Wearable Technology in Mobility and Falls Health Care: Finding Consensus on Their Clinical Utility and Identifying a Roadmap to Actual Use.

Background: Despite the promise wearable technology offers through detailed insight into mobility and fall risk, timely identification of high risk, assessment of risk severity, evaluation of clinical interventions, and potential to redefine the assessment of behaviours which influence health, they are not routinely used in clinical practice.

Objective: Establish consensus on how wearable technology can be applied to support clinical care for people aged 50 and over experiencing changes to mobility and/or who are at increased risk of falling.

Methods: A Delphi study was conducted among 17 hospital-based health professionals.

Clinician acceptability of the ReacStep reactive balance training program for fall prevention.

Aim: To examine if a novel reactive balance training program (ReacStep) designed for clinical settings is acceptable to clinicians prescribing balance and mobility training.

Methods: ReacStep consists of tether-release reactive step training, volitional trip and slip training, and functional strength training. An open survey comprising 11-point visual analog scale items (0 = strongly disagree to 10 = strongly agree) based on the Theoretical Framework of Acceptability was sent to clinicians working in balance and mobility training.

Implementing digital devices to increase mobility training for people receiving inpatient rehabilitation: protocol for a feasibility hybrid type II randomized controlled trial.

Background: People with mobility limitations can benefit from rehabilitation programs incorporating intensive, repetitive, and task-specific exercises using digital devices such as virtual reality gaming systems, tablet and smartphone applications, and wearable devices. The Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial (n = 300) showed improvements in mobility in people using these types of digital devices in addition to their usual rehabilitation care when the intervention was provided by an additional study-funded physiotherapist. However, it is not clear if this intervention can be implemented by hospital physiotherapists with a usual clinical load.

Economic evaluation of digitally enabled aged and neurological rehabilitation care in the Activity and MObility UsiNg Technology (AMOUNT) trial.

Objective: To investigate the trial-based cost-effectiveness of the addition of a tailored digitally enabled exercise intervention to usual care shown to be clinically effective in improving mobility in the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial compared to usual care alone.

Design: Economic evaluation alongside a pragmatic randomized controlled trial.

Participants: 300 people receiving inpatient aged and neurological rehabilitation were randomized to the intervention ( = 149) or usual care control group ( = 151).

Mobility training for increasing mobility and functioning in older people with frailty.

Background: Frailty is common in older people and is characterised by decline across multiple body systems, causing decreased physiological reserve and increased vulnerability to adverse health outcomes. It is estimated that 21% of the community-dwelling population over 65 years are frail. Frailty is independently predictive of falls, worsening mobility, deteriorating functioning, impaired activities of daily living, and death.

Physical therapists demonstrate clinical behaviors consistent with established clinical practice guidelines in managing individuals following amputation.

Background And Purpose: Investigating physical therapy in amputation management offers insights into clinical practice. This study explores the self-reported clinical practice of physical therapists in amputation management and compares it to established clinical practice guidelines to determine whether physical therapists are delivering care that is considered recommended clinical practice.

Method: An online survey of Australian physical therapists with limited or extensive experience in managing individuals following amputation.

Planning implementation and scale-up of physical activity interventions for people with walking difficulties: study protocol for the process evaluation of the ComeBACK trial.

Background: There is currently little evidence of planning for real-world implementation of physical activity interventions. We are undertaking the ComeBACK (Coaching and Exercise for Better Walking) study, a 3-arm hybrid Type 1 randomised controlled trial evaluating a health coaching intervention and a text messaging intervention. We used an implementation planning framework, the PRACTical planning for Implementation and Scale-up (PRACTIS), to guide the process evaluation for the trial.

Physical activity coaching for adults with mobility limitations: protocol for the ComeBACK pragmatic hybrid effectiveness-implementation type 1 randomised controlled trial.

Introduction: Mobility limitation is common and often results from neurological and musculoskeletal health conditions, ageing and/or physical inactivity. In consultation with consumers, clinicians and policymakers, we have developed two affordable and scalable intervention packages designed to enhance physical activity for adults with self-reported mobility limitations. Both are based on behaviour change theories and involve tailored advice from physiotherapists.

Digitally enabled aged care and neurological rehabilitation to enhance outcomes with Activity and MObility UsiNg Technology (AMOUNT) in Australia: A randomised controlled trial.

Background: Digitally enabled rehabilitation may lead to better outcomes but has not been tested in large pragmatic trials. We aimed to evaluate a tailored prescription of affordable digital devices in addition to usual care for people with mobility limitations admitted to aged care and neurological rehabilitation.

Methods And Findings: We conducted a pragmatic, outcome-assessor-blinded, parallel-group randomised trial in 3 Australian hospitals in Sydney and Adelaide recruiting adults 18 to 101 years old with mobility limitations undertaking aged care and neurological inpatient rehabilitation.

Transcriptome alterations in myotonic dystrophy skeletal muscle and heart.

Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized by symptoms in muscle, heart and central nervous system, among others, it is one of the most variable diseases known. A major pathogenic event in DM is the sequestration of muscleblind-like proteins by CUG or CCUG repeat-containing RNAs transcribed from expanded repeats, and differences in the extent of MBNL sequestration dependent on repeat length and expression level may account for some portion of the variability.

Two weeks of additional standing balance circuit classes during inpatient rehabilitation are cost saving and effective: an economic evaluation.

Question: Among people admitted for inpatient rehabilitation, is usual care plus standing balance circuit classes more cost-effective than usual care alone?

Design: Cost-effectiveness study embedded within a randomised controlled trial with concealed allocation, assessor blinding and intention-to-treat analysis.

Participants: 162 rehabilitation inpatients from a metropolitan hospital in Sydney, Australia.

Intervention: The experimental group received a 1-hour standing balance circuit class, delivered three times a week for 2 weeks, in addition to usual therapy.

External validation of approaches to prediction of falls during hospital rehabilitation stays and development of a new simpler tool.

Objectives: To test the external validity of 4 approaches to fall prediction in a rehabilitation setting (Predict_FIRST, Ontario Modified STRATIFY (OMS), physiotherapists' judgement of fall risk (PT_Risk), and falls in the past year (Past_Falls)), and to develop and test the validity of a simpler tool for fall prediction in rehabilitation (Predict_CM2).

Participants: A total of 300 consecutively-admitted rehabilitation inpatients.

Methods: Prospective inception cohort study.

Systematic genomic and translational efficiency studies of uveal melanoma.

To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays.

Validity of Different Activity Monitors to Count Steps in an Inpatient Rehabilitation Setting.

Background: Commonly used activity monitors have been shown to be accurate in counting steps in active people; however, further validation is needed in slower walking populations.

Objectives: To determine the validity of activity monitors for measuring step counts in rehabilitation inpatients compared with visually observed step counts. To explore the influence of gait parameters, activity monitor position, and use of walkers on activity monitor accuracy.

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer.

Unlabelled: PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells.

Effect of affordable technology on physical activity levels and mobility outcomes in rehabilitation: a protocol for the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial.

Introduction: People with mobility limitations can benefit from rehabilitation programmes that provide a high dose of exercise. However, since providing a high dose of exercise is logistically challenging and resource-intensive, people in rehabilitation spend most of the day inactive. This trial aims to evaluate the effect of the addition of affordable technology to usual care on physical activity and mobility in people with mobility limitations admitted to inpatient aged and neurological rehabilitation units compared to usual care alone.

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.

To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase.

Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins.

RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to heart and skeletal muscle development and are implicated in myotonic dystrophy (DM). To understand their genome-wide functions, we analyzed the transcriptome dynamics following induction of CELF1 or CELF2 in adult mouse heart and of CELF1 in muscle by RNA-seq, complemented by crosslinking/immunoprecipitation-sequencing (CLIP-seq) analysis of mouse cells and tissues to distinguish direct from indirect regulatory targets. We identified hundreds of mRNAs bound in their 3' UTRs by both CELF1 and the developmentally induced MBNL1 protein, a threefold greater overlap in target messages than expected, including messages involved in development and cell differentiation.

PLZF, a tumor suppressor genetically lost in metastatic castration-resistant prostate cancer, is a mediator of resistance to androgen deprivation therapy.

Whole-exome sequencing of metastatic castration-resistant prostate cancer (mCRPC) reveals that 5% to 7% of tumors harbor promyelocytic leukemia zinc finger (PLZF) protein homozygous deletions. PLZF is a canonical androgen-regulated putative tumor suppressor gene whose expression is inhibited by androgen deprivation therapy (ADT). Here, we demonstrate that knockdown of PLZF expression promotes a CRPC and enzalutamide-resistant phenotype in prostate cancer cells.

Additional standing balance circuit classes during inpatient rehabilitation improved balance outcomes: an assessor-blinded randomised controlled trial.

Objective: to evaluate the impact on balance (postural control) of six 1-h circuit classes that targeted balance in addition to usual therapy for rehabilitation inpatients.

Design: a randomised controlled trial with 2-week and 3-month follow-up.

Participants: one hundred and sixty-two general rehabilitation inpatients, Bankstown-Lidcombe Hospital, Australia.

ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors.

The use of targeted therapeutics directed against BRAF(V600)-mutant metastatic melanoma improves progression-free survival in many patients; however, acquired drug resistance remains a major medical challenge. By far, the most common clinical resistance mechanism involves reactivation of the MAPK (RAF/MEK/ERK) pathway by a variety of mechanisms. Thus, targeting ERK itself has emerged as an attractive therapeutic concept, and several ERK inhibitors have entered clinical trials.

MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition.

Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP-ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib.

The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma.

Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAF(V600)-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy.