Reliability and Validity of the Monitored Functional Task Evaluation (MFTE) for Patients with Chronic Obstructive Pulmonary Disease (COPD)

This article describes the development of a new functional measure — the Monitored Functional Task Evaluation (MFTE) — a symptom-limited evaluation that is used to measure the functional performance of an individual with chronic obstructive pulmonary disease (COPD), and to document a client's physiological changes through repeated testing. Stage I of the study included developing the content validity of the instrument. Stage II consisted of establishing the performance profile, test-retest and inter-rater reliability using a convenience sample of 27 inpatients and outpatients who had COPD. In stage III, the criterion-related and discriminative validity of the instrument was verified in a retrospective sample of 124 inpatients and day patients who had COPD. Results indicated that there was high intra- and inter-rater reliability for the total score of MFTE. Significant correlation of the MFTE was found with parameters such as Moser's Activities of Daily Living (ADL) class, COPD disability class, 6-minute walking distance, work capacity in terms the ratio of the metabolic rate associated with a given activity to the resting metabolic rate, and the fatigue dimension of the Chronic Respiratory Disease Questionnaire. In addition, prediction of group membership to Moser's ADL class revealed that 52.4% of the original grouped cases could be correctly classified by the MFTE alone. In conclusion, the MFTE is a useful measure to evaluate functional performance as well as document physiological changes in patients with moderate-to-severe COPD from both conceptual and empirical perspectives

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain

A population of >6 million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome-21-gene BACE2, but prevented by combined chemical β and γ-secretase inhibition. We found that T21-organoids secrete increased proportions of Aβ-preventing (Aβ1-19) and Aβ-degradation products (Aβ1-20 and Aβ1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1-inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

BioJAKE: a tool for the creation, visualization and manipulation of metabolic pathways.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing392-40

Reliability improvement using buried capping layer in advanced interconnects

Annual Proceedings - Reliability Physics (Symposium)333-337ARLP

Palladium(II) and platinum(II) complexes containing dimesyloxy-substituted chiral diamines

10.1016/S0957-4166(97)00179-1Tetrahedron Asymmetry8122045-2050TASY

A disordered region in the EvpP protein from the type VI secretion system of Edwardsiella tarda is essential for EvpC binding

10.1371/journal.pone.0110810PLoS ONE911e11081