reasons for admission; and numbers of consultations with health care professionals, overall and by type. Associations between maltreatment and health service use are reported as odds ratios adjusted for age group, gender, socio-economic status, financial hardship (childhood and current), and geographic remoteness. Results A total of 8503 participants completed the survey. Respondents who had experienced child maltreatment were significantly more likely than those who had not to report a hospital admission during the preceding twelve months (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.16–1.66), particularly admission with a mental disorder (aOR, 2.4; 95% CI, 1.03–5.6). The likelihood of six or more visits to general practitioners (aOR, 2.37; 95% CI, 1.87–3.02) or of a consultation with a mental health nurse (aOR, 2.67; 95% CI, 1.75–4.06), psychologist (aOR, 2.40; 95% CI, 2.00–2.88), or psychiatrist (aOR, 3.02; 95% CI, 2.25–4.04) were each higher for people who reported maltreatment during childhood. People who reported three or more maltreatment types were generally most likely to report greater health service use. Conclusions Child maltreatment has a major impact on health service use. Early, targeted interventions are vital, not only for supporting children directly, but also for their longer term wellbeing and reducing their health system use throughout life

2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 paediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have pri-oritised and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question. (C) 2017 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.Peer reviewe