A randomised trial of an internet weight control resource: The UK Weight Control Trial [ISRCTN58621669]

BACKGROUND: Obesity treatment is notoriously unsuccessful and one of the barriers to successful weight loss reported by patients is a lack of social support. The Internet offers a novel and fast approach to the delivery of health information, enabling 24-hour access to help and advice. However, much of the health information available on the Internet is unregulated or not written by qualified health professionals to provide unbiased information. The proposed study aims to compare a web-based weight loss package with traditional dietary treatment of obesity in participants. The project aims to deliver high quality information to the patient and to evaluate the effectiveness of this information, both in terms of weight loss outcomes and cost-effectiveness. METHODS: This study is a randomised controlled trial of a weight loss package against usual care provided within General Practice (GP) surgeries in Leeds, UK. Participants will be recruited via posters placed in participating practices. A target recruitment figure of 220 will enable 180 people to be recruited (allowing for 22% dropout). Participants agreeing to take part in the study will be randomly allocated using minimisation to either the intervention group, receiving access to the Internet site, or the usual care group. The primary outcome of the study will be the ability of the package to promote change in BMI over 6 and 12 months compared with traditional treatment. Secondary outcomes will be the ability of the Internet package to promote change in reported lifestyle behaviours. Data will be collected on participant preferences, adherence to treatment, health care use and time off work. Difference in cost between groups in provision of the intervention and the cost of the primary outcome will also be estimated. CONCLUSION: A positive result from this study would enhance the repertoire of treatment approaches available for the management of obesity. A negative result would be used to inform the research agenda and contribute to redefining future strategies for tackling obesity

What factors promote student resilience on a level 1 distance learning module?

Resilience is understood to be the ability to adapt positively in the face of adversity. In relation to new students on a distance learning module, this can mean how they adapt and make sense of the demands of their chosen study to enable them to persist in their studies. This article reports a small-scale study involving semistructured telephone interviews with students on a level 1 distance learning module at the UK Open University. Students identified the challenges they experienced such as carving out time to study alongside other commitments, as well as developing their academic writing. Students also identified factors that enabled them to adapt to these challenges and be successful in continuing to study. Students rated highly the support they received from tutors in the form of tailored, detailed feedback on their assignments. Other factors that enabled students to persist in their studies were time management, self-belief and motivation

Attributing scientific and technical progress: the case of holography

Holography, the three-dimensional imaging technology, was portrayed widely as a paradigm of progress during its decade of explosive expansion 1964–73, and during its subsequent consolidation for commercial and artistic uses up to the mid 1980s. An unusually seductive and prolific subject, holography successively spawned scientific insights, putative applications and new constituencies of practitioners and consumers. Waves of forecasts, associated with different sponsors and user communities, cast holography as a field on the verge of success—but with the dimensions of success repeatedly refashioned. This retargeting of the subject represented a degree of cynical marketeering, but was underpinned by implicit confidence in philosophical positivism and faith in technological progressivism. Each of its communities defined success in terms of expansion, and anticipated continual progressive increase. This paper discusses the contrasting definitions of progress in holography, and how they were fashioned in changing contexts. Focusing equally on reputed ‘failures’ of some aspects of the subject, it explores the varied attributes by which success and failure were linked with progress by different technical communities. This important case illuminates the peculiar post-World War II environment that melded the military, commercial and popular engagement with scientific and technological subjects, and the competing criteria by which they assessed the products of science

The Internet for weight control in an obese sample: results of a randomised controlled trial

Rising levels of obesity coupled with the limited success of currently available weight control methods highlight the need for investigation of novel approaches to obesity treatment. This study aims to determine the effectiveness and cost-effectiveness of an Internet-based resource for obesity management

Fanny Copeland and the geographical imagination

Raised in Scotland, married and divorced in the English south, an adopted Slovene, Fanny Copeland (1872 – 1970) occupied the intersection of a number of complex spatial and temporal conjunctures. A Slavophile, she played a part in the formation of what subsequently became the Kingdom of Yugoslavia that emerged from the First World War. Living in Ljubljana, she facilitated the first ‘foreign visit’ (in 1932) of the newly formed Le Play Society (a precursor of the Institute of British Geographers) and guided its studies of Solčava (a then ‘remote’ Alpine valley system) which, led by Dudley Stamp and commended by Halford Mackinder, were subsequently hailed as a model for regional studies elsewhere. Arrested by the Gestapo and interned in Italy during the Second World War, she eventually returned to a socialist Yugoslavia, a celebrated figure. An accomplished musician, linguist, and mountaineer, she became an authority on (and populist for) the Julian Alps and was instrumental in the establishment of the Triglav National Park. Copeland’s role as participant observer (and protagonist) enriches our understanding of the particularities of her time and place and illuminates some inter-war relationships within G/geography, inside and outside the academy, suggesting their relative autonomy in the production of geographical knowledge

M-theory lift of brane-antibrane systems and localised closed string tachyons

We discuss the lift of certain D6-antiD6-brane systems to M-theory. These are purely gravitational configurations with a bolt singularity. When reduced along a trivial circle, and for large bolt radius, the bolt is related to a non-supersymmetric orbifold type of singularity where some closed string tachyons are expected in the twisted sectors. This is a kind of open-closed string duality that relates open string tachyons on one side and localised tachyons in the other. We consider the evolution of the system of branes from M-theory point of view. This evolution gives rise to a brane-antibrane annihilation on the brane side. On the gravity side, the evolution is related to a reduction of the order of the orbifold and to a contraction of the bolt to a nut or flat space if the system has non-vanishing or vanishing charge, respectively. We also consider the inverse process of reducing a non-supersymmetric orbifold to a D6-brane system. For $C^2/Z_N\times Z_M$, the reduced system is a fractional D6-brane at an orbifold singularity $C/Z_M$.Comment: 1+22 pages, 5 figures; v2 comments on the M-theory geometry and further references adde

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin