911 resultados para galaxies: groups: individual (HCG 7)
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We present the Pan-STARRS1 discovery and light curves, and follow-up MMT and Gemini spectroscopy of an ultraluminous supernova (ULSN; dubbed PS1-11bam) at a redshift of z = 1.566 with a peak brightness of M UV ≈ -22.3 mag. PS1-11bam is one of the highest redshift spectroscopically confirmed SNe known to date. The spectrum exhibits broad absorption features typical of previous ULSNe (e.g., C II, Si III), and strong and narrow Mg II and Fe II absorption lines from the interstellar medium (ISM) of the host galaxy, confirmed by an [O II]λ3727 emission line at the same redshift. The equivalent widths of the Fe II λ2600 and Mg II λ2803 lines are in the top quartile of the quasar intervening absorption system distribution, but are weaker than those of gamma-ray burst intrinsic absorbers (i.e., GRB host galaxies). We also detect the host galaxy in pre-explosion Pan-STARRS1 data and find that its UV spectral energy distribution is best fit with a young stellar population age of τ* ≈ 15-45 Myr and a stellar mass of M * ≈ (1.1-2.6) × 109 M ⊙ (for Z = 0.05-1 Z ⊙). The star formation rate inferred from the UV continuum and [O II]λ3727 emission line is ≈10 M ⊙ yr-1, higher than in previous ULSN hosts. PS1-11bam provides the first direct demonstration that ULSNe can serve as probes of the ISM in distant galaxies. The depth and red sensitivity of PS1 are uniquely suited to finding such events at cosmologically interesting redshifts (z ~ 1-2); the future combination of LSST and 30 m class telescopes promises to extend this technique to z ~ 4.
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The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.
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Jayne Tierney and colleagues offer guidance on how to spot a well-designed and well-conducted individual participant data meta-analysis.
Summary Points
• Systematic reviews are most commonly based on aggregate data extracted from publications or obtained from trial investigators.
• Systematic reviews involving the central collection and analysis of individual participant data (IPD) usually are larger-scale, international, collaborative projects that can bring about substantial improvements to the quantity and quality of data, give greater scope in the analyses, and provide more detailed and robust results.
• The process of collecting, checking, and analysing IPD is more complex than for aggregate data, and not all IPD meta-analyses are done to the same standard, making it difficult for researchers, clinicians, patients, policy makers, funders, and publishers to judge their quality.
• Following our step-by-step guide will help reviewers and users of IPD meta-analyses to understand them better and recognise those that are well designed and conducted and so help ensure that policy, practice, and research are informed by robust evidence about the effects of interventions.
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Photooxidative damage was induced predominantly at a single guanine base in a target DNA by irradiation (lambda > 330 nm) in the presence of complementary oligodeoxynucleotide conjugates (ODN-5'-linker-[Ru(phen)3]2+) (phen = 1,10-phenanthroline). The target DNA represents the b2a2 variant of the chimeric bcr-abl gene implicated in the pathogenesis of chronic myeloid leukaemia, and the sequence of the 17mer ODN component of the conjugate (3' G G T A G T T A T T C C T T C T T 5') was complementary to the junction region of the sense strand sequence of this oncogene. Two different conjugates were prepared, both of them by reaction of the appropriate succinimide ester with 5'-hexylamino-derivatised 17mer ODN. In Ru-ODN-1 (7) the linker was -(CH2)6-NHCO-bpyMe (-bpyMe = 4'-[4-methyl-2,2'-bipyridyl]), whereas in Ru-ODN-2 (13) it was -(CH2)6-NHCO-(CH2)3-CONH-phen. Photoexcitation of either of the conjugates when hybridised with the 32P-5'-end-labelled target 34mer 5'T G A C C A T C A A T A A G G A A G A A G21 C C C T T C A G C G G C C 3' (ODN binding site underlined) led to an alkali-labile site predominantly (> 90%) at the G21 base, which is at the junction of double-stranded and single-stranded regions of the hybrid. Greater yields were found with Ru-ODN-1 (7) than with Ru ODN-2 (13). In contrast to this specific cleavage with Ru-ODN-1 (7) or Ru-ODN-2 (13), alkali-labile sites were generated at all guanines when the 34mer was photolysed in the presence of the free sensitiser [Ru(phen)3]2+. Since [Ru(phen)3]2+ was shown to react with 2'-deoxyguanosine to form the diastereomers of a spiroiminodihydantoin derivative (the product from 1O2 reaction), 1O2 might also be an oxidizing species in the case of Ru-ODN-1 (7) and Ru-ODN-2 (13). Therefore to determine the range of reaction, a series of 'variant' targets was prepared, in which G21 was replaced with a cytosine and a guanine substituted for a base further towards the 3'-end (e.g. Variant 3; 5'T G A C C A T C A A T A A G G A A G A A C C G23 C T T C A G C G G32 C C3'). While it was noted that efficient reaction took place at distances apparently remote from the photosensitiser (e.g at G32, but not G23 for Variant 3), this effect could be attributed to hairpinning of the single-stranded region of the target. These results are therefore consistent with the photooxidative damage being induced by a reaction close to the photosensitiser rather than by a diffusible species such as 1O2.
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The fortuitous occurrence of a type II-Plateau (IIP) supernova, SN 2014bc, in a galaxy for which distance estimates from a number of primary distance indicators are available provides a means with which to cross-calibrate the standardised candle method (SCM) for type IIP SNe. By applying calibrations from the literature we find distance estimates in line with the most precise measurement to NGC 4258 based on the Keplerian motion of masers (7:6 ± 0:23 Mpc), albeit with significant scatter. We provide an alternative local SCM calibration by only considering type IIP SNe that have occurred in galaxies for which a Cepheid distance estimate is available. We find a considerable reduction in scatter (σ<inf>I</inf> = 0:16 mag), but note that the current sample size is limited. Applying this calibration, we estimate a distance to NGC 4258 of 7:08 ± 0:86 Mpc.
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We present optical and near-infrared (NIR) photometry and spectroscopy as well as modelling of the lightcurves of the Type IIb supernova (SN) 2011dh. Our extensive dataset, for which we present the observations obtained after day 100, spans two years, and complemented with Spitzer mid-infrared (MIR) data, we use it to build an optical-to-MIR bolometric lightcurve between days 3 and 732. To model the bolometric lightcurve before day 400 we use a grid of hydrodynamical SN models, which allows us to determine the errors in the derived quantities, and a bolometric correction determined with steady-state non-local thermodynamic equilibrium (NLTE) modelling. Using this method we find a helium core mass of 3.1<sup>+0.7</sup><inf>-0.4</inf> M<inf>⊙</inf> for SN 2011dh, consistent within error bars with previous results obtained using the bolometric lightcurve before day 80. We compute bolometric and broad-band lightcurves between days 100 and 500 from spectral steady-state NLTE models, presented and discussed in a companion paper. The preferred 12 M<inf>⊙</inf> (initial mass) model, previously found to agree well with the observed spectra, shows a good overall agreement with the observed lightcurves, although some discrepancies exist. Time-dependent NLTE modelling shows that after day ∼600 a steady-state assumption is no longer valid. The radioactive energy deposition in this phase is likely dominated by the positrons emitted in the decay of <sup>56</sup>Co, but seems insufficient to reproduce the lightcurves, and what energy source is dominating the emitted flux is unclear. We find an excess in the K and the MIR bands developing between days 100 and 250, during which an increase in the optical decline rate is also observed. A local origin of the excess is suggested by the depth of the He I 20 581 Å absorption. Steady-state NLTE models with a modest dust opacity in the core (τ = 0.44), turned on during this period, reproduce the observed behaviour, but an additional excess in the Spitzer 4.5 μm band remains. Carbon-monoxide (CO) first-overtone band emission is detected at day 206, and possibly at day 89, and assuming the additional excess to bedominated by CO fundamental band emission, we find fundamental to first-overtone band ratios considerably higher than observed in SN 1987A. The profiles of the [O i] 6300 Å and Mg i] 4571 Å lines show a remarkable similarity, suggesting that these lines originate from a common nuclear burning zone (O/Ne/Mg), and using small scale fluctuations in the line profiles we estimate a filling factor of ≲ 0.07 for the emitting material. This paper concludes our extensive observational and modelling work on SN 2011dh. The results from hydrodynamical modelling, steady-state NLTE modelling, and stellar evolutionary progenitor analysis are all consistent, and suggest an initial mass of ∼12 M<inf>⊙</inf> for the progenitor.
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BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.
METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights.
FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease.
INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems.
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Wnt/β-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.
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PURPOSE: To utilize focus groups (FGs) to identify barriers to cataract surgery specific to older persons in rural Guangdong, China. METHODS: Three focus groups in separate locations were carried out for persons aged 60 years and above with best-corrected vision <= 6/18 due to cataract, either accepting or refusing surgery. Participants also ranked responses to questions about acceptance of surgery among the elderly. FG transcripts were coded independently by two investigators using qualitative data management software. RESULTS: Twenty participants had a mean age of 72.7 ± 6.1 years, 14 (70.0%) were women and 17 (85.0%) were blind (best-corrected vision <= 6/60) in at least one eye. Cost was ranked by two of three groups as the main barrier to surgery, and all groups listed reducing cost as the best strategy to increase surgical uptake. Many respondents planned to use China's New Cooperative Medical Scheme (NCMS) health insurance to pay for surgery. Participants showed poor understanding of cataract, but ranked educational interventions low as methods of increasing uptake. Though opinions of local service quality were poor, respondents did not see quality as an important barrier to accepting service. Participants frequently depended on family members to pay for surgery. CONCLUSIONS: Contrary to some previous reports, cost may be an important barrier to cataract surgery in rural China, which NCMS may help to alleviate. Educational interventions to increase knowledge about cataract are needed, but may face skepticism among patients. Strategies to promote cataract surgery should target the entire family.
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Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.
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OBJECTIVES: The Shape of Training report recommended that full registration is aligned with medical school graduation. As part of a General Medical Council-funded study about the preparedness for practice of UK medical graduates, we explored UK stakeholders' views about this proposal using qualitative interviews (30 group and 87 individual interviews) and Framework Analysis.
SETTING: Four UK study sites, one in each country.Save
PARTICIPANTS: 185 individuals from eight stakeholder groups: (1) foundation year 1 (F1) doctors (n=34); (2) fully registered trainee doctors (n=33); (3) clinical educators (n=32); (4) undergraduate/postgraduate Deans, and Foundation Programme Directors (n=30); (5) other healthcare professionals (n=13); (6) employers (n=7); (7) policy and government (n=11); (8) patient and public representatives (n=25).
RESULTS: We identified four main themes: (1) The F1 year as a safety net: patients were protected by close trainee supervision and 'sign off' to prevent errors; trainees were provided with a safe environment for learning on the job; (2) Implications for undergraduate medical education: if the proposal was accepted, a 'radical review' of undergraduate curricula would be needed; undergraduate education might need to be longer; (3) Implications for F1 work practice: steps to protect healthcare team integration and ensure that F1 doctors stay within competency limits would be required; (4) Financial, structural and political implications: there would be cost implications for trainees; clarification of responsibilities between undergraduate and postgraduate medical education would be needed. Typically, each theme comprised arguments for and against the proposal.
CONCLUSIONS: A policy change to align the timing of full registration with graduation would require considerable planning and preliminary work. These findings will inform policymakers' decision-making. Regardless of the decision, medical students should take on greater responsibility for patient care as undergraduates, assessment methods in clinical practice and professionalism domains need development, and good practice in postgraduate supervision and support must be shared.
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Introduction: The objectives of this study were to examine relationships between neighbourhood-level and individual-level characteristics and physical activity in deprived London neighbourhoods. Methods: In 40 of the most deprived neighbourhoods in London (ranked in top 11% in London by Index of Multiple Deprivation) a cross-sectional survey (n = 4107 adults aged > = 16 years), neighbourhood audit tool, GIS measures and routine data measured neighbourhood and individual-level characteristics. The binary outcome was meeting the minimum recommended (CMO, UK) 5×30 mins moderate physical activity per week. Multilevel modelling was used to examine associations between physical activity and individual and neighbourhood-level characteristics. Results: Respondents living more than 300 m away from accessible greenspace had lower odds of achieving recommended physical activity levels than those who lived within 300 m; from 301–600 m (OR = 0.7; 95% CI 0.5–0.9) and from 601–900 m (OR = 0.6; 95% CI 0.4–0.8). There was substantial residual between-neighbourhood variance in physical activity (median odds ratio = 1.7). Other objectively measured neighbourhood-level characteristics were not associated with physical activity levels. Conclusions Distance to nearest greenspace is associated with meeting recommended physical activity levels in deprived London neighbourhoods. Despite residual variance in physical activity levels between neighbourhoods, we found little evidence for the influence of other measured neighbourhood-level characteristics.
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Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431–1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1–14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life.
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Introduction The objectives of this study were to examine relationships between neighbourhood-level and individual-level characteristics and physical activity in deprived London neighbourhoods. Methods In 40 of the most deprived neighbourhoods in London (ranked in top 11% in London by Index of Multiple Deprivation) a cross-sectional survey (n = 4107 adults aged > = 16 years), neighbourhood audit tool, GIS measures and routine data measured neighbourhood and individual-level characteristics. The binary outcome was meeting the minimum recommended (CMO, UK) 5×30 mins moderate physical activity per week. Multilevel modelling was used to examine associations between physical activity and individual and neighbourhood-level characteristics. Results Respondents living more than 300 m away from accessible greenspace had lower odds of achieving recommended physical activity levels than those who lived within 300 m; from 301–600 m (OR = 0.7; 95% CI 0.5–0.9) and from 601–900 m (OR = 0.6; 95% CI 0.4–0.8). There was substantial residual between-neighbourhood variance in physical activity (median odds ratio = 1.7). Other objectively measured neighbourhood-level characteristics were not associated with physical activity levels. Conclusions Distance to nearest greenspace is associated with meeting recommended physical activity levels in deprived London neighbourhoods. Despite residual variance in physical activity levels between neighbourhoods, we found little evidence for the influence of other measured neighbourhood-level characteristics.
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Background The practice of reading and discussing literature in groups is long established, stretching back into classical antiquity (Fischer, 2004). While benefits of therapeutic reading groups have been highlighted, research into participants’ perceptions of these groups has been limited (Walwyn & Rowley, 2011). Aims To explore the experiences of those attending therapeutic reading groups, considering the role of both the group, and the literature itself, in participants’ ongoing experiences of distress. Method Eleven participants were recruited from two reading groups in the South East of England. One focus group was run, and eight individuals self selected for individual interviews. The data were analysed together using a thematic analysis drawing on dialogical theories. Results Participants described the group as an anchor, which enabled them to use fiction to facilitate the discussion of difficult emotional topics, without referring directly to personal experience. Two aspects of this process are explored in detail: the use of narratives as transportation, helping to mitigate the intensity of distress; and using fiction to explore possibilities, alternative selves and lives. Conclusions For those who are interested and able, reading groups offer a relatively de-stigmatised route to exploring and mediating experiences of distress. Implications in the present UK funding environment are discussed.