Search

Multifunctional nature-based solutions (NBS) can help urban areas become more climate proof and adaptable and provide a range of societal goals. Alongside chronic impacts from climate change, the Covid-19 pandemic has illustrated the disruption that unexpected and acute shocks can bring to society. Measures such as NBS can help reduce the vulnerability of urban areas and increase resilience. Traditional infrastructure planning relies on strong business cases to demonstrate the economic value of a scheme. Numerous approaches assign economic value to the benefits from using NBS. However, this value is more than what can be accounted for by traditional finance methods, as there are many different perspectives on ‘value’. Decision making processes for selection of NBS measures require stronger integration of these value perspectives. This paper considers these perspectives in the business models that are being used in the decision processes regarding use and selection of NBS. Examples are drawn from case studies in the EU Begin project and also from the Living with Water partnership in the UK, which illustrate how value perspectives can be included in business cases for NBS, also signposting the need to account for potential future changes using scenario planning.

Purpose To explore symptoms and disease impacts of Crohn’s disease and to develop a new patient-reported outcomes (PRO) measure according to industry best practices. Methods A conceptual model of relevant symptoms experienced by patients with Crohn’s disease was developed following a literature review. Three rounds of combined qualitative semi-structured concept elicitation and cognitive debriefing interviews with 36 patients (≥ 16 years) with Crohn’s disease and 4 clinicians were conducted to further explore the most commonly reported and most bothersome symptoms to patients. Interview results were used to update the conceptual model as well as items and response options included in The Crohn’s Disease Diary, a new PRO measure. Results All patients (N = 36) reported abdominal pain, loose or liquid bowel movements, and high or increased frequency of bowel movements, with most reporting these symptoms spontaneously (100%, 92%, and 75%, respectively). All patients reported bowel movement urgency, but 61% reported this symptom only when probed. Most also reported that symptoms impacted activities of daily living, work/school, and emotional, social, and physical functioning (overall, 78%–100%; spontaneously, 79% – 92%). Data regarding core symptoms of Crohn’s disease from clinician concept elicitation interviews supported patient data. The 17-item Crohn’s Disease Diary assesses core symptoms and impacts of Crohn’s disease over 24 h, and extraintestinal manifestations over 7 days. The content validity of the diary was confirmed during cognitive debriefing interviews. Conclusion The Crohn’s Disease Diary is a new PRO measure for the assessment of Crohn’s disease symptoms and impacts, developed according to industry best practices.

Objective\ud Breaking bad news (BBN) in healthcare is common. Guidelines abound but little is documented in an African context. We wanted to describe Zulu speaking patients’ BBN experience and assess their opinions of internationally recommended techniques.\ud \ud Methods\ud BBN techniques were highlighted from the literature using systematic review methods. Semi-structured focus group interviews with Zulu speaking cancer patients were conducted. Data were analysed using Framework Analysis.\ud \ud Results\ud Language concordance was central – regardless of whether this necessitated a nurse acting as translator. While non-abandonment, empathy and maintenance of hope was valued by participants, an oft-expressed belief in positive outcomes accounted for mixed responses to phrases implying ambiguity. In contrast, “I wish” phrases were appreciated. Silence received mixed responses with a strong dislike for silence as a front for non-disclosure.\ud \ud Conclusion\ud Language-related concerns dictated the bulk of participants BBN perspectives. While cultural and linguistic differences exist, good communication skills, empathy and the maintenance of hope remain central.\ud \ud Practice Implications\ud BBN in a language in which the patient is fluent, whether mediated or not, should be the standard of care. Cultural and linguistic variance must be born in mind and clinicians should become familiar with the preferences of the communities they serve.

BACKGROUND ChatGPT-4 is the latest release of a novel AI chatbot able to answer freely formulated complex questions. It could become the new standard for healthcare professionals and patients to access medical information in the near future. Howerver, little is known about the quality of medical information provided by the AI. OBJECTIVE To analyse the quality of medical information provided by ChatGPT. METHODS Medical information provided by ChatGPT-4 on the five Hepato-Pancreatico-Biliary (HPB) conditions with the hightest global disease burden (GBD) was measured with the 36 items Ensuring Quality Information for Patients (EQIP) tool. Five guideline recommendations per analysed condition were rephrased as a question and input to ChatGPT, and agreement between the guidelines and the AI answer was measured by two authors independently. All queries were repeated three times to measure internal consistency of ChatGPT. RESULTS Five conditions were identified (gallstone disease, pancreatitis, liver cirrhosis, pancreatic cancer and hepatocellular carcinoma). The median (IQR) EQIP score across all conditions was 16 (14.5-18) from a total of 36. Divided by subsection, median (IQR) scores for content, identification and structure data were 10 (9.5-12.5), 1 (1-1), and 4 (4-5), respectively. Agreement between guideline recommendations and answers provided by ChatGPT was 60% (15/25). Inter-rater agreement as measured by Cohens Kappa was 0.83 (95% confidence interval: 0.61– 1.05), indicading a very high level of agreement. Internal consistency of provided answers by Chat GPT was complete (100%). CONCLUSIONS ChatGPT provides medical information of comparable quality to available static internet information. Altough currently of limited quality, larger language models could become the future standard for patients and healthcare professionals to gather medical information. CLINICALTRIAL None

Background Accurate symptom monitoring is vital when managing pediatric asthma, providing an opportunity to improve control and relieve associated burden. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) has been validated for asthma control assessment in children; however, there are concerns that response option images used in the C-ACT are not culturally universal and could be misinterpreted. This cross-sectional, qualitative study developed and evaluated alternative response option images using interviews with children with asthma aged 4–11 years (and their parents/caregivers) in the United States, Spain, Poland, and Argentina. Interviews were conducted in two stages (with expert input) to evaluate the appropriateness, understanding and qualitative equivalence of the alternative images (both on paper and electronically). This included comparing the new images with the original C-ACT response scale, to provide context for equivalence results. Results Alternative response option images included scale A (simple faces), scale B (circles of decreasing size), and scale C (squares of decreasing quantity). In Stage 1, most children logically ranked images using scales A, B and C (66.7%, 79.0% and 70.6%, respectively). However, some children ranked the images in scales B (26.7%) and C (58.3%) in reverse order. Slightly more children could interpret the images within the context of their asthma in scale B (68.4%) than A (55.6%) and C (47.5%). Based on Stage 1 results, experts recommended scales A (with slight modifications) and B be investigated further. In Stage 2, similar proportions of children logically ranked the images used in modified scales A (69.7%) and B (75.7%). However, a majority of children ranked the images in scale B in the reverse order (60.0%). Slightly more children were able to interpret the images in the context of their asthma using scale B (57.6%) than modified scale A (48.5%). Children and parents/caregivers preferred modified scale A over scale B (78.8% and 90.9%, respectively). Compared with the original C-ACT, most children selected the same response option on items using both scales, supporting equivalency. Following review of Stage 2 results, all five experts agreed modified scale A was the optimal response scale. Conclusions This study developed alternative response option images for use in the C-ACT and provides qualitative evidence of the equivalency of these response options to the originals. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00390-2., Plain English summary Accurate monitoring of the symptoms associated with pediatric asthma is important when managing the condition. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) is a questionnaire widely used to measure asthma severity in young children (aged 4–11 years). Each question answered by the child in the C-ACT has four possible answer choices. To help children answer, each choice is presented alongside an image of a male child’s face ranging from sad to happy. However, there are concerns that the images used are not culturally universal and could be misinterpreted—due to difficulties translating to electronic formats and a lack of differentiation between the images used. Through interviewing children with asthma, we aimed to address these concerns by developing and testing new images. Alternative image options developed included simpler faces, circles of decreasing size and squares of decreasing quantity. Children aged 4–11 years old were interviewed to test whether they understood the response scale using the new images and if they answered in the same way as with the original images. Interviews were conducted in two stages, with expert guidance at key stages. Results showed that children can interpret and understand the newly developed images and that they answer the questions the same as they would using the original images. These new images have the advantages of being culturally neutral and easier to implement on an electronic device. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00390-2.

Background: Evidence of effectiveness of the Interprofessional Education (IPE) in improving collaboration practice, patient and family satisfaction, and patient outcomes had been widely published. Most of developed countries, including United Kingdom, have implemented IPE in their healthcare curriculum, whereas some developing countries are starting the IPE initiative program. Purpose: This study aims to examine the challenges in implementing IPE. Methods : Primary studies to be included in this systematic review were searched from electronic databases such as MEDLINE (OVID) 1996, CINAHL, and ERIC (EBSCO). Hand searching through journal of inter-professional care was also conducted. The included studies were critically appraised using JBI QARI appraisal tool. The findings of the included studies were extracted using JBI finding extraction form and appraised based on the JBI level of credibility. The analysis of the study was presented in narrative form. Results : This review produced five qualitative studies using focus groups and interview methods. A total of 5 out of 88 papers met the inclusion criteria included in this systematic review. Three synthesis findings of the challenges in implementing IPE and possible solutions were identified in the literature: inter-professional relationship, IPE curriculum, and administration and resources. Conclusions : The evidence of implementing IPE in developing countries is limited. However, the challenges in implementing IPE in developing countries remain similar with those faced by developed countries. This can be guidance for developing countries to plan, initiate and implement IPE. Future studies about implementation of IPE in developing countries are highly recommended.

The connection between Netherton syndrome and overactivation of epidermal/dermal proteases particularly KLK5 has been well established. To treat sufferers of this severe condition we wished to develop a topical KLK5 inhibitor in order to normalise epidermal shedding and reduce the associated inflammation and itching. In this paper we describe structure-based optimisation of a series of brightly coloured weak KLK5 inhibitors into colourless, non-irritant molecules with good KLK5 activity and selectivity over a range of serine proteases.

Patient experience in healthcare has long been recognised in the UK and internationally as a crucial benchmark for assessing quality of care in healthcare settings. It is increasingly becoming part of a nurse's role to conduct, analyse and present the findings of patient satisfaction audits and research projects, and to implement changes to services based on the data collected. To undertake these audits and projects effectively, nurses require knowledge of how to use various data collection methods and research tools, determine their validity and reliability, and minimise bias. This article provides information about these areas, with the aim of assisting nurses in designing and implementing patient satisfaction audits and research projects in their clinical area, which can subsequently be used to improve patient experience.

Objectives To investigate midwifery students’ experiences of viewing childbirth on mainstream factual television and to explore implications for student career intentions and potential pedagogical uses of television excerpts in midwifery education. Design Twenty-two undergraduate midwifery students at one of two universities took place in focus groups between February and June 2019. Ethical approval was obtained at both sites. Thematic analysis was employed to generate key themes from the data. Setting Two UK universities based in the East Midlands and East Yorkshire regions of England. Participants Twenty-two midwifery students at any stage of their studies. Findings Researchers generated four key themes from the data a) Changed Perspectives on Televised Childbirth, b) Representations of Midwives and Social Implications, c) Representation of Childbirth and Social Implications and d) The Role of Televising Childbirth in Midwifery Education. Key conclusions Midwifery students often experience a change of perspective on birth on television as they acquire new knowledge and skills. They recognise the potential social implications of how childbirth and midwifery are represented on television. Pedagogical use of televised birth has potential benefits but needs further investigation in the context of midwifery education. Implications for practice Midwifery students are likely to begin their studies with pre-existing views and experiences around how birth is represented on mainstream factual television. They may need support to reflect on these to consider their expectations of the profession, to effectively support childbearing women and to potentially influence future production of media images of childbirth.

Portfolios are a frequently used tool for recording, cataloguing and presenting reflections for revalidation purposes, and are used by a number of healthcare professions. More recently, with the development of online resources, the webfolio has become more commonplace in midwifery undergraduate programmes. This article will review the literature in relation to portfolios and outline the key stages in the development and implementation of a webfolio in a midwifery undergraduate programme. The audit of compliance in students and sign off midwifery mentors for the first cohort who used the webfolio will be presented.

Many hand water pumps across Sub-Saharan Africa break down prematurely and remain out of service for significant periods of time. This issue has been well documented, with reports suggesting that between 20% and 65% of hand pumps in a number of African countries are broken. It has also been reported that broken hand pumps in this region have represented between $1.2 and $1.5 billion of ineffective investment over the last twenty years. Regular post-construction monitoring of remote water pumps can help address these problems. However, in many instances traditional monitoring programmes require regular site visits to remote locations, which can delay the implementation of repairs and place heavy time and resource demands on supervisory bodies. In response there has been an emerging interest in the use of mobile phone based technologies to monitor water pumps. The authors describe a new monitoring system, called MANTIS (Monitoring & ANalytics To Improve Service), which is intended to be a context-appropriate monitoring tool for hand pumps in developing regions. The paper introduces field trials of this system that have been conducted in Sierra Leone and The Gambia. The unit relays ‘near real time’ operational data from the water pump via an SMS (Short Message Service) server to an accessible on-line platform.

Background Contemporary higher education requires that all midwifery students have insight and understanding of global health practice and demonstrate intercultural sensitivity. However, the mobility models currently offered do not often fit the lives of large numbers of midwifery students. Objectives To investigate midwifery students' international physical mobility activities and factors that affect mobility; to determine midwifery students' learning needs and preferences for related e-learning packages. Design Multi-centre, descriptive quantitative survey. Settings Four European Higher Education Institutions based in the United Kingdom, Estonia, Italy and the Netherlands offering an undergraduate midwifery programme. Participants The sample included 205 midwifery students from Italy (n = 93), the Netherlands (n = 51); United Kingdom (n = 35) and Estonia (n = 26). Methods Data were collected in June–July 2020 through an online cross-sectional, bespoke questionnaire and analysed using summary statistical analysis. Results There is a high level of interest across a range of mobility opportunities, especially those of shorter duration. Barriers to mobility comprised finance, caring responsibilities, concerns about fitting mobility activities into the midwifery programme, negative impact on studies and language barriers. The most frequently identified facilitators of mobility included professional perspectives such as interest in other cultures and midwifery in other settings and an endorsement that mobility would add value to their development as a midwife. When engaging in virtual learning, the most preferred resources mentioned by the students were videos, video calls with peers, choice quiz and discussion forum. Conclusions The barriers identified require new approaches to enable all midwifery students to benefit from transnational learning. The survey findings provide insights into midwifery students' perspectives from which a new mobility model can be developed.

The nature of both pre-registration and post-registration midwifery education has changed dramatically over the last two decades, being firmly established within academia and the higher education domain. Notwithstanding the changes to midwifery education, midwives' perceptions of post-registration education, and continual professional development in particular, are mixed. The terms professional training and post-registration education are used interchangeably despite representing different goals. This article will explore professional perceptions of the post-registration educational journey, the concept of further academic development for individual midwives through postgraduate study and how engagement of midwives in postgraduate study could benefit both individual midwives and the collective profession of midwifery.

The increasing spread of urbanisation is a common phenomenon witnessed in most parts of the world due to the perceived benefits of urban living. A compounding issue is the growing shortage of safe and reliable water sources. Perennial water shortages are becoming a common feature in many parts of the world. It is important to recognise stormwater reuse as a key resource for securing adequate future water supplies based on the concept of ‘water fit for purpose’. These require careful prioritisation of vulnerabilities, identification of the areas requiring adaptation and provide certainty of outcomes. Given the increasing inevitability of climate change it should be viewed as an opportunity to take advantage of new opportunities which stormwater reuse presents. This study identified key barriers to stormwater reuse and the difficulties in removing them.

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design., Kynurenine-3-monooxygenase (KMO) is an emerging clinical target for treatment of neurodegenerative diseases and acute pancreatitis. Here, the authors report potent inhibitors that bind KMO in an unexpected conformation, offering structural and mechanistic insights for future drug discovery ventures.

PurposeThe purpose of this paper is to explore the characteristics of office cake (OC) consumption and the associated attitudes and behaviours among UK office workers to gain insight into the implications for workplace health.Design/methodology/approachA cross-sectional online questionnaire was completed by 940 respondents. Data were analysed using descriptive statistics and cross-tabulation withχ2tests for between-group difference.FindingsRespondents reported both positive social and negative health-related consequences of OC. OC influenced eating behaviour through increased salience and availability, and the effects of social influencing. Almost all (94.8 per cent) reported ideal OC frequency to be once/week or less. Gender and age significantly affected attitudes and behaviour.Research limitations/implicationsThe questionnaire was not validated so data accuracy could have been diminished or biased. Portion size was not examined and consumption data were self-reported which could have resulted in under-reporting. Only office workers were investigated therefore results may not be applicable to other workplaces.Practical implicationsOC appears to influence both the workplace eating environment and employee eating behaviour. It could therefore affect employee health and workplace health promotion programme efficacy. However the findings suggest that nudge-based initiatives could reduce OC consumption to make workplaces healthier while retaining social benefits.Originality/valueThe present study provides the first data on OC culture and insights on how to address it sensitively. It also highlights that sweet treats used for celebration and employee recognition should be considered a relevant part of workplace food provision alongside canteens and vending.

The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described. The biochemical robustness of the crystallographic surrogate and the suitability of the system for the study of small nonpeptidic fragments and lead-like molecules are demonstrated.

B-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing a BTB–POZ (BR-C, ttk, and bab for BTB; pox virus and zinc finger for POZ) domain, which is required for homodimerization and association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, and some types of lymphoma. Mice bearing disrupted BCL6 loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens. The corepressor binding groove in the BTB–POZ domain is a potential target for small compound-mediated therapy. Several inhibitors targeting this binding groove have been described, but these compounds have limited or absent in vivo activity. Biophysical studies of a novel compound, GSK137, showed an in vitro pIC50 of 8 and a cellular pIC50 of 7.3 for blocking binding of a peptide derived from the corepressor silencing mediator for retinoid or thyroid hormone receptors to the BCL6 BTB–POZ domain. The compound has good solubility (128 μg/ml) and permeability (86 nM/s). GSK137 caused little change in cell viability or proliferation in four BCL6-expressing B-cell lymphoma lines, although there was modest dose-dependent accumulation of G1 phase cells. Pharmacokinetic studies in mice showed a profile compatible with achieving good levels of target engagement. GSK137, administered orally, suppressed immunoglobulin G responses and reduced numbers of germinal centers and germinal center B cells following immunization of mice with the hapten trinitrophenol. Overall, we report a novel small-molecule BCL6 inhibitor with in vivo activity that inhibits the T-dependent antigen immune response.

Aims To investigate the pharmacodynamics, pharmacokinetics and safety/tolerability of blocking reuptake of bile acids using the inhibitor GSK2330672 (GSK672) in patients with type 2 diabetes (T2D). Methods Subjects with T2D taking metformin were enrolled in two studies in which they took metformin 850 mg twice daily for 2 weeks prior to and during the randomized treatment periods. In the first crossover study (n = 15), subjects received GSK672 45 mg, escalating to 90 mg, twice daily, or placebo for 7 days. The second parallel-group study (n = 75) investigated GSK672 10-90 mg twice daily, placebo or sitagliptin for 14 days. Results In both studies, GSK672 reduced circulating bile acids and increased serum 7-α-hydroxy-4-cholesten-3-one (C4), an intermediate in the hepatic synthesis of bile acids. Compared with placebo, in the parallel-group study 90 mg GSK672 twice daily reduced fasting plasma glucose [FPG; -1.21 mmol/l; 95% confidence interval (CI) -2.14, -0.28] and weighted-mean glucose area under the curve (AUC)0-24 h (-1.33 mmol/l; 95% CI -2.30, -0.36), as well as fasting and weighted-mean insulin AUC0 -24 h . GSK672 also reduced cholesterol (LDL, non-HDL and total cholesterol) and apolipoprotein B concentrations; the maximum LDL cholesterol reduction was ∼40%. There was no change in HDL cholesterol but there was a trend towards increased fasting triglyceride levels in the GSK672 groups compared with placebo. In both studies, the most common adverse events associated with GSK672 were gastrointestinal, mostly diarrhoea (22-100%), which appeared to be independent of dose. Conclusions In subjects with T2D on metformin, GSK672 improved glucose and lipids, but there was a high incidence of gastrointestinal adverse events.

Netherton syndrome (NS) is a rare and debilitating severe autosomal recessive genetic skin disease with high mortality rates particularly in neonates. NS is caused by loss-of-function SPINK5 mutations leading to unregulated kallikrein 5 (KLK5) and kallikrein 7 (KLK7) activity. Furthermore, KLK5 inhibition has been proposed as a potential therapeutic treatment for NS. Identification of potent and selective KLK5 inhibitors would enable further exploration of the disease biology and could ultimately lead to a treatment for NS. This publication describes how fragmentation of known trypsin-like serine protease (TLSP) inhibitors resulted in the identification of a series of phenolic amidine-based KLK5 inhibitors 1. X-ray crystallography was used to find alternatives to the phenol interaction leading to identification of carbonyl analogues such as lactam 13 and benzimidazole 15. These reversible inhibitors, with selectivity over KLK1 (10-100 fold), provided novel starting points for the guided growth towards suitable tool molecules for the exploration of KLK5 biology.

Urban drainage has developed from an engineering discipline, concerned principally with public health and safety outcomes, into a multifaceted vision linking drainage with environmental and wider social and economic imperatives to deliver multifunctional outcomes. UK attention is too often focused on surface water as ‘a problem’, despite international progress and initiatives showing that an ‘opportunity-centred’ approach needs to be taken. Sustainable drainage systems, or ‘Suds’, can, when they are part of an integrated approach to water management, cost-effectively provide many benefits beyond management of water quality and quantity. New tools are available that can design Suds for maximum value to society but this requires greater collaboration across disciplines to seize all of the opportunities available. This paper introduces those tools and a roadmap for their use, including guidance, design objectives and criteria for maximising benefits. These new supporting tools and guidance can help to provide a business case for greater use of Suds in future.

A series of potent, competitive and highly selective kynurenine monooxygenase inhibitors have been discovered via a substrate-based approach for the treatment of acute pancreatitis. The lead compound demonstrated good cellular potency and clear pharmacodynamic activity in vivo.