CRASH2p: Closed-loop Two Photon Imaging in a Freely Moving Animal.

Direct measurement of neural activity in freely moving animals is essential for understanding how the brain controls and represents behaviors. Genetically encoded calcium indicators report neural activity as changes in fluorescence intensity, but brain motion confounds quantitative measurement of fluorescence. Translation, rotation, and deformation of the brain and the movements of intervening scattering or auto-fluorescent tissue all alter the amount of fluorescent light captured by a microscope.

Developing a web-based app for non-mental health nurses to assess the mental health needs and risks of children and young people.

There is high demand for specialist mental health services for children and young people in the UK. Non-mental health nurses are well-placed to assess the mental health needs and risks of children and young people to maximise opportunities for early intervention and relieve the pressure on child and adolescent mental health services. This article provides an overview of a service development project to develop a web-based application (app) to support non-mental health nurses when assessing the mental health needs and risks of children and young people.

Multi-neuronal recording in unrestrained animals with all acousto-optic random-access line-scanning two-photon microscopy.

To understand how neural activity encodes and coordinates behavior, it is desirable to record multi-neuronal activity in freely behaving animals. Imaging in unrestrained animals is challenging, especially for those, like larval , whose brains are deformed by body motion. A previously demonstrated two-photon tracking microscope recorded from individual neurons in freely crawling larvae but faced limits in multi-neuronal recording.

Psychometric evaluation of the Symptoms of Infection with Coronavirus-19 (SIC): results from a cross-sectional study and a phase 3 clinical trial.

Background: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and longitudinal psychometric evaluations, qualitative exit interviews were conducted to support the content validity of the SIC.

Methods: In a cross-sectional study, adults diagnosed with COVID-19 in the United States completed the web-based SIC and additional PRO measures.

Development of a novel patient-reported outcome measure to assess signs and symptoms of COVID-19.

Background: Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development.

Methods: An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method.

The Impact of a Machine Learning Early Warning Score on Hospital Mortality: A Multicenter Clinical Intervention Trial.

Objectives: To determine the impact of a machine learning early warning risk score, electronic Cardiac Arrest Risk Triage (eCART), on mortality for elevated-risk adult inpatients.

Design: A pragmatic pre- and post-intervention study conducted over the same 10-month period in 2 consecutive years.

Setting: Four-hospital community-academic health system.

U.S. Food and Drug Administration's Patient-Focused Drug Development Initiative: Experience with Integration of Patient-Experience Data in a New Drug Application for Esketamine Nasal Spray Plus a Newly Initiated Oral Antidepressant for Treatment-Resistant Depression.

The Patient-Focused Drug Development initiative of the U.S. Food and Drug Administration (FDA) aims to ensure that the patient experience of disease and treatment is an integral component of the drug development process.

Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials.

Objectives: There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge.

Methods: Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges.

Revisiting Poststroke Upper Limb Stratification: Resilience in a Larger Cohort.

Background: Upper limb (UL) impairment in stroke survivors is both multifactorial and heterogeneous. Stratification of motor function helps identify the most sensitive and appropriate assessments, which in turn aids the design of effective and individualized rehabilitation strategies. We previously developed a stratification method combining the Grooved Pegboard Test (GPT) and Box and Block Test (BBT) to stratify poststroke UL motor function.

Clinical Analytics Prediction Engine (CAPE): Development, electronic health record integration and prospective validation of hospital mortality, 180-day mortality and 30-day readmission risk prediction models.

Background: Numerous predictive models in the literature stratify patients by risk of mortality and readmission. Few prediction models have been developed to optimize impact while sustaining sufficient performance.

Objective: We aimed to derive models for hospital mortality, 180-day mortality and 30-day readmission, implement these models within our electronic health record and prospectively validate these models for use across an entire health system.

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018.

Improved Kinematics and Motor Control in a Longitudinal Study of a Complex Therapy Movement in Chronic Stroke.

Impaired motor control post-stroke is typically measured using clinical assessments employing categorical and subjective scoring. We investigated quantitative kinematic parameters of a complex movement with therapy in chronic stroke. Tri-axial accelerometry of the more-affected arm of 24 patients was recorded during early- (day 2-3) and late- (days 12-14) therapy, and for 13 patients at 6-month follow-up.

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study.

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers.

Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis.

Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days.

A Longitudinal Electromyography Study of Complex Movements in Poststroke Therapy. 1: Heterogeneous Changes Despite Consistent Improvements in Clinical Assessments.

Poststroke weakness on the more-affected side may arise from reduced corticospinal drive, disuse muscle atrophy, spasticity, and abnormal coordination. This study investigated changes in muscle activation patterns to understand therapy-induced improvements in motor-function in chronic stroke compared to clinical assessments and to identify the effect of motor-function level on muscle activation changes. Electromyography (EMG) was recorded from five upper limb muscles on the more-affected side of 24 patients during early and late therapy sessions of an intensive 14-day program of Wii-based Movement Therapy (WMT) and for a subset of 13 patients at 6-month follow-up.

A Longitudinal Electromyography Study of Complex Movements in Poststroke Therapy. 2: Changes in Coordinated Muscle Activation.

Fine motor control is achieved through the coordinated activation of groups of muscles, or "muscle synergies." Muscle synergies change after stroke as a consequence of the motor deficit. We investigated the pattern and longitudinal changes in upper limb muscle synergies therapy in a largely unconstrained movement in patients with a broad spectrum of poststroke residual voluntary motor capacity.

Targeted upper-limb Wii-based Movement Therapy also improves lower-limb muscle activation and functional movement in chronic stroke.

Purpose: Post-stroke hemiparesis may manifest as asymmetric gait, poor balance, and inefficient movement patterns. We investigated improvements in lower-limb muscle activation and function during Wii-based Movement Therapy (WMT), a rehabilitation program specifically targeting upper-limb motor-function.

Methods: Electromyography (EMG) was recorded bilaterally from tibialis anterior (TA) in 20 stroke patients during a 14-day WMT program.

BDNF Genotype Interacts with Motor Function to Influence Rehabilitation Responsiveness Poststroke.

Background: Persistent motor impairment is common but highly heterogeneous poststroke. Genetic polymorphisms, including those identified on the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes, may contribute to this variability by limiting the capacity for use-dependent neuroplasticity, and hence rehabilitation responsiveness.

Objective: To determine whether BDNF and APOE genotypes influence motor improvement facilitated by poststroke upper-limb rehabilitation.

Cardiovascular fitness is improved post-stroke with upper-limb Wii-based Movement Therapy but not dose-matched constraint therapy.

Introduction: Post-stroke cardiovascular fitness is typically half that of healthy age-matched people. Cardiovascular deconditioning is a risk factor for recurrent stroke that may be overlooked during routine rehabilitation. This study investigated the cardiovascular responses of two upper limb rehabilitation protocols.

Cortical beta oscillations and motor thresholds differ across the spectrum of post-stroke motor impairment, a preliminary MEG and TMS study.

Background: Cortical oscillatory activity in the beta frequency band (13-30Hz) is associated with voluntary movement and may be altered in motor disorders such as stroke.

Methods: We used a multimodal case-series approach to investigate movement-related beta oscillations, cortical excitability and upper-limb motor-function in 10 chronic stroke-patients across a broad range of motor-impairment. Assessments included: (i) whole-head magnetoencephalography (MEG) during a voluntary motor task; (ii) resting and active motor-thresholds to transcranial magnetic stimulation (TMS); and (iii) assessments of upper-limb motor-function.

The efficacy of Wii-based Movement Therapy for upper limb rehabilitation in the chronic poststroke period: a randomized controlled trial.

Background: More effective and efficient rehabilitation is urgently needed to address the prevalence of unmet rehabilitation needs after stroke. This study compared the efficacy of two poststroke upper limb therapy protocols.

Aims And/or Hypothesis: We tested the hypothesis that Wii-based movement therapy would be as effective as modified constraint-induced movement therapy for post-stroke upper-limb motor rehabilitation.