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Cardiac transverse (t)‐tubules are altered during disease and may be regulated by stretch‐sensitive molecules. The relationship between variations in the degree and duration of load and t‐tubule structure remains unknown, as well as its implications for local Ca2+‐induced Ca2+ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t‐tubule structure were assessed using confocal‐microscopy, patch‐clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart‐only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time‐dependent manner. Ca2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t‐tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t‐tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca2+ transient, increased Ca2+ spark frequency or impaired t‐tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t‐tubule structure in a time‐ and degree‐dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible.

Specialist centres have been developed to deliver high-quality Hepatology care. However, there is geographical inequity in accessing these centres in the United Kingdom (UK). We aimed to assess the impact of these centres on decompensated cirrhosis patient outcomes and understand which patients transfer to specialist centres. A UK multicentred retrospective observational study was performed including emergency admissions for patients with decompensated cirrhosis in November 2019. Admissions were grouped by specialist/non-specialist centre designation, National Health Service region and whether a transfer to a more specialist centre occurred or not. Univariable and multivariable comparisons were made. 1224 admissions (1168 patients) from 104 acute hospitals were included in this analysis. Patients at specialist centres were more likely to be managed by a Consultant Gastroenterologist/Hepatologist on a Gastroenterology/Hepatology ward. Only 24 patients were transferred to a more specialist centre. These patients were more likely to be admitted for gastrointestinal bleeding and were not using alcohol. Specialist centres eliminated regional variations in mortality which were present at non-specialist centres. Low specialist Consultant staffing numbers impacted mortality at non-specialist centres (aOR 2.15 (95% CI 1.18 to 4.07)) but not at specialist centres. Hospitals within areas of high prevalence of deprivation were more likely to have lower specialist Consultant staffing numbers. Specialist Hepatology centres improve patient care and standardise outcomes for patients with decompensated cirrhosis. There is a need to support service development and care delivery at non-specialist centres. Formal referral pathways are required to ensure all patients receive access to specialist interventions.

Cardiac transverse (t)‐tubules are altered during disease and may be regulated by stretch‐sensitive molecules. The relationship between variations in the degree and duration of load and t‐tubule structure remains unknown, as well as its implications for local Ca 2+ ‐induced Ca 2+ release ( CICR ). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung transplantation ( HAHLT )] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR , cell and t‐tubule structure were assessed using confocal‐microscopy, patch‐clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart‐only transplantation ( HAHT )]. Mechanical unloading reduced cardiomyocyte volume in a time‐dependent manner. Ca 2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca 2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t‐tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t‐tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca 2+ transient, increased Ca 2+ spark frequency or impaired t‐tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t‐tubule structure in a time‐ and degree‐dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible.

Now the basics are set to be used elsewhere after the West Midlands Road Safety Group agreed to offer it in Birmingham, Coventry, Sandwell, Walsall and Wolverhampton. Solihull mayor Coun Joe Tildesley collected the award on behalf of the council from Adrian Walsh, the director of RoadSafe - the organisation behind the awards.