Beyond cycle lanes and large-scale infrastructure: a scoping review of initiatives that groups and organisations can implement to promote cycling for the Cycle Nation Project

Background/objectives: Cycling has well-established positive relationships with health. Evidence suggests that large-scale infrastructure and built-environment initiatives to promote cycling are likely to be necessary but not sufficient to maximise cycling participation. Smaller-scale initiatives that can be implemented by organisations (eg, employers) and groups (eg, community groups) are therefore also important, but the full range of feasible activities to promote cycling is not known. We aimed to scope the literature and map organisational, social and individual level activities to increase cycling.MethodsDesign: Scoping review following an established five-stage process.Eligibility criteria: Studies or publicly available reports describing cycling promotion initiatives deemed feasible for organisations or groups to implement.Sources of evidence and selection: (i) online databases (Ovid (Medline), Ovid (Embase), SportDISCUS (Ebscohost), ProQuest, Web of Science), (ii) existing systematic reviews, (iii) expert stakeholder consultation.Results: We extracted data from 129 studies and reports, from 20 different countries, identifying 145 cycling promotion initiatives. From these initiatives we identified 484 actions within 93 action types within 33 action categories under the nine intervention functions described by Michie et al. Environmental restructuring (micro-level), enablement, education and persuasion were the functions with the most action types, while coercion, modelling and restriction had the fewest action types.Conclusion: This is the first comprehensive map to summarise the broad range of action types feasible for implementation within organisation/group-based cycling promotion initiatives. The map will be a critical tool for communities, employers, practitioners and researchers in designing interventions to increase cycling

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

Best practices for addressing missing data through multiple imputation

A common challenge in developmental research is the amount of incomplete and missing data that occurs from respondents failing to complete tasks or questionnaires, as well as from disengaging from the study (i.e., attrition). This missingness can lead to biases in parameter estimates and, hence, in the interpretation of findings. These biases can be addressed through statistical techniques that adjust for missing data, such as multiple imputation. Although multiple imputation is highly effective, it has not been widely adopted by developmental scientists given barriers such as lack of training or misconceptions about imputation methods. Utilizing default methods within statistical software programs like listwise deletion is common but may introduce additional bias. This manuscript is intended to provide practical guidelines for developmental researchers to follow when examining their data for missingness, making decisions about how to handle that missingness and reporting the extent of missing data biases and specific multiple imputation procedures in publications

Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. An observational follow-up study

BackgroundThe optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown.MethodsWe identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (⩽ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting.ResultsOf 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ⩾ 7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%).ConclusionOur analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression

A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli

Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3

Influence of GluN2 subunit identity on NMDA receptor function

AbstractN-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels (‘ionotropic’ receptors) activated by the major excitatory neurotransmitter, l-glutamate. While the term ‘the NMDAR’ is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling.This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’

Accelerometer Measured Levels of Moderate-to-Vigorous Intensity Physical Activity and Sedentary Time in Children and Adolescents with Chronic Disease: a Systematic Review and Meta-Analysis

Context: Moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) are important for child and adolescent health. Objective: To examine habitual levels of accelerometer measured MVPA and ST in children and adolescents with chronic disease, and how these levels compare with healthy peers. Methods: Data sources: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus and CINAHL from 2000–2017. Study selection: Studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 hours/day to provide estimates of habitual levels) in children 0–19 years of age with chronic diseases but without co-morbidities that would present major impediments to physical activity. In all cases patients were studied while well and clinically stable. Results: Out of 1592 records, 25 studies were eligible, in four chronic disease categories: cardiovascular disease (7 studies), respiratory disease (7 studies), diabetes (8 studies), and malignancy (3 studies). Patient MVPA was generally below the recommended 60 min/day and ST generally high regardless of the disease condition. Comparison with healthy controls suggested no marked differences in MVPA between controls and patients with cardiovascular disease (1 study, n = 42) and type 1 diabetes (5 studies, n = 400; SMD -0.70, 95% CI -1.89 to 0.48, p = 0.25). In patients with respiratory disease, MVPA was lower in patients than controls (4 studies, n = 470; SMD -0.39, 95% CI -0.80, 0.02, p = 0.06). Meta-analysis indicated significantly lower MVPA in patients with malignancies than in the controls (2 studies, n = 90; SMD -2.2, 95% CI -4.08 to -0.26, p = 0.03). Time spent sedentary was significantly higher in patients in 4/10 studies compared with healthy control groups, significantly lower in 1 study, while 5 studies showed no significant group difference. Conclusions: MVPA in children/adolescents with chronic disease appear to be well below guideline recommendations, although comparable with activity levels of their healthy peers except for children with malignancies. Tailored and disease appropriate intervention strategies may be needed to increase MVPA and reduce ST in children and adolescents with chronic disease