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This qualitative study aims to explore how a university-level School of Marketing integrates the Sustainable Development Goals (SDGs) into curriculum, using Bloom's Taxonomy, and to develop a reflective process that could be applied within tertiary education, more broadly. The research investigates the depth of SDG integration, with marketing subject coordinators mapping the Goals within their teachings across Bloom's dimensions, then identifying and reflecting on how they are embedded. The reflective process has revealed that some subjects are directly mapped to SDGs, for example where students are required to work on an assessment task which relates to a specific Global Goal. The results also show that other subjects are indirectly mapped, such as where subject coordinators discuss topics linked to Goals or Targets but do not explicitly state this content is SDG-related. To effectively implement SDGs within teaching and learning practice, marketing subjects require an evaluation method to identify gaps and opportunities. Therefore, this reflective process enabled subject coordinators to recognize gaps in their own SDG knowledge and teaching, a process through which future marketing subject curriculum modifications can be developed, with possible applications in other disciplines.

Abstract The brain must maintain a stable world model while rapidly adapting to the environment, but the underlying mechanisms are not known. Here, we posit that cortico-cerebellar loops play a key role in this process. We introduce a computational model of cerebellar networks that learn to drive cortical networks with task-outcome predictions. First, using sensorimotor tasks, we show that cerebellar feedback in the presence of stable cortical networks is sufficient for rapid task acquisition and switching. Next, we demonstrate that, when trained in working memory tasks, the cerebellum can also underlie the maintenance of cognitive-specific dynamics in the cortex, explaining a range of optogenetic and behavioural observations. Finally, using our model, we introduce a systems consolidation theory in which task information is gradually transferred from the cerebellum to the cortex. In summary, our findings suggest that cortico-cerebellar loops are an important component of task acquisition, switching, and consolidation in the brain.

Abstract Background The path of a complaint and patient satisfaction with complaint resolution is often dependent on the responses of healthcare professionals (HCPs). It is therefore important to understand the influences shaping HCP behaviour. This systematic review aimed to (1) identify the key actors, behaviours and factors influencing HCPs’ responses to complaints, and (2) apply behavioural science frameworks to classify these influences and provide recommendations for more effective complaints handling behaviours. Methods A systematic literature review of UK published and unpublished (so-called grey literature) studies was conducted (PROSPERO registration: CRD42022301980). Five electronic databases [Scopus, MEDLINE/Ovid, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL) and Health Management Information Consortium (HMIC)] were searched up to September 2021. Eligibility criteria included studies reporting primary data, conducted in secondary and tertiary care, written in English and published between 2001 and 2021 (studies from primary care, mental health, forensic, paediatric or dental care services were excluded). Extracted data included study characteristics, participant quotations from qualitative studies, results from questionnaire and survey studies, case studies reported in commentaries and descriptions, and summaries of results from reports. Data were synthesized narratively using inductive thematic analysis, followed by deductive mapping to the Theoretical Domains Framework (TDF). Results In all, 22 articles and three reports met the inclusion criteria. A total of 8 actors, 22 behaviours and 24 influences on behaviour were found. Key factors influencing effective handling of complaints included HCPs’ knowledge of procedures, communication skills and training, available time and resources, inherent contradictions within the role, role authority, HCPs’ beliefs about their ability to handle complaints, beliefs about the value of complaints, managerial and peer support and organizational culture and emotions. Themes mapped onto nine TDF domains: knowledge, skills, environmental context and resources, social/professional role and identity, social influences, beliefs about capability, intentions and beliefs about consequences and emotions. Recommendations were generated using the Behaviour Change Wheel approach. Conclusions Through the application of behavioural science, we identified a wide range of individual, social/organizational and environmental influences on complaints handling. Our behavioural analysis informed recommendations for future intervention strategies, with particular emphasis on reframing and building on the positive aspects of complaints as an underutilized source of feedback at an individual and organizational level.

ABSTRACT Background Patient complaints in healthcare settings can provide feedback for monitoring and improving healthcare services. Behavioural responses to complaints (e.g., talking or apologising to a patient) can influence the trajectory of a complaint for instance, whether a complaint is escalated or not. We aimed to explore healthcare professional (HCP) and service user (patient and carer) views on complaints' management and the perceived factors influencing responses to complaints within a healthcare setting by applying behavioural frameworks. Method A qualitative study was conducted using online or phone‐based interviews with eleven HCPs and seven patients or carers. All participants (N = 18) had experience responding to or submitting a formal complaint in secondary and tertiary public healthcare settings in the United Kingdom. The interviews were structured using the Capability‐Opportunity‐Motivation‐Behaviour (COM‐B) Model. We analysed the transcripts using inductive thematic analysis. Then, themes were deductively mapped onto the COM‐B Model and the more granular Theoretical Domains Framework (TDF). Results Ten themes were generated from the analysis representing the influences on HCPs' responses to complaints from HCP and patient/carer perspectives. This included (with TDF/COM‐B in brackets): ‘Knowledge of complaint procedure’ (Knowledge/Capability), ‘Training and level of skill in complaints handling’ (Skills/Capability), ‘Regulation of emotions associated with complaints’ (Behavioural regulation/Capability), ‘Confidence in handling complaints’ (Beliefs about capabilities/Motivation), ‘Beliefs about the value of complaints’ (Beliefs about consequences/Motivation) and ‘Organisational culture regarding complaints’ (Social influences/Opportunity). Staff highlighted strong support systems and open discussions as part of positive organisational cultures regarding complaints (Social influences/Opportunity), and a lack of certainty around when to treat issues raised by patients as a formal complaint or informal feedback (Knowledge/Capability). Conclusion Our study findings highlight the importance of strong support systems and organisational openness to patient feedback. These findings can be used to design targeted interventions to support more effective responses and enhance patient‐centred approaches to complaints management in healthcare settings. Patient and Public Contribution Patient and public involvement (PPI) was integral in this research. The NIHR PRU in Behavioural and Social Sciences had a dedicated PPI strategy group consisting of six external representatives from the patient and public community (Newcastle University, 2024). These six PPI members actively participated in shaping the research by reviewing and providing feedback on all questionnaire items before the data collection. They were actively involved in supporting participant recruitment by advertising this study on their PPI platform, The VoiceR,1 and through their online social networks. During the analysis stages of the research, preliminary findings were discussed with the PPI group to support ‘sense checking’ and interpretation of the results.

Abstract Cerebellar computations are necessary for fine behavioural control and may rely on internal models for estimation of behaviourally relevant states. Here, we propose that the central cerebellar function is to estimate how states interact with each other, and to use these estimates to coordinates extra-cerebellar neuronal dynamics underpinning a range of interconnected behaviours. To support this claim, we describe a cerebellar model for state estimation that includes state interactions, and link this model with the neuronal architecture and dynamics observed empirically. This is formalised using the free energy principle, which provides a dual perspective on a system in terms of both the dynamics of its physical—in this case neuronal—states, and the inferential process they entail. As a demonstration of this proposal, we simulate cerebellar-dependent synchronisation of whisking and respiration, which are known to be tightly coupled in rodents, as well as limb and tail coordination during locomotion. In summary, we propose that the ubiquitous involvement of the cerebellum in behaviour arises from its central role in precisely coupling behavioural domains.

Positive schizotypy can uniquely predict the development of psychosis with suspiciousness/paranoia having emerged as a key risk factor, pointing to significant worth in reducing this aspect in individuals with high positive schizotypy. Reduced paranoia in the general population following brief online mindfulness training has been previously reported. This study investigated the feasibility of a 40-day online mindfulness-based intervention (MBI) (n = 12) in the individuals with high positive schizotypy characterized by high suspiciousness/paranoia and to estimate its effect on paranoia as compared with an active control condition using reflective journaling (n = 12). The outcome measures were self-reported trait and VR-induced state paranoia, completed at baseline, after 10 days and post-intervention. The feasibility criteria included retention, adherence, engagement, and acceptability. There was 100% retention, excellent adherence to content and engagement, with an average MBI session completion rate of 91%. Acceptability, indexed by a self-rated motivation to continue practice post-intervention, was also high. No MBI effect on trait paranoia was observed; however, the MBI group showed a reduction in the VR-induced state paranoia with a medium-to-large effect (d = 0.63). The findings support conducting larger-scale randomized controlled trials to evaluate the effects of online MBIs on reducing suspiciousness/paranoia to mitigate psychosis risk in individuals with high positive schizotypy.Clinical Trial Registration:https://www.isrctn.com/, identifier ISRCTN78697391.

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.

The treatment of chronic, non-healing wounds is one of the biggest challenges faced by healthcare providers (Irving, 2019), costing the NHS £5.3 billion per annum (Guest et al, 2015). PROMOGRAN™ Matrix and PROMOGRAN PRISMA™ Matrix have been shown to help stimulate healing and reduce the risk of a wound becoming hard-to-heal. A working group of key opinion leaders met in June 2019 to discuss the use of PROMOGRAN™ Matrix and PROMOGRAN PRISMA™ Matrix to kick-start the treatment of chronic wounds, and to develop a decision pathway for clinical practice to support clinicians. The group's recommendations on appropriate use are presented here. [ABSTRACT FROM AUTHOR]

Behavioral feedback is critical for learning, but it is often not available. Here, the authors introduce a deep learning model in which the cerebellum provides the cerebrum with feedback predictions, thereby facilitating learning, reducing dysmetria, and making several experimental predictions.

BackgroundMeta-dehumanisation and self-dehumanisation have been identified as potentially relevant phenomena for developing a deeper understanding of distress related to voice-hearing, particularly those experiencing voices as part of psychosis. Chadwick has previously argued that those with psychosis, including those who hear distressing voices, typically feel “dehumanised and set apart by their experiences of psychosis and trauma.” The present study explores the subjective experience of self-dehumanisation in people who experience distressing voices, which was selected as a useful starting point to inform future research focused on understanding dehumanisation in people with psychosis.MethodsQualitative data was obtained through twenty semi-structured interviews with self-identifying voice hearers and analysed using reflexive thematic analysis. This followed the recursive six phase procedure of Braun and Clarke, and this was conducted from a critical realist, contextualist position.ResultsReflexive thematic analysis of participant’s experiences produced a core theme, Dehumanisation as the End of Experiential Continua, and six subthemes: Extent of Distressing Sensory Fragmentation; Sense of Belonging with Other Humans; Integrity of Self as a Private, Coherent Entity; Sense of Worth as a Human Being; Strength of Personal Agency; and Trust in Own Credibility and Reliability. Two further themes, The Push and Pull of Dehumanising Forces and Reclaiming Life through Humanising Forces, were identified. Findings were presented to a panel of five experts by experience, all with lived experience of psychosis and service-use; all five strongly endorsed the themes as fitting with and expressing their own experiences of self-dehumanisation.ConclusionReflexive thematic analysis of voice hearers’ accounts identified self-dehumanisation as the endpoint where six experiential continua coalesce. Experiential movement along these continua was affected by a range of interpersonal, intrapersonal, and societal forces over time, including dehumanising attitudes of others and voice malevolence and omnipotence. Future research might examine if and how psychological therapies aimed at those experiencing distressing voices, such as people experiencing psychosis may address feelings of self-dehumanisation.

Abstract Psilocybin is a hallucinogenic compound that is showing promise in the ability to treat neurological conditions such as depression and post-traumatic stress disorder. There have been several investigations into the neural correlates of psilocybin administration using non-invasive methods, however, there has yet to be an invasive study of the mechanism of action in awake rodents. Using multi-unit extracellular recordings, we recorded local field potential and spiking activity from populations of neurons in the anterior cingulate cortex of awake mice during the administration of psilocybin (2 mg/kg). The power of low frequency bands in the local field potential was found to significantly decrease in response to psilocybin administration, whilst gamma band activity trended towards an increase. The population firing rate was found to increase overall, with just under half of individual neurons showing a significant increase. Psilocybin significantly decreased the level of phase modulation of cells with each neural frequency band except high-gamma oscillations, consistent with a desynchronization of cortical populations. Furthermore, bursting behavior was altered in a subset of cells, with both positive and negative changes in the rate of bursting. Neurons that increased their burst firing following psilocybin administration were highly likely to transition from a phase-modulated to a phase unmodulated state. Taken together, psilocybin reduces low frequency oscillatory power, increases overall firing rates and desynchronizes local neural activity. These findings are consistent with dissolution of the default mode network under psilocybin, and may be indicative of disruption of top-down processing in the acute psychedelic state.

Background Diabetic foot ulcers (DFUs) cause significant morbidity and mortality. Faster referral to specialist clinics is associated with a reduced risk of severe DFUs. The INTELLIN ® diabetes management platform is a novel mHealth application for the management of recently healed DFUs and other complications, promoting engagement and expediting self-referral. Methods To determine the acceptability, suitability, and usability of the INTELLIN ® platform, time until reulceration, site, ischemia, neuropathy, bacterial infection, and depth (SINBAD) score and incidence of self-referral for recurrence were assessed in patients from the Salford Royal NHS Foundation Trust. Patients and clinic staff also assessed platform usability. A Markov cost-utility model was used for the health economics and outcomes research analysis. Results 197 patients were assessed for eligibility and 15 entered the full analysis set (FAS). Through Week 52, 8/15 patients experienced recurrence, with a mean SINBAD score of 2.1 and mean duration of 2.6 days. Mean time to recurrence was 273.0 days (95% confidence interval 74.0, 484.0). No patients self-referred. Initial qualitative data showed high platform usability. The INTELLIN ® platform only required a relative reduction in recurrence of 5% versus standard of care (SoC) for an incremental cost effectiveness ratio of £20,000 per quality-adjusted life-year, suggesting potential for significant cost savings upon wider adoption. The barriers to enrollment encountered demonstrate the impact of socioeconomics on mHealth. Conclusions These results suggest that the INTELLIN ® platform is required to provide only a small reduction in recurrence compared to SoC to be a cost-effective strategy for prevention of recurrent DFUs.

We compared intention to receive the seasonal influenza vaccine with a prospective coronavirus (COVID-19) vaccine among undecided or COVID-19 vaccine hesitant individuals to better understand the underlying differences and similarities in factors associated with vaccine intention. We delivered a cross-sectional online survey in October–November 2020. We included psychological constructs and sociodemographic variables informed by theory. We conducted pairwise comparisons and multiple linear regression models to explore associations between vaccine intention and psychological constructs. We recruited 1,660 participants, where 47.6% responded that they would likely receive the influenza vaccine, 31.0% that they would probably not accept the vaccination and 21.4% were unsure. In relation to the prospective COVID-19 vaccine, 39.0% responded that they would likely receive the vaccination, 23.7% that they would probably not accept the vaccination and 37.3% were unsure. Unique factors positively associated with COVID-19 vaccine intention were: perceived knowledge sufficiency about vaccine safety, beliefs about vaccine safety, and living in an area of low deprivation. The only unique factor positively associated with influenza intention was past influenza behavior. The strongest common predictors positively associated with intention were: favorable vaccine attitudes, the anticipated regret they may feel following infection if they were not to receive a vaccine, and the expectation from family or friends to accept the vaccine. Despite overall similarities in those factors associated with vaccination intention, we identified unique influences on intention. This additional insight will help support the planning and tailoring of future immunizations programmes for the respective viruses.

Although there is much interest in the development of prosocial behaviour in young children, and many interventions that attempt to cultivate kindness in children, there is a paucity of research exploring children’s lived experiences of kindness and including their voices. In this study, children’s understanding of kindness is approached through qualitative interviews using puppets. Interviews were conducted with 33 children aged 5-6 years in 3 schools in the United Kingdom. Through thematic analysis, 4 themes were developed: (a) doing things for others, (b) relating with others, (c) rules and values, and (d) kindness affects us. These themes are examined in light of current thinking on prosocial and sociomoral development, and several key insights are highlighted, including types of prosocial behaviour, social connection, kindness-by-omission and defending, in-group bias, universal kindness versus personal safety, self-image, and a desire to improve the condition of society. These findings have implications for future research on prosocial development and for the design of kindness-based interventions, as well as providing an ecologically valid method of inquiry for use with young children.

Abstract Background The arrival of the novel coronavirus (SARS-CoV-2) has impacted the many aspects of modern life, especially, in the immediate term, the delivery of healthcare. Context This commentary examines the profession of podiatry and how it has adapted and responded to the emerging crisis. It focusses on but is not exclusive to the position in the United Kingdom (UK) and the edicts and direction from the UK Government. Podiatry roles during the pandemic It describes the role of podiatry in the pandemic and highlights the deployment of podiatry resources to fight the pandemic beyond traditional podiatric practice. It also looks at the shift from conventional consultation to digital solutions for managing patients in an effort to achieve the goals of maintenance of foot health whilst reducing the spread of the virus. The commentary summarises the emerging data related to a possible foot related presentation of the coronavirus. Conclusion The podiatry profession proved its flexibility and adaptability during the pandemic, to adjust rapidly to ensure that patients were able to access treatment to reduce risk of infection, ulceration and amputation. Dermatological presentations on the feet have been associated with Covid-19 in adolescents as is often the case in viral infections. CPD webinars to support clinicians and manage and prevent the spread of Covid-19 have been widely disseminated along with algorithms to ensure that patients that need treatment are being treated appropriately. Podiatrists have embraced remote technology to ensure that patients are correctly and safely triaged and, signposted and given appropriate self-care advice. MSK podiatrists have the ability to play an intrinsic role within the post discharge rehabilitation pathway.

Abstract Background Inpatient psychiatric care is a scarce and expensive resource in the National Health Service (NHS), with chronic bed shortages being partly driven by high re-admission rates. Brief inpatient talking therapies for psychosis could help reduce re-admission rates. The primary aim was to assess feasibility and acceptability of a novel, brief, mindfulness-based intervention for inpatients with psychosis. The secondary aim was to collect pilot outcome data on readmission rate, at 6 and 12 months (m) post discharge, and self-report symptom measures at 6 m. Methods The amBITION study (BrIef Talking therapIes ON wards) was a parallel group, feasibility randomised controlled trial (RCT). In addition to treatment as usual (TAU), eligible inpatients with psychotic symptoms were randomly allocated to receive either (Mindfulness-Based Crisis Intervention; MBCI) or a control intervention (Social Activity Therapy; SAT), for 1–5 sessions. Results Fifty participants were recruited (26 MBCI; 24 SAT); all received at least 1 therapy session (mean = 3). Follow-up rates were 98% at 6 m and 96% at 12 m for service use data extracted from clinical notes, and 86% for self-report measures. At 6 m follow-up, re-admission rates were similar across groups (MBCI = 6, SAT = 5; odds ratio = 1.20, 95% CI: 0.312–4.61). At 12 m follow-up, re-admissions were lower in the MBCI group (MBCI = 7, SAT = 11; odds ratio = 0.46, 95% CI: 0.14–1.51). Three participants experienced adverse events; none was related to trial participation. Conclusions Delivering a brief mindfulness-based inpatient intervention for psychosis is feasible and acceptable, and may reduce risk of short-term readmission. These promising findings warrant progression to a larger clinical effectiveness trial. Trial registration ISRCTN37625384 .

Background: Intervention Mapping (IM) is a systematic approach for developing theory-based interventions across a variety of contexts and settings. This paper describes the development of a complex intervention designed to reduce the dose of ultraviolet radiation (UVR) reaching the face of adults with Xeroderma Pigmentosum (XP), by improving photoprotection. XP is a genetic condition that without extreme UVR photoprotection, leads to high risk of developing skin cancer. Methods: The IM protocol of 6 steps was applied, involving comprehensive mixed-methods formative research. Key stakeholders (XP clinical staff and Patient and Public Involvement Panel), were instrumental at every step. Behaviour change methods were informed by the IM taxonomy, therapeutic approaches (e.g. ACT, CBT) and coded according to the taxonomy of behaviour change techniques (version 1). Results: We designed a personalised modular intervention to target psychosocial determinants of photoprotective activities that influence the amount of UVR reaching the face. Content was developed to target determinants of motivation to protect and factors preventing the enactment of behaviours. Participants received personalised content addressing determinants/barriers most relevant to them, as well as core ‘behaviour-change’ material, considered important for all (e.g. SMART goals). Core and personalised content was delivered via 7 one-to-one sessions with a trained facilitator using a manual and purpose designed materials: Magazine; text messages; sunscreen application video; goal-setting tools (e.g. UVR dial and face protection guide); activity sheets. Novel features included use of ACT-based values to enhance intrinsic motivation, targeting of emotional barriers to photoprotection, addressing appearance concerns and facilitating habit formation. Conclusion: IM was an effective approach for complex intervention design. The structure (e.g. use of matrices) tethered the intervention tightly to theory and evidence-based approaches. The significant amount of time required needs to be considered and may hinder translation of IM into clinical and non-academic settings.

Introduction The successful treatment of type 1 diabetes (T1D) requires those affected to employ insulin therapy to maintain their blood glucose levels as close to normal to avoid complications in the long-term. The Dose Adjustment For Normal Eating (DAFNE) intervention is a group education course designed to help adults with T1D develop and sustain the complex self-management skills needed to adjust insulin in everyday life. It leads to improved glucose levels in the short term (manifest by falls in glycated haemoglobin, HbA1c), reduced rates of hypoglycaemia and sustained improvements in quality of life but overall glucose levels remain well above national targets. The DAFNEplus intervention is a development of DAFNE designed to incorporate behavioural change techniques, technology and longer-term structured support from healthcare professionals (HCPs).Methods and analysis A pragmatic cluster randomised controlled trial in adults with T1D, delivered in diabetes centres in National Health Service secondary care hospitals in the UK. Centres will be randomised on a 1:1 basis to standard DAFNE or DAFNEplus. Primary clinical outcome is the change in HbA1c and the primary endpoint is HbA1c at 12 months, in those entering the trial with HbA1c >7.5% (58 mmol/mol), and HbA1c at 6 months is the secondary endpoint. Sample size is 662 participants (approximately 47 per centre); 92% power to detect a 0.5% difference in the primary outcome of HbA1c between treatment groups. The trial also measures rates of hypoglycaemia, psychological outcomes, an economic evaluation and process evaluation.Ethics and dissemination Ethics approval was granted by South West-Exeter Research Ethics Committee (REC ref: 18/SW/0100) on 14 May 2018. The results of the trial will be published in a National Institute for Health Research monograph and relevant high-impact journals.Trial registration number ISRCTN42908016.

Introduction Diabetes affects more than 425 million people worldwide with a lifetime risk of diabetic foot ulcer (DFU) of up to 25%. Management includes wound debridement, wound dressings, offloading, treatment of infection and ischaemia, optimising glycaemic control; use of advanced adjuvant therapies is limited by high cost and lack of robust evidence.Methods and analysis A multicentre, seamless phase II/III, open, parallel group, multi-arm multi-stage randomised controlled trial in patients with a hard-to-heal DFU, with blinded outcome assessment. A maximum of 447 participants will be randomised (245 participants in phase II and 202 participants in phase III). The phase II primary objective will determine the efficacy of treatment strategies including hydrosurgical debridement ± decellularised dermal allograft, or the combination with negative pressure wound therapy, as an adjunct to treatment as usual (TAU), compared with TAU alone, with patients randomised in a 1:1:1:2 allocation. The outcome is achieving at least 50% reduction in index ulcer area at 4 weeks post randomisation.The phase III primary objective will determine whether one treatment strategy, continued from phase II, reduces time to healing of the index ulcer compared with TAU alone, with participants randomised in a 1:1 allocation. Secondary objectives will compare healing status of the index ulcer, infection rate, reulceration, quality of life, cost-effectiveness and incidence of adverse events over 52 weeks post randomisation. Phase II and phase III primary endpoint analysis will be conducted using a mixed-effects logistic regression model and Cox proportional hazards regression, respectively. A within-trial economic evaluation will be undertaken; the primary economic analysis will be a cost-utility analysis presenting ICERs for each treatment strategy in rank order of effectiveness, with effects expressed as quality-adjusted life years.The trial has predefined progression criteria for the selection of one treatment strategy into phase III based on efficacy, safety and costs at 4 weeks.Ethics and dissemination Ethics approval has been granted by the National Research Ethics Service (NRES) Committee Yorkshire and The Humber - Bradford Leeds Research Ethics Committee; approved 26 April 2017; (REC reference: 17/YH/0055). There is planned publication of a monograph in National Institute for Health Research journals and main trial results and associated papers in high-impact peer-reviewed journals.Trial registration number ISRCTN64926597; registered on 6 June 2017

Auditory cortex neurons exhibit distinct frequency tuning to sound onset and offset. Here the authors demonstrate that during development ON-OFF receptive fields diverge to occupy adjacent frequency ranges that may underlie their direction selective responses to frequency modulated sweeps.

Cerebellar Purkinje cells (PCs) linearly encode whisker position but the precise circuit mechanisms that generate these signals are not well understood. Here the authors use patch clamp recordings to show that selective tuning of granule cell inputs and bidirectional tuning of interneuron inputs are required to generate the kinematic representations in PCs.

BackgroundMost sepsis and acute kidney injury (AKI) cases are community acquired (CA). The aim of this study was to evaluate the characteristics of suspected community acquired infection (sCA-I) and CA-AKI and their impact upon patient outcomes.MethodsAll adult creatinine blood tests from non-elective, non-dialysis attendances to a single centre over a 29-month period were analysed retrospectively. We defined sCA-I and CA-AKI cases as antibiotic prescription and AKI alert within 48 hours of attendance respectively. Binary logistic regression models were created to determine associations with 30-day mortality, intensive care unit (ICU) admission and length of stay (LOS) dichotomised at median.ResultsOf 61,471 attendances 28.1% and 5.7% suffered sCA-I or CA-AKI in isolation respectively, 3.4% suffered both. sCA-I was present in 58.8% of CA-AKI cases and CA-AKI was present in 11.9% of CA-I cases. The combination of sCA-I and CA-AKI was associated with a higher risk for all outcomes compared to sCA-I or CA-AKI in isolation. The 30-day mortality was 8.1%, 11.8% and 26.2% in patients with sCA-I, CA-AKI and when sCA-I and CA-AKI occurred in combination respectively. The adjusted odds ratios (OR) and 95% confidence intervals (CI) for 30-day mortality, ICU admission and LOS for sCA-I combined with CA-AKI stage 1 were OR 6.09:CI: 5.21-7.12, OR 12.52 CI: 10.54-14.88 and OR 8.97 CI: 7.62-10.56, respectively, and for combined sCA-I and CA-AKI stage 3 were OR 9.23 CI: 6.91-12.33, OR 29.26 CI: 22.46-38.18 and OR 9.48 CI: 6.82-13.18 respectively.ConclusionThe combination of sCA-I and CA-AKI is associated with worse outcomes.

Active whisking is an important model sensorimotor behavior, but the function of the cerebellum in the rodent whisker system is unknown. We have made patch clamp recordings from Purkinje cells in vivo to identify whether cerebellar output encodes kinematic features of whisking including the phase and set point. We show that Purkinje cell spiking activity changes strongly during whisking bouts. On average, the changes in simple spike rate coincide with or slightly precede movement, indicating that the synaptic drive responsible for these changes is predominantly of efferent (motor) rather than re-afferent (sensory) origin. Remarkably, on-going changes in simple spike rate provide an accurate linear read-out of whisker set point. Thus, despite receiving several hundred thousand discrete synaptic inputs across a non-linear dendritic tree, Purkinje cells integrate parallel fiber input to generate precise information about whisking kinematics through linear changes in firing rate.

Background: There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias. Objective: Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture. Design: Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria. Setting: Critical care departments within NHS hospitals in the north-west of England. Participants: Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation. Main outcome measures: SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard. Results: Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4–16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy. Conclusion: SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error. Study registration: The systematic review is registered as PROSPERO CRD42011001289. Funding: The National Institute for Health Research Health Technology Assessment programme. Professor Daniel McAuley and Professor Gavin D Perkins contributed to the systematic review through their funded roles as codirectors of the Intensive Care Foundation (UK).

BackgroundMindfulness as a mode of sustained and receptive attention promotes openness to each incoming stimulus, even if repetitive and/or aversive. Mindful attention has been shown to attenuate sensory habituation in expert meditators; however, others were not able to replicate this effect. The present study used acoustic startle reflex to investigate the effect of mindfulness practice intensity on sensory habituation.MethodsAuditory Startle Response (ASR) to 36 startling probes (12 trials x 3 block with 40 ms inter-block intervals), was measured using electromyography (EMG) in three groups of participants (N = 12/group): meditation-naïve, moderate practice, and intensive practice.ResultsIntensive practice group showed attenuated startle habituation as evidenced by significantly less habituation over the entire experiment relative to the meditation-naïve and moderate practice groups. Furthermore, there was a significant linear effect showing between-block habituation in meditation-naïve and moderate practice groups, but not in the intensive practice group. However, the Block x Group interaction between the intensive practice and the meditation-naive groups was not significant. Moderate practice group was not significantly different from the meditation-naïve in the overall measure of habituation, but showed significantly stronger habituation than both meditation-naïve and intensive practice groups in Block 1. Greater practice intensity was significantly correlated with slower overall habituation and habituation rate in Blocks 2 and 3 in the intensive, but not in the moderate, practice group.ConclusionsThe study provides tentative evidence that intensive mindfulness practice attenuates acoustic startle habituation as measured by EMG, but the effect is modest.Moderate practice, on the other hand, appears to enhance habituation, suggesting the effect of mindfulness practice on startle habituation might be non-linear [corrected] . Better understanding of the effect of mindful attention on startle habituation may shed new light on sensory information processing capacity of the human brain and its potential for de-automatisation of hard-wired processes.

[This corrects the article DOI: 10.1371/journal.pone.0123512.].

Background There is growing interest in the potential utility of real-time PCR in diagnosing bloodstream infection by detecting pathogen DNA in blood samples within a few hours. SeptiFast is a multipathogen probe-based real-time PCR system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection and has European regulatory approval. The SeptiFast pathogen panel is suited to identifying healthcare-associated bloodstream infection acquired during complex healthcare, and the authors report here the protocol for the first detailed health-technology assessment of multiplex real-time PCR in this setting.Methods/design A Phase III multicentre double-blinded diagnostic study will determine the clinical validity of SeptiFast for the rapid detection of healthcare-associated bloodstream infection, against the current service standard of microbiological culture, in an adequately sized population of critically ill adult patients. Results from SeptiFast and standard microbiological culture procedures in each patient will be compared at study conclusion and the metrics of clinical diagnostic accuracy of SeptiFast determined in this population setting. In addition, this study aims to assess further the preliminary evidence that the detection of pathogen DNA in the bloodstream using SeptiFast may have value in identifying the presence of infection elsewhere in the body. Furthermore, differences in circulating immune-inflammatory markers in patient groups differentiated by the presence/absence of culturable pathogens and pathogen DNA will help elucidate further the patho-physiology of infection developing in the critically ill.Ethics and dissemination Ethical approval has been granted by the North West 6 Research Ethics Committee (09/H1003/109). Based on the results of this first non-commercial study, independent recommendations will be made to The Department of Health (open-access health technology assessment report) as to whether SeptiFast has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.