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Abstract Background Delayed discharge is problematic. It is financially costly and can create barriers to delivering best patient care, by preventing return to usual functioning and delaying admissions of others in need. This systematic review aimed to collate existing evidence on delayed discharge in psychiatric inpatient settings and to develop understanding of factors and outcomes of delays in these services. Methods A search of relevant literature published between 2002 and 2022 was conducted on Pubmed, PsycInfo and Embase. Studies of any design, which published data on delayed discharge from psychiatric inpatient care in high income countries were included. Studies examining child and adolescent, general medical or forensic settings were excluded. A narrative synthesis method was utilised. Quality of research was appraised using the Mixed Methods Appraisal Tool (MMAT). Results Eighteen studies from England, Canada, Australia, Ireland, and Norway met the inclusion criteria. Six main reasons for delayed discharge were identified: (1) accommodation needs, (2) challenges securing community or rehabilitation support, (3) funding difficulties, (4) family/carer factors, (5) forensic considerations and (6) person being out of area. Some demographic and clinical factors were also found to relate to delays, such as having a diagnosis of schizophrenia or other psychotic disorder, cognitive impairment, and increased service input prior to admission. Being unemployed and socially isolated were also linked to delays. Only one study commented on consequences of delays for patients, finding they experienced feelings of lack of choice and control. Four studies examined consequences on services, identifying high financial costs. Conclusion Overall, the findings suggest there are multiple interlinked factors relevant in delayed discharge that should be considered in practice and policy. Suggestions for future research are discussed, including investigating delayed discharge in other high-income countries, examining delayed discharge from child and forensic psychiatric settings, and exploring consequences of delays on patients and staff. We suggest that future research be consistent in terms used to define delayed discharge, to enhance the clarity of the evidence base. Review registration number on PROSPERO 292515. Date of registration 9th December 2021.

Abstract Objective To determine the acceptability of a non‐invasive urinary biomarker test in place of conventional flexible cystoscopy for the diagnosis of bladder cancer in patients referred to a Rapid Access Haematuria Clinic (RAHC) with suspected urological malignancy. Patients and methods Patients attending a RAHC were recruited to a prospective observational study evaluating a novel urinary biomarker (URO17™) for the detection of bladder cancer and invited to complete a two‐part structured questionnaire. Questions related to demographics, attitudes towards conventional cystoscopy and the minimal acceptable sensitivity (MAS) at which a urinary biomarker would be considered an alternative to flexible cystoscopy both before and after undergoing the procedure. Results A total of 250 patients completed the survey; the majority of whom were referred with visible haematuria (75.2%). One hundred seventy‐one (68.4%) would be willing to accept a urinary biomarker in place of cystoscopy, with 59 (23.6%) expressing preference for the biomarker with a MAS as low as 85%. Conversely, 74 patients (29.6%) would not be willing to accept a urinary biomarker, regardless of its sensitivity. A significant number of patients reported a change in MAS after undergoing cystoscopy, with 80 (32.0%) and 16 (6.4%) increasing and decreasing the required value respectively (P = 0.001). The greatest increase was seen in the proportion of patients unwilling to accept a urinary biomarker regardless of its sensitivity, rising from 29.6% to 38.4%. Conclusions Although many patients attending a RAHC would be willing to accept a urinary biomarker test in place of conventional flexible cystoscopy for the detection of bladder cancer, effective patient, public and clinician engagement will be necessary at all stages of implementation if it is to become an established component of the diagnostic pathway.

Abstract Background There is limited research on what, when and how outcomes should be measured in psychological therapy trials in acute mental health inpatient wards. Objectives This study aimed to consider what outcomes service users think are important to measure. Methods This qualitative study explored the views of 14 participants, who had an inpatient admission within the last year, on outcomes of psychological therapies using semistructured interviews. Data were analysed using thematic analysis from a critical realist perspective with both inductive and deductive coding. Results The 126 outcomes that were important to participants were mapped onto an established taxonomy of outcomes across different health areas and the socioecological framework to consider the wider context and help summarise the outcomes. Most of the outcomes were mapped to the intrapersonal and interpersonal level. In addition to the outcome mapping, three themes were constructed from the qualitative data: (1) I am not a problem I am a person, (2) Feeling cared for and loved, (3) What does getting better look like. Conclusions Our results highlight the need for patient‐reported outcomes which are cocreated with service users, disseminating research and training on preventing dehumanising experiences, enhancing psychological safety and therapeutic relationships and improving access to psychological therapy. Patient or Public Contribution The wider People with Personal Experience Involvement Committee at the University of Bath were consulted which included a focus group during the early planning stages. We also collaborated with a person with personal experience, at every stage of the research. This included developing our research question and aims, protocol, participant documents (e.g., information and debrief forms), advertisement and recruitment strategy, interview topic guide, the codes, the final themes and quotes and reviewing the manuscript. People with lived experience of being admitted to an acute mental health inpatient ward participated in our study.

Marine mammals are vulnerable to a variety of acute and chronic anthropogenic stressors, potentially experiencing these in isolation, successively and/or simultaneously. Formal assessment of the likely impact(s) of the cumulative effects of multiple stressors on a defined population is carried out through a Cumulative Effects Assessment (CEA), which is a mandatory component of the Environmental Impact Assessment (EIA) process in many countries. However, for marine mammals, the information required to feed into CEA, such as thresholds for disturbance, frequency of multiple (and simultaneous) exposures, interactions between stressors, and individual variation in response, is extremely limited, though our understanding is slowly improving. The gaps in knowledge make it challenging to effectively quantify and subsequently assess the risk of individual and population consequences of multiple disturbances in the form of a CEA. To assess the current state of practice for assessing cumulative effects on marine mammals within UK waters, 93 CEAs were reviewed across eleven maritime industries. An objective framework of thirteen evaluative criteria was used to score each assessment on a scale of 13-52 (weak - strong). Scores varied significantly by industry. On average, the aquaculture industry produced the lowest scoring CEAs, whilst the large offshore windfarm industry (≥ 20 turbines) scored highest, according to the scoring criteria used. There was a significant increase in scores over the sample period (2009-2019), though this was mostly attributed to five industries (cable, large and small offshore wind farms, tidal and wave energy). There was inconsistency in the language used to define and describe cumulative effects and a lack of routinely applied methodology. We use the findings presented here, along with a wider review of the literature, to provide recommendations and discussion points aimed at supporting the standardisation and improvement of CEA practice. Although this research focused on how marine mammals were considered within UK CEAs, recommendations made are broadly applicable to assessments conducted for other receptors, countries and/or environments. Adoption of these proposals would help to ensure a more consistent approach, and would aid decision-makers and practitioners in mitigating any potential impacts, to ensure conservation objectives of marine mammal populations are not compromised.

Maintaining adherence to treatment for tuberculosis (TB) is essential if the disease is to be eliminated. As part of formative research to develop an intervention to improve adherence, we documented the lived experiences of adults receiving anti-TB treatment (ATT) in three UK cities and examined how personal, social, and structural circumstances interacted to impact on individuals’ adherence to treatment. Using a topic guide that explored social circumstances and experiences of TB care, we conducted in-depth interviews with 18 adults (six women) who were being or had been treated for TB (patients) and four adults (all women) who were caring for a friend, relative, or partner being treated for TB (caregivers). We analysed transcripts using an adapted framework method that classified factors affecting adherence as personal, social, structural, health systems, or treatment-related. Eleven of 18 patients were born outside the UK (in South, Central, and East Asia, and Eastern and Southern Africa); among the seven who were UK-born, four were Black, Asian, or Minority Ethnic and three were White British. TB and its treatment were often disruptive: in addition to debilitating symptoms and side effects of ATT, participants faced job insecurity, unstable housing, stigma, social isolation, worsening mental health, and damaged relationships. Those who had a strong support network, stable employment, a routine that could easily be adapted, a trusting relationship with their TB team, and clear understanding of the need for treatment reported finding it easier to adhere to ATT. Changes in circumstances sometimes had dramatic effects on an individual’s ability to take ATT; participants described how the impact of certain acute events (e.g., the onset of side effects or fatigue, episodes of stigmatisation, loss of income) were amplified by their timing or through their interaction with other elements of the individual’s life. We suggest that the dynamic and fluctuating nature of these factors necessitates comprehensive and regular review of needs and potential problems, conducted before and during ATT; this, coupled with supportive measures that consider (and seek to mitigate) the influence of social and structural factors, may help improve adherence.

An ever-increasing number of strong-field applications, such as ultrafast coherent control over matter and light, require driver light pulses that are both high power and spectrally tunable. The realization of such a source in the terahertz (THz) band has long been a formidable challenge. Here, we demonstrate, via experiment and theory, efficient production of terawatt (TW)-level THz pulses from high-intensity picosecond laser irradiation on a metal foil. It is shown that the THz spectrum can be manipulated effectively by tuning the laser pulse duration or target size. A general analytical framework for THz generation is developed, involving both the high-current electron emission and a time-varying electron sheath at the target rear, and the spectral tunability is found to stem from the change of the dominant THz generation mechanism. In addition to being an ultrabright source (brightness temperature of about 10^{21} K) for extreme THz science, the THz radiation presented here also enables a unique in situ laser-plasma diagnostic. Employing the THz radiation to quantify the escaping electrons and the transient sheath shows good agreement with experimental measurements.

Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P. Following rescreen and validation in a second cancer cell line, HCT116 colorectal carcinoma, a panel of 16 of the most robust hits were selected for further validation based on significance and the potential to be targeted by drug-like molecules. Using secondary assays for detection of senescence biomarkers p21, 53BP1 and senescence associated beta-galactosidase (SAβGal) in a panel of HCT116 cell lines carrying cancer-relevant mutations, we show that partial senescence phenotypes can be induced to varying degrees in a context dependent manner, even in the absence of p21 or p53 expression. However, proliferation arrest varied among genetic backgrounds with predominantly toxic effects in p21 null cells, while cells lacking PI3K mutation failed to arrest. Furthermore, we show that the oncogene ECT2 induces partial senescence phenotypes in all mutant backgrounds tested, demonstrating a dependence on activating KRASG13D for growth suppression and a complete senescence response. These results suggest a potential mechanism to target mutant KRAS signalling through ECT2 in cancers that are reliant on activating KRAS mutations and remain refractory to current treatments.

Rituximab is a CD20 monoclonal antibody commonly used in the treatment of haematological malignancies. It causes lymphopenia with subsequent compromised humoral immunity resulting in an increased risk of infection. A number of infections and viral reactivations have been described as complicating Rituximab therapy. We report an apparently unique case of echovirus 9 (an enterovirus) infection causing an acute hepatitis and significant morbidity in an adult patient on maintenance treatment of Rituximab for follicular lymphoma. We also describe potential missed opportunities to employ more robust screening for viral infections which may have prevented delays in the appropriate treatment and thus may have altered the patient’s clinical course. We also make suggestions for lowering the threshold of viral testing in similar patients in the future.

Wastewater is a by-product of numerous industrial processes that have been demonstrated to have adverse effects on human and natural health due to the pollutants it contains. The pollutants in these substances are organic or inorganic molecules and heavy metal ions that significantly harm the environment and human health. A variety of techniques have been devised for the removal of heavy metal ions from wastewater. The adsorption process has attracted significant attention due to its straightforward implementation, cost-effectiveness, and the environmentally friendly production of adsorbent materials using biocompatible substances. In this study, the removal of Cu 2+ ions from wastewater was conducted using chitosan pullulan, a biocompatible and biodegradable polymer. In addition to chitosan and pullulan, waste refractory materials from a furnace used in iron and steel production were added to these polymer materials to increase the adsorption capacity. The initial step involved grinding the waste refractory brick material. Subsequently, chitosan was dissolved in acetic acid. After that, the refractory material was suspended in this solution, facilitating the formation of hydrogel beads using a NaOH solution. The obtained hydrogels were coated with pullulan to produce polyelectrolyte gel. Pullulan was oxidized to 6-carboxypullulan by the TEMPO (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl) oxidation method and the negatively charged groups in its structure interacted with the positively charged groups in the chitosan structure to produce a complex gel. The chemical structure, morphological analysis, thermal analysis, and water release analysis of the produced waste refractory brick material added chitosan/oxidized pullulan complex gels were examined. The impact of the 6-carboxypullulan coating on the gels' properties was elucidated. Furthermore, the adsorption of Cu 2 ⁺ was conducted using solutions containing 100, 500, and 1000 ppm Cu 2 ⁺ ions. It has been observed that the material can clean water with over 98% efficiency, even in solutions that exceed the standards set for wastewater. The material's efficacy in cleaning solutions with concentrations above the standard for wastewater cleaning is evidence of its high performance. Furthermore, the kinetics and isotherm of the adsorption reaction were examined. The kinetics were determined to be consistent with the Pseudo Second Order (chemical reaction controlled) and aligned with the Langmuir and Freundlich Isotherm (mixed adsorption occurred on homogeneous and heterogeneous surfaces)., (© 2024. The Author(s).)

Objectives: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time., Materials and Methods: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels., Results: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels., Conclusions: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.