We present replication-aware single-molecule accessibility mapping (RASAM), a method to nondestructively measure replication status and protein-DNA interactions on chromatin genome-wide. Using RASAM, we uncover a genome-wide state of single-molecule "hyperaccessibility" post-replication that resolves over several hours. Combining RASAM with cellular models for rapid protein degradation, we demonstrate that histone chaperone CAF-1 reduces nascent chromatin accessibility by filling single-molecular "gaps" and generating closely spaced dinucleosomes on replicated DNA.
View Article and Find Full Text PDFBackground: Public demand and scrutiny, an aging population, inefficient funding and the legacy of Covid-19 are just some of the challenges the United Kingdom's health service faces. In imaging and oncology, there has been an exponential growth in service need against a workforce which is struggling to recruit and retain. This project aims to explore what the current, and future, workforce perceive the main opportunities and solutions, threats and risks are.
View Article and Find Full Text PDFWe describe a case of brucellosis in a man in his 20s, who presented to the emergency department with a 1-month history of fevers, dry cough and knee pain. Blood cultures were positive after 55 hours and was identified on matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry. spp are Gram-negative organisms that are phylogenetically related to spp but commercially available MALDI-TOF libraries cannot distinguish between the two genera.
View Article and Find Full Text PDFMind Body Connect is a charity that delivers community-based physical exercise (PE) classes to people in recovery from substance use disorders. This study aimed to identify the contribution that strength training played in the development of positive short- and long-term psychological attributes for people recovering from substance use disorders by assessing (a) the short-term associations between participation in group exercise classes ( = 43, = 2,940) and (b) the prospective long-term association between strength development and individuals' self-assessed level of "grit" among participants for whom strength training became a habitual activity ( = 13, median 8 weeks supported training). Participants completed demographic, Profile of Mood States-Adapted Short Form, and Short Grit Scale questionnaires before and after each strength training session over a period of 45 noncompulsory training sessions between February 2020 and March 2021.
View Article and Find Full Text PDFthe main agent of bovine tuberculosis (bTB), presents as a series of spatially-localised micro-epidemics across landscapes. Classical molecular typing methods applied to these micro-epidemics, based on genotyping a few variable loci, have significantly improved our understanding of potential epidemiological links between outbreaks. However, they have limited utility owing to low resolution.
View Article and Find Full Text PDFNearly all essential nuclear processes act on DNA packaged into arrays of nucleosomes. However, our understanding of how these processes (for example, DNA replication, RNA transcription, chromatin extrusion and nucleosome remodeling) occur on individual chromatin arrays remains unresolved. Here, to address this deficit, we present SAMOSA-ChAAT: a massively multiplex single-molecule footprinting approach to map the primary structure of individual, reconstituted chromatin templates subject to virtually any chromatin-associated reaction.
View Article and Find Full Text PDFEur Heart J Case Rep
September 2023
Background: Kawasaki disease (KD) is an acute systemic vasculitis which predominantly occurs in childhood but rarely in adulthood. Diagnosis relies on the presence of typical clinical features; however, patients may present atypically, increasing the challenge of timely diagnosis for physicians.
Case Summary: We report a case of a 40-year-old male presenting with persistent fever, rash, and unilateral neck swelling.
Background: Electronic early warning systems have been used in adults for many years to prevent critical deterioration events (CDEs). However, implementation of similar technologies for monitoring children across the entire hospital poses additional challenges. While the concept of such technologies is promising, their cost-effectiveness is not established for use in children.
View Article and Find Full Text PDFSeawater intrusion is a growing pressure in coastal communities worldwide, putting millions of people at risk of excess salinity in drinking water. This study examines the impact of saline water on people's health and labor allocation as potential pathways towards chronic poverty. Using a transdisciplinary approach based on a coupled human-water system framework, we test these linkages combining field data on well water salinity levels and rich household survey data in coastal Tanzania.
View Article and Find Full Text PDFTumour hypoxia is a well-established contributor to prostate cancer progression and is also known to alter the expression of several microRNAs. The over-expression of microRNA-21 (miR-21) has been consistently linked with many cancers, but its role in the hypoxic prostate tumour environment has not been well studied. In this paper, the link between hypoxia and miR-21 in prostate cancer is investigated.
View Article and Find Full Text PDFBackground: Ending tuberculosis (TB) is a global priority and targets for doing so are outlined in the World Health Organization (WHO) End TB Strategy. For low-incidence countries, eliminating TB requires high levels of wealth, low levels of income inequality and effective TB programmes and services that can meet the needs of people who have not benefited from these and are still at risk of TB. In Ireland, numerous reports have noted a need for more funding for TB prevention and control.
View Article and Find Full Text PDFBackground: The current study explored the perspectives of preparedness for dental practice from a range of relevant stakeholders (i.e., educators, employers, final-year students, graduates, practitioners, and professional associations) using an anonymous online survey in which participants described either their preparedness for practice, or the preparedness of graduates they have encountered, across six domains.
View Article and Find Full Text PDFBackground: Health services implemented a range of initiatives during the COVID-19 pandemic to support employee wellbeing and assist employees to manage the professional and personal challenges they experienced. However, it is not known if such initiatives were acceptable to employees or met their needs.
Aims: To evaluate the wellbeing and support initiatives implemented at an Australian health service during the COVID-19 pandemic from the perspectives of employees (both users and non-users) and key stakeholders.
This case highlights the use of (1,3)-beta-d glucan to direct treatment of a cervical spinal cord Aspergillus fumigatus infection in a 22-year-old woman immunocompromised due to steroid and anti-TNF therapy in the context of ulcerative colitis and interferon gamma deficiency. A 4-year treatment course requiring neurosurgical intervention on four occasions and prolonged antifungal therapy, including isavuconazole, resulted in clinical cure with a corresponding decrease in CSF beta-d-glucan to <30 pg/mL. Serum and CSF galactomannan levels were not elevated at any point during the clinical course.
View Article and Find Full Text PDFBackground: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) elimination requires high-quality, timely care. In countries with a low incidence of TB, such as Ireland, delayed diagnosis is common. This evaluation aimed to determine the factors that predict patient-related and health care provider-related delays in TB management and to establish how TB care cost is affected by care delays.
View Article and Find Full Text PDFBackground: Limited data regarding the perspectives of other observers (i.e. those who educate, employ or receive care from) of new graduates' preparedness to practice is available.
View Article and Find Full Text PDFUnlabelled: Ireland is a country with a low incidence of tuberculosis (TB) (5.6 cases per 100,000 population in 2019) that should be aiming for TB elimination (fewer than 1 case per million of population). To achieve TB elimination in low-incidence countries, programmatic latent tuberculosis infection (LTBI) management is important.
View Article and Find Full Text PDFArrhythmogenic cardiomyopathy is an inherited disease in which the normal myocardium is replaced by fibroadipose infiltrates. It is increasingly being recognized as a separate entity to arrhythmogenic right ventricular cardiomyopathy though is rarely diagnosed. We report a 47-year-old female who presented to her local emergency department with a history of presyncope while driving.
View Article and Find Full Text PDFAim Knowledge of latent tuberculosis infection (LTBI) screening and treatment practices are lacking in Ireland, where LTBI is not programmatically surveyed or managed. The aim of this research was to describe current clinical practice when screening and treating patients for LTBI in a tertiary referral centre in Ireland. Methods A 17-question survey relating to LTBI screening and management practices with both open-ended questions and close ended multiple-choice questions was created using SurveyMonkey.
View Article and Find Full Text PDFBackground: Early evidence of COVID-19-associated coagulopathy disseminated rapidly online during the first months of 2020, followed by clinical debate about how best to manage thrombotic risks in these patients. The rapid online spread of case reports was followed by online interim guidelines, discussions, and worldwide online searches for further information. The impact of global online search trends and online discussion on local approaches to coagulopathy in patients with COVID-19 has not been studied.
View Article and Find Full Text PDFObjectives: An estimated 1% of endovascular aneurysm repair (EVAR) devices become infected, carrying a high mortality rate. Surgical explantation is recommended and prognosis is guarded. This retrospective cohort analysis focuses on the role of outpatient parenteral antimicrobial therapy (OPAT) in the management of aortic vascular graft infections following EVAR.
View Article and Find Full Text PDFObjective: To compare the stiffness of constructs fixed with a type II external skeletal fixator (ESF) or a 3.5-mm locking compression plate (LCP) in axial compression and bending with a fracture gap model.
Study Design: Quasi-static four-point bending and axial compression tests.