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\"It's been decades since Governor Lex Luthor turned Gotham City into a modern utopia, saving his people from the devastation that made the rest of the continent a wasteland. But his city isn't paradise for everyone. If the Lexes Network misfires, and a citizen wakes up and steps out of line, the Bat and his minions are brutal in restoring the status quo. So when young Kara Gordon, whose ridealong tech has never functioned optimally, rushes headlong into the Freescape, she's shocked to find Gotham City Garage--where new friends might become family, if she lives long enough!\"-- Provided by publisher.

IntroductionCommunity pharmacists and their teams have remained accessible to the public providing essential services despite immense pressures during the COVID-19 pandemic. They have successfully expanded the influenza vaccination programme and are now supporting the delivery of the COVID-19 vaccination roll-out.AimThis rapid realist review aims to understand how community pharmacy can most effectively deliver essential and advanced services, with a focus on vaccination, during the pandemic and in the future.MethodAn embryonic programme theory was generated using four diverse and complementary documents along with the expertise of the project team. Academic databases, preprint services and grey literature were searched and screened for documents meeting our inclusion criteria. The data were extracted from 103 documents to develop and refine a programme theory using a realist logic of analysis. Our analysis generated 13 context-mechanism-outcome configurations explaining when, why and how community pharmacy can support public health vaccination campaigns, maintain essential services during pandemics and capitalise on opportunities for expanded, sustainable public health service roles. The views of stakeholders including pharmacy users, pharmacists, pharmacy teams and other healthcare professionals were sought throughout to refine the 13 explanatory configurations.ResultsThe 13 context-mechanism-outcome configurations are organised according to decision makers, community pharmacy teams and community pharmacy users as key actors. Review findings include: supporting a clear role for community pharmacies in public health; clarifying pharmacists’ legal and professional liabilities; involving pharmacy teams in service specification design; providing suitable guidance, adequate compensation and resources; and leveraging accessible, convenient locations of community pharmacy.DiscussionCommunity pharmacy has been able to offer key services during the pandemic. Decision makers must endorse, articulate and support a clear public health role for community pharmacy. We provide key recommendations for decision makers to optimise such a role during these unprecedented times and in the future.

Feedback inhibitory motifs are thought to be important for pattern separation across species. How feedback circuits may implement pattern separation of biologically plausible, temporally structured input in mammals is, however, poorly understood. We have quantitatively determined key properties of netfeedback inhibition in the mouse dentate gyrus, a region critically involved in pattern separation. Feedback inhibition is recruited steeply with a low dynamic range (0% to 4% of active GCs), and with a non-uniform spatial profile. Additionally, net feedback inhibition shows frequency-dependent facilitation, driven by strongly facilitating mossy fiber inputs. Computational analyses show a significant contribution of the feedback circuit to pattern separation of theta modulated inputs, even within individual theta cycles. Moreover, pattern separation was selectively boosted at gamma frequencies, in particular for highly similar inputs. This effect was highly robust, suggesting that frequency-dependent pattern separation is a key feature of the feedback inhibitory microcircuit. You can probably recall where you left your car this morning without too much trouble. But assuming you use the same busy parking lot every day, can you remember which space you parked in yesterday? Or the day before that? Most people find this difficult not because they cannot remember what happened two or three days ago, but because it requires distinguishing between very similar memories. The car, the parking lot, and the time of day were the same on each occasion. So how do you remember where you parked this morning? This ability to distinguish between memories of similar events depends on a brain region called the hippocampus. A subregion of the hippocampus called the dentate gyrus generates different patterns of activity in response to events that are similar but distinct. This process is called pattern separation, and it helps ensure that you do not look for your car in yesterday’s parking space. Pattern separation in the dentate gyrus is thought to involve a form of negative feedback called feedback inhibition, a phenomenon where the output of a process acts to limit or stop the same process. To test this idea, Braganza et al. studied feedback inhibition in the dentate gyrus of mice, before building a computer model simulating the inhibition process and supplying the model with two types of realistic input. The first consisted of low-frequency theta brainwaves, which occur, for instance, in the dentate gyrus when animals explore their environment. The second consisted of higher frequency gamma brainwaves, which occur, for example, when animals experience something new. Testing the model showed that feedback inhibition contributes to pattern separation with both theta and gamma inputs. However, pattern separation is stronger with gamma input. This suggests that high frequency brainwaves in the hippocampus could help animals distinguish new events from old ones by promoting pattern separation. Various brain disorders, including Alzheimer’s disease, schizophrenia and epilepsy, involve changes in the dentate gyrus and altered brain rhythms. The current findings could help reveal how these changes contribute to memory impairments and to a reduced ability to distinguish similar experiences.

When Rebecca Lister and Tony Kelly move from Melbourne to Mount Isa to care for Rebecca's elderly mother, Diana, they have no idea what they've signed up for.The isolation, sweltering heat, and limited employment opportunities make settling into the mining town a challenge.

Background People from Black African Diaspora Communities (BAFDC) experience poorer health outcomes and are persistently under‐represented in health and care research. There is limited understanding about how to support their greater inclusion and participation. Objectives Explore secondary data providing insights for the co‐development of a realist theory of inclusion and participation for people from BAFDC in health and care research in the United Kingdom. Drawing on these theories, co‐produce a realist review with a diverse range of people from BAFDC. Methods A realist approach underpinned the study. Pawson's five steps to a realist approach were taken to shape the review, identify relevant sources, extract the data and then analyse and synthesise to inform an overarching programme theory. Initial programme theories (IPTs) were developed through context (C), mechanism (M), outcome (O) configurations (CMOCs). Main Results The review identified 43 relevant documents. Synthesis of evidence from the documents resulted in 8 IPTs and 17 CMOCs helping to understand and explain the inclusion and participation of people from BAFDC. Four key thematic clusters emerged: (1) Health and care research as a White space, (2) Trust deficit: the expansiveness of broken trust, (3) Implicit and complicit bias and (4) Processes that affect inclusion and participation. Findings were underpinned by five existing mid‐range theories (MRTs) around central concepts of candidacy, social dominance, networks, narratives and racism that guided analysis and synthesis, supporting conceptualisation of CMOCs. An overarching programme theory was developed. Conclusion The review identifies how the influence of perspectives, attitudes and beliefs held by individuals or groups about people from BAFDC operates in health and care research, resulting in exclusion, lack of trust and deficit thinking. The findings should be used to inform interventions aimed at increasing inclusion and participation of people from BAFDC. Patient or Public Contribution The co‐production group comprised a diverse range of individuals from within the health and care research system with different lived experiences of being Black. They contributed to the entire review process, including the development of initial programme theories and retroductive thinking and interpretation of the evidence. Clinical Trial Registration Not applicable.

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca 2+ microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca 2+ microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca 2+ microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca 2+ -indicator AAV transduction procedures can produce artefactual Ca 2+ responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca 2+ microwaves, and we provide a potential solution.

IntroductionPeople from Black African Diaspora Communities (BAFDC) experience poorer health outcomes, have many long-term conditions and are persistently under-represented in health and care research. There is limited focus on programmes, or interventions that support inclusion and participation of people from BAFDC in research. Through coproduction, this realist review seeks to provide a programme theory explaining what context and mechanisms may be required, to produce outcomes that facilitate inclusion and participation for people from BAFDC in health and care research, in the UK.Methods and analysisA group of people from BAFDC with lived and professional experience, representing all levels of the health and care research system, will coproduce a realist review with a team of African-Caribbean, white British and white British of Polish origin health and care researchers. They will follow Pawson’s five steps: (1) shaping the scope of the review; (2) searching for evidence; (3) document selection and appraisal; (4) data extraction and (5) data synthesis. The coproduction group will help to map the current landscape, identifying key issues that may inhibit or facilitate inclusion. Data will be extracted, analysed and synthesised following realist logic analysis, identifying and explaining how context and mechanisms are conceptualised in the literature and the types of contextual factors that exist and impact on inclusion and participation. Findings will be reported in accordance with Realist and Meta-narrative Evidence Synthesis Evolving Standards .Ethics and disseminationThe coproduction group will agree an ethical approach considering accountability, responsibility and power dynamics, by establishing a terms of reference, taking a reflexive approach and coproducing an ethical framework. Findings will be disseminated to BAFDC and the research community through arts-based methods, peer-reviewed publications and conference presentations, agreeing a coproduced strategy for dissemination. Ethical review is not required.PROSPERO registration numberCRD42024517124.

ObjectiveTo derive a new maternity early warning score (MEWS) from prospectively collected data on maternity vital signs and to design clinical response pathways with a Delphi consensus exercise.DesignCentile based score development and Delphi informed escalation pathways.SettingPregnancy Physiology Pattern Prediction (4P) prospective UK cohort study, 1 August 2012 to 28 December 2016.ParticipantsPregnant people from the 4P study, recruited before 20 weeks' gestation at three UK maternity centres (Oxford, Newcastle, and London). 841, 998, and 889 women provided data in the early antenatal, antenatal, and postnatal periods.Main outcome measuresDevelopment of a new national MEWS, assigning numerical weights to measurements in the lower and upper extremes of distributions of individual vital signs from the 4P prospective cohort study. Comparison of escalation rates of the new national MEWS with the Scottish and Irish MEWS systems from 18 to 40 weeks' gestation. Delphi consensus exercise to agree clinical responses to raised scores.ResultsA new national MEWS was developed by assigning numerical weights to measurements in the lower and upper extremes (5%, 1%) of distributions of vital signs, except for oxygen saturation where lower centiles (10%, 2%) were used. For the new national MEWS, in a healthy population, 56% of observation sets resulted in a total score of 0 points, 26% a score of 1 point, 12% a score of 2 points, and 18% a score of ≥2 points (escalation of care is triggered at a total score of ≥2 points). Corresponding values for the Irish MEWS were 37%, 25%, 22%, and 38%, respectively; and for the Scottish MEWS, 50%, 18%, 21%, and 32%, respectively. All three MEWS were similar at the beginning of pregnancy, averaging 0.7-0.9 points. The new national MEWS had a lower mean score for the rest of pregnancy, with the mean score broadly constant (0.6-0.8 points). The new national MEWS had an even distribution of healthy population alerts across the antenatal period. In the postnatal period, heart rate threshold values were adjusted to align with postnatal changes. The centile based score derivation approach meant that each vital sign component in the new national MEWS had a similar alert rate. Suggested clinical responses to different MEWS values were agreed by consensus of an independent expert panel.ConclusionsThe centile based MEWS alerted escalation of care evenly across the antenatal period in a healthy population, while reducing alerts in healthy women compared with other MEWS systems. How well the tool predicted adverse outcomes, however, was not assessed and therefore external validation studies in large datasets are needed. Unlike other MEWS systems, the new national MEWS was developed with prospectively collected data on vital signs and used a systematic, expert informed process to design an associated escalation protocol.

Background Patient and Public Involvement (PPI) in clinical trial research is recognised as relevant but the active involvement of patients and the public in basic science or laboratory-based research is seen as more challenging and not often reported. PPI within the UK Coronavirus Immunology Consortium (UK-CIC), a translational research project aimed at tackling some of the key questions about the immune system’s response to SARS-CoV-2, is an example of overcoming negative perceptions and obstacles. Given the widespread impact of COVID-19, it was important to consider the impact of UK-CIC research on patients and the public throughout, and the PPI panel were an integral part of the consortium. Findings Building in funding for a PPI panel to value involvement and ensuring effective expert administrative support and management of PPI were crucial to success. Facilitating relationships and quality interactions between public contributors and researchers required time and commitment to the project from all parties. Through creating a platform and open space to explore diverse views and a wide range of perspectives, PPI was able to influence researchers’ ways of thinking about their research and impact future research questions about COVID-19 immunology. Moreover, there was long-term impact from the involvement of the PPI panel in COVID-19 research and their value was reflected in invitations to contribute to additional immunology projects. Conclusion The ability to conduct meaningful PPI with basic immunology research has been shown possible through the UK-CIC in the context of the fast-moving COVID-19 pandemic. The UK-CIC project has laid the foundations for PPI in immunology and this should now be built upon for the advantage of future basic scientific research; PPI can impact greatly on laboratory-based research when given the opportunity to do so. Plain English summary The UK Coronavirus Immunology Consortium (UK-CIC) was established to address key questions about the immune system’s response to SARS-CoV-2, the virus which caused the COVID-19 pandemic, to benefit patient and public health at pace. The project brought together immunology laboratory-based research with the lived experience of patient and public contributors to ensure that the priorities for these groups and impacts of the research on the wider public were considered throughout. A Patient and Public Involvement (PPI) panel was set up to meet regularly with the scientists to provide a unique perspective, ask pertinent questions about the implications of the research, and discuss what was important to the public and patient groups. This paper examines the practical resources, support, and relationship building necessary to embed PPI in basic scientific research as well as how this can be achieved within urgent, critical research conducted during a pandemic situation. It explores the successes, impacts and legacy of involvement for researchers, the research, and importantly, the patient and public contributors. By sharing experiences from UK-CIC to help dispel any existing misconceptions that PPI can act as a hindrance, this paper proposes greater encouragement of PPI in all basic science research.

People of Black African and Black Caribbean ethnicity experience higher rates and poorer outcomes of type 2 diabetes (T2D) than people of White European ethnicity; these inequalities are compounded by poor healthcare access. Cultural tailoring of diabetes self-management education and support (DSMES) programs has the potential to improve healthcare engagement and clinical outcomes for ethnic minority groups. Healthy Eating & Active Lifestyles for Diabetes (HEAL-D) is a co-designed, culturally tailored group-based DSMES program for adults of Black African and Black Caribbean ethnicity. This trial aims to evaluate the clinical and cost effectiveness of the HEAL-D intervention, compared to standard DSMES programs, in Black African and Black Caribbean adults living with T2D. A 24-month, multicenter, pragmatic, open-label, 2-arm, parallel-group, individually randomized group treatment trial will be conducted, with primary end point (glycated hemoglobin [HbA ]) assessment at 12 months. Black African and Black Caribbean adults with T2D (n=300), recruited from 3 to 5 centers in the United Kingdom (including London, West Midlands, and Greater Manchester), will be randomized in a 1:1 ratio to HEAL-D (intervention) or a standard DSMES program (control). HbA , blood lipids, anthropometric outcomes, blood pressure, physical activity, and patient-reported outcome measures relating to psychological well-being and self-management support, lifestyle behaviors, and health economics will be collected at baseline and follow-up visits (6, 12, and 24 months). Cost-effectiveness will be assessed through a cost-utility analysis conducted from a health and social care perspective. A mixed methods process evaluation will provide a formative evaluation of delivery, intervention fidelity, and implementation of HEAL-D, and an embedded study within a project will assess the impact of multiple long-term conditions on uptake of, and engagement with HEAL-D, and the impact of HEAL-D on multiple long-term conditions. The trial received Research Authority and Research Ethics Council approval on April 22, 2024. Funding began in August 2023. Site \"green light\" was received on August 15, 2024, for London; November 29, 2024, for Manchester; and January 31, 2025, for the West Midlands. Recruitment commenced in August 2024 and is due to run for 11 months. As of March 26, 2025, a total of 76 participants have consented. Last patient, last visit is expected in June 2027; primary data analysis is expected to begin in July 2027. Final results are anticipated to be available in September 2027, and publication is expected by the end of 2027. The HEAL-D trial will address whether a culturally tailored DSMES program, provided in-person or via videoconferencing, is clinically and cost-effective compared to standard DSMES at improving diabetes management in Black African and Black Caribbean adults. If effective, this would provide an evidence-based model of equitable DSMES services and improve the implementation of healthcare programs for ethnic minority groups. ISRCTN 1434448; https://www.isrctn.com/ISRCTN14344948. DERR1-10.2196/71861.