Stem cells tightly regulate dead cell clearance to maintain tissue fitness.

Billions of cells are eliminated daily from our bodies. Although macrophages and dendritic cells are dedicated to migrating and engulfing dying cells and debris, many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses. How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear.

Stem cells tightly regulate dead cell clearance to maintain tissue fitness.

Macrophages and dendritic cells have long been appreciated for their ability to migrate to and engulf dying cells and debris, including some of the billions of cells that are naturally eliminated from our body daily. However, a substantial number of these dying cells are cleared by 'non-professional phagocytes', local epithelial cells that are critical to organismal fitness. How non-professional phagocytes sense and digest nearby apoptotic corpses while still performing their normal tissue functions is unclear.

A tissue injury sensing and repair pathway distinct from host pathogen defense.

Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections and induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast to most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after tissue injury and is independent of microbiome or adaptive immunity.

Impact of COVID-19 on the Health Response to Family Violence in Aotearoa New Zealand: A Qualitative Study.

COVID-19 pandemic planning and response has resulted in unprecedented upheaval within health systems internationally. With a concern for increasing frequency and escalation of family violence, the so called "shadow pandemic," we wondered how health system violence intervention programs were operating during this time. In Aotearoa New Zealand, the Ministry of Health Violence Intervention Program (VIP), using a systems approach, seeks to reduce and prevent the health impacts of family violence and abuse through early identification, assessment, and referral of victims presenting to designated health services.

How to design and implement a university-based COVID-19 testing programme? An evaluation of a novel RT-LAMP COVID-19 testing programme in a UK university.

Background: Little is known about how asymptomatic testing as a method to control transmission of COVID-19 can be implemented, and the prevalence of asymptomatic infection within university populations. The objective of this study was to investigate how to effectively set-up and implement a COVID-19 testing programme using novel reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) technology and to quantify the scale of asymptomatic infection on a university campus.

Methods: An observational study to describe the set-up and implementation of a novel COVID-19 testing programme on a UK university campus between September and December 2020.

A rapid RT-LAMP SARS-CoV-2 screening assay for collapsing asymptomatic COVID-19 transmission.

Purpose: To demonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population.

Methods: RT-LAMP diagnostic specificity (DSe) and sensitivity (DSe) was determined using 114 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. A swab-based RT-LAMP SARS-CoV-2 screening programme was subsequently made available to all staff and students at the University of Leicester (Autumn 2020), implemented to ISO 15189:2012 standards using NHS IT infrastructure and supported by University Hospital Leicester via confirmatory NHS diagnostic laboratory testing of RT-LAMP 'positive' samples.

Characterization of sequence determinants of enhancer function using natural genetic variation.

Sequence variation in enhancers that control cell-type-specific gene transcription contributes significantly to phenotypic variation within human populations. However, it remains difficult to predict precisely the effect of any given sequence variant on enhancer function due to the complexity of DNA sequence motifs that determine transcription factor (TF) binding to enhancers in their native genomic context. Using F-hybrid cells derived from crosses between distantly related inbred strains of mice, we identified thousands of enhancers with allele-specific TF binding and/or activity.

Designing and testing a blockchain application for patient identity management in healthcare.

Objective: Healthcare systems suffer from a lack of interoperability that creates "data silos," causing patient linkage and data sharing problems. Blockchain technology's unique architecture provides individuals greater control over their information and may help address some of the problems related to health data. A multidisciplinary team designed and tested a blockchain application, MediLinker, as a patient-centric identity management system.

Establishment, maintenance, and recall of inflammatory memory.

Known for nearly a century but through mechanisms that remain elusive, cells retain a memory of inflammation that equips them to react quickly and broadly to diverse secondary stimuli. Using murine epidermal stem cells as a model, we elucidate how cells establish, maintain, and recall inflammatory memory. Specifically, we landscape and functionally interrogate temporal, dynamic changes to chromatin accessibility, histone modifications, and transcription factor binding that occur during inflammation, post-resolution, and in memory recall following injury.

Reducing Unnecessary Diagnostic Testing in Pediatric Syncope: A Quality Improvement Initiative.

Our aim was to reduce the frequency of unnecessary testing used by pediatric cardiologists in the evaluation of pediatric patients with syncope or pre-syncopal symptoms without negatively affecting patient outcomes. Guidelines for cardiac testing in pediatric patients with syncope were developed and disseminated to members of our pediatric cardiology division. Educational brochures and water bottles labeled with tips on preventing syncope were made available to families and providers in our clinics.

Robust impurity detection and tracking for tokamaks.

A robust impurity detection and tracking code, able to generate large sets of dust tracks from tokamak camera footage, is presented. This machine learning-based code is tested with cameras from the Joint European Torus, Doublet-III-D, and Magnum-PSI and is able to generate dust tracks with a 65-100% classification accuracy. Moreover, the number dust particles detected from a single camera shot can be up to the order of 1000.

Epithelial cells: liaisons of immunity.

The surface and lining tissues of our body are exposed to the external environment, and as such these epithelial tissues must form structural barriers able to defend against microbes, environmental toxins, and mechanical stress. Their cells are equipped to detect a diverse array of surface perturbations, and then launch signaling relays to the immune system. The aim of these liaisons is to coordinate the requisite immune cell response needed to preserve and/or restore barrier integrity and defend the host.

Selective Conscientious Objection in Healthcare.

Most discussions of conscientious objection in healthcare assume that the objection is : a doctor objects to all abortions. I want to investigate objections, where a doctor objects to one abortion but not to another, depending on the circumstances. I consider not only objections to abortion, but also objections to the withdrawal of life-saving treatment at the request of a competent patient, which is almost always selective.

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease.

Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or "niche," they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body.

AP-1 Transcription Factors and the BAF Complex Mediate Signal-Dependent Enhancer Selection.

Enhancer elements are genomic regulatory sequences that direct the selective expression of genes so that genetically identical cells can differentiate and acquire the highly specialized forms and functions required to build a functioning animal. To differentiate, cells must select from among the ∼10 enhancers encoded in the genome the thousands of enhancers that drive the gene programs that impart their distinct features. We used a genetic approach to identify transcription factors (TFs) required for enhancer selection in fibroblasts.

Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer.

The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed late so that surgery is rarely curative. Earlier detection could significantly increase the likelihood of successful treatment and improve survival. The aim of the study was to provide proof of principle that point mutations in key cancer genes can be identified by sequencing circulating free DNA (cfDNA) and that this could be used to detect early PDACs and potentially, premalignant lesions, to help target early effective treatment.

Dementia, identity and the role of friends.

Ronald Dworkin (1993) introduced the example of Margo, who was so severely demented that she could not recognise any family or friends, and could not remember anything of her life. At the same time, however, she seemed full of childish delight. Dworkin also imagines that, before her dementia, Margo signed an advance refusal of life-saving treatment.

Rapid Health Care Improvement Science Curriculum Integration Across Programs in a School of Nursing.

This article describes the systematic efforts undertaken by a school of nursing in the Northeastern United States to foster innovation in health professions education. We present an application of modified team coaching and plan-do-study-act improvement methods in an educational context to rapidly integrate a quality and safety curriculum across programs. We discuss applications in generalist, advanced practice, doctoral, residency, and advanced fellowship programs and provide examples of each.

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline.

Conscientious objection in healthcare and the duty to refer.

Although some healthcare professionals have the legal right to conscientiously object to authorise or perform certain lawful medical services, they have an associated duty to provide the patient with enough information to seek out another professional willing to authorise or provide the service (the 'duty to refer'). Does the duty to refer morally undermine the professional's conscientious objection (CO)? I narrow my discussion to the National Health Service in Britain, and the case of a general practitioner (GP) being asked by a pregnant woman to authorise an abortion. I will be careful not to enter the debate about whether abortion should be legalised, or the debate about whether CO should be permitted-I will take both as given.

A Defence of Conscientious Objection in Medicine: A Reply to Schuklenk and Savulescu.

In a recent (2015) Bioethics editorial, Udo Schuklenk argues against allowing Canadian doctors to conscientiously object to any new euthanasia procedures approved by Parliament. In this he follows Julian Savulescu's 2006 BMJ paper which argued for the removal of the conscientious objection clause in the 1967 UK Abortion Act. Both authors advance powerful arguments based on the need for uniformity of service and on analogies with reprehensible kinds of personal exemption.