Endogenous biological rhythms synchronise human physiology with daily cycles of light-dark, wake-sleep, feeding-fasting. Proper circadian alignment is crucial for physiological function, reflected in the rhythmic expression of molecular clock genes in various tissues, especially in skeletal muscle. Circadian disruption, such as misaligned feeding, dysregulates metabolism and increases the risk of metabolic disorders like type 2 diabetes. Such disturbances are common in critically ill patients, especially those who rely on enteral nutrition. Whilst continuous provision of enteral nutrition is currently the most common practice in ciritical care, this is largely dictated by convenience rather than evidence. Conversely, some findings indicate that that intermittent provision of enteral nutrition aligned with daylight may better support physiological functions and improve clinical/metabolic outcomes. However, there is a critical need for studies of skeletal muscle responses to acutely divergent feeding patterns, in addition to complementary translational research to map tissue-level physiology to whole-body and clinical outcomes.

This paper examines the population of corporate directors of Britain at the turn of the twentieth century. Over the period 1881-1911 the corporate form became the most common mode of business organisation for large businesses. As their number increased, the population of directors expanded and reflected an increasingly diversified corporate landscape. Based on a large-scale dataset, this paper analyses the characteristics and networks of this wider population of directors. The study goes beyond previous work, which has mainly focused on elite directors or prominent companies, and shows three key findings. First, the population of directors was very connected into a large network, complete isolation from this network was rare. Second, over 1881-1911 director interlocks with banks became less important for most sectors, while interlocks with other financial institutions such as trusts became increasingly important. Insurance companies stood out as the most connected sector spanning smaller local companies and larger international ones. Third, during the period studied there was a shift from director clusters that were mainly based on proximity, to those that were connected through industries.

The range of digital sources available to historians has expanded at an enormous rate over the last fifty years; this has enabled all kinds of innovative scholarship to flourish. However, this process has also shaped recent historical work in ways that have not been fully discussed or documented. This article considers how we might reconcile the digitisation of archival sources with their materiality, with a particular focus on the probate records of the Prerogative Court of Canterbury (PCC). The article first considers the variety of digital sources available to historians of the United Kingdom, highlighting the particular influence of genealogical companies in shaping what material is available, how it has been digitised and how those sources are accessed. Secondly, we examine the PCC wills’ digitisation, what was gained and what was lost in that process, notably important material aspects of the wills. This article does not seek to champion archival research in opposition to digitally based scholarship; instead, we remind historians of the many ways in which the creation of sources shape their potential use, and call on historians to push for improvements in the United Kingdom’s digital infrastructure to avoid these problems in future.

The provision of pensions for Civil Servants and other employees in public office, such as the police, as well as in large private businesses, became more widespread in the second half of the nineteenth century. Such pensions, and other non-pay benefits, including sick pay, not only helped with recruitment but also provided a means of managing the retirement of workers who were deemed to be incapable of performing their roles. The rules governing eligibility to receive a pension in the Metropolitan Police in London were closely linked to the certification of poor health. Police doctors restricted the certification of sickness as a reason for retirement because it impacted the size of the force, resulted in the loss of more experienced men, and added to the cost of the pension fund. This strategy generated conflict with the workforce, resulting in industrial unrest. Piecemeal reforms failed to address workers’ concerns until 1890, when the rights to receive a pension were improved. These reforms, rather than stricter vigilance by police doctors, were an effective way of retaining experienced officers in the police force.

The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of β-lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β-lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l−1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l−1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902).

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.

Rotavirus (RV) was a common healthcare-associated infection prior to the introduction of the RV vaccine. Following widespread RV vaccination, healthcare-associated rotavirus cases are rare. We describe an investigation of a cluster of rotavirus infections in a pediatric hospital in which an uncommon genotype not typically circulating in the United States was detected.

The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

With the exponential growth in investment attention to brain health—solutions spanning brain wellness to mental health to neurological disorders—tech giants, payers, and biotechnology companies have been making forays into this field to identify technology solutions and pharmaceutical amplifiers. So far, their investments have had mixed results. The concept of open innovation (OI) was first coined by Henry Chesbrough to describe the paradigm by which enterprises allow free flow of ideas, products, and services from the outside to the inside and vice versa in order to remain competitive, particularly in rapidly evolving fields where there is abundant, relevant knowledge outside the traditional walls of the enterprise. In this article, we advocate for further exploration and advancement of OI in brain health.

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).

The article links the digital records of individual proprietors in the manuscript censuses 1851–81 for the whole of England and Wales using the BBCE database to identify career changes of employers and own account proprietors. It investigates continuing proprietorship, entry to business from previous activity, and switching out of business. The article identifies the effects on switching of demography, gender, household relationships, sector markets, and opportunity/necessity measured by location and access to railways. Previous analysis of nineteenth-century proprietor careers has been based mainly on local case studies and large firms. This article allows examination across the spectrum of small and large businesses for a representative sample large enough to generalize to the behavior of the whole population. The analysis shows a larger proportion of flows between employer, own account, and worker status than often expected, indicating a relatively open and flexible Victorian economy, and higher than in the modern United Kingdom. Farm and nonfarm activities show contrasted patterns, with farm proprietors more stable with less switching, as to be expected. Switching appears to have slowed slightly over time, with incumbency increasing for both farm and nonfarm employers, and for both men and women, but own account proprietorship was often relatively ephemeral. The article assesses the factors influencing switching using logistic regression. This confirms age, sex, marital status, family position, location, and sector as significant for explaining switching/nonswitching. The results demonstrate that although open and flexible, proprietorship was highly varied between sectors, with changes of railway accessibility mainly significant for farmers.

A global ageing population presents opportunities and challenges to designing urban environments that support ageing in place. The World Health Organization's Global Age-Friendly Cities movement has identified the need to develop communities that optimise health, participation and security in order to enhance quality of life as people age. Ensuring that age-friendly urban environments create the conditions for active ageing requires cities and communities to support older adults’ rights to access and move around the city (‘appropriation’) and for them to be actively involved in the transformation (‘making and remaking’) of the city. These opportunities raise important questions: What are older adults’ everyday experiences in exercising their rights to the city? What are the challenges and opportunities in supporting a rights to the city approach? How can the delivery of age-friendly cities support rights to the city for older adults? This paper aims to respond to these questions by examining the lived experiences of older adults across three cities and nine neighbourhoods in the United Kingdom. Drawing on 104 semi-structured interviews with older adults between the ages of 51 and 94, the discussion centres on the themes of: right to use urban space; respect and visibility; and the right to participate in planning and decision-making. These themes are illustrated as areas in which older adults’ rights to access and shape urban environments need to be addressed, along with recommendations for age-friendly cities that support a rights-based approach.

A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.