Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium.

Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines

Evidence-based practice: a practice manual.

The Practice Manual is set out in five colour-coded chapters with each chapter corresponding to one of the five basic steps of EBP. Use the colour-coded tabs to quickly refer to the section of the Practice Manual you need. We hope that you find the guide useful and informative and that it can help improve the quality of patient care in your ward, unit or other clinical setting

Efficacy of an intensive outpatient rehabilitation program in alcoholism: Predictors of outcome 6 months after treatment

Treatment of alcohol-dependent patients was primarily focused on inpatient settings in the past decades. The efficacy of these treatment programs has been evaluated in several studies and proven to be sufficient. However, with regard to the increasing costs in public healthcare systems, questions about alternative treatment strategies have been raised. Meanwhile, there is growing evidence that outpatient treatment might be comparably effective as inpatient treatment, at least for subgroups of alcohol dependents. On that background, the present study aimed to evaluate the efficacy of a high-structured outpatient treatment program in 103 alcohol-dependent patients. 74 patients (72%) terminated the outpatient treatment regularly. At 6 months' follow-up, 95% patients were successfully located and personally re-interviewed. Analyses revealed that 65 patients (64%) were abstinent at the 6-month follow-up evaluation and 37 patients ( 36%) were judged to be non-abstinent. Pretreatment variables which were found to have a negative impact (non-abstinence) on the 6-month outcome after treatment were a higher severity of alcohol dependence measured by a longer duration of alcohol dependence, a higher number of prior treatments and a stronger alcohol craving (measured by the Obsessive Compulsive Drinking Scale). Further patients with a higher degree of psychopathology measured by the Beck Depression Inventory (depression) and State-Trait Anxiety Inventory (anxiety) relapsed more often. In summary, results of this study indicate a favorable outcome of socially stable alcohol-dependent patients and patients with a lower degree of depression, anxiety and craving in an intensive outpatient rehabilitation program

Converting the United States and United Kingdom defence sector to civil production: the views of defence workers

There are many social, environmental, and economic reasons for converting from defence manufacturing to civil production. Importantly, such a transformation could support more peace in the world while still ensuring the secure jobs that the defence sector has historically provided. The views of defence workers on such a transition are important to understanding how this change could effectively and equitably occur. To capture some of these views, the research project on which this paper is based involved interviewing 58 former and current defence sector workers in the United States and the United Kingdom and convening key leadership focus groups which included their trade union representatives. Though these workers' opinions were not entirely polarized and some interviewees had mixed and nuanced views, they loosely fell into three categories (a) opposed to defence diversification, (b) supportive of defence diversification, and (c) supportive in principle but thought that it would be unlikely to happen. The (a) category of defence workers primarily based their view on the idea that the defence sector is necessary for security and a feeling of pride in supporting this endeavor. The (b) category views were built on the perceived harm of the sector, the potential ‘peace dividend’ that would arise from transition, and feelings of guilt about working in the sector. The (c) group of workers identified the profit motive, worker attachment to defence jobs, technological issues, and the economic and political power of the defence companies as the key barriers to change. Proposals for effectively converting included economic incentives, government regulation, and organizing trade unions to push for change. A unified view was that workers want to be involved in discussions about these issues in their workplace and unions

Urban blue acupuncture:A protocol for evaluating a complex landscape design intervention to improve health and wellbeing in a coastal Ccommunity

Within the BlueHealth project, funded under the Horizon 2020 European Union researchframework, a number of targeted experimental design interventions were used to test the effectand impact of planning and design on encouraging people to use various blue spaces. Complexinterventions were implemented and evaluations before and after each were made using a set oftools which triangulate with each other—a site assessment tool, a behaviour observation tool, aquestionnaire survey (including an economic evaluation) and qualitative interviews. The theoreticalbasis for the research is that of affordances, and the projects each involved modest changes to thelandscape using the approach of “urban acupuncture” where a small intervention can potentiallyhave an effect out of all proportion to the investment. This paper is a protocol paper and describesthe research strategy and methodology in detail for one of the intervention sites, located in Plymouthin the UK. The aim is to present the methodology as a whole so as to act as (a) a reference frameworkfor the results of all the projects which will be reported separately in a series of research articles onceall the results are in and analysed and (b) a useful reference for other researchers wishing to carry outsuch complex projects and where a comprehensive presentation of the strategy and methodology isunavailable. We offer this protocol for reference, for critique and for inspiration to those following us

Estuarine Processes and Their Stratigraphic Record: Paleosalinity and Sedimentation Changes in the Hudson Estuary (North America)

Paleosalinity estimates and rates of sedimentation inferred from core samples from the Hudson estuary for the interval between 6.4 and 1.3 ka indicate a possible role for the estuarine turbidity maximum (ETM) in influencing patterns of estuarine sedimentation at centennial to millennial time scales. Currently in the estuary, sedimentation is localized via sediment trapping particularly in the vicinity of the ETM, 13–26 km upstream from Battery Park (FBP) at the southern tip of Manhattan, in water depths greater than 4 m, and on the western side of the estuary. Data presented in this paper are from cores located within the segment of the estuary 29–50 km FBP. Age constraints are provided by C-14 dating. Paleoenvironmental interpretations are based upon paleosalinity estimates, grain size variability, and sedimentary structures. Paleosalinity was inferred on the basis of foraminiferal biofacies analysis and a new method for estimating summertime paleosalinity using oxygen isotope measurements in bivalve shell material. The isotopic analysis of a narrow size fraction (1.0–1.7 mm) representing summer growth of a single bivalve species (Gemma gemma) reduces the uncertainty related to annual changes in temperature. Data from ∼45 km FBP indicate a gradual decrease in summertime paleosalinity between 6.4 and 2.0 ka from 25–20‰ to 15–10‰ (the latter is similar to present-day values). These results are consistent with the conclusion of an earlier low-resolution study. Sedimentation rates are generally low and are similar to the rate of sea-level rise in the Hudson River. Lowest sedimentation rates are noted in short (lower than 2 m) cores from north of the Tappan Zee Bridge (40–50 km FBP from 2.4 ka to present); in shallow water (∼2 m at mean low water, core SD-11) ∼45 km FBP; and on the eastern side of the estuary from ∼50 to 29 km FBP. Exceptions are high sedimentation rates (up to four times background) observed in cores from the western flats (SD 30, ∼45 km FBP, 4.9 to 3.4 ka) in water depths of 4 m and from the western part of the main channel (P21.7 core, ∼32 km FBP, greater than 2.3 to ∼1.3 ka). We hypothesize that the observed pattern in sediment accumulation relates to a location for the ETM some 20 km upstream of its present position at 3 ka. Downstream migration of the ETM since 3 ka is ascribed to shoaling of the estuary, effectively squeezing the marine saltwater wedge in the same direction, and off marginal flats into the channel. Such shoaling would have enhanced the role of waves in mixing marine and fresher surface water, and reduced the effect of the ETM in focusing sediment accumulation. The results of this study are consistent with the idea that at any time, estuarine sedimentation is highly localized, suggesting a more complex depositional pattern than previously indicated in estuarine stratigraphic models

Urban blue space renovation and local resident and visitor well-being:A case study from Plymouth, UK

Observational studies have suggested that people with better access to attractive, safe, and inclusive blue spaces enjoy higher psychological well-being, with particular benefits for those living in deprived urban areas. However, intervention studies are scarce. To help bridge this gap we conducted a repeat cross-sectional study exploring local resident and visitor well-being before and after a small-scale intervention aimed at improving the quality of an urban beach area in a deprived neighbourhood in Plymouth, United Kingdom. Physical alterations were co-created with local stakeholders and residents, and accompanied by a series of on-site community events. Key outcomes were self-reported psychological well-being, satisfaction with personal safety and community belonging, and perceptions of site quality. Adjusted linear models showed that positive well-being (B = 7.42; 95% CI = 4.18–10.67) and life satisfaction (B = 0.40; 95% CI = 0.11–0.70) were both higher after the intervention compared to before, with associations for life satisfaction stronger among those who visited the site in the last four weeks. Associations with positive well-being were partially mediated by greater satisfaction with community belonging; and associations with life satisfaction were partially and independently mediated by greater satisfaction with personal safety and community belonging. Although caution needs to be taken due to the repeat cross-sectional design and the sampling of site visitors as well as local residents, the findings support the idea that environmental improvements to urban blue spaces can foster better psychological well-being, and underline the importance of community involvement in the process

HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.

BACKGROUND: Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings. CONCLUSIONS/SIGNIFICANCE: The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined