Weekend admission and mortality for gastrointestinal disorders across England and Wales

BACKGROUND: Little has been reported on mortality following admissions at weekends for many gastrointestinal (GI) disorders. The aim was to establish whether GI disorders are susceptible to increased mortality following unscheduled admission on weekends compared with weekdays. METHODS: Record linkage was undertaken of national administrative inpatient and mortality data for people in England and Wales who were hospitalized as an emergency for one of 19 major GI disorders. RESULTS: The study included 2 254 701 people in England and 155 464 in Wales. For 11 general surgical and medical GI disorders there were little, or no, significant weekend effects on mortality at 30 days in either country. There were large consistent weekend effects in both countries for severe liver disease (England: 26·2 (95 per cent c.i. 21·1 to 31·6) per cent; Wales: 32·0 (12·4 to 55·1 per cent) and GI cancer (England: 21·8 (19·1 to 24·5) per cent; Wales: 25·0 (15·0 to 35·9) per cent), which were lower in patients managed by surgeons. Admission rates were lower at weekends than on weekdays, most strongly for severe liver disease (by 43·3 per cent in England and 51·4 per cent in Wales) and GI cancer (by 44·6 and 52·8 per cent respectively). Both mortality and the weekend mortality effect for GI cancer were lower for patients managed by surgeons. DISCUSSION: There is little, or no, evidence of a weekend mortality effect for most major general surgical or medical GI disorders, but large weekend effects for GI cancer and severe liver disease. Lower admission rates at weekends indicate more severe cases. The findings for severe liver disease may suggest a lack of specialist hepatological resources. For cancers, reduced availability of end-of-life care in the community at weekends may be the cause

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

Mitigating systematic error in topographic models for geomorphic change detection: Accuracy, precision and considerations beyond off‐nadir imagery

Unmanned aerial vehicles (UAVs) and structure-from-motion photogrammetry enable detailed quantification of geomorphic change. However, rigorous precision-based change detection can be compromised by survey accuracy problems producing systematic topographic error (e.g. 'doming'), with error magnitudes greatly exceeding precision estimates. Here, we assess survey sensitivity to systematic error, directly correcting topographic data so that error magnitudes align more closely with precision estimates. By simulating conventional grid-style photogrammetric aerial surveys, we quantify the underlying relationships between survey accuracy, camera model parameters, camera inclination, tie point matching precision and topographic relief, and demonstrate a relative insensitivity to image overlap. We show that a current doming-mitigation strategy of using a gently inclined ( 0 center dot 3 m, representing accuracy issues an order of magnitude greater than precision-based error estimates. For higher-relief topography, and for nadir-imaging surveys of the lower-relief topography, systematic error was <0 center dot 09 m. Modelling and subtracting the systematic error directly from the topographic data successfully reduced error magnitudes to values consistent with twice the estimated precision. Thus, topographic correction can provide a more robust approach to uncertainty-based detection of event-scale geomorphic change than designing surveys with small off-nadir camera inclinations and, furthermore, can substantially reduce ground control requirements. (c) 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Lt

Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study

Background: Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls. Methods: We performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected. Results: All patient groups had reduced peak oxygen consumption compared to healthy controls (p<0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p<0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p<0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p=0.025) and higher myocardial T1 was associated with lower peak stroke volume (p=0.011). Conclusions: Reduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplifed by reduced peak cardiac output

In-host microevolution of Aspergillus fumigatus : a phenotypic and genotypic analysis

Acknowledgments We are thankful to Kenny Ntwari Nindorera for performing the G. mellonella survival studies. EB, AB and AW are supported by the Wellcome Trust Strategic Award (grant 097377), the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen. AB was also supported by the Biotechnology and Biological Research Council (BB/K017365/1) and the Medical Research Council (MR/M026663/1). The work in this paper is funded by a BBSRC EASTBIO grant. The funders had no role in study design, data interpretation, or the decision to submit the work for publication.Peer reviewedPublisher PD

Cardiovascular magnetic resonance-guided right heart catheterization in a conventional CMR environment - predictors of procedure success and duration in pulmonary artery hypertension

Background Cardiovascular magnetic resonance imaging (CMR) is valuable for the investigation and management of pulmonary artery hypertension (PAH), but the direct measurement of pulmonary hemodynamics by right heart catheterization is still necessary. CMR-guided right heart catheterization (CMR-RHC) combines the benefits of CMR and invasive cardiac catheterization, but its feasibility in patients with acquired PAH has not been established. The aims of this study are to: (1) demonstrate the feasibility of CMR-RHC in patients being assessed for PAH in a conventional diagnostic CMR scanner room; (2) determine the predictors of (i) procedure duration, and (ii) procedural failure or technical difficulty as determined by the adjunctive need for a guidewire. Methods Fifty patients investigated for suspected or known PH underwent CMR-RHC. Durations of separate procedural components were recorded, including time taken to pass the catheter from the femoral vein to a stable wedge position (procedure time) and total time the patient spent in the CMR department (department time). Associations between procedural failure/guidewire usage and hemodynamic/CMR measures were assessed using logistic regression. Relationships between procedure times and hemodynamic/CMR measures were evaluated using Spearman’s correlation coefficient. Results A full CMR-RHC study was successfully completed in 47 (94%) patients. CMR-conditional guidewires were used in 6 (12%) patients. Metrics associated with guidewire use/procedural failure were higher mean pulmonary artery (PA) pressures (mPAP: OR = 1.125, p = 0.018), right heart dilatation (right ventricular (RV) end-systolic volume (RVESV): OR = 1.028, p = 0.018), RV hypertrophy (OR = 1.050, p = 0.0067) and RV ejection fraction (EF) (OR = 0.914, p = 0.014). Median catheter and department times were 3.6 (2.0–7.7) minutes and 60.0 (54.0–68.5) minutes, respectively. All procedure times became significantly shorter with increasing procedural experience (p < 0.05). Catheterization time was also associated with PH severity (RV systolic pressure: rho = 0.46, p = 0.0013) and increasing RV end-systolic volume (RVESV: rho = 0.41, p = 0.0043), hypertrophy (rho = 0.43, p = 0.0025) and dysfunction (RVEF: rho = − 0.32, p = 0.031). Conclusions This study demonstrates that CMR-RHC using standard technology can be incorporated into routine clinical practice for the investigation of PAH. Procedural failure was rare but more likely in patients with severe PAH. Procedure time is clinically acceptable and increases with worsening PAH severity

Degradation of ribosomal and chaperone proteins is attenuated during the differentiation of replicatively aged C2C12 myoblasts

Background: Cell assays are important for investigating the mechanisms of ageing, including losses in protein homeostasis and ‘proteostasis collapse’. We used novel isotopic labelling and proteomic methods to investigate protein turnover in replicatively aged (>140 population doublings) murine C2C12 myoblasts that exhibit impaired differentiation and serve as a model for age-related declines in muscle homeostasis. Methods: The Absolute Dynamic Profiling Technique for Proteo-mics (Proteo-ADPT) was used to investigate proteostasis in young (passage 6-10) and replicatively aged (passage 48-50) C2C12 myoblast cultures supplemented with deuterium oxide (D2O) during early (0 h – 24 h) or late (72 h – 96 h) periods of differentiation. Peptide mass spectrometry was used to quantify the absolute rates of abundance change, synthesis and degradation of individual proteins. Results: Young cells exhibited a consistent ~25% rise in protein accretion over the 96-h experimental period. In aged cells, protein accretion increased by 32% (P<0.05) during early differentiation, but then fell back to baseline levels by 96-h. Proteo-ADPT encompassed 116 proteins and 74 proteins exhibited significantly (P<0.05, FDR <5% interaction between age * differentiation stage) different changes in abundance between young and aged cells at early and later periods of differentiation, including proteins associated with translation, glycolysis, cell-cell adhesion, ribosomal biogenesis and the regulation of cell shape. During early differentiation, heat shock and ribosomal protein abundances increased in aged cells due to suppressed degradation rather than heightened synthesis. For instance, HS90A increased at a rate of 10.62 ± 1.60 ng/well/h in aged which was significantly greater than the rate of accretion (1.86 ± 0.49 ng/well/h) in young cells. HS90A synthesis was similar in young (21.23 ± 3.40 ng/well/h) and aged (23.69 ± 1.13 ng/well/h) but HS90A degradation was significantly (P = 0.05) greater in young (19.37 ± 2.93 ng/well/h) versus aged (13.06 ± 0.76 ng/well/h) cells. During later differentiation the HS90A degradation (8.94 ± 0.38 ng/well/h) and synthesis (7.89 ± 1.28 ng/well/h) declined and were significantly less than the positive net balance between synthesis and degradation (ASR = 28.14 ± 3.70 ng/well/h vs ADR = 21.49 ± 3.13 ng/well/h) in young cells. Conclusion: Our results suggest a loss of proteome quality as a precursor to the lack of fusion of aged myoblasts. The quality of key chaperone proteins, including HS90A, HS90B and HSP7C was reduced in aged cells and may account for the disruption to cell signalling required for the later stages of differentiation and fusion

The zygomatic implant perforated (ZIP) flap: a new technique for combined surgical reconstruction and rapid fixed dental rehabilitation following low-level maxillectomy.

Abstract This aim of this report is to describe the development and evolution of a new surgical technique for the immediate surgical reconstruction and rapid post-operative prosthodontic rehabilitation with a fixed dental prosthesis following low-level maxillectomy for malignant disease. The technique involves the use of a zygomatic oncology implant perforated micro-vascular soft tissue flap (ZIP flap) for the primary management of maxillary malignancy with surgical closure of the resultant maxillary defect and the installation of osseointegrated support for a zygomatic implant-supported maxillary fixed dental prosthesis. The use of this technique facilitates extremely rapid oral and dental rehabilitation within a few weeks of resective surgery, providing rapid return to function and restoring appearance following low-level maxillary resection, even in cases where radiotherapy is required as an adjuvant treatment post-operatively. The ZIP flap technique has been adopted as a standard procedure in the unit for the management of low-level maxillary malignancy, and this report provides a detailed step-by-step approach to treatment and discusses modifications developed over the treatment of an initial cohort of patients

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders