Travel from Durham to York (and back) in the fourteenth century

Legal documents provide rare evidence of routes taken by those travelling between the city of Durham and York, and information about crossings of the Tees. There are also indications of the staging posts and of different times taken for each journey

Linking secondary school physical education with community sport and recreation for girls: a process evaluation

Background: The purpose of this study was to undertake a process evaluation to examine the reach, adoption and implementation of a school-community linked physical activity (PA) program for girls aged 12 - 15 years (School Years 7 - 9) using the RE-AIM framework.Methods. Various approaches were used to assess 'reach', 'adoption' and implementation: (a) a school environment survey of intervention schools (n = 6); (b) teacher feedback regarding the professional development component (91.1% response rate) and lesson implementation (60.8% response rate); and (c) post-intervention focus group interviews with physical education (PE) teachers (n = 29), students (n = 125), coaches (n = 13) and instructors (n = 8) regarding program experiences. However, there was a lack of individual and organisational readiness to adopt program principles. For some deliverers there were deeply embedded ideologies that were not aligned with the Game Sense teaching approach upon which the program was based. Further, cognitive components of the program such as self-management were not widely adopted as other components of the program tended to be prioritised. Conclusion: The program design and resources supported the success of the program, however, some aspects were not implemented as intended, which may have affected the likelihood of achieving further positive outcomes. Barriers to program implementation were identified and should be considered when designing school-community linked interventions. In particular, future programs should seek to assess and adjust for organizational readiness within the study design. For example, shared commitment and abilities of program deliverers to implement the program needs to be determined to support program implementation

Participation in modified sports programs: a longitudinal study of children’s transition to club sport competition

Background Many children are not physically active enough for a health benefit. One avenue of physical activity is modified sport programs, designed as an introduction to sport for young children. This longitudinal study identified trends in participation among children aged 4–12 years. Outcomes included continuation in the modified sports program, withdrawal from the program or transition to club sport competition. Methods De-identified data on participant membership registrations in three popular sports in the Australian state of Victoria were obtained from each sport’s state governing body over a 4-year period (2009–2012 for Sport A and 2010–2013 for Sports B and C). From the membership registrations, those who were enrolled in a modified sports program in the first year were tracked over the subsequent three years and classified as one of: transition (member transitioned from a modified sport program to a club competition); continue (member continued participation in a modified sport program; or withdraw (member discontinued a modified program and did not transition to club competition). Results Many modified sports participants were very young, especially males aged 4–6 years. More children withdrew from their modified sport program rather than transitioning. There were age differences between when boys and girls started, withdrew and transitioned from the modified sports programs. Conclusions If we can retain children in sport it is likely to be beneficial for their health. This study highlights considerations for the development and implementation of sport policies and programming to ensure lifelong participation is encouraged for both males and females

Missense Mutation R338W in ARHGEF9 in a Family with X-linked Intellectual Disability with Variable Macrocephaly and Macro-Orchidism

Non-syndromal X-linked intellectual disability (NS-XLID) represents a broad group of clinical disorders in which ID is the only clinically consistent manifestation. Although in many cases either chromosomal linkage data or knowledge of the >100 existing XLID genes has assisted mutation discovery, the underlying cause of disease remains unresolved in many families. We report the resolution of a large family (K8010) with NS-XLID, with variable macrocephaly and macro-orchidism. Although a previous linkage study had mapped the locus to Xq12-q21, this region contained too many candidate genes to be analyzed using conventional approaches. However, X-chromosome exome sequencing, bioinformatics analysis and segregation analysis revealed a novel missense mutation (c.1012C>T; p.R338W) in ARHGEF9. This gene encodes collybistin (CB), a neuronal GDP-GTP exchange factor previously implicated in several cases of XLID, as well as clustering of gephyrin and GABAA receptors at inhibitory synapses. Molecular modeling of the CB R338W substitution revealed that this change results in the substitution of a long electropositive side-chain with a large non-charged hydrophobic side-chain. The R338W change is predicted to result in clashes with adjacent amino acids (K363 and N335) and disruption of electrostatic potential and local folding of the PH domain, which is known to bind phosphatidylinositol-3-phosphate (PI3P/PtdIns-3-P). Consistent with this finding, functional assays revealed that recombinant CB CB2SH3- (R338W) was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Taken together, these results suggest that the R338W mutation in ARHGEF9 is the underlying cause of NS-XLID in this family

The contribution of sport participation to overall health enhancing physical activity levels in Australia: A population-based study

Background: The contribution of sport to overall health-enhancing leisure-time physical activity (HELPA) in adults is not well understood. The aim was to examine this in a national sample of Australians aged 15+ years, and to extend this examination to other ostensibly sport-associated activities. Methods: The 2010 Exercise, Recreation and Sport Survey (ERASS) was conducted by telephone interview in four quarterly waves. Data from this survey were analysed to categorise leisure-time physical activity (LTPA) as HELPA or non-HELPA, and to categorise HELPA activities and sessions of HELPA activity by setting and frequency. The contribution of sport to HELPA was estimated, both directly through activities and settings classified as sport per se, and indirectly through other fitness activities ostensibly related to preparation for sport and enhancement of sport performance. Results: Of 21,602 respondents, 82 % reported some LTPA in the 12 months prior to the survey. In aggregate, respondents reported 37,020 activity types in the previous 12 months, of which 94 % were HELPA. Of HELPA activities, 71 % were non-organised, 11 % were organised but not sport club-based, and 18 % were sport club-based. Of all sport activities, 52 % were HELPA. Of sport HELPA, 33 % was sport club-based and 78 % was undertaken ≥12 times/year. Sport club members were significantly more likely to have participated in running, but significantly less likely to have participated in walking or aerobics/fitness training, than non-club members. Conclusions: Club sport participation contributes considerably to LTPA at health enhancing levels. Health promotion policies, and more specifically physical activity policies, should emphasize the role of sport in enhancing health. Sport policy should recognise the health-promoting role of community-based sport in addition to the current predominant focus on elite pathways. © 2015 Eime et al

Understanding patient options, utilization patterns, and burdens associated with breast cancer screening.

Abstract Despite ongoing awareness, educational campaigns, and advances in technology, breast cancer screening remains a complex topic for women and for the health care system. Lack of consensus among organizations developing screening guidelines has caused confusion for patients and providers. The psychosocial factors related to breast cancer screening are not well understood. The prevailing algorithm for screening results in significant rates of patient recall for further diagnostic imaging or procedures, the majority of which rule out breast cancer rather than confirming it. For women, the consequences of the status quo range from unnecessary stress to additional out-of-pocket expenses to indirect costs that are more difficult to quantify. A more thoughtful approach to breast cancer screening, coupled with a research agenda that recognizes the indirect and intangible costs that women bear, is needed to improve cost and quality outcomes in this area

Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy. MATERIALS AND METHODS: We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines. RESULTS: Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling. CONCLUSION: The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM

Inverse Association between trans Isomeric and Long-Chain Polyunsaturated Fatty Acids in Pregnant Women and Their Newborns: Data from Three European Countries

Background: trans unsaturated fatty acids are thought to interfere with essential fatty acid metabolism. To extend our knowledge of this phenomenon, we investigated the relationship between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their infants at birth. Methods: Fatty acid composition of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and 30th week of gestation, at delivery and in their newborns. Results: At the 20th week of gestation, the sum of trans fatty acids in PE was significantly (p < 0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values in PE were significantly (p < 0.01) higher in Hungarian {[}5.65 (2.09)] than in Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p < 0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women, and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001), but not in Hungarian (r = -0.02) women. Significant inverse correlations were seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n = 241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in cord lipids (n = 218, r = -0.28, p < 0.001). Conclusion: Because humans cannot synthesize trans isomeric fatty acids, the data obtained in the present study support the concept that high maternal trans isomeric fatty acid intake may interfere with the availability of LCPUFA both for the mother and the fetus. Copyright (C) 2011 S. Karger AG, Base

Clinical and Immunologic Investigations in Patients With Stiff-Person Spectrum Disorder

Importance: Symptoms of stiff-person syndrome (SPS), stiff-limb syndrome (SLS), or progressive encephalomyelitis with rigidity, myoclonus, or other symptoms (SPS-plus) can occur with several autoantibodies, but the relative frequency of each antibody, syndrome specificity, and prognostic implications are unclear. Objective: To report the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD), including SPS, SLS, and SPS-plus. Design, Setting, and Patients: This study retrospectively examined a case series (January 1, 1998, through December 31, 2014) of immunologic investigations performed in a neuroimmunology referral center. The study included 121 patients with clinical features of SPSD. Data analysis was performed from July 1, 2015, through November 1, 2015. Main Outcomes and Measures: Analysis of clinical-immunologic associations, including autoantibodies to 8 proteins expressed in inhibitory synapses. Results: The median age of the patients was 51 years (interquartile range, 40-61 years), and 75 (62.0%) were female. Fifty (41.3%) had SPS, 37 (30.6%) had SPS-plus, 24 (19.8%) had SLS, and 10 (8.3%) had SPS or SLS overlapping with ataxia, epilepsy, or encephalitis. Fifty-two patients (43.0%) had glutamic acid decarboxylase (GAD65) antibodies (2 with γ-aminobutyric acid-A [GABA-A] receptor antibodies), 24 (19.8%) had α1-subunit of the glycine receptor (GlyR) antibodies (2 with GAD65 antibodies), 5 (4.1%) had other antibodies, and 40 (33.1%) tested negative for antibodies. None had gephyrin or glycine transporter antibodies. Among the main immunologic groups (GAD65 antibodies, GlyR antibodies, and antibody negative), those with GAD65 antibodies were more likely to be female (45 [86.5%] of 52, 8 [36.4%] of 22, and 18 [45.0%] of 40, respectively; P < .001), have systemic autoimmunity (34 [65.4%] of 52, 7 [31.8%] of 22, and 13 [32.5%] of 40, respectively; P = .004), and have longer delays in being tested for antibodies (median, 3 vs 0.5 and 1 year; P < .001). Patients with GAD65 antibodies were more likely to develop SPS (27 [51.9%] of 52) or overlapping syndromes (8 [15.4%] of 52) than patients with GlyR antibodies (5 [22.7%] and 0 [0%] of 22, respectively), who more often developed SPS-plus (12 [54.5%] of 22 vs 7 [13.5%] in those with GAD65 antibodies); antibody-negative patients had an intermediate syndrome distribution. In multivariable analysis, symptom severity (P = .001) and immunologic group (P = .01) were independently associated with outcome. Compared with patients with GlyR antibodies, those with GAD65 antibodies (odds ratio, 11.1, 95% CI, 2.3-53.7; P = .003) had worse outcome. Patients without antibodies had similar outcome than patients with GlyR antibodies (odds ratio, 4.2, 95% CI, 0.9-20.0; P = .07). Conclusions and Relevance: In SPSD, symptom severity and presence and type of antibodies are predictors of outcome

Effects of UV-B radiation on the structural and physiological diversity of bacterioneuston and bacterioplankton

The effects of UV radiation (UVR) on estuarine bacterioneuston and bacterioplankton were assessed in microcosm experiments. Bacterial abundance and DNA synthesis were more affected in bacterioplankton. Protein synthesis was more inhibited in bacterioneuston. Community analysis indicated that UVR has the potential to select resistant bacteria (e.g., Gammaproteobacteria), particularly abundant in bacterioneuston