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Mrk 590 is a known changing-look active galactic nuclei (AGNs) which almost turned off in 2012, and then in 2017 partially re-ignited into a repeat flaring state, unusual for an AGN. Our Swift observations since 2013 allow us to characterize the accretion-generated emission and its reprocessing in the central engine of a changing-look AGN. The X-ray and UV variability amplitudes are higher than those typically observed in 'steady-state' AGN at similar moderate accretion rates; instead, the variability is similar to that of highly accreting AGN. The unusually strong X-ray to UV correlation suggests that the UV-emitting region is directly illuminated by X-ray outbursts. We find evidence that the X-rays are reprocessed by two UV components, with the dominant one at ∼3 d and a faint additional reprocessor at near-zero lag. However, we exclude a significant contribution from diffuse broad line region continuum, known to contribute for bonafide AGN. A near-zero lag is expected for a standard 'lamp-post' disc reprocessing model with a driving continuum source near the black hole. That the overall UV response is dominated by the ∼3-d lagged component suggests a complicated reprocessing geometry, with most of the UV continuum not produced in a compact disc, as also found in recent studies of NGC 5548 and NGC 4151. None the less, the observed flares display characteristic time-scales of ∼100 rest-frame days, consistent with the expected thermal time-scale in an accretion disc. [ABSTRACT FROM AUTHOR]

One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 in cancer cells with MTAP deletion. We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages. In vitro, PRMT5 inhibition induces DNA damage, cell cycle arrest, and aberrant alternative mRNA splicing in MTAP-deleted cells. In human cell line and patient-derived xenograft models, AMG 193 induces robust antitumor activity and is well tolerated with no impact on normal hematopoietic cell lineages. AMG 193 synergizes with chemotherapies or the KRAS G12C inhibitor sotorasib in vitro, and combination treatment in vivo significantly inhibits tumor growth. AMG 193 is demonstrating promising clinical activity, including confirmed partial responses in patients with MTAP-deleted solid tumors from an ongoing phase 1/2 study.

Lay Abstract: Selective attention to auditory input is reflected in the brain by an electric amplitude called the P3b amplitude, which is measured using electroencephalography. Previous research has shown that children and adolescents with autism have an attenuated P3b amplitude when they have to attend specific sounds while ignoring other sounds. However, it is unknown whether a reduced P3b amplitude in autistic children and adolescents is associated with their autism features, daily functioning and/or cognitive functions. This study aimed to examine these questions. Therefore, we assessed selective attention to auditory input in 57 children with autism aged 7-14 years and 57 neurotypically developing controls while measuring their brain activity with electroencephalography. Participants further underwent cognitive assessment, and parents reported on autistic traits and daily functioning. As expected, children with autism had lower P3b amplitude compared to their neurotypical peers. Importantly, an attenuated P3b amplitude was associated with more parent-reported social-communication problems and difficulties with daily functioning. Children with autism further had reduced processing speed of visual input, which also was coupled to a lower P3b amplitude. In conclusion, we found attenuated P3b amplitude in children with autism performing an auditory selective attention task, which was related to difficulties with processing visual input and allocating attentional resources critical for social and daily functioning. The results suggest that autistic children are more vulnerable to being disturbed when the environment is filled with conflicting sensory input., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Parent-child informant discrepancies on psychopathology provide important knowledge on the parent-child relationship and the child's mental health, but mechanisms underlying parent-child informant discrepancies are largely unknown. Therefore, we investigated the relationship between attachment problems and mentalizing capacity and parent-child informant discrepancies on borderline personality disorder (BPD) severity, internalizing, and externalizing pathology in a clinical sample of 91 adolescent girls with BPD and their parents. Results showed that more attachment problems to parents and peers were related to adolescents reporting more severe BPD than parents. Adolescents who described more internalizing symptoms relative to parents, reported more parental attachment problems, but enhanced peer attachment, suggesting those adolescents who do not feel recognized by their parents might turn to their friends. When parents rated adolescents higher on externalizing behaviors, the adolescent reported more attachment problems to parents and lower mentalizing capacity, indicating that this sub-group of adolescents may reflect less about how their behavior affects others., (© 2024. The Author(s).)

Purpose: The purpose of the study was to investigate the fit of a two-piece pouching system with a concave-shaped skin barrier on people with an outward peristomal body profile and its effect on leakage, wear time, and quality of life (QoL) related to using an ostomy product., Design: Randomized, controlled, open-label, cross-over trial., Subjects and Settings: The sample comprised 53 subjects with outward peristomal body profiles and problems with leakage of ostomy effluent from their pouching system. Participants were randomized to the concave two-piece pouching system or a comparator (two-piece pouching system with a flat skin barrier) for 3 weeks. Subjects were then crossed over to the opposite skin barrier for an additional 3 weeks. The study was conducted in Denmark, Norway, Germany, and the Netherlands; data were collected in multiple ambulatory clinics or during home visits., Methods: The primary end point was the ability of the skin barrier to fit body contours; secondary outcomes were leakage of effluent from the pouching system, wear time, and QoL related to using an ostomy product via the validated Ostomy-Q questionnaire. Primary comparisons between concave and comparator pouching systems were evaluated using proportional odds models and mixed models taking test period into account., Results: Analysis included randomized subjects who had been exposed to at least one product and with information on at least one end point (full-analysis-set, n = 52). The concave pouching system provided a better fit to body contours than the comparator (P< .001) and reduced the degree of leakage underneath the skin barrier (LS mean difference = -1.84, 95% CI -3.31 to -0.37; P = .016). Participants experienced fewer episodes of leakage outside the skin barrier when using concave versus comparator pouching system (13.0% vs. 26.7%, respectively). Participants reported significant improvements in QoL (LS mean difference = 14.3; 95% CI 9.4 to 19.2; P < .001). No significant difference in wear time between skin barrier shapes was reported., Conclusions: Study findings indicate that a pouching system with a concave skin barrier achieved a better body fit on people with an outward peristomal body profile and resulted in fewer leakage incidents and higher QoL compared to using a pouching system with a flat skin barrier., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Wound, Ostomy, and Continence Nurses Society.)

In postweaning calves, it is a challenge to maintain the plasma vitamin E level at or above the recommended level (3 µg/mL), which is linked to a good immune response. It has been unclear until now why the provision of solid feed with concentrations below 200 mg/kg feed of vitamin E is ineffective in maintaining the plasma vitamin E level of calves above the recommended plasma level postweaning. The present study was conducted to investigate if a high fat to vitamin E ratio in the concentrate could protect and improve the delivery of the natural form of vitamin E (RRR-α-tocopherol) to calves postweaning. Thirty calves were included in the experiment from 2 weeks preweaning until 2 weeks postweaning (Weeks -2, -1, 0 [weaning], 1, and 2 relative to weaning) and fed one of three concentrates in which lecithin mixture provided the fat supplement: control (77 mg/kg of vitamin E and 4.9% DM of crude fat; CONT), medium level of vitamin E supplemented (147 mg/kg of vitamin E and 7.7% DM of crude fat; MedVE) or high level of vitamin E supplemented (238 mg/kg of vitamin E and 12.4% DM of fat; HiVE). Thus, there was a comparable ratio of fat to vitamin E (520-630) in the three concentrates. During the 2 weeks postweaning, final body weight (92 ± 2 kg), average daily gain (917 ± 51 g/day) and concentrate intake (2.2 ± 0.09 kg/day; mean of treatment ± standard error) were unaffected by treatment and the interaction between treatment and week. There was an interaction between treatment and week for vitamin E intake pre- (p < 0.001) and postweaning (p < 0.001). There was an interaction between treatment and week (p < 0.001) for plasma vitamin E level postweaning, and it was 2.5, 3.1, and 3.8 µg/mL in CONT, MedVE, and HiVE, respectively, at Week 1 postweaning. In addition, plasma vitamin E levels at Week 2 postweaning were 2.6, 3.6 and 4.8 µg/mL in CONT, MidVE and HiVE respectively. The results show that 147 mg/kg of lecithin-protected vitamin E in the concentrate is needed to secure a plasma vitamin E level well above the recommended level. In addition, lecithin-protected vitamin E elevated the plasma level of triglycerides and nonesterified fatty acids., (© 2024 The Authors. Journal of Animal Physiology and Animal Nutrition published by Wiley‐VCH GmbH.)

Increased schizotypal traits have previously been associated with atypical semantic cognition in community samples. However, no study has yet examined whether adults diagnosed with schizotypal personality disorder (SPD) display atypical semantic fluency and memory. We hypothesized that 24 adults diagnosed with SPD would name more idiosyncratic words on the semantic fluency task and show decreased semantic recall for animal and fruit category words compared with 29 participants with borderline personality disorder (BPD) and a community sample of 96 age-matched controls. We examined whether atypical semantic cognition was specifically associated with disorganized and eccentric speech and thinking, or more broadly with pathological personality traits and personality functioning. Our main hypothesis was confirmed, as the SPD participants named more idiosyncratic words and recalled fewer semantically related words compared with controls. Surprisingly, participants with BPD likewise named more atypical words compared with controls. More idiosyncratic semantic fluency was associated with more eccentric speech and thinking. Increased idiosyncratic semantic fluency and reduced semantic recall were both coupled to increased detachment and lowered personality functioning, while reduced semantic recall further was related to increased interpersonal problems. Our findings suggest that persons with SPD, and to a lesser degree BPD, show atypical semantic cognition, which is associated with eccentric speech and thinking, and more broadly with impaired personality function, social withdrawal, and emotional flatness. The idiosyncratic semantic cognition may worsen difficulties with social reciprocity seen in SPD and BPD.

Background: Qualitative sensory testing (QualST) is a simple, standardised, chairside method for evaluating somatosensory function; however, testing focuses on detection of cold, touch and pain with no recognition of perceptions of pleasantness and unpleasantness., Objectives: The study aimed to utilise the stimuli in QualST, with the addition of a soft brush, to investigate stimulus-evoked perceptions of pleasantness and unpleasantness on the facial skin and if any side-to-side differences. Additional aims were to determine the inter- and intra-rater reliability using the modified QualST protocol and in the side-to-side differences., Methods: Thirty healthy adult female participants underwent three sessions of sensitivity testing as per the modified QualST protocol. Stimuli were applied bilaterally to the facial skin, and participants provided separate yes/no responses for presence of stimulus-evoked pleasantness, unpleasantness and/or differences between sides., Results: The stimuli were able to evoke sensations of pleasantness and unpleasantness with little differences in responses between the Q-tip and goat hair brush for the perceptions. Side-to-side differences in evoked perceptions were observed and greatest, when evaluating for pinprick-evoked unpleasantness (range between sessions = 18-19 participants). Acceptable percentage (≥90%) and excellent Cohen's Kappa (≥0.762) inter- and intra-rater agreements were identified for one or more positive responses for each stimulus modality and the targeted perception., Conclusion: The modified QualST protocol provides a simple, reproducible method for the investigation of perceptions of pleasantness and unpleasantness, with readily accessible instrumentation to dental professionals and allowing for a more holistic approach in somatosensory testing., (© 2024 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

It is unclear whether children with autism spectrum disorders have atypical semantic fluency and lower memory for the semantics of words. Therefore, we examined semantic typicality, fluency and recall for the categories of fruits and animals in 60 children with autism aged 7-15 years (boys: 48/girls: 12) compared to 60 typically developing controls. Relative to controls, the autism group had reduced animal fluency, fruit typicality and recall for fruits. Notably, these measures were associated with more autistic-like symptoms and/or lower adaptive functioning across the autism and control groups. In conclusion, atypical semantics of fruits in the autism group may reflect development of idiosyncratic semantic networks while their lower semantic fluency and recall suggest impaired executive language functions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Summary: This case report describes a rare presentation of ectopic Cushing's syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy (68Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous., Learning Points: Medullary thyroid carcinoma may secrete CRH and cause ectopic CS. Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test. Plasma CRH measurements can be useful in selected cases.

Despite development of effective SARS-CoV-2 vaccines, a sub-group of vaccine non-responders depends on therapeutic antibodies or small-molecule drugs in cases of severe disease. However, perpetual viral evolution has required continuous efficacy monitoring as well as exploration of new therapeutic antibodies, to circumvent resistance mutations arising in the viral population. We performed SARS-CoV-2-specific B cell sorting and subsequent single-cell sequencing on material from 15 SARS-CoV-2 convalescent participants. Through screening of 455 monoclonal antibodies for SARS-CoV-2 variant binding and virus neutralization, we identified a cluster of activated B cells highly enriched for SARS-CoV-2 neutralizing antibodies. Epitope binning and Cryo-EM structure analysis identified the majority of neutralizing antibodies having epitopes overlapping with the ACE2 receptor binding motif (class 1 binders). Extensive functional antibody characterization identified two potent neutralizing antibodies, one retaining SARS-CoV-1 neutralizing capability, while both bind major common variants of concern and display prophylactic efficacy in vivo. The transcriptomic signature of activated B cells harboring broadly binding neutralizing antibodies with therapeutic potential identified here, may be a guide in future efforts of rapid therapeutic antibody discovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lende et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Stoma surgery is a life-changing event and patients must subsequently make significant adjustments to their lives., Aim: The study set out to understand the level of interaction between patients and stoma care nurses (SCNs) in relation to preparing patients for stoma surgery and in adjustment to life with a stoma., Methods: Retrospective, self-reported questionnaires for patients and SCNs., Findings: Most patients (98%) with planned stoma surgery had pre-operative consultations with health professionals in contrast to 36% of patients with unplanned surgery, who did not. One third of patients with unplanned surgery did not feel prepared for life with a stoma based on the information provided during their hospital stay. Two thirds of the nurses reported having sufficient time to prepare patients for stoma surgery and to life with a stoma., Conclusion: SCNs are key in preparing patients for surgery and for life with a stoma. Variations in care were experienced by patients having planned versus unplanned surgeries., Competing Interests: Declaration of interest: NR has previously received honoraria for being part of the Coloplast Ostomy Forum. JLG, MV, ASH and HK are all full-time employees at Coloplast A/S

The detection of starlight from the host galaxies of quasars during the reionization epoch (z > 6) has been elusive, even with deep Hubble Space Telescope observations 1,2 . The current highest redshift quasar host detected 3 , at z = 4.5, required the magnifying effect of a foreground lensing galaxy. Low-luminosity quasars 4-6 from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) 7 mitigate the challenge of detecting their underlying, previously undetected host galaxies. Here we report rest-frame optical images and spectroscopy of two HSC-SSP quasars at z > 6 with the JWST. Using near-infrared camera imaging at 3.6 and 1.5 μm and subtracting the light from the unresolved quasars, we find that the host galaxies are massive (stellar masses of 13 × and 3.4 × 10 10  M ☉ , respectively), compact and disc-like. Near-infrared spectroscopy at medium resolution shows stellar absorption lines in the more massive quasar, confirming the detection of the host. Velocity-broadened gas in the vicinity of these quasars enables measurements of their black hole masses (1.4 × 10 9 and 2.0 × 10 8  M ☉ , respectively). Their location in the black hole mass-stellar mass plane is consistent with the distribution at low redshift, suggesting that the relation between black holes and their host galaxies was already in place less than a billion years after the Big Bang., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Polyether ionophores are complex natural products known to transport various cations across biological membranes. While several members of this family are used in agriculture (e.g., as anti-coccidiostats) and have potent antibacterial activity, they are not currently being pursued as antibiotics for human use. Polyether ionophores are typically grouped as having similar functions, despite the fact that they significantly differ in structure; for this reason, how their structure and activity are related remains unclear. To determine whether certain members of the family constitute particularly interesting springboards for in-depth investigations and future synthetic optimization, we conducted a systematic comparative study of eight different polyether ionophores for their potential as antibiotics. This includes clinical isolates from bloodstream infections and studies of the compounds' effects on bacterial biofilms and persister cells. We uncover distinct differences within the compound class and identify the compounds lasalocid, calcimycin, and nanchangmycin as having particularly interesting activity profiles for further development. IMPORTANCE Polyether ionophores are complex natural products used in agriculture as anti-coccidiostats in poultry and as growth promoters in cattle, although their precise mechanism is not understood. They are widely regarded as antimicrobials against Gram-positive bacteria and protozoa, but fear of toxicity has so far prevented their use in humans. We show that ionophores generally have very different effects on Staphylococcus aureus, both in standard assays and in more complex systems such as bacterial biofilms and persister cell populations. This will allow us to focus on the most interesting compounds for future in-depth investigations and synthetic optimizations., Competing Interests: The authors declare no conflict of interest.

The International Classification of Diseases 11th Revision (ICD-11) introduces fundamentally new diagnostic descriptions for personality disorder and autism spectrum disorder. Instead of the traditional categorical taxonomies, both personality disorder and autism spectrum disorder are described as being on a continuum. Accumulating research has pointed out that, in some cases, adolescents with autism spectrum disorder are at risk of being confused with having a personality disorder, which particularly applies to female adolescents. Case reports describe how adult autistic women struggled with social and identity roles as children and adolescents, using compensatory strategies such as social imitation and other types of camouflaging. Furthermore, some adolescents with autism display emotion dysregulation and self-injury. The ICD-11 recognizes that features of autism spectrum disorder may resemble features of personality disorder, but the two diagnoses have not yet been formally compared to one another. The present article therefore sought to outline and discuss the overlap and boundaries between the ICD-11 definitions of personality disorder and autism spectrum disorder and propose guiding principles that may assist practitioners in differential diagnosis with female adolescents. We specifically highlight how aspects of the self and interpersonal functioning along with emotional, cognitive, and behavioral manifestations may overlap across the two diagnoses. Restricted, repetitive, and inflexible patterns of behavior, interests, and activities are core features of autism spectrum disorder, which may be masked or less pronounced in female adolescents. Collecting a developmental history of the early presence or absence of autistic features is vital for a conclusive diagnosis, including features that are typically camouflaged in females. A number of future directions for research and clinical practice are proposed.

Background: More than 90% of people with an ostomy worry about leakage, with associated high rates of psychological morbidity., Aims: To assess the performance of a novel digital ostomy leakage notification system in subjects with faecal stomas who experience and worry about leakage., Method: A prospective, single-arm, pilot study (ClinicalTrials.gov: NCT04894084) with 25 subjects testing the product for 21 days. Subjects completed questionnaires at baseline and termination of study evaluating leakage episodes, leakage worry and quality of life (QoL)., Findings: Mean age was 56 years, 60% had an ileostomy, and 40% were females. Mean episodes of leakage outside the baseplate decreased significantly from 2.8 to 0.5 episodes after 21 days' use of the test product ( P <0.001), worry about leakage decreased significantly ( P <0.001) and QoL improved., Conclusion: The findings indicate strong improvements to emotional health with the test product, driven by reductions in leakage incidents outside baseplate and in users' worry about leakage.

Background GLP-1 (glucagon-like peptide-1) receptor agonists exert beneficial long-term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP-1 depends on GLP-1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP-1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1-hour infusion of either GLP-1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R 2 *), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP-1 infusion increased medullary perfusion (32±7%, P <0.001) and cortical perfusion (13±4%, P <0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (-5±2%, P =0.007), whereas cortical perfusion remained unchanged. R 2 * values increased by 3±2% ( P =0.025) in the medulla and 4±1% ( P =0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP-1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP-1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP-1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04337268.

Background: Leakage of stomal effluent outside the baseplate that soils clothes or bedsheets is a common problem for many people with a stoma and significantly impacts their quality of life., Aim: To understand behavioural changes for people experiencing faecal leakage outside the baseplate regarding the usage of pouching systems, supporting products and interactions with health professionals., Methods: Retrospective, self-reported questionnaire., Findings: Respondents on average experienced 1.1 incidents of faecal leakage outside the baseplate per fortnight. In periods with issues of leakage, 21% of respondents had been in contact with health professionals, 40% increased their use of pouching systems, 25% increased their use of existing supporting products, and 21% included additional supporting products to their change routine. The increased use of healthcare resources was estimated to cost £32.47 in the 3 weeks following a leakage incident., Conclusion: Incidents of leakage outside the baseplate lead to increased use of healthcare resources.

Although the generation of movements is a fundamental function of the nervous system, the underlying neural principles remain unclear. As flexor and extensor muscle activities alternate during rhythmic movements such as walking, it is often assumed that the responsible neural circuitry is similarly exhibiting alternating activity 1 . Here we present ensemble recordings of neurons in the lumbar spinal cord that indicate that, rather than alternating, the population is performing a low-dimensional 'rotation' in neural space, in which the neural activity is cycling through all phases continuously during the rhythmic behaviour. The radius of rotation correlates with the intended muscle force, and a perturbation of the low-dimensional trajectory can modify the motor behaviour. As existing models of spinal motor control do not offer an adequate explanation of rotation 1,2 , we propose a theory of neural generation of movements from which this and other unresolved issues, such as speed regulation, force control and multifunctionalism, are readily explained., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: People with a stoma are reported to experience leakage, which negatively impacts patient quality of life (QoL)., Aim: To assess the impact of leakage experienced by individuals with a stoma in the UK., Methods: Data were analysed from 301 patients living in the UK who completed a questionnaire concerning the physical and psychosocial impact of living with a stoma., Findings: Most respondents had had their stoma for more than 5 years. Nine out of 10 worried about leakage to varying degrees and half the respondents accepted that this was a worry they had to live with. Almost 70% experienced leakage onto clothes within the preceding year, and 28% experienced this monthly. Peristomal skin complications were experienced by 82% of respondents, the severity of which correlated with reductions in QoL., Conclusion: Despite the consequential negative impact of leakage on QoL, individuals are not seeking advice to resolve leakage-related issues, including from their specialist stoma care nurse.