The MRE11-RAD50-NBS1 complex both starts and extends DNA end resection in mouse meiosis.

Nucleolytic resection of DNA ends is critical for homologous recombination, but its mechanism is not fully understood, particularly in mammalian meiosis. Here we examine roles of the conserved MRN complex (MRE11, RAD50, and NBS1) through genome-wide analysis of meiotic resection in mice with various MRN mutations, including several that cause chromosomal instability in humans. Meiotic DSBs form at elevated levels but remain unresected if is conditionally deleted, thus MRN is required for both resection initiation and regulation of DSB numbers.

Reflecting on the quality of a methodologically pluralist evaluation of a large-scale Indigenous health research collaboration in Australia.

Background: Indigenous communities worldwide lead calls for all evaluations of research, programmes and policies affecting their communities to reflect the values, priorities and perspectives of the Indigenous peoples and communities involved. Tools, such as the Quality Appraisal Tool (QAT), are available to assess research quality through an Indigenous cultural lens. Good evaluation requires that evaluation efforts be evaluated.

The malignant transformation of endometriosis: Is there a left lateral predisposition of ovarian clear cell and endometrioid carcinomas?

Introduction: Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis.

Producing knowledge together: a participatory approach to synthesising research across a large-scale collaboration in Aboriginal and Torres Strait Islander health.

Background: Despite that stakeholder participation in evidence synthesis could result in more useful outcomes, there are few examples of processes that actively involve them in synthesis work. Techniques are needed that engage diverse stakeholders as equal partners in knowledge co-production. The aims of this paper are to describe an innovative participatory process of synthesising a large body of academic research products and compare the findings of the participatory process against two traditional approaches to synthesis: a rapid review and a structured review.

Pharmacist-led medicines optimisation service in an inpatient mental health setting.

Medicines optimisation ensures that people get the best possible outcomes from their medicines. As those with severe mental illness (SMI) are frequently prescribed psychotropic medicines with potentially significant side-effects, poor adherence to treatment and physical morbidity are common. This results in suboptimal symptom control, physical health problems and negative health outcomes.

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study.

Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts).

Patients And Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab.

Establishing severe acute respiratory infection (SARI) surveillance in a sentinel hospital, Ireland, 2021 to 2022.

BackgroundIn 2020, due to the COVID-19 pandemic, the European Centre for Disease Prevention and Control (ECDC) accelerated development of European-level severe acute respiratory infection (SARI) surveillance.AimWe aimed to establish SARI surveillance in one Irish hospital as part of a European network E-SARI-NET.MethodsWe used routine emergency department records to identify cases in one adult acute hospital.

Supporting reorientation of health services in Indigenous Australian communities: the health promotion systems assessment tool.

Few tools and mechanisms exist to assist the reorientation of health services, especially in the Indigenous Australian health context; where improving health status and life expectancy is a priority. We developed a health promotion systems assessment tool (HPSAT) to provide health services with the information and support they need to drive health system change. Tool development occurred using a participatory, iterative approach that included a literature review, expert input by Indigenous and non-Indigenous stakeholders and annual group workshops in four Indigenous Australian primary health care (PHC) services.

Real world outcomes in cancer patients with COVID-19 infection: Northern Ireland experience.

Background: Cancer has been assumed to be associated with a high-risk of morbidity and mortality from COVID-19. Protective measures have incorporated modifications in cancer treatments. There are conflicting data about the impact of COVID-19 infection and outcomes in cancer patients.

The structure-selective endonucleases GEN1 and MUS81 mediate complementary functions in safeguarding the genome of proliferating B lymphocytes.

During the development of humoral immunity, activated B lymphocytes undergo vigorous proliferative, transcriptional, metabolic, and DNA remodeling activities; hence, their genomes are constantly exposed to an onslaught of genotoxic agents and processes. Branched DNA intermediates generated during replication and recombinational repair pose genomic threats if left unresolved and so, they must be eliminated by structure-selective endonucleases to preserve the integrity of these DNA transactions for the faithful duplication and propagation of genetic information. To investigate the role of two such enzymes, GEN1 and MUS81, in B cell biology, we established B-cell conditional knockout mouse models and found that deletion of GEN1 and MUS81 in early B-cell precursors abrogates the development and maturation of B-lineage cells while the loss of these enzymes in mature B cells inhibit the generation of robust germinal centers.

Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation.

Background: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting.

Restrictive interventions on a psychiatric admission ward before and after COVID-19.

Objectives: Restrictive interventions (seclusion, restraint and special observations) are used on psychiatric wards when there are no other means available to keep a patient or others safe. These measures can be traumatic, and the Mental Health Commission and the Health Service Executive are focused on minimising their use. We set out to determine whether, following a COVID related reduction in bed numbers on a high dependency psychiatric ward in St John of God Hospital in Dublin, there was a change in their incidence.

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer.

For most patients with salivary gland cancer, there are no effective standard systemic therapies. Although clinical trials of biomarker-led drug therapies have delivered significant recent advances, there remains a need to understand the clinical utility of genomic profiling of cancer as a means to match patients with recurrent or metastatic salivary gland cancer to clinical trial therapies. In total, 209 patients with salivary gland cancers were profiled with 24 gene (n = 209)) and >325 gene (n = 32) DNA-based next-generation sequencing panels.

Efficacy of an eConsult service to cure hepatitis C in primary care.

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system.

Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib.

Staff stress and burnout in a community adult mental health service.

Objectives: Burnout has been associated with medical errors and low levels should be considered an indicator of service quality. This study examined the level of personal, work and client-related burnout in medical, other clinical and non-clinical staff in an adult community mental health service.

Methods: An anonymous study-specific questionnaire was designed and circulated to all staff with an explanatory document.

Liquid biopsy in ovarian cancer: Catching the silent killer before it strikes.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in the western world. The majority of women presenting with the disease are asymptomatic and it has been dubbed the "silent killer". To date there is no effective minimally invasive method of stratifying those with the disease or screening for the disease in the general population.

The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma.

Objectives: Despite wide excision and post-operative irradiation, loco-regional and/or metastatic recurrence is a significant clinical problem in salivary adenoid cystic carcinoma (SACC). Reliable biomarkers are required to tailor post-treatment surveillance to patients at highest risk of recurrence. We sought to determine the utility of TP53 and PIK3CA mutations as prognostic biomarkers in SACC.

Check the effects: systematic assessment of antipsychotic side-effects in an inpatient cohort.

Background: Antipsychotics are associated with a range of side-effects that can influence patients' subjective well-being negatively resulting in poor adherence. In order to limit the negative consequences of side-effects, they should be regularly systematically assessed. The aim of this study was to systematically assess antipsychotic side-effects in an inpatient cohort using validated rating scales.

COVID-19 from the perspective of urban and rural general adult mental health services.

COVID-19 has presented society with one of the greatest challenges in living memory. Community Mental Health Teams (CMHTs)have needed to adapt quickly to a rapidly developing situation which has had a dramatic impact on society. In this piece, we describe some of the early challenges for CMHTs within two mental health services based in Dublin and Wicklow.

Changing prescribing patterns in an Irish community mental health service.

Objectives: Medication is an important component of the treatment of many mental illnesses. Very little information is available about the particular medications that are being prescribed by community mental health services and how this has changed over time. We set out to obtain details of psychiatric medications being prescribed by one Irish community mental health service.

Should all community mental health teams be sectorised?

Objectives: Sectorised catchment areas have characterised Irish mental health service delivery since the devolution of institutional care. Unlike other catchment areas, the Cluain Mhuire Community Mental Health Service (CMCMHS) never sectorised. With the development of Community Health Networks (CHNs) and Primary Care Centres, the CMCMHS has come under renewed pressure for structural change.