Domestic electricity use: a high-resolution energy demand model

The pattern of electricity use in an individual domestic dwelling is highly dependent upon the activities of the occupants and their associated use of electrical appliances. This paper presents a high-resolution model of domestic electricity use, that is based upon a combination of patterns of active occupancy (i.e. when people are at home and awake), and daily activity profiles that characterise how people spend their time performing certain activities. One-minute resolution synthetic electricity demand data is created through the simulation of appliance use; the model covers all major appliances commonly found in the domestic environment. In order to validate the model, electricity demand was recorded over the period of a year within 22 dwellings in the East Midlands, UK. A thorough quantitative comparison is made between the synthetic and measured data sets, showing them to have similar statistical characteristics. A freely downloadable example of the model is made available and may be configured to the particular requirements of users or incorporated into other models

Bariatric Endocrinology: Principles of Medical Practice

Obesity, is a chronic, biological, preventable, and treatable disease. The accumulation of fat mass causes physical changes (adiposity), metabolic and hormonal changes due to adipose tissue dysfunction (adiposopathy), and psychological changes. Bariatric endocrinology was conceived from the need to address the neuro-endocrinological derangements that are associated with adiposopathy, and from the need to broaden the scope of the management of its complications. In addition to the well-established metabolic complications of overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin, the development of an inflammatory milieu, and the strong risk of vascular disease. Therapy for adiposopathy hinges on effectively lowering the ratio of orexigenic to anorexigenic signals reaching the the hypothalamus and other relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight and obesity should be treated indefinitely with the specific aims to reduce fat mass for the adiposity complications, and to normalize adipose tissue function for the adiposopathic complications. This paper defines the principles of medical practice in bariatric endocrinology—the treatment of overweight and obesity as means to treat adiposopathy and its accompanying metabolic and hormonal derangements

Genomic alterations and the incidence of brain metastases in advanced and metastatic non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundBrain metastases (BM) in patients with advanced and metastatic non-small cell lung cancer (NSCLC) are linked with poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.Patients and methodsA PRISMA-compliant systematic review and meta-analysis was conducted (PROSPERO ID CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000-May 2022 were included. Prevalence at diagnosis, and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.ResultsSixty-four unique articles were included (24,784 NSCLC patients with prevalence data from forty-five studies and 9,058 NSCLC patients with incidence data from forty studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI 0.11-0.21), 0.17 in the ALK group (5 studies, 95% CI 0.10-0.27), 0.10 in the KRAS group (4 studies, 95% CI 0.06-0.17), 0.13 in the ROS1 group (3 studies, 95% CI 0.06-0.28), and 0.12 in the RET group (2 studies, 95% CI 0.08-0.17).ConclusionsComprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance

Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia

In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists

Hosting an Educational Careers Day Within the Virtual Paradigm: The Neurology and Neurosurgery Interest Group Experience.

INTRODUCTION:  To explore our experience of hosting the 10th Annual Neurology and Neurosurgery Interest Group-Society of British Neurological Surgeons (NANSIG-SBNS) Neurosurgery Careers Day, held virtually for the first time. METHODS:  Reflective feedback and review of an international, virtual neurosurgery careers day. The authors reflect on the logistics of organizing the event, and the pre- and post-event feedback provided by delegates. Recommendations have been made on how to successfully host a virtual event. The key themes that permeated the event have been outlined and discussed in the context of the feedback received. RESULTS:  The event was attended by 231 delegates from 20 countries worldwide. Knowledge of neurosurgery as a career and the application process increased after attending the careers day (4.27/5 to 4.51/5, p=0.003 and 3.12/5 to 4.31/5, p<0.001 respectively). The key themes identified from the event include attendance, networking, and education. Qualitative feedback was positive and indicated a positive perception of the careers day. CONCLUSIONS:  The future of educational events is unclear, and a hybrid approach is recommended to retain the benefits of the online space when in-person events eventually return

Beyond the WHO classification of meningioma: using molecular diagnostics to guide management.

Meningioma are the most common primary brain tumour. Classically, meningioma are phenotypically grouped using the World Health Organisation (WHO) classification system. However, it is now understood that the WHO approach overfits tumours into three grades, resulting in similarly graded tumours displaying phenotypically distinct behaviour. There is a growing body of research investigating the molecular biology of these tumours, including genomic, transcriptomic, metabolomic, proteomic, and methylomic profiling. Such advancements in molecular profiling of meningioma are providing greater accuracy in prognostication of tumours. Furthermore, a clearer understanding of tumour molecular biology highlights potential targets for pharmacotherapies. Currently, the routine application of in-depth tumour molecular analysis is limited, however as it becomes more widely available it will likely result in improved patient care. This review seeks to explore the important developments in meningioma molecular biology, discussed in the context of their clinical importance

Social and psychological impact of the COVID-19 pandemic on UK medical and nursing students: protocol for a national medical and nursing student survey

INTRODUCTION: Healthcare students have played a significant role in the National Health Service during the COVID-19 pandemic. We captured data on the well-being of medical students during the acute phase of the pandemic with the Social and Psychological Impact of COVID-19 on medical students: a national survey Evaluation (SPICE-19) study. We will evaluate changes in mental health and well-being of medical and nursing students 1 year after SPICE-19, in a cross-sectional study, to understand the impact of the pandemic, and inform well-being policies. METHODS AND ANALYSIS: This study will be a national, multi-institution, cross-discipline study. An online 53-item survey of demographics, mental health and well-being will be used to record responses. Students studying for a medical or nursing degree at any UK universities will be eligible to participate. The survey will be advertised through the Neurology and Neurosurgery Interest Group national network. Participation is anonymous and voluntary, with relevant mental health resources made available to participants. ETHICS AND DISSEMINATION: Ethical approval was granted by the University of Oxford Central University Research Ethics Committee (R75719/RE001) on 21 May 2021. Study findings will be presented at national and international meetings, and submitted for publication in a peer-reviewed journal

The effect of paratuberculosis on milk yield—A systematic review and meta-analysis

peer-reviewedBovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis. Substantial between-study heterogeneity was observed. Subgroup analysis by case definition and study design was carried out to investigate heterogeneity. The majority of between-study variation was attributed to studies that defined cases on serology. Calculation of a pooled effect estimate was only appropriate for studies that defined cases by organism detection. A reduction in milk yield, corrected for lactation number and herd of origin of 1.87 kg/d, equivalent to 5.9% of yield, was associated with fecal culture or PCR positivity in individual cows

Volumetric Growth and Growth Curve Analysis of Residual Intracranial Meningioma.

BackgroundAfter meningioma surgery, approximately 1 in 3 patients will have residual tumor that requires ongoing imaging surveillance. The precise volumetric growth rates of these tumors are unknown.ObjectiveTo identify the volumetric growth rates of residual meningioma, growth trajectory, and factors associated with progression.MethodsPatients with residual meningioma identified at a tertiary neurosurgery center between 2004 and 2020 were retrospectively reviewed. Tumor volume was measured using manual segmentation, after surgery and at every follow-up MRI scan. Growth rates were ascertained using a linear mixed-effects model and nonlinear regression analysis of growth trajectories. Progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria (40% volume increase).ResultsThere were 236 patients with residual meningioma. One hundred and thirty-two patients (56.0%) progressed according to the RANO criteria, with 86 patients being conservatively managed (65.2%) after progression. Thirteen patients (5.5%) developed clinical progression. Over a median follow-up of 5.3 years (interquartile range, 3.5-8.6 years), the absolute growth rate was 0.11 cm 3 per year and the relative growth rate 4.3% per year. Factors associated with residual meningioma progression in multivariable Cox regression analysis were skull base location (hazard ratio [HR] 1.60, 95% CI 1.02-2.50) and increasing Ki-67 index (HR 3.43, 95% CI 1.19-9.90). Most meningioma exhibited exponential and logistic growth patterns (median R 2 value 0.84, 95% CI 0.60-0.90).ConclusionAbsolute and relative growth rates of residual meningioma are low, but most meet the RANO criteria for progression. Location and Ki-67 index can be used to stratify adjuvant treatment and surveillance paradigms