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Introduction As a result of improving survival rates, the adverse consequences of rectal cancer surgery are becoming increasingly recognised. Low anterior resection syndrome (LARS) is one such consequence and describes a constellation of bowel symptoms after rectal cancer surgery which includes urgency, faecal incontinence, stool clustering and incomplete evacuation. LARS has a significant adverse impact on quality of life (QoL) and symptoms are present in up to 75% of patients in the first year after surgery. Despite this, little is known about the natural history and there is poor evidence to support current treatment options.Methods and analysis The objectives of POLARiS are to explore the natural history of LARS and to evaluate the clinical and cost-effectiveness of transanal irrigation (TAI) or sacral neuromodulation (SNM) compared with optimised conservative management (OCM) for people with major LARS.POLARiS is a prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort design, with internal pilot phase, qualitative sub-study, process evaluation and economic evaluation. Approximately 1500 adult participants from UK hospitals and 500 from Australian hospitals who have undergone a high or low anterior resection for colorectal cancer in the last 10 years will be recruited into the cohort. Six-hundred participants from the UK and 200 participants from Australia, with major LARS symptoms, defined as a LARS score of ≥30, will be recruited to the randomised controlled trial (RCT) element. Participants entering the RCT will be randomised between OCM, TAI or SNM, all with equal allocation ratios.Cohort and RCT participants will be followed up for a 24-month period, completing a series of questionnaires measuring LARS symptoms and QoL, as well as clinical review for those in the RCT. A process evaluation, qualitative sub-study and economic evaluation will also be conducted.The primary outcome measure of the POLARiS cohort and RCT is the LARS score up to 24 months post-registration/randomisation. Analyses of the RCT will be conducted on an intention-to-treat basis. Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI versus OCM and SNM versus OCM. Secondary outcomes include health-related QoL, adverse events, treatment compliance and cost-effectiveness (up to 24 months post-registration/randomisation).Ethics and dissemination Ethical approval has been granted by Wales REC 4 (reference: 23/WA/0171) in the UK and Sydney Local Health District HREC (reference: 2023/ETH00749) in Australia. The results of this trial will be disseminated to participants on request and published on completion of the trial in a peer-reviewed journal and at international conferences.Trial registration number ISRCTN12834598; ACTRN12623001166662.

Abstract Background LIM (Lineage-11 (LIN-11), Insulin-1 (ISL-1), and Mechanotransduction-3 (MEC-3)) genes belong to a family that hold ubiquitous properties contributing to organ, seed, and pollen development as well as developmental and cellular responses to biotic and abiotic stresses. Lettuce (Lactuca sativa) is a highly consumed vegetable crop susceptible heat stress. High temperatures limit lettuce’s overall yield, quality and marketability. Lettuce LIM genes have not been identified and their role in response to high temperatures is not known. Aiming to identify potential new targets for thermoresilience, we searched for LIM genes in lettuce and compared them with orthologous of several dicotyledons and monocotyledons plant species. Results We identified fourteen lettuce LIM genes distributed into eight different subgroups using a genome-wide analysis strategy. Three belonging to DAR (DA means “large” in Chinese) class I, two DAR class II, one in the WLIM1, two in the WLIM2, one in the PLIM1, two in the PLIM2 class, one ßLIM and two δLIMs. No DAR-like were identified in any of the species analyzed including lettuce. Interestingly, unlike other gene families in lettuce which underwent large genome tandem duplications, LIM genes did not increase in number compared to other plant species. The response to heat stress induced a dynamic transcriptional response on LsLIM genes. All heat stress regimes, including night stress, day stress and day and night stress were largely responsible for changes in LIM transcriptional expression. Conclusions Our global analysis at the genome level provides a detailed identification of LIM genes in lettuce and other dicotyledonous and monocotyledonous plant species. Gene structure, physical and chemical properties as well as chromosomal location and Cis-regulatory element analysis together with our gene expression analysis under different temperature regimes identified LsWLIM1, LsWLIM2b, LsDAR3 and LsDAR5 as candidate genes that could be used by breeding programs aiming to produce lettuce varieties able to withstand high temperatures.

Abstract Over the past 20 years, despite significant advancements in pulmonary arterial hypertension (PAH) medical therapy, many patients require admission to the hospital and are at risk for in‐hospital cardiac arrest (IHCA). Prior data found poor survival in PAH patients after cardiac arrest. The purpose of this study was to explore post‐IHCA outcomes in PAH patients receiving advanced medical therapies. This is a single‐center retrospective study of PAH patients who underwent cardiopulmonary resuscitation for IHCA between July 2005 and May 2021. Patients were identified through an internal cardiac arrest database. Twenty six patients were included. Half of the cohort had idiopathic PAH, with 54% of patients on combination therapy, 27% on monotherapy, and 19% of patients on no therapy. Mean right atrial pressure, mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 13 ± 6 mmHg, 57 ± 13 mmHg, 2.0 ± 0.7 L/min/m2, and 14.5 ± 7.6 Wood units, respectively. Most common etiology of cardiac arrest was circulatory collapse. Initial arrest rhythm in all but one patient was pulseless electrical activity. Six patients (23%) achieved return of spontaneous circulation (ROSC) and one patient (4%) survived to hospital discharge. Rates of ROSC and survival to discharge after IHCA are poor in patients with PAH. Even patients with mild hemodynamics had low likelihood of survival. In patients who are lung transplant candidates, there should be early consideration of extracorporeal support before cardiac arrest.

Glacial ripping is a newly recognized process sequence in which subglacial erosion is triggered by groundwater overpressure. Investigations in gneiss terrain in lowland Sweden indicate that ripping involves three stages of (i) hydraulic jacking, (ii) rock disruption under subglacial traction, and (iii) glacial transport of rock blocks. Evidence for each stage includes, respectively, dilated fractures with sediment fills, disintegrated roches moutonnées, and boulder spreads. Here, we ask: can glacial ripping also occur in sedimentary rocks, and, if so, what are its effects? The case study area is in hard, thinly bedded, gently dipping Cambrian quartz-arenites at Loch Eriboll, NW Scotland. Field surveys reveal dilated, sediment filled, bedding-parallel fractures, open joints, and brecciated zones, interpreted as markers for pervasive, shallow penetration of the quartz-arenite by water at overpressure. Other features, including disintegrated rock surfaces, boulder spreads, and monomict rubble tills, indicate glacial disruption and short distance subglacial transport. The field results together with cosmogenic isotope ages indicate that glacial ripping operated with high impact close to the former ice margin at Loch Eriboll at 17.6–16.5 ka. Glacial ripping thus can operate effectively in bedded, hard sedimentary rocks, and the accompanying brecciation is significant—if not dominant—in till formation. Candidate markers for glacial ripping are identified in other sedimentary terrains in former glaciated areas of the Northern Hemisphere.