Suchergebnisse

Leading change is an essential skill for managers. Instructors in management education must not only teach theories on effectively leading change but also convince students of the necessity of developing their change leadership skills. Students may underestimate the difficulty of convincing others to work toward change; the authors developed the Change Game as a tool to help students experience the difficulties of leading change and identify opportunities for skill development in the area of change leadership. This 45-minute exercise can be used with a range of courses in management curricula, and it scales well for small to large seated classes. Students are divided into two groups (managers and workers) that must cooperate to complete a task and earn a reward. The exercise simulates resistance to change by giving the workers an incentive to stay with the status quo. Classes typically fail to complete the task, which allows for a lively follow-up discussion on successfully leading change, as well as on topics such as communication, intergroup dynamics, trust, power, and motivation.

Purpose
Falls are common in older adults and are associated with injuries and serious ongoing problems. This paper aims to present a participatory evaluation of a Falls Awareness Programme implemented in South Wales for older adults living in sheltered housing schemes or in the community. It identifies methodological issues and provides recommendations for evaluation design and methods for community-based interventions in the future.


Design/methodology/approach
A mixed-methods study combining a non-experimental pretest–posttest design with face-to-face focus groups.


Findings
Concerns about falling and self-reported general health at baseline were worse for participants living in sheltered housing schemes, compared to participants in the community. There was no statistically significant change between baseline and follow-up in general health or concerns about falling; however, the data suggesting the programme may be more effective for people in sheltered housing schemes. Participants reported making small, but sustainable behaviour changes following the programme and described unexpected outcomes from the programme, e.g. socialising and meeting new people.


Originality/value
This paper demonstrates the benefit of engaging older adults in research using a participatory approach, highlights key components of community-based interventions for older people and identifies some methodological issues when conducting evaluations in the community. Specifically, it highlights the importance of selecting appropriate measurement tools for data collection and the utility of continuous monitoring where programme participation is flexible and fluid.

Companion diagnostics (CDx) hail promise of improving the drug development process and precision medicine. However, there are various challenges involved in the clinical development and regulation of CDx, which are considered high-risk in vitro diagnostic medical devices given the role they play in therapeutic decision-making and the complications they may introduce with respect to their sensitivity and specificity. The European Union (E.U.) is currently in the process of bringing into effect in vitro Diagnostic Medical Devices Regulation (IVDR). The new Regulation is introducing a wide range of stringent requirements for scientific validity, analytical and clinical performance, as well as on post-market surveillance activities throughout the lifetime of in vitro diagnostics (IVD). Compliance with General Safety and Performance Requirements (GSPRs) adopts a risk-based approach, which is also the case for the new classification system. This changing regulatory framework has an impact on all stakeholders involved in the IVD Industry, including Authorized Representatives, Distributors, Importers, Notified Bodies, and Reference Laboratories and is expected to have a significant effect on the development of new CDx.

AbstractVerbal–spatial discrepancies are common in healthy individuals and in those with neurodevelopmental disorders associated with cognitive control deficits including: Autism Spectrum Disorder, Non‐Verbal Learning Disability, Fragile X, 22q11 deletion, and Turner Syndrome. Previous data from healthy individuals suggest that the magnitude of the difference between verbal IQ (VIQ) and performance IQ (PIQ) scores (the VIQ>PIQ discrepancy) is associated with reduced thickness in frontal and parietal cortices (inferior frontal, anterior cingulate, inferior parietal lobule, and supramarginal gyrus) that support cognitive control. Unknown is whether the VIQ>PIQ discrepancy is associated with functional deficits in these areas in healthy or ill children and adolescents. We assessed the effects of the VIQ>PIQ discrepancy on fMRI BOLD response during the resolution of cognitive conflict in 55 healthy children and adolescents during performance of a Simon Spatial Incompatibility task. As the magnitude of the VIQ>PIQ discrepancy increased, activation of fronto‐striatal, limbic, and temporal regions decreased during conflict resolution (p < .05, corrected). In exploratory analyses, the VIQ>PIQ discrepancy was associated with reduced functional connectivity from right inferior frontal gyrus to right thalamus and increased functional connectivity to right supramarginal gyrus (ps < .03, uncorrected). The VIQ>PIQ discrepancy may be an important aspect of an individual's cognitive profile and likely contributes to, or is associated with, deficient cognitive control processes characteristic of many childhood disorders.

Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival. These enhanced neutrophil responses were dependent upon increases in glycolytic flux and glycogen stores. Systemic administration of a HIF-prolyl hydroxylase inhibitor replicated the Phd2-deficient phenotype of delayed inflammation resolution. Together, these data identify Phd2 as the dominant HIF-hydroxylase in neutrophils under normoxic conditions and link intrinsic regulation of glycolysis and glycogen stores to the resolution of neutrophil-mediated inflammatory responses. These results demonstrate the therapeutic potential of targeting metabolic pathways in the treatment of inflammatory disease. ; This work was principally supported by a Wellcome Trust Senior Clinical Fellowship award (098516 to SRW), Medical Research Council (MRC) Clinical Training Fellowship awards (G0802255 to AART; MR/K023845/1 to RSD), an Academy of Medical Sciences (AMS) starter grant (to AART), a Wellcome Trust Senior Clinical Fellowship award (076945 to DHD), British Lung Foundation Fellowship (F05/7 to HMM), and a Engineering and Physical Sciences Research Council and Medical Research Council grant (EP/L016559/1, JAW). The MRC /University of Edinburgh Centre for Inflammation Research is supported by an MRC Centre Grant. The work of PC is supported by long-term structural funding-Methusalem funding from the Flemish Government. CJS thanks the Wellcome Trust and Cancer Research UK for support.

We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic beta cells (Fh1 beta KO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1 alpha or Nrf2. Progressive hyperglycemia in Fh1bKO mice led to dysregulated metabolism in b cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+](i) elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1bKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D. ; Wellcome Trust ; Yamagata Prefectural Government ; City of Tsuruoka ; Swedish Research Council ; Knut and Alice Wallenbergs Stiftelse ; FAPESP ; Spanish Ministry of Science and Technology ; Royal Society/Wolfson merit award ; ERC ; Diabetes UK ; Univ Oxford, Churchill Hosp, Radcliffe Dept Med, OCDEM, Oxford OX3 7LE, England ; Univ Oxford, Nuffield Dept Med, Henry Wellcome Bldg Mol Physiol, Oxford OX3 7BN, England ; Univ Oxford, NDMRB, Nuffield Dept Med, Oxford OX3 7FZ, England ; Univ Oxford, Nuffield Dept Med, Jenner Inst, Oxford OX3 7FZ, England ; Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo, Brazil ; Ramon & Cajal Hosp, Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain ; Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, Ctr Genom & Child Hlth, London E1 2AT, England ; Lund Univ, Dept Chem, Ctr Anal & Synth, Box 124, S-22100 Lund, Sweden ; Keio Univ, Inst Adv Biosci, 246-2 Mizukami, Tsuruoka, Yamagata 9970052, Japan ; Univ Oxford, Nuffield Dept Med, Target Discovery Inst, Oxford OX3 7FZ, England ; Univ Complutense Madrid, Sch Med, Biochem Dept, E-28040 Madrid, Spain ; Lund Univ, Malmo Univ Hosp, Clin Res Ctr, Diabet Ctr,Unit Mol Metab, S-20502 Malmo, Sweden ; Univ South Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA ; Univ Oxford, Dept Physiol Anat & Genet, Parks Rd, Oxford OX1 3PT, England ; Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, S-40530 Gothenburg, Sweden ; Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo, Brazil ; Web of Science