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    Patterning of the cell cortex by Rho GTPase Dynamics

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    The Rho GTPases — RHOA, RAC1 and CDC42 — are small GTP binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. This regulation results from active (GTP-bound) Rho GTPases stimulating target proteins that, in turn, promote actin assembly and myosin 2-based contraction to organize the cortex. This basic regulatory scheme, well supported by in vitro studies, led to the natural assumption that Rho GTPases function in vivo in an essentially linear matter, with a given process being initiated by GTPase activation and terminated by GTPase inactivation. However, a growing body of evidence based on live cell imaging, modelling and experimental manipulation indicates that Rho GTPase activation and inactivation are often tightly coupled in space and time via signalling circuits and networks based on positive and negative feedback. In this Review, we present and discuss this evidence, and we address one of the fundamental consequences of coupled activation and inactivation: the ability of the Rho GTPases to self-organize, that is, direct their own transition from states of low order to states of high order. We discuss how Rho GTPase self-organization results in the formation of diverse spatiotemporal cortical patterns such as static clusters, oscillatory pulses, travelling wave trains and ring-like waves. Finally, we discuss the advantages of Rho GTPase self-organization and pattern formation for cell function

    The opportunity and desire to buy:Owner-occupation in Scotland’s new towns, c. 1950-80

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    This article explores the role of the post-war new towns in Scotland in providing people with the opportunity to own their own homes. Most importantly, it traces the development of this policy prior to the ‘Right to Buy’ of the early 1980s when tenants were offered substantial discounts by local authorities, housing associations and crucially, new town development corporations. The article challenges the dominance of rented tenure in existing accounts of Scottish housing, showing that there was demand in Scotland in the decades before the introduction of incentives. This article takes a ‘top down’ and ‘bottom up’ approach to understand a period of expanding opportunity for some, though not all, of those relocating and starting new lives in East Kilbride, Glenrothes and Cumbernauld. Archive evidence exploring policy and the response of the new town development corporations is complemented by analysis of life narratives provided by those that moved to the new towns and their children. In doing so, this article contributes to a growing scholarship that challenges stereotypical perceptions of class and identity in the immediate post-war decades whilst also revealing new insights into the post-war state as an enabler of opportunity for some

    Does energy efficiency of UK SMEs affect their access to finance?

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    To effectively mitigate climate change, a crucial focus area is enhancing energy efficiency in firms and industries. This objective becomes even more imperative in light of the recent escalation in energy prices caused by the Russo-Ukrainian war. Given the limited financial resources of Small and Medium Enterprises (SMEs), facilitating their access to finance becomes a potential avenue for reducing carbon emissions. Based on our knowledge, this is the first study that analyses the potential impact of energy efficiency on access to finance for SMEs in the UK. We consider a dataset of 2,855 UK firms from 2015 to 2021 collected from the Longitudinal Small Business Survey. We find that energy efficient companies and firms that show energy saving behaviours are facing fewer credit constraints. These results are robust if we control for several company characteristics, including age, size, turnover, industry, location, and legal status

    Evidence from the future

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    The outcome of any scientific experiment or intervention will naturally unfold over time. How then should individuals make causal inferences from measurements over time? Across three experiments, we had participants observe experimental and control groups over several days post-treatment in a fictional biological research setting. We identify competing perspectives in the literature: Contingency-driven accounts predict no effect of outcome timing while the contiguity principle suggests people will view a treatment as more harmful to the extent that bad treatment outcomes occur earlier rather than later. In contrast, inference to the functional form of a treatment effect can license extrapolation beyond the measurements and lead to different causal inferences. We find participants’ causal strength and direction judgments in temporal settings vary with minimal manipulations of instruction framing. When it is implied that the observations are made over a pre-planned number of days, causal judgments depend strongly on contiguity. When it is implied that the observation may be ongoing, participants extrapolate current trends into the future and adapt their causal judgments accordingly. When data are revealed sequentially, participants rely on extrapolation regardless of instruction framing. Our results demonstrate human flexibility in interpreting temporal evidence for causal reasoning and emphasize human tendency to generalize from evidence in ways that are acutely sensitive to task framing

    Self-expansion perceptions and behaviors uniquely contribute to relationship quality over time

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    Self-expansion refers to the process of broadening the self via engaging in novel activities, gaining new skills and acquiring new perspectives, and is proposed to be driven in a large part by one’s close relationships. Self-expansion experiences include perceptions of potential (i.e., beliefs about how self-expanding a relationship could be in the future), perceptions of current experiences (i.e., beliefs about how self-expanding a relationship is presently), and enacted behaviors (i.e., engagement in novel, interesting activities). In two preregistered dyadic daily experience studies, we examined whether self-expansion potential is an antecedent to behavioral self-expansion and current perceptions, and how these distinct self-expansion components uniquely and synergistically predict relationship satisfaction and commitment daily and over time. Results revealed that self-expansion potential prospectively predicted both behavioral self-expansion and daily perceptions of current self-expansion. Self-expansion potential, current perceptions, and behaviors separately predicted greater relationship satisfaction and commitment daily. Self-expansion potential—but not behaviors or current perceptions—also positively predicted satisfaction and commitment two months later. Implications regarding the power of potential in relationships are discussed, including the need for future research to consider this important facet of self-expansion

    Practicalities of promoting practice-based learning in end of life care for care home staff:lessons from ‘online’ group supportive reflection sessions

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    IntroductionDeaths in care homes and “at home” are anticipated to account for a third of UK deaths by 2040. Currently, palliative and end of life care are not part of statutory training in care homes. Reflective practice is a tool that can facilitate practice-based learning and support. Following a feasibly study to test “online” supportive conversations and reflection sessions (OSCaRS) to support care home staff in relation to death/dying during the first months of the COVID pandemic, a one-year practice development follow-up project was undertaken with the aim to create a team of NHS/specialist palliative care (SPC)-based facilitators to lead and support OSCaRS provision in up to 50 care homes in one region in Scotland—the focus of this paper.MethodsForty care home managers attended an on-line session explaining the project, with a similar session held for 19 NHS/SPC-based nurses external to care homes. Those interested in facilitating OSCaRS then attended three education sessions. Data collected: records of all activities; reflective notes on OSCaRS organised/delivered; a summary of each OSCaRS reflection/learning points; final interviews with NHS/SPC trainee facilitators.ResultsA total of 19 NHS/SPC facilitators delivered one or more OSCaRS in 22 participating care homes. However, as of January 2022 only six trained facilitators remained active. Out of the 158 OSCaRS arranged, 96 took place with a total of 262 staff attending. There were three important aspects that emerged: the role, remit, and resources of NHS/SPC supporting OSCaRS; requirements within care homes for establishing OSCaRS; and, the practice-based learning topics discussed at each OSCaRS.ConclusionAttempts to establish a team of NHS/SPC facilitators to lead OSCaRS highlights that end of life care education in care homes does not clearly fall within the contractual remit of either group or risks being missed due to more pressing priorities.<br/

    Delirium detection tools show varying completion rates and positive score rates when used at scale in routine care:A systematic review

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    Background: Multiple short delirium detection tools have been validated in research studies and implemented in routine care, but there has been little study of these tools in real-world conditions. This systematic review synthesized literature reporting completion rates and/or delirium positive score rates of detection tools in large clinical populations in general hospital settings.Methods: PROSPERO (CRD42022385166).Medline, Embase, PsycINFO, CINAHL, and gray literature were searched from1980 to December 31, 2022. Included studies or audit reports used a validateddelirium detection tool performed directly with the patient as part of routinecare in large clinical populations (n ≥ 1000) within a general acute hospitalsetting. Narrative synthesis was performed.Results: Twenty-two research studies and four audit reports were included.Tools used alone or in combination were the Confusion Assessment Method(CAM), 4 ‘A's Test (4AT), Delirium Observation Screening Scale (DOSS), BriefCAM (bCAM), Nursing Delirium Screening Scale (NuDESC), and IntensiveCare Delirium Screening Checklist (ICDSC). Populations and settings variedand tools were used at different stages and frequencies in the patient journey,including on admission only; inpatient, daily or more frequently; on admissionand as inpatient; inpatient post-operatively. Tool completion rates ranged from19% to 100%. Admission positive score rates ranged from: CAM 8%–51%; 4AT13%–20%. Inpatient positive score rates ranged from: CAM 2%–20%, DOSS 6%–42%, and NuDESC 5–13%. Postoperative positive score rates were 21% and28% (4AT). All but two studies had moderate–high risk of bias.Conclusions: This systematic review of delirium detection tool implementation in large acute patient populations found clinically important variability intool completion rates, and in delirium positive score rates relative to expecteddelirium prevalence. This study highlights a need for greater reporting andanalysis of relevant healthcare systems data. This is vital to advance understanding of effective delirium detection in routine car

    The disease burden of respiratory syncytial virus in older adults

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    Purpose of reviewTo highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through analysis of RSV epidemiology and the effectiveness of emerging vaccines.Recent findingsIn industrialized countries, RSV incidence rates and hospitalization rates among older adults stand at 600.7 cases per 100,000 person-years and 157 hospitalizations per 100,000 person-years, respectively. Yet, accurately determining RSV morbidity and mortality in older adults is challenging, thus resulting in substantially under-estimating the disease burden. The in-hospital fatality rates vary substantially with age and geographies, sometimes reaching up to 9.1% in developing countries. Two promising RSV vaccines for the elderly have been approved, showcasing efficacies of up to 94.1%, signifying considerable advancement in RSV prevention. However, concerns over potential side effects remain. SummaryRSV is associated with a significant burden in older adults. While the landscape of RSV prevention in older adults is promising with the licensure of vaccines from two companies, current trial data underscore the need for additional studies. Addressing the real-world effectiveness of these vaccines, understanding potential rare side effects, and ensuring broad inclusivity in future trials are crucial steps to maximize their potential benefits.<br/

    Characterization and Control of the Run-and-Tumble Dynamics of Escherichia Coli

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    We characterize the full spatiotemporal gait of populations of swimming Escherichia coli using renewal processes to analyze the measurements of intermediate scattering functions. This allows us to demonstrate quantitatively how the persistence length of an engineered strain can be controlledby a chemical inducer and to report a controlled transition from perpetual tumbling to smooth swimming. For wild-type E. coli, we measure simultaneously the microscopic motility parameters and the large-scale effective diffusivity, hence quantitatively bridging for the first time small-scale directed swimming and macroscopic diffusion

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