Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Evaluation of effect of cooled haemodialysis on cognition in patients with end-stage kidney disease (ECHECKED) feasibility randomised controlled trial results.

Background: Cognitive impairment is common in haemodialysis patients with no known beneficial interventions. Cooler dialysate slows brain white-matter changes, but its effect on cognition is unknown. This feasibility trial was performed to inform a fully-powered, randomised trial to assess this.

Transport starter data kit: Historical passenger and freight transport data for selected countries in Africa, Asia, and South America.

The demand for data-driven models to inform sustainable transportation planning has become more important as countries address the complexities of urban mobility. However, data collection and curation are time-consuming and can be challenging due to data inaccessibility and inaccuracy. The Transport Starter Data Kit therefore aims to address these challenges, offering a one-stop-shop for transport modelling-related data.

Low doses of ionising radiation: definitions and contexts.

The term 'low dose' is applied to different levels of dose depending on the circumstances of exposure, with the potential for confusion unless the reasoning is clear. The United Nations Scientific Committee on the Effects of Ionising Radiation has defined low absorbed doses of ionising radiation as below about 100 mGy, and low dose rates as below 0.1 mGy min-1 (6 mGy h-1).

A meta-ethnography of shared decision-making in mental health care from the perspective of staff and service users.

Background: Human rights, recovery, and value-based approaches are integral to strategic changes and development in mental health care. Successfully integrating such person-centred values in mental health services requires a paradigm shift from traditional biomedical models of care to a more human rights-based approach. An important aspect of this is shared decision making (SDM) between mental health staff and service users.

Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology.

Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer's disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.

Remote data collection speech analysis in people at risk for Alzheimer's disease dementia: usability and acceptability results.

Introduction: Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study.

Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem® for Mild Alzheimer's Disease.

Background: Blood biomarkers are proposed as a diagnostic alternative to amyloid PET or cerebrospinal fluid (CSF) analyses for the diagnosis of Alzheimer's disease (AD). Relatively little is known of the natural history of patients identified by different blood biomarkers.

Objective: To identify patients with elevated plasma phosphorylated tau (pTau)181 from a prior Phase 2a trial, and explore the natural histories of their clinical progression, and potential efficacy of Xanamem, a selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these patients.

Real-World Outcomes for the Fifth-Generation Balloon Expandable Transcatheter Heart Valve in the United States.

Background: The fifth-generation SAPIEN 3 Ultra Resilia valve (S3UR) incorporates several design changes as compared with its predecessors, the SAPIEN 3 (S3) and SAPIEN 3 Ultra (S3U) valves, including bovine leaflets treated with a novel process intended to reduce structural valve deterioration via calcification, as well as a taller external skirt on the 29-mm valve size to reduce paravalvular leak (PVL). The clinical performance of S3UR compared with S3 and S3U in a large patient population has not been previously reported.

Objectives: The aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR).

Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups.

Background And Objectives: It is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups.

Methods: Cognitively unimpaired individuals from the Amsterdam Dementia Cohort and the SCIENCe project with available AD biomarkers, obtained from CSF, PET scans, and plasma at baseline, were followed over time (4.

Does correction of carpal malalignment influence the union rate of scaphoid nonunion surgery?

Unlabelled: The aim of this retrospective study was to assess the relation between carpal malalignment correction and radiological union rates in surgery for scaphoid nonunions. A total of 59 scaphoid waist fracture nonunions treated with open reduction and palmar tricortical autograft were divided according to their pre- and postoperative scapholunate (SL) and radiolunate (RL) angles. We found that carpal malalignment failed to correct in 32 of 59 (54.

Practical pathway for the management of depression in the workplace: a Canadian perspective.

Major depressive disorder (MDD) and other mental health issues pose a substantial burden on the workforce. Approximately half a million Canadians will not be at work in any week because of a mental health disorder, and more than twice that number will work at a reduced level of productivity (presenteeism). Although it is important to determine whether work plays a role in a mental health condition, at initial presentation, patients should be diagnosed and treated per appropriate clinical guidelines.

What's in a score: A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults.

Objective: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire.

Method: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time.

Separation and Characterization of Plastic Waste Packaging Contaminated with Food Residues.

In this paper, we present the development of a novel processing technology to tackle hard-to-recycle plastic packaging waste contaminated with food residues. The proof-of-concept (POC) technology can effectively separate food residual amounts from plastic waste materials to a level acceptable for further re-use or recycling of the plastic packaging. To assess this technology, we have conducted spectroscopic, thermal, and calorimetric characterizations of the obtained fractions, such as cleaned mixed plastics (CMP), food waste with mixed plastics (FWMP), and a mixture of microplastics (MP).

Anatomic Monopolar Press-fit Radial Head Arthroplasty; High Rate of Loosening at Mid-Term Follow Up.

Introduction: Radial head arthroplasty (RHA) is used for the management of unstable or unreconstructable injuries of the radial head. Our aim was to investigate clinical and radiographic outcomes in patients treated with the Acumed anatomic radial head press-fit system for trauma.

Methods: Clinical and radiographic assessment of RHAs undertaken for trauma with minimum 2-year follow-up.

Designing a zero-order energy transition model: How to create a new Starter Data Kit.

The Paris Agreement was signed by 192 Parties, who committed to reducing emissions. Reaching such commitments by developing national decarbonisation strategies requires significant analyses and investment. Analyses for such strategies are often delayed due to a lack of accurate and up-to-date data for creating energy transition models.

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age.

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10Sv, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American).

The ambivalence toward neuropsychology in dementia research, diagnosis, and drug development: Myths and misconceptions.

Clinical assessment remains the gold standard for diagnosing dementia, monitoring progression, and conducting clinical research. Biomarkers hold promise for targeted therapeutic approaches, selection of participants in clinical trials, and direct physiological efficacy readouts. However, the anchoring of biomarker research to clinical symptomatology is often based on short and insensitive cognitive screening.

Techno-economic data and assumptions for long-term energy systems modelling in Viet Nam.

Viet Nam is at a critical juncture in planning for its future energy mix due to its fast-growing economy and recent climate commitments. Robust modelling analyses examining the potential and practical energy mix alternatives are therefore key in providing key stakeholders with critical information on energy policy decision-making. The challenge is that a large volume of data is required to accurately model various energy pathways at the national scale.