Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy.

Introduction/aims: Improved methodologies to monitor the progression of Duchenne muscular dystrophy (DMD) are needed, especially in the context of clinical trials. We report changes in muscle magnetic resonance imaging (MRI) parameters in participants with DMD, including changes in lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) and their relationship to changes in functional parameters.

Methods: MRI data were obtained as part of a clinical study (NCT02310763) of domagrozumab, an antibody-targeting myostatin that negatively regulates skeletal muscle mass.

Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease.

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness.

The use of UV-C radiation for terminal disinfection of pathogenic Gram-negative rods: a pilot study.

In this controlled study, we found that exposure to ultraviolet-C (UV-C) radiation was able to arrest the growth of selected pathogenic enteric and nonfermenting Gram-negative rods. Further studies are needed to confirm the clinical efficacy and determine optimal implementation strategies for utilizing UV-C terminal disinfection.

Repeatability of MRI Biomarkers in Nonalcoholic Fatty Liver Disease: The NIMBLE Consortium.

Background There is a need for reliable noninvasive methods for diagnosing and monitoring nonalcoholic fatty liver disease (NAFLD). Thus, the multidisciplinary Non-invasive Biomarkers of Metabolic Liver disease (NIMBLE) consortium was formed to identify and advance the regulatory qualification of NAFLD imaging biomarkers. Purpose To determine the different-day same-scanner repeatability coefficient of liver MRI biomarkers in patients with NAFLD at risk for steatohepatitis.

Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis.

There are no approved diagnostic biomarkers for at-risk non-alcoholic steatohepatitis (NASH), defined by the presence of NASH, high histological activity and fibrosis stage ≥2, which is associated with higher incidence of liver-related events and mortality. FNIH-NIMBLE is a multi-stakeholder project to support regulatory approval of NASH-related biomarkers. The diagnostic performance of five blood-based panels was evaluated in an observational (NASH CRN DB2) cohort (n = 1,073) with full spectrum of non-alcoholic fatty liver disease (NAFLD).

The use of telehealth-supported stewardship activities in acute-care and long-term care settings: An implementation effectiveness trial.

Background: We assessed the implementation of telehealth-supported stewardship activities in acute-care units and long-term care (LTC) units in Veterans' Administration medical centers (VAMCs).

Design: Before-and-after, quasi-experimental implementation effectiveness study with a baseline period (2019-2020) and an intervention period (2021).

Setting: The study was conducted in 3 VAMCs without onsite infectious disease (ID) support.

The Nimble Stage 1 Study Validates Diagnostic Circulating Biomarkers for Nonalcoholic Steatohepatitis.

Background There are no approved noninvasive tests (NIT) for the diagnosis of nonalcoholic steatohepatitis (NASH) and its histological phenotypes. Methods The FNIH-NIMBLE consortium tested 5 serum-based NIT panels for the following intended uses: NIS4: At-risk NASH, a composite of NASH with NAFLD activity score (NAS) ≥ 4 and fibrosis stage ≥ 2, OWLiver: NASH and NAS ≥ 4, enhanced liver fibrosis (ELF), PROC3 and Fibrometer VCTE: fibrosis stages ≥ 2, ≥ 3 or 4. Aliquots from a single blood sample obtained within 90 days of histological confirmation of NAFLD were tested.

How perceived maternal gatekeeping affects fathers: An 8-week study.

Maternal gatekeeping describes mothers' attempts to influence father involvement in child-rearing. While the effect of maternal gatekeeping on the father-child relationship has been explored, less is known about how fluctuations in the perception of maternal gatekeeping influences fathers' family outcomes and whether father's attachment might moderate these associations. Building on family systems theory, this study explores the within-person effect of negative maternal gatekeeping on father's weekly reports of romantic relationship quality and feelings of exclusion from the family and tests father attachment as a moderator of these associations.

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy.

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks.

Inter-Reader Consistency and Exclusionary Findings During Radiographic Screening for Phase 3 Trials of Tanezumab in Patients With Osteoarthritis.

Objective: Describe the radiograph-based screening program and frequencies of ineligibility in 3 large, international, randomized, double-blind, phase 3 studies of subcutaneous tanezumab in patients with osteoarthritis (OA).

Design: Standardized bilateral shoulder, hip, and knee screening radiographs were obtained by trained imaging technologists and centrally read by 1 of 5 musculoskeletal radiology experts trained using a program-specific imaging atlas. Inter-reader consistency was tracked with test cases blindly inserted into the reader queue.

Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab.

Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (n = 120 aged 6 to < 16 years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol.

Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests.

Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment. Patients (n = 120) underwent examinations of one thigh, with MRI sequences to enable measurements of muscle volume (MV), MV index, mean T2 relaxation time via T2-mapping and fat fraction.

Acceptability and effectiveness of antimicrobial stewardship implementation strategies on fluoroquinolone prescribing.

Objective: To assess the effectiveness and acceptability of antimicrobial stewardship-focused implementation strategies on inpatient fluoroquinolones.

Methods: Stewardship champions at 15 hospitals were surveyed regarding the use and acceptability of strategies to improve fluoroquinolone prescribing. Antibiotic days of therapy (DOT) per 1,000 days present (DP) for sites with and without prospective audit and feedback (PAF) and/or prior approval were compared.

Hyperbaric oxygen for sudden hearing loss: Influence of international guidelines on practice in Australia and New Zealand.

Introduction: Idiopathic sudden sensorineural hearing loss (ISSHL) is an otolaryngologic emergency. The Undersea and Hyperbaric Medicine Society (UHMS) revised practice guidelines in 2014 adding ISSHL to approved indications. This study investigated whether the UHMS guidelines influenced referral and practice in Australia and New Zealand.

A Middle Eocene lowland humid subtropical "Shangri-La" ecosystem in central Tibet.

Tibet's ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem.

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy.

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49.

Uplift, climate and biotic changes at the Eocene-Oligocene transition in south-eastern Tibet.

The uplift history of south-eastern Tibet is crucial to understanding processes driving the tectonic evolution of the Tibetan Plateau and surrounding areas. Underpinning existing palaeoaltimetric studies has been regional mapping based in large part on biostratigraphy that assumes a Neogene modernization of the highly diverse, but threatened, Asian biota. Here, with new radiometric dating and newly collected plant-fossil archives, we quantify the surface height of part of the south-eastern margin of Tibet in the latest Eocene (∼34 Ma) to be ∼3 km and rising, possibly attaining its present elevation (3.

Hyperbaric oxygen treatment for the management of radiation-induced xerostomia.

Introduction: Hyperbaric oxygen therapy (HBOT) is widely used for the treatment of the late effects of radiation therapy. We report a prospective observational cohort study of 51 patients designed to examine the effectiveness of hyperbaric oxygen treatment (HBOT) for xerostomia following radiotherapy.

Methods: Objective (saliva volume) and subjective (quality of life scoring and visual analogue scale (VAS) of discomfort) measurements associated with xerostomia were compared prior to commencement of HBOT, after 30 sessions (over 6 weeks) of HBOT at 243 kPa for 90 minutes daily for five days per week and at 6-week review (12 weeks from commencement).

Audit of practice in Australasian hyperbaric units on the incidence of central nervous system oxygen toxicity.

Introduction: Central nervous system oxygen toxicity (CNS-OT) is an uncommon complication of hyperbaric oxygen treatment (HBOT). Different facilities have developed local protocols in an attempt to reduce the risk of CNS-OT. This audit was performed to elucidate which protocols might be of benefit in mitigating CNS-OT and to open discussion on adopting a common protocol for Treatment Table 14 (TT14) to enable future multicentre clinical trials.